Pravastatin reduced all-cause mortality, CHD mortality, and cardiovascular disease mortality in patients with existing CHD
ACP J Club. 1999 Mar-April;130:31. doi:10.7326/ACPJC-1999-130-2-031
The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998 Nov 5;339:1349-57.
In patients with coronary heart disease (CHD), can pravastatin reduce cardiovascular events and death?
Double-blind, placebo-controlled trial with mean follow-up of 6.1 years.
67 clinical centers in Australia and 20 in New Zealand.
9014 patients (median age 62 y, 83% men) with acute myocardial infarction (MI) or confirmed unstable angina at hospital discharge, cholesterol levels 4.0 to 7.0 mmol/L (155 to 271 mg/dL), and fasting triglyceride levels < 5 mmol/L (445 mg/dL). Exclusion criteria were recent medical or surgical events, cardiac failure, renal or hepatic disease, or use of cholesterol-lowering agents. All patients included in the final analysis.
During an 8-week run-in period, patients received dietary advice to reduce their fat intake and were then allocated to pravastatin, 40 mg/d (n = 4512), or placebo (n = 4502).
Main outcome measures
CHD mortality (death from MI, heart failure, or other cardiac causes or sudden death). Secondary outcomes were other causes of death, MI, stroke, coronary revascularization, hospitalization for angina, and lipid profiles.
The trial was stopped early, after predetermined stopping rules were met. Pravastatin reduced all-cause mortality and mortality from CHD and all cardiovascular causes (Table) (P < 0.001). Pravastatin improved lipid levels (decreased total cholesterol, triglyceride, and low-density lipoprotein [LDL] cholesterol levels and increased high-density lipoprotein cholesterol levels) and reduced rates of death from CHD or nonfatal MI (12.3% v 15.9%, P < 0.001), any MI (7.4% vs 10.3%, P < 0.001), coronary artery bypass grafting (9.2% vs 11.6%, P < 0.001), or hospitalization for unstable angina (22.3% v 24.6%, P = 0.005). The groups did not differ for adverse effects.
Pravastatin reduced all-cause mortality, mortality from CHD and cardiovascular disease, MI, coronary artery bypass grafting, and hospitalization for unstable angina in patients with existing CHD.
Source of funding: Bristol-Myers Squibb Pharmaceutical Research Institute.
For correspondence: Dr. A. Tonkin, National Health and Medical Research Council Clinical Trials Centre, Mallett St. Campus, University of Sydney, New South Wales 2006, Australia. FAX 61-2-9565-1863.
Table. Pravastatin vs placebo for patients with existing coronary heart disease (CHD)*
|Outcomes at 6.1 y||Pravastatin||Placebo||RRR (95% CI)||NNT (CI)|
|Mortality from CHD||6.4%||8.3%||23.2% (11.0 to 33.8)||52 (33 to 118)|
|All-cause mortality||11.0%||14.1%||21.5% (12.4 to 29.7)||33 (23 to 60)|
|Mortality from CVD||7.3%||9.6%||23.7% (12.5 to 33.5)||44 (29 to 88)|
*CVD = cardiovascular disease. Other abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
This secondary prevention trial adds convincing evidence that treatment with a statin can safely reduce coronary events and improve survival for patients with MI and unstable angina with a broad range of cholesterol levels. The trial had inadequate power to show a benefit among women, the elderly, and those with diabetes or initial LDL cholesterol levels < 3.5 mmol/L (135 mg/dL).
Clinicians and their patients with CHD should decide when the benefits of treatment with statins exceed the risk at affordable cost. This and previous trials (1, 2) convincingly show that treatment with statins can prevent CHD events and save lives among men < 70 years of age with clinically evident CHD. Although the evidence favoring treatment for middle-aged women with CHD has been less convincing, this trial shows a trend toward benefit for women. Because no trials have studied persons older than 75 years of age, the benefits may not apply to this group. Previous studies showed possible relations between cholesterol lowering and noncardiovascular mortality (3) and breast cancer (2). This trial provided reassuring evidence of safety in both of these categories.
Whether society can afford the widespread use of statins in patients with CHD and can make these drugs available equitably has not been determined.
William C. Taylor, MD
Beth Israel Deaconess Medical CenterBoston, Massachusetts, USA
1. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:383-9.
2. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial Investigators. N Engl J Med. 1996;335:1001-9.