Showing papers by "Henry R. Black published in 2002"

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)

Abstract: 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

Abstract: 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).

Abstract: Context Blood pressure control ( Objective To determine the success and predictors of blood pressure control in a large hypertension trial involving a multiethnic population in diverse practice settings. Design The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial is a randomized, double-blind, active-controlled clinical trial with a mean follow-up of 4.9 years. Participant enrollment began in February 1994 and follow-up was completed in March 2002. Setting A total of 623 centers in the United States, Canada, and the Caribbean. Participants A total of 33,357 participants (aged > 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 ( Main outcome measures The outcome measures for this report are systolic and diastolic blood pressure, the proportion of participants achieving blood pressure control ( Results Mean age was 67 years, 47% were women, 35% black, 36% diabetic; 90% were on antihypertensive drug treatment at entry. At the first of two pre-randomization visits, blood pressure was 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

Goal-Oriented Hypertension Management: Translating Clinical Trials to Practice

Abstract: Several clinical trials using a blood pressure (BP) treatment algorithm focused on a predetermined goal have achieved better control rates than those of national survey data. These trials reached the Sixth Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI) diastolic blood pressure (DBP) goal of 90% of volunteers and systolic blood pressure (SBP) goal of 60% of volunteers. We evaluated BP control of 437 consecutive patients after at least one year of follow up in a specialist clinic which employed “goal-oriented management,” ie, treating to a specific BP goal without a formal drug treatment algorithm, to determine whether JNC VI goals could be achieved. Overall, 276 (63%) patients achieved SBP goal, with 376 (86%) at DBP goal and 358 (59%) at both goals. Only 23% of patients were on monotherapy, with 34% requiring 2 drugs and 37% requiring 3 or more medications. There was no substantial difference in BP control rates among age, gender, and ethnicity subgroups. However, in the 20% of patients who were diabetic, only 52% had a BP of

Pharmacogenetic approaches to hypertension therapy: design and rationale for the Genetics of Hypertension Associated Treatment (GenHAT) study.

Abstract: The Genetics of Hypertension Associated Treatment (GenHAT) study will determine whether variants in hypertension susceptibility genes interact with antihypertensive medication to modify coronary heart disease (CHD) risk in hypertensives. GenHAT is an ancillary study of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial, ALLHAT, a double-blind, randomized trial of 42 418 hypertensives, 55 years of age or older, with systolic or diastolic hypertension and one or more risk factors for cardiovascular disease. About 50% are non-white, and about half are female. ALLHAT completes follow-up in March 2002. GenHAT is typing variants in hypertension genes; completion of genotyping is scheduled for 2003. Analysis of gene-treatment interactions in relation to outcomes include CHD, stroke, heart failure, and blood pressure lowering. To our knowledge, GenHAT is the largest pharmacogenetic study ever conducted. An added strength is its ability to link gene-treatment interactions with important clinical outcomes across diverse ethnic and gender groups.

Current concepts of pharmacotherapy in hypertension: ACE inhibitor-related angioedema: can angiotensin-receptor blockers be safely used?

Abstract: Angioedema is a well-recognized side effect of angiotensin-converting enzyme (ACE) inhibitor therapy. Angioedema can also be seen with angiotensin receptor blocker therapy but much less frequently than is the case with ACE inhibitors. For unclear reasons, ACE inhibitor-related angioedema occurs more commonly in black patients. Angioedema can be life threatening but more times than not its occurrence can be managed with conservative treatment measures including discontinuation of the medication and/or administration of an antihistamine. Occasionally, epinephrine and/or steroid therapy may be warranted. In a patient having experienced ACE inhibitor-related angioedema, angiotensin receptor blockers should be used cautiously if at all. If angiotensin receptor blocker therapy is being considered in a patient with prior ACE inhibitor-related angioedema there should be some justification for the use. Such justification might include the presence of heart failure or proteinuric nephropathic states among other considerations.

Angioedema in Heart Failure: Occurrence With ACE Inhibitors and Safety of Angiotensin Receptor Blocker Therapy

Abstract: Angioedema is a well-known side effect of treatment with an angiotensin-converting enzyme (ACE) inhibitor and one that we have been willing to accept in view of the incidence of the problem and the clear benefits of this class of agents in numerous clinical situations. Angioedema is also seen with angiotensin receptor blocker (ARB) therapy but much less frequently than with ACE inhibitors. The mechanism for angioedema with ARB therapy remains poorly defined. ACE inhibitor-related angioedema occurs more commonly in black patients. The basis for an increased risk of angioedema in black patients remains unclear. Angioedema can be life-threatening but more times than not it can be managed with conservative treatment measures including specifically the discontinuation of the medication and/or administration of an antihistamine and/or epinephrine. Occasionally, maneuvers to protect the integrity of the airway may be needed. In a heart failure patient having previously experienced ACE inhibitor-related angioedema, ARBs should be used cautiously since angioedema has been reported with ARB therapy in heart failure patients. The need to reduce renin-angiotensin aldosterone system activity in a heart failure patient would seem to justify the small risk of angioedema with ARB therapy in a patient having previously experienced ACE inhibitor-related angioedema.

Treatment of Hypertension in the Elderly

Abstract: Hypertension is a common condition among older people in most developed countries, and is a very important, if not the most important, risk factor for all subtypes of vascular disease and death. Many clinical trials in older people have demonstrated significant reductions in myocardial infarctions and strokes when antihypertensive drugs are provided. Lifestyle modifications are still recommended because they can lower a surrogate end point--blood pressure--but there are no data showing they reduce event rates. It is not appropriate to limit the choice of initial drug for hypertensive older individuals to a single class of agents, since so many older people have other medical problems that affect this decision. Monotherapy with an alpha blocker, however, is no longer recommended, even for men with hypertension and benign prostatic hypertrophy, as doxazosin was associated with a higher rate of cardiovascular events in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. The classic strategy of an initial diuretic (for at least 1 month) will likely be verified by the final results of ongoing randomized trials, expected in 2003. Until then, this strategy is effective, inexpensive, and unlikely to cause many adverse effects. Probably the most important exhortation, however, should be to achieve the blood pressure goal appropriate for the patient's risk status. Numerous clinical trials in older hypertensive patients have shown that more benefits accrue when the goal blood pressure is achieved than if a specific antihypertensive agent is chosen as initial therapy. Future cardiovascular risk may be related directly to the blood pressure attained, rather than to how it was attained.

Chrono: a community-based hypertension trial of a chronotherapeutic formulation of verapamil.

Abstract: An open-label, multicenter, dose-titration study evaluated 2,556 patients with stage I or II essential hypertension (untreated or previously treated with one antihypertensive agent) to assess the effect of a chronotherapeutic formulation of verapamil (Verelan PM) designed to provide maximum plasma concentrations in the midmorning hours. After starting with 200 mg/d at bedtime, the dose of Verelan PM was titrated to a maximum of 400 mg/d at 4-week intervals to achieve a target blood pressure (BP) <140/90 mm Hg using morning BP measurements. In 85.3% of patients, a diastolic blood pressure (DBP) response to less than 90 mm Hg or a 10-mm Hg decline from baseline DBP was achieved. The systolic BP response (<140 mm Hg or 10% decline from baseline) was attained in 76.9% of patients. Blood pressure was controlled in 62.6% of patients with Verelan PM monotherapy. Upward titration of Verelan PM from 200 to 400 mg nearly doubled the DBP response rate (45.8% to 85.3%). This chronotherapeutic formulation of verapamil was well tolerated in this community trial.