Evidence-based Use of Statins for Primary Prevention of Cardiovascular Disease


      Three-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly known as statins, are widely available, inexpensive, and represent a potent therapy for treating elevated cholesterol. Current national guidelines put forth by the Adult Treatment Panel III recommend statins as part of a comprehensive primary prevention strategy for patients with elevated low-density lipoprotein cholesterol at increased risk for developing coronary heart disease within 10 years. Lack of a clear-cut mortality benefit in primary prevention has caused some to question the use of statins for patients without known coronary heart disease. On review of the literature, we conclude that current data support only a modest mortality benefit for statin primary prevention when assessed in the short term (<5 years). Of note, statin primary prevention results in a significant decrease in cardiovascular morbidity over the short and long term and a trend toward increased reduction in mortality over the long term. When appraised together, these data provide compelling evidence to support the use of statins for primary prevention in patients with risk factors for developing coronary heart disease over the next 10 years.


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        • Ray K.K.
        • Seshasai S.R.
        • Erqou S.
        • et al.
        Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants.
        Arch Intern Med. 2010; 170: 1024-1031
        • Giugliano D.
        • Esposito K.
        Clinical inertia as a clinical safeguard.
        JAMA. 2011; 305: 1591-1592
        • Redberg R.
        • Katz M.
        • Grady D.
        Diagnostic tests: another frontier for less is more: or why talking to your patient is a safe and effective method of reassurance.
        Arch Intern Med. 2011; 171: 619
        • Heidenreich P.A.
        • Trogdon J.G.
        • Khavjou O.A.
        • et al.
        Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association.
        Circulation. 2011; 123: 933-944
        • Brugts J.J.
        • Yetgin T.
        • Hoeks S.E.
        • et al.
        The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials.
        BMJ. 2009; 338: 2376
        • Taylor F.
        • Ward K.
        • Moore T.H.
        • et al.
        Statins for the primary prevention of cardiovascular disease.
        Cochrane Database Syst Rev. 2011; (CD004816)
        • Mills E.J.
        • Rachlis B.
        • Wu P.
        • Devereaux P.J.
        • Arora P.
        • Perri D.
        Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients.
        J Am Coll Cardiol. 2008; 52: 1769-1781
        • Thavendiranathan P.
        • Bagai A.
        • Brookhart M.A.
        • Choudhry N.K.
        Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials.
        Arch Intern Med. 2006; 166: 2307-2313
      1. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III).
        JAMA. 2001; 285: 2486-2497
        • Kaul S.
        • Morrissey R.P.
        • Diamond G.A.
        By Jove! What is a clinician to make of JUPITER?.
        Arch Intern Med. 2010; 170: 1073-1077
        • Ridker P.M.
        • Macfadyen J.G.
        • Nordestgaard B.G.
        • et al.
        Rosuvastatin for primary prevention among individuals with elevated high-sensitivity C-reactive protein and 5% to 10% and 10% to 20% 10-year risk.
        Circ Cardiovasc Qual Outcomes. 2010; 3: 447-452
        • Ford I.
        • Murray H.
        • Packard C.J.
        • Shepherd J.
        • Macfarlane P.W.
        • Cobbe S.M.
        Long-term follow-up of the West of Scotland Coronary Prevention Study.
        N Engl J Med. 2007; 357: 1477-1486
        • Sever P.S.
        • Poulter N.R.
        • Dahlof B.
        • et al.
        The Anglo-Scandinavian Cardiac Outcomes Trial lipid lowering arm: extended observations 2 years after trial closure.
        Eur Heart J. 2008; 29: 499-508
        • Steinberg D.
        Earlier intervention in the management of hypercholesterolemia: what are we waiting for?.
        J Am Coll Cardiol. 2010; 56: 627-629
        • Kashani A.
        • Phillips C.O.
        • Foody J.M.
        • et al.
        Risks associated with statin therapy: a systematic overview of randomized clinical trials.
        Circulation. 2006; 114: 2788-2797
        • Downs J.R.
        • Clearfield M.
        • Weis S.
        • et al.
        Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS.
        JAMA. 1998; 279: 1615-1622
        • Dale K.M.
        • Coleman C.I.
        • Henyan N.N.
        • Kluger J.
        • White C.M.
        Statins and cancer risk: a meta-analysis.
        JAMA. 2006; 295: 74-80
        • Muldoon M.F.
        • Barger S.D.
        • Ryan C.M.
        • et al.
        Effects of lovastatin on cognitive function and psychological well-being.
        Am J Med. 2000; 108: 538-546
        • Sattar N.
        • Preiss D.
        • Murray H.M.
        • et al.
        Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.
        Lancet. 2010; 375: 735-742
        • Manuel D.G.
        • Kwong K.
        • Tanuseputro P.
        • et al.
        Effectiveness and efficiency of different guidelines on statin treatment for preventing deaths from coronary heart disease: modelling study.
        BMJ. 2006; 332: 1419
        • Brugts J.J.
        • Deckers J.W.
        Statin prescription in men and women at cardiovascular risk: to whom and when?.
        Curr Opin Cardiol. 2010; 25: 484-489
      2. Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement.
        Ann Intern Med. 2009; 150: 396-404
        • Berger J.S.
        • Roncaglioni M.C.
        • Avanzini F.
        • Pangrazzi I.
        • Tognoni G.
        • Brown D.L.
        Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials.
        JAMA. 2006; 295: 306-313
        • Baigent C.
        • Blackwell L.
        • Collins R.
        • et al.
        Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.
        Lancet. 2009; 373: 1849-1860
        • Wright J.M.
        • Musini V.M.
        First-line drugs for hypertension.
        Cochrane Database Syst Rev. 2009; (CD001841)
        • Chobanian A.V.
        • Bakris G.L.
        • Black H.R.
        • et al.
        The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 report.
        JAMA. 2003; 289: 2560-2572
        • Pletcher M.J.
        • Lazar L.
        • Bibbins-Domingo K.
        • et al.
        Comparing impact and cost-effectiveness of primary prevention strategies for lipid-lowering.
        Ann Intern Med. 2009; 150: 243-254
        • Lazar L.D.
        • Pletcher M.J.
        • Coxson P.G.
        • Bibbins-Domingo K.
        • Goldman L.
        Cost-effectiveness of statin therapy for primary prevention in a low-cost statin era.
        Circulation. 2011; 124: 146-153
        • Gotto Jr, A.M.
        • Boccuzzi S.J.
        • Cook J.R.
        • et al.
        Effect of lovastatin on cardiovascular resource utilization and costs in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS).
        Am J Cardiol. 2000; 86: 1176-1181
        • Lindgren P.
        • Buxton M.
        • Kahan T.
        • et al.
        Cost-effectiveness of atorvastatin for the prevention of coronary and stroke events: an economic analysis of the Anglo-Scandinavian Cardiac Outcomes Trial—lipid-lowering arm (ASCOT-LLA).
        Eur J Cardiovasc Prev Rehabil. 2005; 12: 29-36
        • Caro J.
        • Klittich W.
        • McGuire A.
        • et al.
        The West of Scotland coronary prevention study: economic benefit analysis of primary prevention with pravastatin.
        BMJ. 1997; 315: 1577-1582
        • Strong J.P.
        • Malcom G.T.
        • McMahan C.A.
        • et al.
        Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study.
        JAMA. 1999; 281: 727-735
        • Nissen S.E.
        • Nicholls S.J.
        • Sipahi I.
        • et al.
        Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial.
        JAMA. 2006; 295: 1556-1565
        • Berenson G.S.
        • Srinivasan S.R.
        • Bao W.
        • Newman 3rd, W.P.
        • Tracy R.E.
        • Wattigney W.A.
        Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults.
        N Engl J Med. 1998; 338: 1650-1656