Many trials have shown that inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (or statins) reduce the risk of death and major cardiovascular events after acute myocardial infarction and unstable angina pectoris. [1][2][3][4] One of these, the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) trial, showed that 6 years of pravastatin treatment resulted in better survival. 4 The longer-term effects of statins on cause-specific mortality and net clinical benefit are still debated, particularly in terms of effects on cancer and other noncardiovascular disease (CVD) mortality. Older epidemiological and randomized studies of cholesterol lowering had raised safety concerns, Background-We aimed to assess the long-term effects of treatment with statin therapy on all-cause mortality, causespecific mortality, and cancer incidence from extended follow-up of the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) trial. Methods and Results-LIPID initially compared pravastatin and placebo over 6 years in 9014 patients with previous coronary heart disease. After the double-blind period, all patients were offered open-label statin therapy. Data were obtained over a further 10 years from 7721 patients, by direct contact for 2 years, by questionnaires thereafter, and from mortality and cancer registries. During extended follow-up, 85% assigned pravastatin and 84% assigned placebo took statin therapy. Patients assigned pravastatin maintained a significantly lower risk of death from coronary heart disease (relative risk [RR]
83).There were no significant differences in cancer mortality, or in the incidence of organ-specific cancers. Cancer findings were confirmed in a meta-analysis with other large statin trials with extended follow-up. Conclusions-In LIPID, the absolute survival benefit from 6 years of pravastatin treatment appeared to be maintained for the next 10 years, with a similar risk of death among survivors in both groups after the initial period. including possible increased incidence of cancer, overall or for particular cancer sites. [5][6][7][8] Conversely, the possibility of beneficial effects of statins on other non-CVD deaths has also been raised.
9Large statin trials have demonstrated safety over an average of 5 years of treatment.10 For outcomes such as cancer, there may be a long lag between a causal exposure and clinical evidence of disease. In this study, cancer incidence and mortality, and mortality from other causes, as well, were evaluated during 16 years follow-up in the LIPID trial. In addition, we undertook a meta-analysis of cancer events in LIPID together with those in other large statin trials during long-term follow-up.
Methods
Double-Blind PeriodThe design and results of the original study have been published. 4 Between 1990 and 1992, the trial randomly assigned 9014 patients from 67 centers in Australia and 20 centers in New Zealand with a previous diagnosis of acute myocardial infarction or unstable angina pectoris to pravastatin 40 mg per day ...