Long-term effectiveness and safety of pravastatin in 9014 patients with coronary heart disease and average cholesterol concentrations: the LIPID trial follow-up

Lancet. 2002 Apr 20;359(9315):1379-87. doi: 10.1016/S0140-6736(02)08351-4.

Abstract

Background: The Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) study showed that pravastatin therapy over 6 years reduced mortality and cardiovascular events in patients with previous acute coronary syndromes and average cholesterol concentrations. We assessed the longer-term effects of initial treatment with pravastatin on further cardiovascular events and mortality over a total follow-up period of 8 years.

Methods: In the main trial, 9014 patients with previous myocardial infarction or unstable angina and a baseline plasma cholesterol concentration of 4.0-7.0 mmol/L were randomly assigned pravastatin 40 mg daily or placebo and followed up for 6 years. Subsequently, all patients were offered open-label pravastatin for 2 more years. Major cardiovascular events and adverse events were compared according to initial treatment assignment.

Findings: 7680 (97% of those still alive) had 2 years of extended follow-up. 3766 (86%) of those assigned placebo and 3914 (88%) assigned pravastatin agreed to take open-label pravastatin. During this period, patients originally assigned pravastatin had almost identical cholesterol concentrations to those assigned placebo, but a lower risk of death from all causes (219 [5.6%] vs 255 [6.8%], p=0.029), coronary heart disease (CHD) death (108 [2.8%] vs 137 [3.6%], p=0.026), and CHD death or non-fatal myocardial infarction (176 [4.5%] vs 196 [5.2%], p=0.08). Over the total 8-year period, all-cause mortality was 888 (19.7%) in the group originally assigned placebo and 717 (15.9%) in the group originally assigned pravastatin, CHD mortality was 510 (11.3%) versus 395 (8.8%), myocardial infarction was 570 (12.7%) versus 435 (9.6%; each p < 0.0001), and stroke was 272 (6.0%) versus 224 (5.0%; p=0.015). Stronger evidence of separate treatment benefits than in the main trial was seen in important prespecified subgroups (women, patients aged > or = 70 years, and those with total cholesterol < 5.5 mmol/L). Pravastatin had no significant adverse effects.

Interpretation: The evidence of sustained treatment benefits and safety of long-term pravastatin treatment reinforces the importance of long-term cholesterol-lowering treatment for almost all patients with previous CHD events.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Angina, Unstable / blood
  • Angina, Unstable / drug therapy
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / therapeutic use*
  • Cholesterol / blood*
  • Cholesterol, LDL / blood
  • Coronary Disease / blood*
  • Coronary Disease / drug therapy*
  • Coronary Disease / mortality
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / drug therapy
  • Pravastatin / administration & dosage
  • Pravastatin / adverse effects
  • Pravastatin / therapeutic use*
  • Risk
  • Survival Analysis
  • Time Factors
  • Treatment Outcome

Substances

  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol
  • Pravastatin