Long-Term Effectiveness and Safety of Pravastatin in Patients With Coronary Heart Disease: Sixteen Years of Follow-Up of the LIPID Study

Circulation. 2016 May 10;133(19):1851-60. doi: 10.1161/CIRCULATIONAHA.115.018580. Epub 2016 Mar 25.

Abstract

Background: We aimed to assess the long-term effects of treatment with statin therapy on all-cause mortality, cause-specific 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] 0.89; 95% confidence interval [CI], 0.81-0.97; P=0.009), from cardiovascular disease (RR, 0.88; 95% CI, 0.81-0.95; P=0.002), and from any cause (RR, 0.91; 95% CI, 0.85-0.97; absolute risk reduction, 2.6%; P=0.003).Cancer incidence was similar by original treatment group during the double-blind period (RR, 0.94; 95% CI, 0.82-1.08; P=0.41), later follow-up (RR, 1.02; 95% CI, 0.91-1.14; P=0.74), and overall (RR, 0.99; 95% CI, 0.91-1.08; P=0.83). 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. Treatment with statins does not influence cancer or death from noncardiovascular causes during long-term follow-up.

Keywords: cardiovascular diseases; cholesterol; coronary disease; hydroxymethylglutaryl-CoA reductase inhibitors; lipids.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / mortality*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Longitudinal Studies
  • Male
  • Multicenter Studies as Topic
  • Pravastatin / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Survival Rate / trends
  • Time Factors

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pravastatin