- randomn thoughts that cross my mind.
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
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