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

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.