- randomn thoughts that cross my mind.
Treatment of allergic rhinitis can improve blood pressure control.
http://www.nature.com.libproxy1.nus.edu.sg/jhh/journal/v20/n11/abs/1002088a.html;jsessionid=71A8C061270F3E1BC7102C07264E51F6
Owing to high prevalence of arterial hypertension (AH) and allergic rhinitis (AR), these diseases frequently coexist. The study aimed to assess whether improvement of AR by conventional treatment can improve blood pressure (BP) control in this population. Sixty-eight subjects of both sexes aged 35–60 years with AR and AH were randomized into two groups to receive in addition to their antihypertensive medications: treatment group (n=34) Fluticasone nasal 50 g/spray b.i.d. and Fenoxifenadine 180 mg tablets q.d., and control group (n=34) 0.9% NaCl nasal drops b.i.d. Office BP and AR severity (using the Relative Quality of Life Questionnaire (RQLQ)) and high-sensitive C-reactive protein (hs-CRP) were measured at study entry and after 8 weeks in both groups, without changing of antihypertensive medications. In Treatment group an improvement in RQLQ, significant reduction of systolic BP (SBP) (DSBP 7.44.3 mm Hg, P=0.006) and reduction of hs-CRP level (DCRP 2.051.08; P=0.028) were observed, whereas diastolic BP (DBP) remained unchanged (DDBP 0.91.7 mm Hg, P=0.7). There was a significant correlation between DRQLQ and DSBP (r=0.86; P=0.019) and between DCRP and DSBP (r=0.56; P=0.027). No statistically significant changes of RQLQ, BP and CRP were observed in the control group. In patients with coincidence of AH and AR, medications meant to improve AR attenuate low-grade systemic inflammation and can lower SBP, but not DBP.
Friday, April 20, 2007
Wednesday, April 18, 2007
Tuesday, April 17, 2007
Improtant Articles - Hypertension
Rationale and design of the Dietary Approaches to Stop Hypertension trial (DASH). A multicenter controlled-feeding study of dietary patterns to lower blood pressure. 1: Ann Epidemiol. 1995 Mar;5(2):108-18
Epidemiologic studies have found that dietary patterns characterized by high intakes of certain minerals and fiber are associated with low blood pressure. Dietary Approaches to Stop Hypertension (DASH) is a multicenter, randomized, controlled-feeding trial designed to test the effects on blood pressure of two such dietary patterns consumed for 8 weeks. The two experimental diets will be compared with each other and with a control dietary pattern that is relatively low in potassium, magnesium, calcium, and fiber, and has a fat and protein profile mirroring current US consumption. The first experimental diet, arguably termed “ideal,” is high in fruits, vegetables, whole cereal products, low-fat dairy products, fish, chicken, and lean meats designed to be low in saturated fat and cholesterol; moderately high in protein; and high in minerals and fiber. The second experimental diet tests the effect of fruits and vegetables alone. Its potassium, magnesium, and dietary fiber content will be at the same high levels as the ideal dietary pattern, while its fat, protein, and calcium content will resemble that of the control dietary pattern. The study population will consist of 456 healthy men and women, aged 22 years or older, with systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg. African-American and other minority groups will comprise 67% of the population. Participants will eat one of the three dietary patterns. The DASH trial has unique features. First, dietary patterns rather than single nutrients are being tested. Second, all food for the experimental diets is provided to the participants using a standardized multicenter protocol. Because the dietary patterns are constructed with commonly consumed food items, the results, if positive, may be conveniently implemented in dietary recommandations to the general public.
The EPHESUS trial: eplerenone in patients with heart failure due to systolic dysfunction complicating acute myocardial infarction. Eplerenone Post-AMI Heart Failure Efficacy and Survival Study.Cardiovasc Drugs Ther. 2001 Jan;15(1):79-87
http://www.springerlink.com/content/w27uv2w0015747g3/
Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
JAMA. 2002 Dec 18;288(23):2981-97. Erratum in: JAMA 2003 Jan 8;289(2):178. JAMA. 2004 May 12;291(18):2196.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12479763&query_hl=7&itool=pubmed_DocSum
CONTEXT: Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is unknown. OBJECTIVE: To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. DESIGN: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, active-controlled clinical trial conducted from February 1994 through March 2002. SETTING AND PARTICIPANTS: A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers. INTERVENTIONS: Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15 255); amlodipine, 2.5 to 10 mg/d (n = 9048); or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately 4 to 8 years. MAIN OUTCOME MEASURES: The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure [HF], and peripheral arterial disease). RESULTS: Mean follow-up was 4.9 years. The primary outcome occurred in 2956 participants, with no difference between treatments. Compared with chlorthalidone (6-year rate, 11.5%), the relative risks (RRs) were 0.98 (95% CI, 0.90-1.07) for amlodipine (6-year rate, 11.3%) and 0.99 (95% CI, 0.91-1.08) for lisinopril (6-year rate, 11.4%). Likewise, all-cause mortality did not differ between groups. Five-year systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P =.03) and lisinopril (2 mm Hg, P<.001) groups compared with chlorthalidone, and 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg, P<.001). For amlodipine vs chlorthalidone, secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52). For lisinopril vs chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3% vs 30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI, 1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31). CONCLUSION: Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.
Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002 Dec 18;288(23):2998-3007.
http://jama.ama-assn.org/cgi/content/full/288/23/2998
CONTEXT: Studies have demonstrated that statins administered to individuals with risk factors for coronary heart disease (CHD) reduce CHD events. However, many of these studies were too small to assess all-cause mortality or outcomes in important subgroups. OBJECTIVE: To determine whether pravastatin compared with usual care reduces all-cause mortality in older, moderately hypercholesterolemic, hypertensive participants with at least 1 additional CHD risk factor. DESIGN AND SETTING: Multicenter (513 primarily community-based North American clinical centers), randomized, nonblinded trial conducted from 1994 through March 2002 in a subset of participants from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). PARTICIPANTS: Ambulatory persons (n = 10 355), aged 55 years or older, with low-density lipoprotein cholesterol (LDL-C) of 120 to 189 mg/dL (100 to 129 mg/dL if known CHD) and triglycerides lower than 350 mg/dL, were randomized to pravastatin (n = 5170) or to usual care (n = 5185). Baseline mean total cholesterol was 224 mg/dL; LDL-C, 146 mg/dL; high-density lipoprotein cholesterol, 48 mg/dL; and triglycerides, 152 mg/dL. Mean age was 66 years, 49% were women, 38% black and 23% Hispanic, 14% had a history of CHD, and 35% had type 2 diabetes. INTERVENTION: Pravastatin, 40 mg/d, vs usual care. MAIN OUTCOME MEASURES: The primary outcome was all-cause mortality, with follow-up for up to 8 years. Secondary outcomes included nonfatal myocardial infarction or fatal CHD (CHD events) combined, cause-specific mortality, and cancer. RESULTS: Mean follow-up was 4.8 years. During the trial, 32% of usual care participants with and 29% without CHD started taking lipid-lowering drugs. At year 4, total cholesterol levels were reduced by 17% with pravastatin vs 8% with usual care; among the random sample who had LDL-C levels assessed, levels were reduced by 28% with pravastatin vs 11% with usual care. All-cause mortality was similar for the 2 groups (relative risk [RR], 0.99; 95% confidence interval [CI], 0.89-1.11; P =.88), with 6-year mortality rates of 14.9% for pravastatin vs 15.3% with usual care. CHD event rates were not significantly different between the groups (RR, 0.91; 95% CI, 0.79-1.04; P =.16), with 6-year CHD event rates of 9.3% for pravastatin and 10.4% for usual care. CONCLUSIONS: Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C. The results may be due to the modest differential in total cholesterol (9.6%) and LDL-C (16.7%) between pravastatin and usual care compared with prior statin trials supporting cardiovascular disease prevention
Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT).J Clin Hypertens (Greenwich). 2002 Nov-Dec;4(6):393-404.
http://www.lejacq.com/Search_ArticleDetail.cfm?PID=JClinHypertens_4;6:393&CFID=2020179&CFTOKEN=67713014
CONTEXT: Blood pressure control (<140/90> or =55 years) with hypertension and at least one other coronary heart disease risk factor. INTERVENTIONS: Participants were randomly assigned to receive (double-blind) chlorthalidone, 12.5-25 mg/d (n=15,255), amlodipine 2.5-10 mg/d (n=9048), or lisinopril 10-40 mg/d (n=9054) after other medication was discontinued. Doses were increased within these ranges and additional drugs from other classes were added as needed to achieve blood pressure control (<140/90> or =2 drugs was 63%. Blood pressure control varied by geographic regions, practice settings, and demographic and clinical characteristics of participants. CONCLUSIONS: These data demonstrate that blood pressure may be controlled in two thirds of a multiethnic hypertensive population in diverse practice settings. Systolic blood pressure is more difficult to control than diastolic blood pressure, and at least two antihypertensive medications are required for most patients to achieve blood pressure control. It is likely that the majority of people with hypertension could achieve a blood pressure <140/90 _ob="ArticleURL&_udi="B6T1B-3R4YGP2-2S&_user="10&_coverDate="09%2F13%2F1997&_rdoc="1&_fmt="&_orig="search&_sort="d&view="c&_acct="C000050221&_version="1&_urlVersion="0&_userid="10&md5="c9d322fac328249db4c17c13f69d25e9"> 60 years) were initially started on masked placebo. At three run-in visits 1 month apart, their average sitting systolic blood pressure was 160-219 mm Hg with a diastolic blood pressure lower than 95 mm Hg. After stratification for centre, sex, and previous cardiovascular complications, 4695 patients were randomly assigned to nitrendipine 10-40 mg daily, with the possible addition of enalapril 5-20 mg daily and hydrochlorothiazide 12.5-25.0 mg daily, or matching placebos. Patients withdrawing from double-blind treatment were still followed up. We compared occurrence of major endpoints by intention to treat. FINDINGS: At a median of 2 years' follow-up, sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group (n = 2297) and by 23 mm Hg and 7 mm Hg in the active treatment group (n = 2398). The between-group differences were systolic 10.1 mm Hg (95% CI 8.8-11.4) and diastolic, 4.5 mm Hg (3.9-5.1). Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years (42% reduction; p = 0.003). Non-fatal stroke decreased by 44% (p = 0.007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p = 0.03). Non-fatal cardiac endpoints decreased by 33% (p = 0.03) and all fatal and non-fatal cardiovascular endpoints by 31% (p < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, p = 0.07), but all-cause mortality was not influenced (-14%; p = 0.22). INTERPRETATION: Among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications. Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints.
The HOPE (Heart Outcomes Prevention Evaluation) Study: the design of a large, simple randomized trial of an angiotensin-converting enzyme inhibitor (ramipril) and vitamin E in patients at high risk of cardiovascular events. The HOPE study investigators. Can J Cardiol. 1996 Feb;12(2):127-37.
http://www.pulsus.com/CARDIOL/12_02/yusu_ed.htm
OBJECTIVE: To describe the design of the HOPE (Heart Outcomes Prevention Evaluation) study. DESIGN: Description of the key design features of HOPE, a large, simple randomized trial of two widely applicable treatments--ramipril, an angiotensin-converting enzyme inhibitor; and vitamin E, a naturally occurring antioxidant vitamin--in the prevention of myocardial infarction, stroke or cardiovascular death. SETTING: Two-hundred and sixty-seven hospitals, physician offices and clinics in Canada, the United States, Mexico, Europe and South America. PATIENTS: Over 9000 women and men aged 55 years and above at high risk for cardiovascular events such as myocardial infarction and stroke were recruited over 18 months. INTERVENTIONS: A 2X2 factorial design with ramipril and vitamin E with follow-up for up to four years. CONCLUSIONS: HOPE will be one of the largest trials of two new interventions to prevent myocardial infarction, stroke or cardiovascular death in high risk patients. The results of HOPE will have direct public health impact and are likely to be readily incorporated into clinical practice. Key design features of HOPE are inclusion of individuals at high risk of cardiovascular disease, inclusion of a substantial proportion of patients with diabetes (36%) and women (27%), and detailed substudies to provide data on mechanisms of benefit.
Australian comparative outcome trial of angiotensin-converting enzyme inhibitor- and diuretic-based treatment of hypertension in the elderly (ANBP2): objectives and protocol. Management Committee on behalf of the High Blood Pressure Research Council of Australia. Clin Exp Pharmacol Physiol. 1997 Feb;24(2):188-92
http://www.blackwellpublishing.com/journal.asp?ref=0305-1870
ANBP2 is a comparative outcome trial of angiotensin-converting enzyme inhibitor- and diuretic-based treatment of hypertension in the elderly using a prospective randomized open-label design with blinding of endpoint assessments. 2. The primary objective is to determine, in hypertensive subjects 65-84 years of age, whether there is any difference in total cardiovascular events (fatal and non-fatal) over a 5 year treatment period between the two treatment regimens. 3. The study is being conducted in general practices throughout Australia and will recruit 6000 subjects over 2-3 years (3000 in each arm of the study) to provide 30,000 years of patient observation. This will allow detection of a 25% difference in the primary outcome variable at the 5% level with a power of 90%. 4. Following randomization to one of the treatment arms, each subject's blood pressure (BP) is managed by the general practitioner according to his/her usual practice to achieve goal BP with guidelines for drug therapy relevant to each treatment arm. 5. Study endpoint information is gained from a review of practice records every 3 months and these data are then assessed by an Endpoint Committee blinded for treatment randomization. 6. Interim analyses of endpoint data will be conducted at the end of randomization and then annually until the final analysis after 5 years of observation in each subject.
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure JAMA. 2003;289:(doi:10.1001/jama.289.19.2560).
http://jama.ama-assn.org/cgi/content/full/289.19.2560v1
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages: (1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, -blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount
Epidemiologic studies have found that dietary patterns characterized by high intakes of certain minerals and fiber are associated with low blood pressure. Dietary Approaches to Stop Hypertension (DASH) is a multicenter, randomized, controlled-feeding trial designed to test the effects on blood pressure of two such dietary patterns consumed for 8 weeks. The two experimental diets will be compared with each other and with a control dietary pattern that is relatively low in potassium, magnesium, calcium, and fiber, and has a fat and protein profile mirroring current US consumption. The first experimental diet, arguably termed “ideal,” is high in fruits, vegetables, whole cereal products, low-fat dairy products, fish, chicken, and lean meats designed to be low in saturated fat and cholesterol; moderately high in protein; and high in minerals and fiber. The second experimental diet tests the effect of fruits and vegetables alone. Its potassium, magnesium, and dietary fiber content will be at the same high levels as the ideal dietary pattern, while its fat, protein, and calcium content will resemble that of the control dietary pattern. The study population will consist of 456 healthy men and women, aged 22 years or older, with systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg. African-American and other minority groups will comprise 67% of the population. Participants will eat one of the three dietary patterns. The DASH trial has unique features. First, dietary patterns rather than single nutrients are being tested. Second, all food for the experimental diets is provided to the participants using a standardized multicenter protocol. Because the dietary patterns are constructed with commonly consumed food items, the results, if positive, may be conveniently implemented in dietary recommandations to the general public.
The EPHESUS trial: eplerenone in patients with heart failure due to systolic dysfunction complicating acute myocardial infarction. Eplerenone Post-AMI Heart Failure Efficacy and Survival Study.Cardiovasc Drugs Ther. 2001 Jan;15(1):79-87
http://www.springerlink.com/content/w27uv2w0015747g3/
Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
JAMA. 2002 Dec 18;288(23):2981-97. Erratum in: JAMA 2003 Jan 8;289(2):178. JAMA. 2004 May 12;291(18):2196.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12479763&query_hl=7&itool=pubmed_DocSum
CONTEXT: Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is unknown. OBJECTIVE: To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. DESIGN: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, active-controlled clinical trial conducted from February 1994 through March 2002. SETTING AND PARTICIPANTS: A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers. INTERVENTIONS: Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15 255); amlodipine, 2.5 to 10 mg/d (n = 9048); or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately 4 to 8 years. MAIN OUTCOME MEASURES: The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure [HF], and peripheral arterial disease). RESULTS: Mean follow-up was 4.9 years. The primary outcome occurred in 2956 participants, with no difference between treatments. Compared with chlorthalidone (6-year rate, 11.5%), the relative risks (RRs) were 0.98 (95% CI, 0.90-1.07) for amlodipine (6-year rate, 11.3%) and 0.99 (95% CI, 0.91-1.08) for lisinopril (6-year rate, 11.4%). Likewise, all-cause mortality did not differ between groups. Five-year systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P =.03) and lisinopril (2 mm Hg, P<.001) groups compared with chlorthalidone, and 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg, P<.001). For amlodipine vs chlorthalidone, secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52). For lisinopril vs chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3% vs 30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI, 1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31). CONCLUSION: Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.
Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002 Dec 18;288(23):2998-3007.
http://jama.ama-assn.org/cgi/content/full/288/23/2998
CONTEXT: Studies have demonstrated that statins administered to individuals with risk factors for coronary heart disease (CHD) reduce CHD events. However, many of these studies were too small to assess all-cause mortality or outcomes in important subgroups. OBJECTIVE: To determine whether pravastatin compared with usual care reduces all-cause mortality in older, moderately hypercholesterolemic, hypertensive participants with at least 1 additional CHD risk factor. DESIGN AND SETTING: Multicenter (513 primarily community-based North American clinical centers), randomized, nonblinded trial conducted from 1994 through March 2002 in a subset of participants from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). PARTICIPANTS: Ambulatory persons (n = 10 355), aged 55 years or older, with low-density lipoprotein cholesterol (LDL-C) of 120 to 189 mg/dL (100 to 129 mg/dL if known CHD) and triglycerides lower than 350 mg/dL, were randomized to pravastatin (n = 5170) or to usual care (n = 5185). Baseline mean total cholesterol was 224 mg/dL; LDL-C, 146 mg/dL; high-density lipoprotein cholesterol, 48 mg/dL; and triglycerides, 152 mg/dL. Mean age was 66 years, 49% were women, 38% black and 23% Hispanic, 14% had a history of CHD, and 35% had type 2 diabetes. INTERVENTION: Pravastatin, 40 mg/d, vs usual care. MAIN OUTCOME MEASURES: The primary outcome was all-cause mortality, with follow-up for up to 8 years. Secondary outcomes included nonfatal myocardial infarction or fatal CHD (CHD events) combined, cause-specific mortality, and cancer. RESULTS: Mean follow-up was 4.8 years. During the trial, 32% of usual care participants with and 29% without CHD started taking lipid-lowering drugs. At year 4, total cholesterol levels were reduced by 17% with pravastatin vs 8% with usual care; among the random sample who had LDL-C levels assessed, levels were reduced by 28% with pravastatin vs 11% with usual care. All-cause mortality was similar for the 2 groups (relative risk [RR], 0.99; 95% confidence interval [CI], 0.89-1.11; P =.88), with 6-year mortality rates of 14.9% for pravastatin vs 15.3% with usual care. CHD event rates were not significantly different between the groups (RR, 0.91; 95% CI, 0.79-1.04; P =.16), with 6-year CHD event rates of 9.3% for pravastatin and 10.4% for usual care. CONCLUSIONS: Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C. The results may be due to the modest differential in total cholesterol (9.6%) and LDL-C (16.7%) between pravastatin and usual care compared with prior statin trials supporting cardiovascular disease prevention
Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT).J Clin Hypertens (Greenwich). 2002 Nov-Dec;4(6):393-404.
http://www.lejacq.com/Search_ArticleDetail.cfm?PID=JClinHypertens_4;6:393&CFID=2020179&CFTOKEN=67713014
CONTEXT: Blood pressure control (<140/90> or =55 years) with hypertension and at least one other coronary heart disease risk factor. INTERVENTIONS: Participants were randomly assigned to receive (double-blind) chlorthalidone, 12.5-25 mg/d (n=15,255), amlodipine 2.5-10 mg/d (n=9048), or lisinopril 10-40 mg/d (n=9054) after other medication was discontinued. Doses were increased within these ranges and additional drugs from other classes were added as needed to achieve blood pressure control (<140/90> or =2 drugs was 63%. Blood pressure control varied by geographic regions, practice settings, and demographic and clinical characteristics of participants. CONCLUSIONS: These data demonstrate that blood pressure may be controlled in two thirds of a multiethnic hypertensive population in diverse practice settings. Systolic blood pressure is more difficult to control than diastolic blood pressure, and at least two antihypertensive medications are required for most patients to achieve blood pressure control. It is likely that the majority of people with hypertension could achieve a blood pressure <140/90 _ob="ArticleURL&_udi="B6T1B-3R4YGP2-2S&_user="10&_coverDate="09%2F13%2F1997&_rdoc="1&_fmt="&_orig="search&_sort="d&view="c&_acct="C000050221&_version="1&_urlVersion="0&_userid="10&md5="c9d322fac328249db4c17c13f69d25e9"> 60 years) were initially started on masked placebo. At three run-in visits 1 month apart, their average sitting systolic blood pressure was 160-219 mm Hg with a diastolic blood pressure lower than 95 mm Hg. After stratification for centre, sex, and previous cardiovascular complications, 4695 patients were randomly assigned to nitrendipine 10-40 mg daily, with the possible addition of enalapril 5-20 mg daily and hydrochlorothiazide 12.5-25.0 mg daily, or matching placebos. Patients withdrawing from double-blind treatment were still followed up. We compared occurrence of major endpoints by intention to treat. FINDINGS: At a median of 2 years' follow-up, sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group (n = 2297) and by 23 mm Hg and 7 mm Hg in the active treatment group (n = 2398). The between-group differences were systolic 10.1 mm Hg (95% CI 8.8-11.4) and diastolic, 4.5 mm Hg (3.9-5.1). Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years (42% reduction; p = 0.003). Non-fatal stroke decreased by 44% (p = 0.007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p = 0.03). Non-fatal cardiac endpoints decreased by 33% (p = 0.03) and all fatal and non-fatal cardiovascular endpoints by 31% (p < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, p = 0.07), but all-cause mortality was not influenced (-14%; p = 0.22). INTERPRETATION: Among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications. Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints.
The HOPE (Heart Outcomes Prevention Evaluation) Study: the design of a large, simple randomized trial of an angiotensin-converting enzyme inhibitor (ramipril) and vitamin E in patients at high risk of cardiovascular events. The HOPE study investigators. Can J Cardiol. 1996 Feb;12(2):127-37.
http://www.pulsus.com/CARDIOL/12_02/yusu_ed.htm
OBJECTIVE: To describe the design of the HOPE (Heart Outcomes Prevention Evaluation) study. DESIGN: Description of the key design features of HOPE, a large, simple randomized trial of two widely applicable treatments--ramipril, an angiotensin-converting enzyme inhibitor; and vitamin E, a naturally occurring antioxidant vitamin--in the prevention of myocardial infarction, stroke or cardiovascular death. SETTING: Two-hundred and sixty-seven hospitals, physician offices and clinics in Canada, the United States, Mexico, Europe and South America. PATIENTS: Over 9000 women and men aged 55 years and above at high risk for cardiovascular events such as myocardial infarction and stroke were recruited over 18 months. INTERVENTIONS: A 2X2 factorial design with ramipril and vitamin E with follow-up for up to four years. CONCLUSIONS: HOPE will be one of the largest trials of two new interventions to prevent myocardial infarction, stroke or cardiovascular death in high risk patients. The results of HOPE will have direct public health impact and are likely to be readily incorporated into clinical practice. Key design features of HOPE are inclusion of individuals at high risk of cardiovascular disease, inclusion of a substantial proportion of patients with diabetes (36%) and women (27%), and detailed substudies to provide data on mechanisms of benefit.
Australian comparative outcome trial of angiotensin-converting enzyme inhibitor- and diuretic-based treatment of hypertension in the elderly (ANBP2): objectives and protocol. Management Committee on behalf of the High Blood Pressure Research Council of Australia. Clin Exp Pharmacol Physiol. 1997 Feb;24(2):188-92
http://www.blackwellpublishing.com/journal.asp?ref=0305-1870
ANBP2 is a comparative outcome trial of angiotensin-converting enzyme inhibitor- and diuretic-based treatment of hypertension in the elderly using a prospective randomized open-label design with blinding of endpoint assessments. 2. The primary objective is to determine, in hypertensive subjects 65-84 years of age, whether there is any difference in total cardiovascular events (fatal and non-fatal) over a 5 year treatment period between the two treatment regimens. 3. The study is being conducted in general practices throughout Australia and will recruit 6000 subjects over 2-3 years (3000 in each arm of the study) to provide 30,000 years of patient observation. This will allow detection of a 25% difference in the primary outcome variable at the 5% level with a power of 90%. 4. Following randomization to one of the treatment arms, each subject's blood pressure (BP) is managed by the general practitioner according to his/her usual practice to achieve goal BP with guidelines for drug therapy relevant to each treatment arm. 5. Study endpoint information is gained from a review of practice records every 3 months and these data are then assessed by an Endpoint Committee blinded for treatment randomization. 6. Interim analyses of endpoint data will be conducted at the end of randomization and then annually until the final analysis after 5 years of observation in each subject.
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure JAMA. 2003;289:(doi:10.1001/jama.289.19.2560).
http://jama.ama-assn.org/cgi/content/full/289.19.2560v1
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages: (1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, -blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount
Do not shortchange on your doctor and choose your doctor wisely
Or you'll get this treatment on your next checkup
Recommended readings - Heart Failure
For the NYHA classification of HF (see bottom)
For American College of Cardiology/American Heart Association guidelines on Management of Chronic Heart Failure
Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group N Engl J Med 1987; 316:1429-1435, Jun 4, 1987.
To evaluate the influence of the angiotensin-converting-enzyme inhibitor enalapril (2.5 to 40 mg per day) on the prognosis of severe congestive heart failure (New York Heart Association [NYHA] functional class IV), we randomly assigned 253 patients in a double-blind study to receive either placebo (n = 126) or enalapril (n = 127). Conventional treatment for heart failure, including the use of other vasodilators, was continued in both groups. Follow-up averaged 188 days (range, 1 day to 20 months). The crude mortality at the end of six months (primary end point) was 26 percent in the enalapril group and 44 percent in the placebo group--a reduction of 40 percent (P = 0.002). Mortality was reduced by 31 percent at one year (P = 0.001). By the end of the study, there had been 68 deaths in the placebo group and 50 in the enalapril group--a reduction of 27 percent (P = 0.003). The entire reduction in total mortality was found to be among patients with progressive heart failure (a reduction of 50 percent), whereas no difference was seen in the incidence of sudden cardiac death. A significant improvement in NYHA classification was observed in the enalapril group, together with a reduction in heart size and a reduced requirement for other medication for heart failure. The overall withdrawal rate was similar in both groups, but hypotension requiring withdrawal occurred in seven patients in the enalapril group and in no patients in the placebo group. After the initial dose of enalapril was reduced to 2.5 mg daily in high-risk patients, this side effect was less frequent. We conclude that the addition of enalapril to conventional therapy in patients with severe congestive heart failure can reduce mortality and improve symptoms. The beneficial effect on mortality is due to a reduction in death from the progression of heart failure.
Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD Investigators N Engl J Med 1992; 327:685-691, Sep 3, 1992.
http://content.nejm.org/cgi/content/short/327/10/685
It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity. We studied the effect of an angiotensin-converting--enzyme inhibitor, enalapril, on total mortality and mortality from cardiovascular causes, the development of heart failure, and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure. METHODS. Patients were randomly assigned to receive either placebo (n = 2117) or enalapril (n = 2111) at doses of 2.5 to 20 mg per day in a double-blind trial. Follow-up averaged 37.4 months. RESULTS. There were 334 deaths in the placebo group, as compared with 313 in the enalapril group (reduction in risk, 8 percent by the log-rank test; 95 percent confidence interval, -8 percent [an increase of 8 percent] to 21 percent; P = 0.30). The reduction in mortality from cardiovascular causes was larger but was not statistically significant (298 deaths in the placebo group vs. 265 in the enalapril group; risk reduction, 12 percent; 95 percent confidence interval, -3 to 26 percent; P = 0.12). When we combined patients in whom heart failure developed and those who died, the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group (630 vs. 818; risk reduction, 29 percent; 95 percent confidence interval, 21 to 36 percent; P less than 0.001). In addition, fewer patients given enalapril died or were hospitalized for heart failure (434 in the enalapril group; vs. 518 in the placebo group; risk reduction, 20 percent; 95 percent confidence interval, 9 to 30 percent; P less than 0.001). CONCLUSIONS. The angiotensin-converting--enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations, as compared with the rates in the group given placebo, among patients with asymptomatic left ventricular dysfunction. There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril
Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study J Am Coll Cardiol, 2000; 36:2090-2095
http://content.onlinejacc.org/cgi/content/abstract/36/7/2090?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Assessment+of+Treatment+with+Lisinopril+and+Survival&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&volume=36&firstpage=2090&resourcetype=HWCIT
OBJECTIVES
We sought to prospectively and randomly compare survival with clinical and hemodynamic variables in patients with congestive heart failure (CHF) treated with standard versus high doses of enalapril.
BACKGROUND
Angiotensin-converting enzyme (ACE) inhibitors produce hemodynamic and symptomatic benefits in patients with CHF, but there is still controversy about the optimal dose in this clinical setting.
METHODS
Two hundred and forty-eight patients with advanced CHF (age 56.3 ± 12 years) were randomized to receive a maximal tolerated dose of enalapril, up to 20 mg/day in group 1 (mean dose achieved 17.9 ± 4.3 mg/day, n = 122) and 60 mg/day in group 2 (mean dose achieved 42 ± 19.3 mg/day, n = 126).
RESULTS
At enrollment, patients in group 1 were in New York Heart Association (NYHA) functional class 2.6 ± 0.7 and had a mean systolic blood pressure (SBP) of 117 ± 18 mm Hg, a mean heart rate (HR) of 85 ± 16 beats/min and a left ventricular ejection fraction (LVEF) of 20.0 ± 9.8%. In group 2, patients were in NYHA class 2.6 ± 0.7; their SBP was 118 ± 17 mm Hg, HR 83 ± 15 beats/min and LVEF 18.8 ± 8.1%. There were no significant differences in these characteristics between the two groups of patients at enrollment. After 12 months of follow-up, 22 (18%) of 122 patients in group 1 and 23 (18%) of 126 patients in group 2 had died (p = 0.995, with 80% power of the study to detect a delta difference of 13%). The NYHA class was the same (1.9 ± 0.7) in both groups; SBP was 111 ± 16 and 111 ± 17 mm Hg, HR 77 ± 12 and 79 ± 13 beats/min and LVEF 31 ± 19% and 30 ± 12% in groups 1 and 2, respectively. These differences were not statistically significant. The study had a power of 80% to detect (p = 0.05) the following changes: 13% in death rate, 0.25 units in NYHA class, 6 mm Hg in SBP, 5 beats/min in HR and 6% in LVEF.
CONCLUSIONS
No significant differences were found in survival and clinical and hemodynamic variables between patients receiving standard and those receiving high doses of enalapril.
COPERNICUS Effect of Carvedilol on Survival in Severe Chronic Heart Failure N Engl J Med 2001; 344:1651-1658, May 31, 2001.
Methods We evaluated 2289 patients who had symptoms of heart failure at rest or on minimal exertion, who were clinically euvolemic, and who had an ejection fraction of less than 25 percent. In a double-blind fashion, we randomly assigned 1133 patients to placebo and 1156 patients to treatment with carvedilol for a mean period of 10.4 months, during which standard therapy for heart failure was continued. Patients who required intensive care, had marked fluid retention, or were receiving intravenous vasodilators or positive inotropic drugs were excluded.
Results There were 190 deaths in the placebo group and 130 deaths in the carvedilol group. This difference reflected a 35 percent decrease in the risk of death with carvedilol (95 percent confidence interval, 19 to 48 percent; P=0.0014, adjusted for interim analyses). A total of 507 patients died or were hospitalized in the placebo group, as compared with 425 in the carvedilol group. This difference reflected a 24 percent decrease in the combined risk of death or hospitalization with carvedilol. The favorable effects on both end points were seen consistently in all the subgroups we examined. Fewer patients in the carvedilol group than in the placebo group withdrew because of adverse effects or for other reasons (P=0.02).
Conclusions The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also found in the patients with severe heart failure who were evaluated in this trial.
The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial
The Lancet - Vol. 353, Issue 9146, 02 January 1999, Pages 9-13
http://www.thelancet.com/journals/lancet/article/PIIS0140673698111819/fulltext
Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in-Congestive Heart Failure (MERIT-HF) The Lancet - Vol. 353, Issue 9169, 12 June 1999, Pages 2001-2007
http://www.thelancet.com/journals/lancet/article/PIIS0140673699044402/fulltext
BACKGROUND: Metoprolol can improve haemodynamics in chronic heart failure, but survival benefit has not been proven. We investigated whether metoprolol controlled release/extended release (CR/XL) once daily, in addition to standard therapy, would lower mortality in patients with decreased ejection fraction and symptoms of heart failure. METHODS: We enrolled 3991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with ejection fraction of 0.40 or less, stabilised with optimum standard therapy, in a double-blind randomised controlled study. Randomisation was preceded by a 2-week single-blind placebo run-in period. 1990 patients were randomly assigned metoprolol CR/XL 12.5 mg (NYHA III-IV) or 25.0 mg once daily (NYHA II) and 2001 were assigned placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analysed by intention to treat. FINDINGS: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in the metoprolol CR/XL group than in the placebo group (145 [7.2%, per patient-year of follow-up]) vs 217 deaths [11.0%], relative risk 0.66 [95% CI 0.53-0.81]; p=0.00009 or adjusted for interim analyses p=0.0062). There were fewer sudden deaths in the metoprolol CR/XL group than in the placebo group (79 vs 132, 0.59 [0.45-0.78]; p=0.0002) and deaths from worsening heart failure (30 vs 58, 0.51 [0.33-0.79]; p=0.0023). INTERPRETATION: Metoprolol CR/XL once daily in addition to optimum standard therapy improved survival. The drug was well tolerated.
The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure N Engl J Med 1999:341:709-17
Background and Methods Aldosterone is important in the pathophysiology of heart failure. In a double-blind study, we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting–enzyme inhibitor, a loop diuretic, and in most cases digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily, and 841 to receive placebo. The primary end point was death from all causes.
Results The trial was discontinued early, after a mean follow-up period of 24 months, because an interim analysis determined that spironolactone was efficacious. There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent; relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001).
Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE) The Lancet - Vol. 349, Issue 9054, 15 March 1997, Pages 747-752
Background Actions of angiotensin II may contribute to the progression of heart failure despite treatment with currently recommended drugs. We therefore evaluated the long-term effects of the addition of the angiotensin-receptor blocker valsartan to standard therapy for heart failure.
Methods A total of 5010 patients with heart failure of New York Heart Association (NYHA) class II, III, or IV were randomly assigned to receive 160 mg of valsartan or placebo twice daily. The primary outcomes were mortality and the combined end point of mortality and morbidity, defined as the incidence of cardiac arrest with resuscitation, hospitalization for heart failure, or receipt of intravenous inotropic or vasodilator therapy for at least four hours.
Results Overall mortality was similar in the two groups. The incidence of the combined end point, however, was 13.2 percent lower with valsartan than with placebo (relative risk, 0.87; 97.5 percent confidence interval, 0.77 to 0.97; P=0.009), predominantly because of a lower number of patients hospitalized for heart failure: 455 (18.2 percent) in the placebo group and 346 (13.8 percent) in the valsartan group (P<0.001). style="COLOR: #000000; TEXT-DECORATION: none" href="http://content.nejm.org/cgi/content/short/336/8/525">The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure The Digitalis Investigation Group N Engl J Med 1997; 336:525-533, Feb 20, 1997
http://content.nejm.org/cgi/content/abstract/336/8/525?andorexacttitleabs=and&search_tab=articles&tocsectionid=Original+Articles&tocsectionid=Special+Reports&tocsectionid=Special+Articles&tocsectionid=Videos+in+Clinical+Medicine&tocsectionid=Clinical+PracticeAORBClinical+Therapeutics&tocsectionid=Review+ArticlesAORBClinical+PracticeAORBClinical+Implications+of+Basic+ResearchAORBMolecular+MedicineAORBClinical+TherapeuticsAORBVideos+in+Clinical+Medicine&tocsectionid=EditorialsAORBPerspectiveAORBOutlookAORBBehind+the+Research&tocsectionid=Sounding+BoardAORBClinical+Debate&tocsectionid=Clinical+Implications+of+Basic+Research&tocsectionid=Health+Policy+ReportsAORBHealth+Policy+2001AORBQuality+of+Health+Care&searchtitle=Articles&excludeflag=TWEEK_element&sortspec=Score+desc+PUBDATE_SORTDATE+desc&hits=20&where=fulltext&andorexactfulltext=and&fyear=1996&fmonth=Nov&searchterm=the+digitalis+investigation+group&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
Background The role of cardiac glycosides in treating patients with chronic heart failure and normal sinus rhythm remains controversial. We studied the effect of digoxin on mortality and hospitalization in a randomized, double-blind clinical trial.
Methods In the main trial, patients with left ventricular ejection fractions of 0.45 or less were randomly assigned to digoxin (3397 patients) or placebo (3403 patients) in addition to diuretics and angiotensin-converting–enzyme inhibitors (median dose of digoxin, 0.25 mg per day; average follow-up, 37 months). In an ancillary trial of patients with ejection fractions greater than 0.45, 492 patients were randomly assigned to digoxin and 496 to placebo.
Results In the main trial, mortality was unaffected. There were 1181 deaths (34.8 percent) with digoxin and 1194 deaths (35.1 percent) with placebo (risk ratio when digoxin was compared with placebo, 0.99; 95 percent confidence interval, 0.91 to 1.07; P = 0.80). In the digoxin group, there was a trend toward a decrease in the risk of death attributed to worsening heart failure (risk ratio, 0.88; 95 percent confidence interval, 0.77 to 1.01; P = 0.06). There were 6 percent fewer hospitalizations overall in that group than in the placebo group, and fewer patients were hospitalized for worsening heart failure (26.8 percent vs. 34.7 percent; risk ratio, 0.72; 95 percent confidence interval, 0.66 to 0.79; P<0.001). style="COLOR: #000000; TEXT-DECORATION: none" href="http://content.nejm.org/cgi/content/short/314/24/1547">Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study N Engl J Med 1986; 314:1547-1552, Jun 12, 1986
http://content.nejm.org/cgi/content/abstract/314/24/1547?firstpage=1547&volume=314&sendit=GO&searchid=1&FIRSTINDEX=0&volume=314&firstpage=1547&resourcetype=HWCIT
To evaluate the effects of vasodilator therapy on mortality among patients with chronic congestive heart failure, we randomly assigned 642 men with impaired cardiac function and reduced exercise tolerance who were taking digoxin and a diuretic to receive additional double-blind treatment with placebo, prazosin (20 mg per day), or the combination of hydralazine (300 mg per day) and isosorbide dinitrate (160 mg per day). Follow-up averaged 2.3 years (range, 6 months to 5.7 years). Mortality over the entire follow-up period was lower in the group that received hydralazine and isosorbide dinitrate than in the placebo group. This difference was of borderline statistical significance. For mortality by two years, a major end point specified in the protocol, the risk reduction among patients treated with both hydralazine and isosorbide dinitrate was 34 percent (P less than 0.028). The cumulative mortality rates at two years were 25.6 percent in the hydralazine--isosorbide dinitrate group and 34.3 percent in the placebo group; at three years, the mortality rate was 36.2 percent versus 46.9 percent. The mortality-risk reduction in the group treated with hydralazine and isosorbide dinitrate was 36 percent by three years. The mortality in the prazosin group was similar to that in the placebo group. Left ventricular ejection fraction (measured sequentially) rose significantly at eight weeks and at one year in the group treated with hydralazine and isosorbide dinitrate but not in the placebo or prazosin groups. Our data suggest that the addition of hydralazine and isosorbide dinitrate to the therapeutic regimen of digoxin and diuretics in patients with chronic congestive heart failure can have a favorable effect on left ventricular function and mortality.
A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure N Engl J Med 1991; 325:303-310, Aug 1, 1991.
For American College of Cardiology/American Heart Association guidelines on Management of Chronic Heart Failure
Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group N Engl J Med 1987; 316:1429-1435, Jun 4, 1987.
To evaluate the influence of the angiotensin-converting-enzyme inhibitor enalapril (2.5 to 40 mg per day) on the prognosis of severe congestive heart failure (New York Heart Association [NYHA] functional class IV), we randomly assigned 253 patients in a double-blind study to receive either placebo (n = 126) or enalapril (n = 127). Conventional treatment for heart failure, including the use of other vasodilators, was continued in both groups. Follow-up averaged 188 days (range, 1 day to 20 months). The crude mortality at the end of six months (primary end point) was 26 percent in the enalapril group and 44 percent in the placebo group--a reduction of 40 percent (P = 0.002). Mortality was reduced by 31 percent at one year (P = 0.001). By the end of the study, there had been 68 deaths in the placebo group and 50 in the enalapril group--a reduction of 27 percent (P = 0.003). The entire reduction in total mortality was found to be among patients with progressive heart failure (a reduction of 50 percent), whereas no difference was seen in the incidence of sudden cardiac death. A significant improvement in NYHA classification was observed in the enalapril group, together with a reduction in heart size and a reduced requirement for other medication for heart failure. The overall withdrawal rate was similar in both groups, but hypotension requiring withdrawal occurred in seven patients in the enalapril group and in no patients in the placebo group. After the initial dose of enalapril was reduced to 2.5 mg daily in high-risk patients, this side effect was less frequent. We conclude that the addition of enalapril to conventional therapy in patients with severe congestive heart failure can reduce mortality and improve symptoms. The beneficial effect on mortality is due to a reduction in death from the progression of heart failure.
Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD Investigators N Engl J Med 1992; 327:685-691, Sep 3, 1992.
http://content.nejm.org/cgi/content/short/327/10/685
It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity. We studied the effect of an angiotensin-converting--enzyme inhibitor, enalapril, on total mortality and mortality from cardiovascular causes, the development of heart failure, and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure. METHODS. Patients were randomly assigned to receive either placebo (n = 2117) or enalapril (n = 2111) at doses of 2.5 to 20 mg per day in a double-blind trial. Follow-up averaged 37.4 months. RESULTS. There were 334 deaths in the placebo group, as compared with 313 in the enalapril group (reduction in risk, 8 percent by the log-rank test; 95 percent confidence interval, -8 percent [an increase of 8 percent] to 21 percent; P = 0.30). The reduction in mortality from cardiovascular causes was larger but was not statistically significant (298 deaths in the placebo group vs. 265 in the enalapril group; risk reduction, 12 percent; 95 percent confidence interval, -3 to 26 percent; P = 0.12). When we combined patients in whom heart failure developed and those who died, the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group (630 vs. 818; risk reduction, 29 percent; 95 percent confidence interval, 21 to 36 percent; P less than 0.001). In addition, fewer patients given enalapril died or were hospitalized for heart failure (434 in the enalapril group; vs. 518 in the placebo group; risk reduction, 20 percent; 95 percent confidence interval, 9 to 30 percent; P less than 0.001). CONCLUSIONS. The angiotensin-converting--enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations, as compared with the rates in the group given placebo, among patients with asymptomatic left ventricular dysfunction. There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril
Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study J Am Coll Cardiol, 2000; 36:2090-2095
http://content.onlinejacc.org/cgi/content/abstract/36/7/2090?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Assessment+of+Treatment+with+Lisinopril+and+Survival&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&volume=36&firstpage=2090&resourcetype=HWCIT
OBJECTIVES
We sought to prospectively and randomly compare survival with clinical and hemodynamic variables in patients with congestive heart failure (CHF) treated with standard versus high doses of enalapril.
BACKGROUND
Angiotensin-converting enzyme (ACE) inhibitors produce hemodynamic and symptomatic benefits in patients with CHF, but there is still controversy about the optimal dose in this clinical setting.
METHODS
Two hundred and forty-eight patients with advanced CHF (age 56.3 ± 12 years) were randomized to receive a maximal tolerated dose of enalapril, up to 20 mg/day in group 1 (mean dose achieved 17.9 ± 4.3 mg/day, n = 122) and 60 mg/day in group 2 (mean dose achieved 42 ± 19.3 mg/day, n = 126).
RESULTS
At enrollment, patients in group 1 were in New York Heart Association (NYHA) functional class 2.6 ± 0.7 and had a mean systolic blood pressure (SBP) of 117 ± 18 mm Hg, a mean heart rate (HR) of 85 ± 16 beats/min and a left ventricular ejection fraction (LVEF) of 20.0 ± 9.8%. In group 2, patients were in NYHA class 2.6 ± 0.7; their SBP was 118 ± 17 mm Hg, HR 83 ± 15 beats/min and LVEF 18.8 ± 8.1%. There were no significant differences in these characteristics between the two groups of patients at enrollment. After 12 months of follow-up, 22 (18%) of 122 patients in group 1 and 23 (18%) of 126 patients in group 2 had died (p = 0.995, with 80% power of the study to detect a delta difference of 13%). The NYHA class was the same (1.9 ± 0.7) in both groups; SBP was 111 ± 16 and 111 ± 17 mm Hg, HR 77 ± 12 and 79 ± 13 beats/min and LVEF 31 ± 19% and 30 ± 12% in groups 1 and 2, respectively. These differences were not statistically significant. The study had a power of 80% to detect (p = 0.05) the following changes: 13% in death rate, 0.25 units in NYHA class, 6 mm Hg in SBP, 5 beats/min in HR and 6% in LVEF.
CONCLUSIONS
No significant differences were found in survival and clinical and hemodynamic variables between patients receiving standard and those receiving high doses of enalapril.
COPERNICUS Effect of Carvedilol on Survival in Severe Chronic Heart Failure N Engl J Med 2001; 344:1651-1658, May 31, 2001.
Background Beta-blocking agents reduce the risk of hospitalization and death in patients with mild-to-moderate heart failure, but little is known about their effects in severe heart failure.
Methods We evaluated 2289 patients who had symptoms of heart failure at rest or on minimal exertion, who were clinically euvolemic, and who had an ejection fraction of less than 25 percent. In a double-blind fashion, we randomly assigned 1133 patients to placebo and 1156 patients to treatment with carvedilol for a mean period of 10.4 months, during which standard therapy for heart failure was continued. Patients who required intensive care, had marked fluid retention, or were receiving intravenous vasodilators or positive inotropic drugs were excluded.
Results There were 190 deaths in the placebo group and 130 deaths in the carvedilol group. This difference reflected a 35 percent decrease in the risk of death with carvedilol (95 percent confidence interval, 19 to 48 percent; P=0.0014, adjusted for interim analyses). A total of 507 patients died or were hospitalized in the placebo group, as compared with 425 in the carvedilol group. This difference reflected a 24 percent decrease in the combined risk of death or hospitalization with carvedilol. The favorable effects on both end points were seen consistently in all the subgroups we examined. Fewer patients in the carvedilol group than in the placebo group withdrew because of adverse effects or for other reasons (P=0.02).
Conclusions The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also found in the patients with severe heart failure who were evaluated in this trial.
The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial
The Lancet - Vol. 353, Issue 9146, 02 January 1999, Pages 9-13
http://www.thelancet.com/journals/lancet/article/PIIS0140673698111819/fulltext
Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in-Congestive Heart Failure (MERIT-HF) The Lancet - Vol. 353, Issue 9169, 12 June 1999, Pages 2001-2007
http://www.thelancet.com/journals/lancet/article/PIIS0140673699044402/fulltext
BACKGROUND: Metoprolol can improve haemodynamics in chronic heart failure, but survival benefit has not been proven. We investigated whether metoprolol controlled release/extended release (CR/XL) once daily, in addition to standard therapy, would lower mortality in patients with decreased ejection fraction and symptoms of heart failure. METHODS: We enrolled 3991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with ejection fraction of 0.40 or less, stabilised with optimum standard therapy, in a double-blind randomised controlled study. Randomisation was preceded by a 2-week single-blind placebo run-in period. 1990 patients were randomly assigned metoprolol CR/XL 12.5 mg (NYHA III-IV) or 25.0 mg once daily (NYHA II) and 2001 were assigned placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analysed by intention to treat. FINDINGS: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in the metoprolol CR/XL group than in the placebo group (145 [7.2%, per patient-year of follow-up]) vs 217 deaths [11.0%], relative risk 0.66 [95% CI 0.53-0.81]; p=0.00009 or adjusted for interim analyses p=0.0062). There were fewer sudden deaths in the metoprolol CR/XL group than in the placebo group (79 vs 132, 0.59 [0.45-0.78]; p=0.0002) and deaths from worsening heart failure (30 vs 58, 0.51 [0.33-0.79]; p=0.0023). INTERPRETATION: Metoprolol CR/XL once daily in addition to optimum standard therapy improved survival. The drug was well tolerated.
The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure N Engl J Med 1999:341:709-17
Background and Methods Aldosterone is important in the pathophysiology of heart failure. In a double-blind study, we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting–enzyme inhibitor, a loop diuretic, and in most cases digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily, and 841 to receive placebo. The primary end point was death from all causes.
Results The trial was discontinued early, after a mean follow-up period of 24 months, because an interim analysis determined that spironolactone was efficacious. There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent; relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001).
Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE) The Lancet - Vol. 349, Issue 9054, 15 March 1997, Pages 747-752
http://www.thelancet.com/journals/lancet/article/PIIS0140673697011872/fulltext
Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial—the Losartan Heart Failure Survival Study ELITE II The Lancet - Vol. 355, Issue 9215, 06 May 2000, Pages 1582-1587
http://www.thelancet.com/journals/lancet/article/PIIS0140673600022133/fulltext
Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial The Lancet - Vol. 362, Issue 9386, 06 September 2003, Pages 772-776
http://www.thelancet.com/journals/lancet/article/PIIS0140673603142845/fulltext
A Randomized Trial of the Angiotensin-Receptor Blocker Valsartan in Chronic Heart Failure N Engl J Med 2001; 345:1667-1675, Dec 6, 2001.
Background Actions of angiotensin II may contribute to the progression of heart failure despite treatment with currently recommended drugs. We therefore evaluated the long-term effects of the addition of the angiotensin-receptor blocker valsartan to standard therapy for heart failure.
Methods A total of 5010 patients with heart failure of New York Heart Association (NYHA) class II, III, or IV were randomly assigned to receive 160 mg of valsartan or placebo twice daily. The primary outcomes were mortality and the combined end point of mortality and morbidity, defined as the incidence of cardiac arrest with resuscitation, hospitalization for heart failure, or receipt of intravenous inotropic or vasodilator therapy for at least four hours.
Results Overall mortality was similar in the two groups. The incidence of the combined end point, however, was 13.2 percent lower with valsartan than with placebo (relative risk, 0.87; 97.5 percent confidence interval, 0.77 to 0.97; P=0.009), predominantly because of a lower number of patients hospitalized for heart failure: 455 (18.2 percent) in the placebo group and 346 (13.8 percent) in the valsartan group (P<0.001). style="COLOR: #000000; TEXT-DECORATION: none" href="http://content.nejm.org/cgi/content/short/336/8/525">The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure The Digitalis Investigation Group N Engl J Med 1997; 336:525-533, Feb 20, 1997
http://content.nejm.org/cgi/content/abstract/336/8/525?andorexacttitleabs=and&search_tab=articles&tocsectionid=Original+Articles&tocsectionid=Special+Reports&tocsectionid=Special+Articles&tocsectionid=Videos+in+Clinical+Medicine&tocsectionid=Clinical+PracticeAORBClinical+Therapeutics&tocsectionid=Review+ArticlesAORBClinical+PracticeAORBClinical+Implications+of+Basic+ResearchAORBMolecular+MedicineAORBClinical+TherapeuticsAORBVideos+in+Clinical+Medicine&tocsectionid=EditorialsAORBPerspectiveAORBOutlookAORBBehind+the+Research&tocsectionid=Sounding+BoardAORBClinical+Debate&tocsectionid=Clinical+Implications+of+Basic+Research&tocsectionid=Health+Policy+ReportsAORBHealth+Policy+2001AORBQuality+of+Health+Care&searchtitle=Articles&excludeflag=TWEEK_element&sortspec=Score+desc+PUBDATE_SORTDATE+desc&hits=20&where=fulltext&andorexactfulltext=and&fyear=1996&fmonth=Nov&searchterm=the+digitalis+investigation+group&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
Background The role of cardiac glycosides in treating patients with chronic heart failure and normal sinus rhythm remains controversial. We studied the effect of digoxin on mortality and hospitalization in a randomized, double-blind clinical trial.
Methods In the main trial, patients with left ventricular ejection fractions of 0.45 or less were randomly assigned to digoxin (3397 patients) or placebo (3403 patients) in addition to diuretics and angiotensin-converting–enzyme inhibitors (median dose of digoxin, 0.25 mg per day; average follow-up, 37 months). In an ancillary trial of patients with ejection fractions greater than 0.45, 492 patients were randomly assigned to digoxin and 496 to placebo.
Results In the main trial, mortality was unaffected. There were 1181 deaths (34.8 percent) with digoxin and 1194 deaths (35.1 percent) with placebo (risk ratio when digoxin was compared with placebo, 0.99; 95 percent confidence interval, 0.91 to 1.07; P = 0.80). In the digoxin group, there was a trend toward a decrease in the risk of death attributed to worsening heart failure (risk ratio, 0.88; 95 percent confidence interval, 0.77 to 1.01; P = 0.06). There were 6 percent fewer hospitalizations overall in that group than in the placebo group, and fewer patients were hospitalized for worsening heart failure (26.8 percent vs. 34.7 percent; risk ratio, 0.72; 95 percent confidence interval, 0.66 to 0.79; P<0.001). style="COLOR: #000000; TEXT-DECORATION: none" href="http://content.nejm.org/cgi/content/short/314/24/1547">Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study N Engl J Med 1986; 314:1547-1552, Jun 12, 1986
http://content.nejm.org/cgi/content/abstract/314/24/1547?firstpage=1547&volume=314&sendit=GO&searchid=1&FIRSTINDEX=0&volume=314&firstpage=1547&resourcetype=HWCIT
To evaluate the effects of vasodilator therapy on mortality among patients with chronic congestive heart failure, we randomly assigned 642 men with impaired cardiac function and reduced exercise tolerance who were taking digoxin and a diuretic to receive additional double-blind treatment with placebo, prazosin (20 mg per day), or the combination of hydralazine (300 mg per day) and isosorbide dinitrate (160 mg per day). Follow-up averaged 2.3 years (range, 6 months to 5.7 years). Mortality over the entire follow-up period was lower in the group that received hydralazine and isosorbide dinitrate than in the placebo group. This difference was of borderline statistical significance. For mortality by two years, a major end point specified in the protocol, the risk reduction among patients treated with both hydralazine and isosorbide dinitrate was 34 percent (P less than 0.028). The cumulative mortality rates at two years were 25.6 percent in the hydralazine--isosorbide dinitrate group and 34.3 percent in the placebo group; at three years, the mortality rate was 36.2 percent versus 46.9 percent. The mortality-risk reduction in the group treated with hydralazine and isosorbide dinitrate was 36 percent by three years. The mortality in the prazosin group was similar to that in the placebo group. Left ventricular ejection fraction (measured sequentially) rose significantly at eight weeks and at one year in the group treated with hydralazine and isosorbide dinitrate but not in the placebo or prazosin groups. Our data suggest that the addition of hydralazine and isosorbide dinitrate to the therapeutic regimen of digoxin and diuretics in patients with chronic congestive heart failure can have a favorable effect on left ventricular function and mortality.
A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure N Engl J Med 1991; 325:303-310, Aug 1, 1991.
BACKGROUND. To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS. The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination
Recommended readings - Chronic Stable Angina
N Engl J Med. 2005 Jun 16;352(24):2524-33
Clinical practice. Chronic stable angina.Abrams J.
Division of Cardiology, Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
Clinical practice. Chronic stable angina.Abrams J.
Division of Cardiology, Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
Monday, April 16, 2007
Let the public take control
THE Singapore Medical Association's announcement on the withdrawal of fee guidelines has sparked furious debate among the public.
This reflects the public's concern on health-care costs.
The Pharmaceutical Society of Singapore understands this concern and advocates the need for greater billing transparency and other checks and balances to reduce possible inefficiencies of the health-care market in Singapore.
Providing the breakdown of the bill to individual item level will at least allow consumers to compare the costs and assess the value of the services for which they are paying, much like a car workshop repair service or groceries bill.
When it comes to medications, consumers can discuss with their doctors if they prefer more cost-effective options like generic alternatives.
Prescriptions could also be offered to patients to allow them the free choice to shop around for their medicines.
This is particularly pertinent for patients with chronic disease conditions where long-term consumption of mediation is required. Prudent and cost-effective choice of medicines can therefore translate into direct savings.
Pharmacists can complement the services of doctors by adding value to the whole disease-management process through their expert knowledge in medication.
An accurately diagnosed and prudent treatment plan may be wasted when medications are used inappropriately.
Some of the value-added services provided by pharmacists such as identification of medication side effects/allergies, drug interactions and optimal dosages and choice of medication help to promote a safe and cost-effective delivery of health care to the consumer.
In Singapore, pharmacists are also trained to offer professional advice on minor ailments and the safe use of over-the-counter medicines.
Consumers should consult the pharmacist when self-medicating so that appropriate basic assessments could be made and, where necessary, the pharmacist would refer them to a doctor.
We encourage employers and insurance companies to consider reimbursing their employees/policy holders for medicines purchased at pharmacies to treat minor ailments.
This could greatly empower their staff/policy holders to take more personal responsibility towards their own well-being and, at the same time, improve the overall cost-effective utilisation of health-care resources.
Ng Cheng Tiang
President
Pharmaceutical Society of Singapore
______________________________________________________________________________
PS your pharmacist-friends are just a phone call/ sms / e-mail away
This reflects the public's concern on health-care costs.
The Pharmaceutical Society of Singapore understands this concern and advocates the need for greater billing transparency and other checks and balances to reduce possible inefficiencies of the health-care market in Singapore.
Providing the breakdown of the bill to individual item level will at least allow consumers to compare the costs and assess the value of the services for which they are paying, much like a car workshop repair service or groceries bill.
When it comes to medications, consumers can discuss with their doctors if they prefer more cost-effective options like generic alternatives.
Prescriptions could also be offered to patients to allow them the free choice to shop around for their medicines.
This is particularly pertinent for patients with chronic disease conditions where long-term consumption of mediation is required. Prudent and cost-effective choice of medicines can therefore translate into direct savings.
Pharmacists can complement the services of doctors by adding value to the whole disease-management process through their expert knowledge in medication.
An accurately diagnosed and prudent treatment plan may be wasted when medications are used inappropriately.
Some of the value-added services provided by pharmacists such as identification of medication side effects/allergies, drug interactions and optimal dosages and choice of medication help to promote a safe and cost-effective delivery of health care to the consumer.
In Singapore, pharmacists are also trained to offer professional advice on minor ailments and the safe use of over-the-counter medicines.
Consumers should consult the pharmacist when self-medicating so that appropriate basic assessments could be made and, where necessary, the pharmacist would refer them to a doctor.
We encourage employers and insurance companies to consider reimbursing their employees/policy holders for medicines purchased at pharmacies to treat minor ailments.
This could greatly empower their staff/policy holders to take more personal responsibility towards their own well-being and, at the same time, improve the overall cost-effective utilisation of health-care resources.
Ng Cheng Tiang
President
Pharmaceutical Society of Singapore
______________________________________________________________________________
PS your pharmacist-friends are just a phone call/ sms / e-mail away
Orchid culture in TW and SG - Red Pine bark
Hmm it gets a bit annoying at times when you can read read read but can't post because tio disabled.
Let's get back to AG's question on YYYY TW can grow their plants in pine bark and not SG growers.
Let's take a look at TW's culture methods:
- If plants are grown in TP, they have wintering where the temperature drops below 25 oC for about 40% of the year. If grown in other parts, they have a lower ambient temperature than SG. This low temperature actually slows down fermentation - potting mix will last longer.
- The average life span of the plants from TW exported is normally 1 year - when the plants are in the final potting stage for about 6 months and budding, they are sent over to be sold as potted plants. The normal practice in JP and TW is that once the (mericloned /mass produced) plant has finished flowering, they are dumped. SG people usually tries ways and means to rescucitate the plant and continue to grow them in the original potting mix - thinking what's good there is good for here. Mainly aesthetic, not functional and practical in our climate. If you look into the pots grown by collectors, they do not use fir bark. Usually osmunda, treefern or NZ/Chilean/Argentinian/Canadian sphag. SG, we use charcoal as mainstay.
- The processes in TW commercial nurseries are very tightly controlled (some of them have annual visits from USDA) almost all their potting mixes are autoclaved and water purified. Autoclaving potting mix will slow down break down as you lower microbial load. The purified water helps in leaching of the salts before they build up and starts depositing.
If you look carefully at the exports from TW, the collectors' items are rarely potted in fir bark - unless required. Mericloned stuff may be potted in ticking time bomb mixes - china sphag or fir bark or peat.
If you have a hefty plant like Grammatophyllum speciosum the last thing on your mind is repotting. It's a massive operation - need to hold one partay to ask people help you lift the plant one. In fact, the one at Mandai Gardens was sitting aroung for about 2 decades before they decided to split the plant into soooo many puny pieces.
PS - pH changes are some times used to trigger flowering but if control not good, it comes swan song flowering.
A painful lesson learnt by the Laojiao orchid growers during the hey day of fir bark imports - better not repeat the same olde silly mistake.
A look at the entry requirements.
Let's get back to AG's question on YYYY TW can grow their plants in pine bark and not SG growers.
Let's take a look at TW's culture methods:
- If plants are grown in TP, they have wintering where the temperature drops below 25 oC for about 40% of the year. If grown in other parts, they have a lower ambient temperature than SG. This low temperature actually slows down fermentation - potting mix will last longer.
- The average life span of the plants from TW exported is normally 1 year - when the plants are in the final potting stage for about 6 months and budding, they are sent over to be sold as potted plants. The normal practice in JP and TW is that once the (mericloned /mass produced) plant has finished flowering, they are dumped. SG people usually tries ways and means to rescucitate the plant and continue to grow them in the original potting mix - thinking what's good there is good for here. Mainly aesthetic, not functional and practical in our climate. If you look into the pots grown by collectors, they do not use fir bark. Usually osmunda, treefern or NZ/Chilean/Argentinian/Canadian sphag. SG, we use charcoal as mainstay.
- The processes in TW commercial nurseries are very tightly controlled (some of them have annual visits from USDA) almost all their potting mixes are autoclaved and water purified. Autoclaving potting mix will slow down break down as you lower microbial load. The purified water helps in leaching of the salts before they build up and starts depositing.
If you look carefully at the exports from TW, the collectors' items are rarely potted in fir bark - unless required. Mericloned stuff may be potted in ticking time bomb mixes - china sphag or fir bark or peat.
If you have a hefty plant like Grammatophyllum speciosum the last thing on your mind is repotting. It's a massive operation - need to hold one partay to ask people help you lift the plant one. In fact, the one at Mandai Gardens was sitting aroung for about 2 decades before they decided to split the plant into soooo many puny pieces.
PS - pH changes are some times used to trigger flowering but if control not good, it comes swan song flowering.
A painful lesson learnt by the Laojiao orchid growers during the hey day of fir bark imports - better not repeat the same olde silly mistake.
A look at the entry requirements.
Warning - watch this when u are alone
Got second round of bee hoon kuey flying out of my nose follow by a burst of rescusitating laughter.
Sunday, April 15, 2007
An appeal to people who can take in dogs and care for them
From a classmate:
Hey animal/nature/ pet lovers,
A pet shop at Joo Chiat is closing down....
There are 2 huskies, 1 black Labrador, 1 shitxzu, 1huskie terrier cross
breed. They'll be put to sleep if no one adopts them, sadly. If you're
interested and able to take care of them, please call Mariam at 9730 2064
for more details. Pass it around too! Thanks!
Hey animal/nature/ pet lovers,
A pet shop at Joo Chiat is closing down....
There are 2 huskies, 1 black Labrador, 1 shitxzu, 1huskie terrier cross
breed. They'll be put to sleep if no one adopts them, sadly. If you're
interested and able to take care of them, please call Mariam at 9730 2064
for more details. Pass it around too! Thanks!
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