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. doi: 10.1001/jama.288.23.2998.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Anticholesteremic Agents / therapeutic use*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control
  • Cause of Death
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / complications*
  • Hypercholesterolemia / drug therapy*
  • Hypertension / complications*
  • Hypertension / drug therapy
  • Lipids / blood
  • Male
  • Middle Aged
  • Pravastatin / therapeutic use*
  • Proportional Hazards Models
  • Risk Factors

Substances

  • Anticholesteremic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Pravastatin