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, et al.
Circulation. 2016;133:1851-1860

Background

The LIPID (Long-term Intervention with Pravastatin in Ischemic Disease) trial, showed that 6 years of pravastatin treatment resulted in better survival, in line with other statin trials [1-4]. However, there are concerns about the long-term use of statins regarding non-CV mortality and increased incidence of cancer [5-8], although large statin trials with an average follow-up of 5 years demonstrated safety [9]. 
In this study, the long-term effects of statins on cancer incidence and mortality, as well as the mortality from other causes was evaluated, based on a 16-years follow-up of the LIPID trial, including 7721 patients with a history of CHD.

Main results

Type of statin treatment:

• pravastatin prescription was initially (first 6 years) 49%, and decreased to 25% (last 10 years),
• simvastatin prescription increased from 27% to 32%
• atorvastatin prescription increased from 19% to 31%
• other statins prescription increased from 3% to 11%

Patients assigned pravastatin maintained a significantly lower risk of death compared to the placebo group, regarding:  

• CHD; RR: 0.89; 95% CI: 0.81−0.97; P=0.009
• CV disease; RR: 0.88; 95% CI: 0.81−0.95; P=0.002
• any cause; RR: 0.91; 95% CI: 0.85−0.97; absolute RR: 2.6%; P=0.003

For every 1000 patients assigned to pravastatin, compared with placebo, over 16 years there were:

• 26 fewer deaths (31 over 6 years)
• 25 fewer CVD deaths (23 over 6 years)
• 18 fewer CHD deaths (19 over 6 years)

Cancer incidence after 16 year of pravastatin treatment was comparable to the placebo group and to the incidence after the initial 6 year:

• 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
• overall; RR: 0.99; 95% CI: 0.91–1.08; P=0.83

During the extend follow-up period, there were no significant differences in cancer mortality, or in the incidence of organ-specific cancers between pravastatin and placebo-treated patients Cancer findings were confirmed in a meta-analysis with other large statin trials with extended follow-up.

Conclusion

In 7721 patients with a history of CHD who participated in the extended follow-up of the LIPID study, the absolute survival benefit from 6 years of pravastatin treatment appeared to be maintained over another 10 years. The survival benefit was primarily related to CV-deaths and treatment with statins did not influence cancer incidence/death nor death from other non-CV causes during long-term follow-up. These results support the long-term use of statin therapy in patients at risk of CV events.

Find this article online at Circulation

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