Long-Term Effectiveness and Safety of Pravastatin in Patients With Coronary Heart Disease: Sixteen Years of Follow-Up of the LIPID Study
Hague WE, Simes J, Kirby A, Keech AC, White HD, Hunt D, Nestel PJ, Colquhoun DM, Pater H, Stewart RA, Sullivan DR, Thompson PL, West M, Glasziou PP, Tonkin AM; LIPID study investigators.
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.
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.