Review: Statins reduce mortality and major vascular events in patients with no history of CV disease
Authors: C. Raina Elley
Journal: Annals of Internal Medicine (2013)

ACP Journal ClubJuly 16, 2013Review: Statins reduce mortality and major vascular events in patients with no history of CV diseaseC. Raina Elley, MDC. Raina Elley, MDUniversity of Auckland, Auckland, New Zealand (C.R.E.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-159-2-201307160-02002 SectionsAboutVisual AbstractAbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationTaylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;(1):CD004816. https://pubmed.ncbi.nlm.nih.gov/23440795Clinical Impact RatingsGIM/FP/GP: Cardiology: AbstractQuestionIn patients with no history of cardiovascular disease (CVD), what are the benefits and harms of statins?Review scopeIncluded studies compared statins with placebo or usual care in adults ≥ 18 years of age; and had treatment duration ≥ 12 months and follow-up ≥ 6 months. Studies in which > 10% of patients had previous CVD or in which statins were used to treat or control chronic conditions were excluded. Outcomes included all-cause mortality, coronary heart disease (CHD), CVD, stroke, revascularizations, type 2 diabetes, and adverse events.Review methodsMEDLINE and EMBASE/Excerpta Medica (Jan 2012), and Cochrane Central Register of Controlled Trials (Issue 4, 2011) were searched for randomized controlled trials (RCTs); reference lists of review articles and included RCTs were also reviewed. 18 RCTs with 19 groups (n = 56 934, mean age 57 y [range 28 to 97 y]) met the inclusion criteria. Sample size ranged from 47 to 17 802 patients, and duration of follow-up ranged from 1 to 5.3 years. 16 RCTs adequately reported random sequence generation, 15 used double-blinding of outcome assessment, and 13 used intention-to-treat analyses.Main resultsMeta-analysis showed that statins reduced all-cause mortality, CHD, CVD, stroke, and revascularizations (Table). Statins increased risk for type 2 diabetes but not other adverse events (Table).ConclusionIn patients with no history of cardiovascular disease, statins reduce mortality and major vascular events and increase the risk for diabetes without increasing other adverse events.Statins vs control in patients with no history of cardiovascular disease (CVD)*OutcomesNumber of trials (n)Weighted event ratesRRR (95% CI) at 1 to 5.3 yNNT (CI) at 5 yStatinsControlMortality13 (48 060)4.2%5.2%12% (5 to 19)138 (92 to 321)†CHD14 (48 049)3.7%4.7%27% (20 to 33)56 (46 to 75)†CVD9 (23 805)9.2%12%25% (19 to 30)49 (40 to 66)†Stroke10 (40 295)2.2%2.2%22% (11 to 32)155 (106 to 309)†Revascularization7 (42 403)1.2%2.2%38% (28 to 46)122 (101 to 165)‡RRI (CI)NNH (CI)Type 2 diabetes2 (24407)2.4%2.4%18% (1 to 38)198 (105 to 889)†Other adverse events12 (40 716)25%25%0% (−3 to 3)Not significant*CHD = coronary heart disease; other abbreviations defined in Glossary. RRR, RRI, and CI calculated from risk ratios in article using a fixed-effect model.†NNT provided by author.‡NNT and CI calculated from risk ratio and control event rate in article.CommentaryThe meta-analysis by Taylor and colleagues found that statins reduce risk for mortality and CVD in patients with no history of CVD. The relative risk reductions (RRRs) in this primary prevention review are similar to the RRRs found in studies of secondary prevention of CVD and mortality (1), although the numbers needed to treat (NNTs) are very different. To avoid 1 additional death, about 30 persons would need to be treated with statins for 5 years in secondary prevention (1) but, as shown in this review, about 138 would need to be treated in primary prevention. The cost-effectiveness also differs. A UK report estimated costs equivalent to approximately $20 000 to $34 000/quality-adjusted life-year (QALY) in secondary prevention, but $20 000 to $96 000/QALY in primary prevention (1), although this would probably be less with generic statins. In secondary prevention, such interventions as exercise-based cardiac rehabilitation are as clinically effective (2) and cost-effective (3) as statins, yet do not receive the attention or funding that statins do. Some lifestyle interventions are probably as cost-effective as statins in primary prevention as well. More cost-effectiveness analyses are needed, including comparisons with lifestyle interventions.There are reasons to be cautious about the findings of the meta-analysis by Taylor and colleagues. As the authors note, all but 1 of the trials were partly or fully funded by pharmaceutical companies. Trials funded by for-profit organizations are more likely to recommend the experimental drug than are trials funded by nonprofit organizations (4). Further, adverse event reporting in the original trials was poor, with few details about type or severity, and quality of life was rarely assessed. Some adverse events, such as cognitive impairment, are rarer and not assessed. Despite these concerns, statins seem to be effective in primary prevention, especially in persons at high risk for CVD (≥ 20% 10-y risk for CVD) (5), in whom cost-effectiveness will be better than in patients at lower risk.References1 Ward S, Lloyd Jones M, Pandor A, et al. A systematic review and economic evaluation of statins for the prevention of coronary events. Health Technol Assess. 2007;11:1-160, iii-iv. [PMID: 17408535] Google Scholar2 Lawler PR, Filion KB, Eisenberg MJ. Efficacy of exercise-based cardiac rehabilitation post-myocardial infarction: a systematic review and meta-analysis of randomized controlled trials. Am Heart J. 2011;162:571-84.e2. [PMID: 21982647] Google Scholar3 Briffa TG, Eckermann SD, Griffiths AD, et al. Cost-effectiveness of rehabilitation after an acute coronary event: a randomised controlled trial. Med J Aust. 2005;183:450-5. [PMID: 16274344] Google Scholar4 Als-Nielsen B, Chen W, Gluud C, Kjaergard LL. Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? JAMA. 2003;290:921-8. [PMID: 12928469] Google Scholar5 National Institute for Health and Clinical Excellence. Technology Appraisal TA94: Statins for the prevention of cardiovascular events in patients at increased risk of developing cardiovascular disease or those with established cardiovascular disease. 2006. www.nice.org.uk/TA094 (accessed 3 Apr 2012). Google Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Auckland, Auckland, New Zealand (C.R.E.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics July 16, 2013Volume 159, Issue 2Page: JC2KeywordsAdverse eventsCardiac rehabilitationCardiovascular diseasesCognitive impairmentCoronary heart diseaseDrugsMyocardial infarctionQuality of lifeRevascularizationSequence analysisStatinsStrokeType 2 diabetes Issue Published: July 16, 2013 CopyrightCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...