Statin therapy and delaying death in women

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What evidence exists that statin therapy delays death in women either in primary or secondary prevention?

PICO terms

Population / Problem: Women Intervention: Statins  Comparison: none specified Outcome: Delay in death

Comments

Only one paper identified that looked at mortality in women versus men.

Top papers identified

Title: Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.
Citation: Lancet (London, England), Jun 2015, vol. 385, no. 9984, p. 2264-2271, 1474-547X (June 6, 2015)
Author(s): Mega, Jessica L, Stitziel, Nathan O, Smith, J Gustav, Chasman, Daniel I, Caulfield, Mark J, Devlin, James J, Nordio, Francesco, Hyde, Craig L, Cannon, Christopher P, Sacks, Frank M, Poulter, Neil R, Sever, Peter S, Ridker, Paul M, Braunwald, Eugene, Melander, Olle, Kathiresan, Sekar, Sabatine, Marc S
Abstract: Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, p<0·0001) and that for the high genetic risk category was 1·72 (1·55-1·92, p<0·0001). In terms of the benefit of statin therapy in the four randomised trials, we noted a significant gradient (p=0·0277) of increasing relative risk reductions across the low (13%), intermediate (29%), and high (48%) genetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high genetic risk in JUPITER, and 57, 47, and 20, respectively, in ASCOT. A genetic risk score identified individuals at increased risk for both incident and recurrent coronary heart disease events. People with the highest burden of genetic risk derived the largest relative and absolute clinical benefit from statin therapy. National Institutes of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Available from Elsevier in Lancet

Title: Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants.
Citation: Archives of internal medicine, Jun 2010, vol. 170, no. 12, p. 1024-1031, 1538-3679 (June 28, 2010)
Author(s): Ray, Kausik K, Seshasai, Sreenivasa Rao Kondapally, Erqou, Sebhat, Sever, Peter, Jukema, J Wouter, Ford, Ian, Sattar, Naveed
Abstract: Statins have been shown to reduce the risk of all-cause mortality among individuals with clinical history of coronary heart disease. However, it remains uncertain whether statins have similar mortality benefit in a high-risk primary prevention setting. Notably, all systematic reviews to date included trials that in part incorporated participants with prior cardiovascular disease (CVD) at baseline. Our objective was to reliably determine if statin therapy reduces all-cause mortality among intermediate to high-risk individuals without a history of CVD. Trials were identified through computerized literature searches of MEDLINE and Cochrane databases (January 1970-May 2009) using terms related to statins, clinical trials, and cardiovascular end points and through bibliographies of retrieved studies. Prospective, randomized controlled trials of statin therapy performed in individuals free from CVD at baseline and that reported details, or could supply data, on all-cause mortality. Relevant data including the number of patients randomized, mean duration of follow-up, and the number of incident deaths were obtained from the principal publication or by correspondence with the investigators. Data were combined from 11 studies and effect estimates were pooled using a random-effects model meta-analysis, with heterogeneity assessed with the I(2) statistic. Data were available on 65,229 participants followed for approximately 244,000 person-years, during which 2793 deaths occurred. The use of statins in this high-risk primary prevention setting was not associated with a statistically significant reduction (risk ratio, 0.91; 95% confidence interval, 0.83-1.01) in the risk of all-cause mortality. There was no statistical evidence of heterogeneity among studies (I(2) = 23%; 95% confidence interval, 0%-61% [P = .23]). This literature-based meta-analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up.
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Available from EBSCOhost in Archives of Internal Medicine
Available from Silverchair Information Systems in Archives of Internal Medicine

Title: Statins for the primary prevention of cardiovascular disease.
Citation: The Cochrane database of systematic reviews, Jan 2013, no. 1, p. CD004816., 1469-493X (2013)
Author(s): Taylor, Fiona, Huffman, Mark D, Macedo, Ana Filipa, Moore, Theresa H M, Burke, Margaret, Davey Smith, George, Ward, Kirsten, Ebrahim, Shah
Abstract: Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of CVD is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with CVD. The case for primary prevention was uncertain when the last version of this review was published (2011) and in light of new data an update of this review is required. To assess the effects, both harms and benefits, of statins in people with no history of CVD. To avoid duplication of effort, we checked reference lists of previous systematic reviews. The searches conducted in 2007 were updated in January 2012. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2022, Issue 4), MEDLINE OVID (1950 to December Week 4 2011) and EMBASE OVID (1980 to 2012 Week 1).There were no language restrictions. We included randomised controlled trials of statins versus placebo or usual care control with minimum treatment duration of one year and follow-up of six months, in adults with no restrictions on total, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD. Two review authors independently selected studies for inclusion and extracted data. Outcomes included all-cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), revascularisation, change in total and LDL cholesterol concentrations, adverse events, quality of life and costs. Odds ratios (OR) and risk ratios (RR) were calculated for dichotomous data, and for continuous data, pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated. We contacted trial authors to obtain missing data. The latest search found four new trials and updated follow-up data on three trials included in the original review. Eighteen randomised control trials (19 trial arms; 56,934 participants) were included. Fourteen trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (OR 0.86, 95% CI 0.79 to 0.94); as was combined fatal and non-fatal CVD RR 0.75 (95% CI 0.70 to 0.81), combined fatal and non-fatal CHD events RR 0.73 (95% CI 0.67 to 0.80) and combined fatal and non-fatal stroke (RR 0.78, 95% CI 0.68 to 0.89). Reduction of revascularisation rates (RR 0.62, 95% CI 0.54 to 0.72) was also seen. Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no evidence of any serious harm caused by statin prescription. Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life. Recent findings from the Cholesterol Treatment Trialists study using individual patient data meta-analysis indicate that these benefits are similar in people at lower (< 1% per year) risk of a major cardiovascular event. Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of adverse events among people without evidence of CVD treated with statins.
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Available from Wiley in Cochrane Library, The

Title: Meta-analysis of statin effects in women versus men.
Citation: Journal of the American College of Cardiology, Feb 2012, vol. 59, no. 6, p. 572-582, 1558-3597 (February 7, 2012)
Author(s): Kostis, William J, Cheng, Jerry Q, Dobrzynski, Jeanne M, Cabrera, Javier, Kostis, John B
Abstract: The aim of this study was to evaluate the effect of statins in decreasing cardiovascular events in women and men. Published data reviews have suggested that statins might not be as effective in women as in men in decreasing cardiovascular events. Published data searches and contacts with investigators identified 18 randomized clinical trials of statins with sex-specific outcomes (N = 141,235, 40,275 women, 21,468 cardiovascular events). Odds ratios (ORs) and 95% confidence intervals (CIs) for cardiovascular events were calculated for women and men separately with random effects meta-analyses. The cardiovascular event rate was lower among those randomized to statin intervention than in those randomized to control (low-dose statin in 4 studies, placebo in 11 studies, usual care in 3 studies) and similar in women and men (OR: 0.81, 95% CI: 0.75 to 0.89; p < 0.0001, and OR: 0.77, 95% CI: 0.71 to 0.83, p < 0.0001, respectively). The benefit of statins was statistically significant in both sexes, regardless of the type of control, baseline risk, or type of endpoint and in both primary and secondary prevention. All-cause mortality was also lower with statin therapy both in women and men without significant interaction by sex (p for interaction = 0.4457). Statin therapy is associated with significant decreases in cardiovascular events and in all-cause mortality in women and men. Statin therapy should be used in appropriate patients without regard to sex. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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