Long-Term Effectiveness and Safety of Pravastatin in Patients With Coronary Heart Disease

Abstract

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 ...

Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Small-Cell Lung Cancer (LUNGSTAR)

“…Alternatively, hydrophilic statins, such as pravastatin, may not be as effective as lipophilic agents, such as simvastatin; some studies have suggested clearer benefits for simvastatin in lung cancer, 21 with a lack of benefit for pravastatin in cancer prevention or cancer death observed in a trial of patients with coronary heart disease. 29 However, there is insufficient evidence to reliably conclude whether any one type of statin is better than another, and biologic plausibility for a difference is lacking. 22 Of interest, more recent evidence in glioma cells has suggested that statins may fail to work in certain cancer cells because of a phosphatidylinositol 3-kinase–mediated pathway connected to LDL receptors.…”

Persistent psychological distress and mortality in patients with stable coronary artery disease

“…From this time, surviving patients were followed up centrally by the National Health and Medical Research Council Clinical Trials Centre until the end of 2007 7. Information on cause-specific mortality and cancer incidence was also obtained through data linkage with national death registries and state-based cancer registries in Australia and New Zealand 7. The outcome measures were CV death and all-cause mortality obtained for all patients after 48 months for further follow-up over a median of 12.1 (IQR 8.6–12.5) years.…”

L‐TRUST: Long‐term risk of cancer in patients under statins therapy. A systematic review and meta‐analysis

“…Over the total period, the reductions in all‐cause mortality remained statistically significant (RR, 0.91; 95% CI, 0.85‐0.97; P = .003). There were no significant differences in cancer mortality (RR, 1.01; 95% CI, 0.85‐1.15; P = .87), nor in cancer incidence (RR, 0.99; 95% CI, 0.91‐1.08; P = .83) . The Scandinavian Simvastatin Survival Study Group (4S) trial was also a double‐blind RCT of simvastatin or placebo in 4444 patients with coronary heart disease with a total median follow‐up of 5.4 years.…”