Research Article| Volume 254, P215-227, November 2016

Download started.


Efficacy and safety of long-term treatment with statins for coronary heart disease: A Bayesian network meta-analysis


      • Used a Bayesian network meta-analysis to study CHD with using different statins.
      • Studied the efficacy and safety for treatment CHD with using different statins.
      • Only considered prospective cohort study, which has reliable data, less recall bias, better explain causal relationships.
      • Outcome included not only clinical indicators, but also ultimate outcomes, which better explained which statin is the best choice.


      Background and aims

      Our study aims to evaluate the efficacy and safety of long-term treatment of statins for coronary heart disease (CHD).


      Efficacy outcomes included changes in blood lipids, risk of CHD mortality and all-cause mortality. Safety outcomes were evaluated by the risk of adverse events (AE). Bayesian network meta-analysis was used to compare the direct and indirect effects between different statins.


      The systematic review showed that levels of blood lipids decreased during statin treatment. High dose of atorvastatin was the most obvious treatment for the reduction of blood lipids. Network meta-analysis showed that statins were significantly more effective than the control in reducing the risk of CHD mortality (Odds Ratio (OR) 0.69, 95% CI 0.61–0.77) and all-cause mortality (OR 0.84, 95% CI 0.80–0.87). In terms of reducing the risk of CHD morality, fluvastatin (77.3%), atorvastatin (72.3%) and lovastatin (68.4%) had higher cumulative probability than other statins, which were more effective treatments for the reduction of CHD morality. In terms of reducing all-cause mortality, atorvastatin (78.6%), fluvastatin (77.1%) and pitavastatin (74.1%) had higher cumulative probability than other statins, which were more effective treatment for reducing the all-cause mortality. Compared with placebo, statins increased the incidence risk of muscle disease (OR 1.05, 95% CI 1.00–1.10) and kidney disease (OR 1.11, 95% CI 1.05–1.72).


      Statins significantly reduced levels of blood lipids, with a high dose of atorvastatin being the most effective in blood-lipid level modification. Statins reduced the risk of CHD mortality and all-cause mortality, with atorvastatin and fluvastatin being the most effective in reducing the risk of CHD mortality and all-cause mortality. Statins increased the risk of muscle disease and kidney damage.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Celermajer D.S.
        • Chow C.K.
        • Marijon E.
        • Anstey N.M.
        • Woo K.S.
        Cardiovascular disease in the developing world.
        J. Am. Coll. Cardiol. 2012; 60: 1207-1216
        • Lopez A.D.
        • Mathers C.D.
        • Ezzati M.
        • Jamison D.T.
        • Murray C.J.
        Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data.
        Lancet. 2006; 367: 1747-1757
        • Finegold J.A.
        • Asaria P.
        • Francis D.P.
        Mortality from ischaemic heart disease by country, region, and age: statistics from world health organisation and United Nations ☆.
        Int. J. Cardiol. 2013; 168: 934-945
        • Mozaffarian D.
        • Benjamin E.J.
        • Go A.S.
        • Arnett D.K.
        • Blaha M.J.
        • et al.
        Heart disease and stroke statistics–2015 update: a report from the American Heart Association.
        Circulation. 2015; 131: 29-322
        • Reiner Zeljko
        • Catapano Alberico L.
        • De Backer Guy
        • Graham Ian
        • Taskinen Marja-Riitta
        • Wiklund Olov
        • et al.
        ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European society of Cardiology (ESC) and the European atherosclerosis society (EAS).
        Eur. Heart J. 2011; 32: 1769-1818
        • Davidson M.H.
        • Robinson J.G.
        Safety of aggressive lipid management.
        J. Am. Coll. Cardiol. 2007; 49: 1753-1762
        • Members A.F.
        • Perk J.
        • Backer G.D.
        • Gohlke H.
        • Graham I.
        • et al.
        ‘European guidelines on cardiovascular disease prevention in clinical practice (version 2012)’ the fifth joint task force of the European society of Cardiology and other societies on cardiovascular disease prevention in clinical practice.
        Eur. Heart J. 2012; 33: 1635-1701
        • Reiner Ž.
        Statins in the primary prevention of cardiovascular disease.
        Nat. Rev. Cardiol. 2013; 10: 453-464
        • Rajpathak S.N.
        • Kumbhani D.J.
        • Crandall J.
        • Barzilai N.
        • Alderman M.
        • et al.
        Statin therapy and risk of developing type 2 diabetes: a meta-analysis.
        Diabetes Care. 2009; 32: 1924-1929
        • Schönbeck U.
        • Libby P.
        Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents?.
        Circulation. 2004; 109: 18-26
        • Ando H.
        • Takamura T.
        • Ota T.
        • Nagai Y.
        • Kobayashi K.
        Cerivastatin improves survival of mice with lipopolysaccharide-induced sepsis.
        J. Pharmacol. Exp. Ther. 2000; 294: 1043-1046
        • Rosenson R.S.
        • Tangney C.C.
        • Casey L.C.
        Inhibition of proinflammatory cytokine production by pravastatin.
        Lancet. 1999; 353: 983-984
        • Naci H.
        • Brugts J.J.
        • Fleurence R.
        • Tsoi B.
        • Toor H.
        • et al.
        Comparative benefits of statins in the primary and secondary prevention of major coronary events and all-cause mortality: a network meta-analysis of placebo-controlled and active-comparator trials.
        Eur. J. Prev. Cardiol. 2013; 20: 641-657
        • Mills E.J.
        • Wu P.
        • Chong G.
        • Ghement I.
        • Singh S.
        • et al.
        Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials.
        QJM Mon. J. Assoc. Physicians. 2011; 104: 109-124
        • Higgins J.P.T.
        • Altman D.G.
        • Gøtzsche P.C.
        • Jüni P.
        • Moher D.
        • et al.
        The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343 (d5928-d)
        • Higgins J.P.T.
        • Thompson S.G.
        Quantifying heterogeneity in a meta-analysis.
        Statistics Med. 2002; 21: 1539-1558
        • Sheehe P.R.
        Combination of log relative risk in retrospective studies of disease.
        Am. J. Public Health & Nations Health. 1966; 56: 1745-1750
        • Caldwell D.M.
        • Ades A.E.
        • Higgins J.P.T.
        Simultaneous comparison of multiple treatments: combining direct and indirect evidence.
        BMJ. 2005; 331: 897-900
        • Jansen J.P.
        • Fleurence R.
        • Devine B.
        • Itzler R.
        • Barrett A.
        • et al.
        Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on indirect treatment comparisons good research practices: part 1.
        Value Health. 2011; 14: 417-428
        • Lu G.
        • Ades A.E.
        Combination of direct and indirect evidence in mixed treatment comparisons.
        Statistics Med. 2004; 23: 3105-3124
        • Salanti G.
        • Ades A.E.
        • Ioannidis J.P.A.
        Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial.
        J. Clin. Epidemiol. 2011; 64: 163-171
        • Song F.
        • Xiong T.
        • Parekh-Bhurke S.
        • Loke Y.K.
        • Sutton A.J.
        • et al.
        Inconsistency between direct and indirect comparisons of competing interventions: meta-epidemiological study.
        BMJ. 2011; 343: 767-768
        • Liberati A.
        • Altman D.G.
        • Tetzlaff J.
        • Mulrow C.
        • Gøtzsche P.C.
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
        Bmj. 2009; 339: e1-e34
        • Kleemann A.
        • Eckert S.
        • Eckardstein A.V.
        • Lepper W.
        • Schernikau U.
        • et al.
        Effects of lovastatin on progression of non-dilated and dilated coronary segments and on restenosis in patients after PTCA. The cholesterol lowering atherosclerosis PTCA trial (CLAPT).
        Eur. Heart J. 1999; 20: 1393-1406
        • Holdaas H.
        • Fellstrom B.
        • Nyberg G.
        • Fauchald P.
        • Gronhagen-Riska C.
        • et al.
        Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial.
        Lancet. 2003; 361: 2024-2031
        • Colhoun H.M.
        • Betteridge D.J.
        • Durrington P.N.
        • Hitman G.A.
        • Neil H.A.
        • et al.
        Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.
        Lancet. 2004; 364: 685-696
        • Nakagawa T.
        • Kobayashi T.
        • Awata N.
        • Sato S.
        • Reiber J.H.C.
        • et al.
        Randomized, controlled trial of secondary prevention of coronary sclerosis in normocholesterolemic patients using pravastatin: final 5-year angiographic follow-up of the Prevention of Coronary Sclerosis (PCS) study.
        Int. J. Cardiol. 2004; 97: 107-114
        • Sawayama Y.
        • Shimizu C.
        • Maeda N.
        • Tatsukawa M.
        • Kinukawa N.
        • et al.
        Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia.
        J. Am. Coll. Cardiol. 2002; 39: 610-616
        • Koren M.J.
        • Hunninghake D.B.
        Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics.
        J. Am. Coll. Cardiol. 2004; 44: 1772-1779
        • Bertrand M.E.
        • Mcfadden E.P.
        • Fruchart J.C.
        • Belle E.V.
        • Commeau P.
        • et al.
        Effect of pravastatin on angiographic restenosis after coronary balloon angioplasty fn1.
        J. Am. Coll. Cardiol. 1997; 30: 863-869
        • Makuuchi H.
        • Furuse A.
        • Endo M.
        • Nakamura H.
        • Daida H.
        • et al.
        Effect of pravastatin on progression of coronary atherosclerosis in patients after coronary artery bypass surgery.
        Circulation J. 2005; 69: 636-643
        • Downs J.R.
        • Clearfield M.
        • Weis S.
        • Whitney E.
        • Shapiro D.R.
        • et al.
        Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels.
        JAMA. 1998; 279: 1615-1622
        • Knopp R.H.
        • D'Emden M.
        • Smilde J.G.
        • Pocock S.J.
        Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the atorvastatin study for prevention of coronary heart disease endpoints in non-insulin-dependent diabetes mellitus (ASPEN).
        Diabetes Care. 2006; 29: 1478-1485
        • Asselbergs F.W.
        • Diercks G.F.H.
        • Hillege H.L.
        Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria.
        Circulation. 2005; 14: 2809-2816
        • Teo K.K.
        • Burton J.R.
        • Buller C.E.
        • Plante S.
        • Catellier D.
        • et al.
        Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: the Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT). [J].
        Circulation. 2000; 102: 1748-1754
        • Deedwania P.
        • Stone P.H.
        • Bairey Merz C.N.
        • Cosinaguilar J.
        • Koylan N.
        • et al.
        Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE).
        Circulation. 2007; 115: 700-707
        • Hong Y.J.
        • Jeong M.H.
        • Hwang S.H.
        • Yun N.S.
        • Lee S.R.
        • et al.
        Effect of combination therapy with simvastatin and carvedilol in patients with left ventricular dysfunction complicated with acute myocardial infarction who underwent percutaneous coronary intervention.
        Circulation J. 2006; 70: 1269-1274
        • Izawa A.
        • Kashima Y.
        • Miura T.
        • Ebisawa S.
        • Kitabayashi H.
        • et al.
        Assessment of lipophilic vs. Hydrophilic statin therapy in acute myocardial infarction.
        Circulation J. Off J. Jpn. Circulation Soc. 2015; 79: 161-168
        • Group. TLS
        Long-term effectiveness and safety of pravastatin in 9014 patients with coronary heart disease and average cholesterol concentrations: the LIPID trial follow-up.
        Lancet. 2002; 359: 1379-1387
        • Nissen S.E.
        • Tuzcu E.M.
        • Al P.S.
        Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis. a randomized controlled trial.
        Jama J. Am. Med. Assoc. 2004; 291: 18
        • Investigators M.
        Effect of simvastatin on coronary atheroma: the multicentre anti-atheroma study (MAAS).
        Lancet. 1994; 344: 633-638
        • Kayikçioğlu M.
        • Can L.
        • Kültürsay H.
        • Payzin S.
        • Turkoğlu C.
        Early use of pravastatin in patients with acute myocardial infarction undergoing coronary angioplasty.
        Acta Cardiol. 2002; 57: 295-302
        • Rahman M.
        • Baimbridge C.
        • Davis B.R.
        • Barzilay J.I.
        • Basile J.N.
        • et al.
        Pravastatin and cardiovascular outcomes stratified by baseline eGFR in the lipid- lowering component of ALLHAT.
        Clin. Nephrol. 2013; 80: 235-248
        • Tikkanen M.J.
        Comparison of efficacy and safety of atorvastatin (80 mg) to simvastatin (20 to 40 mg) in patients aged.
        Am. J. Cardiol. 2009; 2009: 577-582
        • Vigen C.
        • Hodis H.N.
        • Selzer R.H.
        • Mahrer P.R.
        • Mack W.J.
        Relation of progression of coronary artery atherosclerosis to risk of cardiovascular events (from the monitored atherosclerosis regression study).
        Am. J. Cardiol. 2005; 95: 1277-1282
        • Stefano S.
        • K Lance G.
        • Linda Guilds Z.
        • Richard M.L.
        • Jennifer G.
        A 6 month randomized, double blind, placebo controlled, multi-center trial of high dose atorvastatin on myocardial perfusion abnormalities by positron emission tomography in coronary artery disease.
        Am. Heart J. 2008; 155: 245-253
        • Yamada T.
        • Node K.
        • Mine T.
        • Morita T.
        • Kioka H.
        • et al.
        Long-term effect of atorvastatin on neurohumoral activation and cardiac function in patients with chronic heart failure: a prospective randomized controlled study.
        Am. Heart J. 2007; 153: 1-8
        • Arntz H.R.
        • Agrawal R.
        • Wunderlich W.
        • Schnitzer L.
        • Stern R.
        • et al.
        Iconography: beneficial effects of pravastatin (±cholestyramine/niacin) initiated immediately after a coronary event (the randomized lipid-coronary artery disease [L-CAD] study).
        Am. J. Cardiol. 2000; 86: 1293-1298
        • Rwilczek W.
        Usefulness of Atorvastatin in patients with heart failure due to inflammatory dilated cardiomyopathy and elevated cholesterol levels.
        Am. J. Cardiol. 2006; 97: 899-904
        • § J.H.L.
        • Mortensen M.E.
        • Zweig S.
        • Fusco M.J.
        • Medoff J.R.
        • et al.
        Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial † ‡.
        Hepatology. 2007; 46: 1453-1463
        • Gotto Jr., A.M.
        • Whitney E.
        • Stein E.A.
        • Shapiro D.R.
        • Clearfield M.
        • et al.
        Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS).
        Circulation. 2000; 101: 477-484
        • Taylor A.J.
        • Kent S.M.
        • Flaherty P.J.
        • Coyle L.C.
        • Markwood T.T.
        • et al.
        ARBITER: arterial biology for the investigation of the treatment effects of reducing cholesterol A randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness.
        Circulation. 2002; 106: 2055-2060
        • Waters D.
        • Higginson L.
        • Gladstone P.
        • Kimball B.
        • Le M.M.
        • et al.
        Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography. The Canadian Coronary Atherosclerosis Intervention Trial.
        Circulation. 1994; 89: 959-968
        • ED B
        • MA vdR
        • JW J
        • JT T
        • JC vdV
        • et al.
        Two-year statin therapy does not alter the progression of intima-media thickness in patients with type 2 diabetes without manifest cardiovascular disease.
        Diabetes Care. 2004; 27: 2887-2892
        • Colquhoun D.
        • Keech A.
        • Hunt D.
        • Marschner I.
        • Simes J.
        • et al.
        Effects of pravastatin on coronary events in 2073 patients with low levels of both low-density lipoprotein cholesterol and high-density lipoprotein cholesterol: results from the LIPID study.
        Eur. Heart J. 2004; 25: 771-777
        • Athyros V.G.
        • Papageorgiou A.A.
        • Mercouris B.R.
        • Athyrou V.V.
        • Symeonidis A.N.
        • et al.
        Treatment with atorvastatin to the national cholesterol educational program goal versus 'usual' care in secondary coronary heart disease prevention. The GREek atorvastatin and coronary-heart-disease evaluation (GREACE) study.
        Curr. Med. Res. Opin. 2002; 18: 220-228
        • Semb Anne Grete
        • Kvien Tore K.
        • DeMicco David A.
        • Fayyad Rana
        • Wun Chuan-Chuan
        • et al.
        Effect of intensive lipid-lowering therapy on cardiovascular outcome in patients with and those without inflammatory joint disease †.
        Arthritis & Rheumatol. 2012; 64: 2836-2846
        • Ahmed S.
        • Cannon C.P.
        • Murphy S.A.
        • Braunwald E.
        • Ahmed S.
        • et al.
        Acute coronary syndromes and diabetes: is intensive lipid lowering beneficial? Results of the PROVE IT-TIMI 22 trial.
        Eur. Heart J. 2006; 27: 2323-2329
        • Brilakis E.S.
        • Lemos J.D.
        Outcomes of patients with acute coronary syndrome and previous coronary artery bypass grafting (from the pravastatin or atorvastatin evaluation and infection therapy [PROVE IT-TIMI 22] and the Aggrastat to Zocor [A to Z] Trials) – American Journal of Cardi.
        Am. J. Cardiol. 2008; 102: 552-558
        • Cannon C.P.
        • Braunwald E.
        • Mccabe C.H.
        • Rader D.J.
        • Rouleau J.L.
        • et al.
        Intensive versus moderate lipid lowering with statins after acute coronary syndromes.
        N. Engl. J. Med. 2004; 350: 1495-1504
        • Cowell S.J.
        • Newby D.E.
        • Prescott R.J.
        • Bloomfield P.
        • Reid J.
        • et al.
        A randomized trial of intensive lipid-lower-ing therapy in calcific aortic stenosis.
        N. Engl. J. Med. 2005; 352: 2389-2397
        • Fellström B.C.
        • Jardine A.G.
        • Schmieder R.E.
        • Holdaas H.
        • Bannister K.
        • et al.
        Rosuvastatin and cardiovascular events in patients undergoing hemodialysis.
        N. Engl. J. Med. 2009; 360: 1395-1407
        • Holdaas H.
        • Fellström B.
        • Cole E.
        • Nyberg G.
        • Olsson A.G.
        • et al.
        Long-term cardiac outcomes in renal transplant recipients receiving fluvastatin: the ALERT extension study.
        Am. J. Transplant. Off J. Am. Soc. Transplant. Am. Soc. Transpl. Surg. 2005; 5: 2929-2936
        • Ishigaki Y.
        • Kono S.
        • Katagiri H.
        • Oka Y.
        • Oikawa S.
        Elevation of HDL-C in response to statin treatment is involved in the regression of carotid atherosclerosis.
        J. Atheroscler. Thrombosis. 2014; 21: 1055-1065
        • Saia F.
        • Feyter P.D.
        • Serruys P.W.
        • Lemos P.A.
        • Arampatzis C.A.
        • et al.
        Effect of fluvastatin on long-term outcome after coronary revascularization with stent implantation.
        Am. J. Cardiol. 2004; 93: 92-95
        • Serruys P.W.J.C.
        • Feyter P.D.
        • Macaya C.
        Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention. A randomized controlled clinical trial ☆.
        Acc Curr. J. Rev. 2002; 11: 3215-3222
        • Serruysa P.W.
        • Foleya D.P.
        • Jacksonb G.
        • Bonnierc H.
        • Macayad C.
        • et al.
        A randomized placebo-controlled trial of fluvastatin for prevention of restenosis after successful coronary balloon angioplasty; final results of the fluvastatin angiographic restenosis (FLARE) trial.
        Eur. Heart J. 1999; 20: 58-69
        • Srikanth S.
        • Mir M.Q.S.
        • Stamatios L.
        • Neeraj T.
        • Khan B.V.
        Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure.
        J. Am. Coll. Cardiol. 2006; 47: 332-337
        • Tonelli M.
        • Isles C.
        • Curhan G.C.
        Effect of pravastatin on cardiovascular events in people with chronic kidney disease.
        Circulation. 2004; 110: 1557-1563
        • Hague W.
        • Forder P.
        • Simes J.
        • Hunt D.
        • Tonkin A.
        Effect of pravastatin on cardiovascular events and mortality in 1516 women with coronary heart disease: results from the long-term intervention with pravastatin in ischemic disease (LIPID) study ☆.
        Am. Heart J. 2003; 145: 643-651
        • Hunt D.
        • Young P.
        • Simes J.
        Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: results from the LIPID trial☆.
        Ann. Intern. Med. 2001; 134: 931-940
        • Kjekshus J.
        • Apetrei E.
        • Barrios V.
        • Böhm M.
        • Cleland J.G.
        • et al.
        Rosuvastatin in older patients with systolic heart failure.
        N. Engl. J. Med. 2007; 357: 2248-2261
        • MPH KLMM
        • PhD BRDM
        • Charles Baimbridge M.S.
        • Ciocon J.O.
        • Cuyjet A.B.
        • et al.
        Long-term follow-up of moderately hypercholesterolemic hypertensive patients following randomization to pravastatin vs usual care: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT-LLT).
        J. Clin. Hypertens. 2013; 15: 542-554
        • Shepherd J.
        • Blauw G.J.
        • Murphy M.B.
        • Bollen E.L.
        • Buckley B.M.
        • et al.
        Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.
        Lancet. 2002; 360: 1623-1630
        • Shepherd J.
        • Cobbe S.
        • Lorimer A.
        • Mckillop J.
        • Ford I.
        • et al.
        Compliance and adverse event withdrawal: their impact on the West of Scotland coronary prevention study.
        Eur. Heart J. 1997; 18: 1718-1724
        • Strandberg T.E.
        • Pyörälä K.
        • Cook T.J.
        • Wilhelmsen L.
        • Faergeman O.
        • et al.
        Mortality and incidence of cancer during 10-year follow-up of the Scandinavian simvastatin survival study (4S).
        Lancet. 2004; 364: 771-777
        • Aihara K.
        • Miyauchi K.T.
        • Kubota N.
        • Kajimoto K.
        • Tamura H.
        • et al.
        Long-term efficacy of pravastatin therapy in diabetic patients undergoing complete coronary revascularization.
        J. Atheroscler. Thrombosis. 2010; 17: 350-355
        • Drewes Y.M.
        • Poortvliet R.K.E.
        • PhD JWBM
        • PhD WdRM
        • PhD RGJWM
        • et al.
        Homocysteine Levels and treatment effect in the prospective study of pravastatin in the elderly at risk.
        J. Am. Geriatrics Soc. 2014; 62: 213-221
        • events Poc
        • disease dwpipwch
        • Group. Abroicltliwpiids
        Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group.
        N. Engl. J. Med. 1998; 339: 1349-1357
        • Flaker G.C.
        • Warnica J.W.
        • Sacks F.M.
        • Davis B.R.
        • Rouleau J.L.
        • et al.
        Pravastatin prevents clinical events in revascularized patients with average cholesterol concentrations.
        J. Am. Coll. Cardiol. 1999; 34: 106-112
        • Ford I.
        • Murray H.
        • Mccowan C.
        • Packard C.J.
        Long term safety and efficacy of lowering LDL cholesterol with statin therapy: 20-year follow-up of west of scotland coronary prevention study.
        Kardiologia Pol. 2016; 12: 75-81
        • Furberg C.D.
        • Pitt B.
        • Byington R.P.
        • Park J.S.
        • Mcgovern M.E.
        Reduction in coronary events during treatment with pravastatin. PLAC I and PLAC II Investigators. Pravastatin limitation of atherosclerosis in the coronary arteries.
        Am. J. Cardiol. 1995; 76 (60C–3C)
        • Furuta H.
        • Kimura A.
        • Miyataka M.
        • Taniguchi M.
        • Katayama K.
        • et al.
        Pravastatin reduces the incidence of cardiac events among patients with myocardial infarction.
        Jpn. Heart J. 2003; 44: 873-887
        • Goldberg R.B.
        • Mellies M.J.
        • Sacks F.M.
        • Moyé L.A.
        • Howard B.V.
        • et al.
        Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial.
        Circulation. 1998; 98: 2513-2519
        • Group HPSC
        MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial.
        Lancet. 2002; 360: 7-22
        • Holme I.
        • Fayyad R.
        • Faergeman O.
        • Kastelein J.J.P.
        • Olsson A.G.
        • et al.
        Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: results from the IDEAL trial.
        J. Intern. Med. 2010; 267: 567-575
        • Hong Y.J.
        • Jeong M.H.
        • Hyun D.W.
        • Hur S.H.
        • Kim K.B.
        • et al.
        Prognostic significance of simvastatin therapy in patients with ischemic heart failure who underwent percutaneous coronary intervention for acute myocardial infarction.
        Am. J. Cardiol. 2005; 95: 619-622
        • Hopewell J.C.
        • Parish S.
        • Clarke R.
        • Armitage J.
        • Bowman L.
        • et al.
        No Impact of KIF6 genotype on vascular risk and statin response among 18,348 randomized patients in the heart protection study.
        J. Am. Coll. Cardiol. 2011; 57: 2000-2007
        • Lewis S.J.
        • Sacks F.M.
        • Mitchell J.S.
        • East C.
        • Glasser S.
        • et al.
        Effect of pravastatin on cardiovascular events in women after myocardial infarction: the Cholesterol and Recurrent Events (CARE) trial ☆.
        J. Am. Coll. Cardiol. 1998; 32: 140-146
        • Liao J.K.
        Long-term follow-up of the West of Scotland coronary prevention study.
        N. Engl. J. Med. 2008; 357: 194-198
        • Lloyd S.M.
        • Stott D.J.
        • Craen A.J.M.D.
        • Kearney P.M.
        • Sattar N.
        • et al.
        Long-term effects of statin treatment in elderly people: extended follow-up of the prospective study of pravastatin in the elderly at risk (PROSPER).
        Plos One. 2013; 8: e72642
        • Lotfi A.
        • Schweiger M.J.
        • Giugliano G.R.
        • Murphy S.A.
        • Cannon C.P.
        High-dose atorvastatin does not negatively influence clinical outcomes among clopidogrel treated acute coronary syndrome patients—A Pravastatin or atorvastatin evaluation and infection therapy–thrombolysis in myocardial infarction 22 (PROVE IT–TIMI 2.
        Am. Heart J. 2008; 155: 954-958
        • Sacks F M.
        • Pfeffer M A.
        • Moye L A.
        • Rouleau J L.
        • Rutherford J D.
        • et al.
        The effect of pravastatin on coronary events after mycocardial infarction in patients with average cholesterol levels.
        N. Engl. J. Med. 1996; 17: 1001-1009
        • Macmahon S.
        • Shaw J.
        • Simes R.J.
        Effects of pravastatin in 3260 patients with unstable angina: results from the LIPID study.
        Lancet. 2001; 356: 1871-1875
        • Maitland A.H.
        Absence of an interaction between the angiotensin converting enzyme insertion-deletion polymorphism and pravastatin on cardiovascular disease in high-risk hypertensive patients: the Genetics of Hypertension-Associated Treatment (GenHAT) study.
        Am. Heart J. 2007; 153: 54-58
        • Murphy S.A.
        • Cannon C.P.
        • Wiviott S.D.
        • de Lemos J.A.
        • Blazing M.A.
        • et al.
        Effect of intensive lipid-lowering therapy on mortality after acute coronary syndrome (a patient-level analysis of the Aggrastat to Zocor and pravastatin or atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction 22 trials).
        Am. J. Cardiol. 2007; 100: 1047-1051
        • Ostadal P.
        • Alan D.
        • Vejvoda J.
        • Kukacka J.
        • Macek M.
        • et al.
        Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial).
        Trials. 2009; 11: 1-8
        • Pedersen T.R.
        • Faergeman O.
        • Kastelein J.J.P.
        • Olsson A.G.
        • Tikkanen M.J.
        • et al.
        High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction.
        JAMA. 2005; 294: 2437-2445
        • Pedersen T.R.
        • Wilhelmsen L.
        • Færgeman O.
        • Strandberg T.E.
        • Thorgeirsson G.
        • et al.
        Follow-up study of patients randomized in the scandinavian simvastatin survival study (4S) of cholesterol lowering ☆.
        Am. J. Cardiol. 2000; 86: 257-262
        • Pyörälä K.
        • Ballantyne C.M.
        • Gumbiner B.
        • Lee M.W.
        • Shah A.
        • et al.
        Reduction of cardiovascular events by simvastatin in nondiabetic coronary heart disease patients with and without the metabolic syndrome: subgroup analyses of the Scandinavian Simvastatin Survival Study (4S).
        Diabetes Care. 2004; 27: 1735-1740
        • Riegger G.
        • Abletshauser C.
        • Ludwig M.
        • Schwandt P.
        • Widimsky J.
        • et al.
        The effect of fluvastatin on cardiac events in patients with symptomatic coronary artery disease during one year of treatment.
        Atherosclerosis. 1999; 144: 263-270
        • Sato H.
        • Kinjo K.
        • Ito H.
        • Hirayama A.
        • Nanto S.
        • et al.
        Effect of early use of low-dose pravastatin on major adverse cardiac events in patients with acute myocardial infarction.
        Circulation J. 2008; 72: 17-22
        • Shepherd J.
        Cholesterol lowering with statins: how WOSCOPS confounded the skeptics.
        Atheroscler. Suppl. 2007; 8: 9-12
        • Shepherd J.
        • Cobbe S.M.
        • Ford I.
        • Isles C.G.
        • Lorimer A.R.
        • et al.
        Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.
        J. Cardiopulm. Rehabilitation. 1932; 5: 91-97
        • Simes J.
        • Furberg C.D.
        • Braunwald E.
        • Davis B.R.
        • Ford I.
        • et al.
        Effects of pravastatin on mortality in patients with and without coronary heart disease across a broad range of cholesterol levels. The Prospective Pravastatin Pooling project.
        Eur. Heart J. 2002; 23: 207-215
        • Skerrett P.J.
        ALLHAT-LLT: questions, questions, and more questions (and some answers).
        Curr. Atheroscler. Rep. 2004; 6: 375-380
        • Takano H.
        • Mizuma H.
        • Kuwabara Y.
        • Sato Y.
        • Shindo S.
        • et al.
        Effects of pitavastatin in Japanese patients with chronic heart failure: the pitavastatin heart failure study (PEARL study).
        Circulation J. Off J. Jpn. Circulation Soc. 2013; 77: 917-925
        • Tavazzi L.
        • Maggioni A.P.
        • Marchioli R.
        • Barlera S.
        • Franzosi M.G.
        • et al.
        Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial.
        Lancet. 2008; 372: 1231-1239
        • Murphy S.A.
        • Cannon C.P.
        • Wiviott S.D.
        • Mccabe C.H.
        • Braunwald E.
        Reduction in recurrent cardiovascular events with intensive lipid-lowering statin therapy compared with moderate lipid-lowering statin therapy after acute coronary syndromes: from the PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection.
        J. Am. Coll. Cardiol. 2009; 54: 2358-2362
        • Truong Q.A.
        • Murphy S.A.
        • Mccabe C.H.
        • Armani A.
        • Cannon C.P.
        Benefit of intensive statin therapy in women: results from PROVE IT-TIMI 22.
        Circulation Cardiovasc. Qual. Outcomes. 2011; 4: 328-336
        • Zhou Z.
        • Rahme E.
        • Abrahamowicz M.
        • Tu J.V.
        • Eisenberg M.J.
        • et al.
        Effectiveness of statins for secondary prevention in elderly patients after acute myocardial infarction: an evaluation of class effect.
        CMAJ Can. Med. Assoc. J. = J. de l'Association Med. Can. 2005; 172: 1187-1194
        • Davis M.
        • Diamond J.
        • Montgomery D.
        • Krishnan S.
        • Eagle K.
        • et al.
        Acute coronary syndrome in young women under 55 years of age: clinical characteristics, treatment, and outcomes.
        Clin. Res. Cardiol. 2015; 104: 1-8
        • Ewen S.
        • Baumgarten T.
        • Rettig-Ewen V.
        • Mahfoud F.
        • Griese-Mammen N.
        • et al.
        Analyses of drugs stored at home by elderly patients with chronic heart failure.
        Clin. Res. Cardiol. Off J. Ger. Cardiac Soc. 2015; 104: 320-327
        • SA P.
        • Y S
        • D M
        • RR H
        • M W
        Total cholesterol as a risk factor for coronary heart disease and stroke in women compared with men: a systematic review and meta-analysis.
        Atherosclerosis. 2016; 248: 123-131
        • Wang Y.
        • Lammi-Keefe C.J.
        • Hou L.
        • Hu G.
        Impact of low-density lipoprotein cholesterol on cardiovascular outcomes in people with type 2 diabetes: a meta-analysis of prospective cohort studies.
        Diabetes Res. Clin. Pract. 2013; 102: 65-75
        • Genser B.
        • März W.
        Low density lipoprotein cholesterol, statins and cardiovascular events: a meta–analysis.
        Clin. Res. Cardiol. Off J. Ger. Cardiac Soc. 2006; 95: 393-404
        • Teng M.
        • Lin L.
        • Zhao Y.J.
        • Ai L.K.
        • Davis B.R.
        • et al.
        Statins for primary prevention of cardiovascular disease in elderly patients: systematic review and meta-analysis.
        Drugs & Aging. 2015; 32: 649-661
        • Zhang X.
        • Xiang C.
        • Zhou Y.H.
        • Jiang A.
        • Qin Y.Y.
        • et al.
        Effect of statins on cardiovascular events in patients with mild to moderate chronic kidney disease: a systematic review and meta-analysis of randomized clinical trials.
        Bmc Cardiovasc. Disord. 2014; 14: 1-12
        • Nicholls S.J.
        • Brandrup-Wognsen G.
        • Palmer M.
        • Barter P.J.
        Meta-analysis of comparative efficacy of increasing dose of atorvastatin versus rosuvastatin versus simvastatin on lowering levels of atherogenic lipids (from VOYAGER).
        Am. J. Cardiol. 2010; 105: 69-76
        • Martineau P.
        • Gaw A.
        • Teresa E.D.
        • Farsang C.
        • Gensini G.F.
        • et al.
        Effect of individualizing starting doses of a statin according to baseline LDL-cholesterol levels on achieving cholesterol targets: the achieve cholesterol targets fast with atorvastatin stratified titration (ACTFAST) study.
        Atherosclerosis. 2007; 191: 135-146
        • Members A.T.F.
        • Steg P.G.
        • James S.K.
        • Dan A.
        • Badano L.P.
        • et al.
        ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation.
        Eur. heart J. 2012; 33: 2569-2619
        • Physicians ACOE
        • Al. E
        ACCF/AHA Guideline for the Management of ST-elevation Myocardial Infarction: a Report of the American College of Cardiology Foundation/American.
        PubMed – NCBI, 2013
        • Choi H.D.
        • Shin W.G.
        Safety and efficacy of statin treatment alone and in combination with fibrates in patients with dyslipidemia: a meta-analysis.
        Curr. Med. Res. Opin. 2013; 30: 1-10
        • Bader T.
        Liver tests are irrelevant when prescribing statins.
        Lancet. 2010; 376: 1882-1883
        • Acharya T.
        • Huang J.
        • Tringali S.
        • Frei C.R.
        • Mortensen E.M.
        • et al.
        Statin use and the risk of kidney disease with long-term follow-up (8.4-Year Study).
        Am. J. Cardiol. 2015; 21: 144-149
        • Simić I.
        • Reiner Z.
        Adverse effects of statins-myths and reality.
        Curr. Pharm. Des. 2014; 21: 1220-1226
        • Plosker G.L.
        • Wagstaff A.J.
        Fluvastatin: a review of its pharmacology and use in the management of hypercholesterolaemia.
        Drugs. 1996; 51: 433-459
        • Blum C.B.
        Comparison properties of four inhibitors of 3-hydroxy-3-methilglutaryl-coenzyme A reductase.
        Am. J. Cardiol. 1994; 73: 3D-11D
        • Ikewaki K.
        • Terao Y.
        • Ozasa H,Nakada Y.
        • Tohyama J.
        • et al.
        Effects of atorvastatin on nuclear magnetic resonance-defined lipoprotein subclasses and inflammatory markers in patients with hypercholesterolemia.
        J. Atheroscler. Thrombosis. 2009; 16: 51-56
        • Kaesemeyer W.H.
        • Caldwell R.B.
        • Huang J.
        • Caldwell R.W.
        Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions.
        J. Am. Coll. Cardiol. 1999; 33: 234-241
        • Li D.
        • Mehta J.L.
        Upregulation of endothelial receptor for oxidized LDL (LOX-1) by oxidized LDL and implications in apoptosis of human coronary artery endothelial cells: evidence from use of antisense LOX-1 mRNA and chemical inhibitors.
        Arteriosclerosis Thrombosis Vasc. Biol. 2000; 20: 1116-1122
        • Inoue T.
        • Hayashi M.
        • Kan T.
        • Morooka S.
        Lipid-lowering therapy with fluvastatin inhibits oxidative modification of low density lipoprotein and improves vascular endothelial function in hypercholesterolemic patients.
        Atherosclerosis. 2002; 160: 369-376
        • Phipps R.P.
        Atherosclerosis: the emerging role of inflammation and the CD40-CD40 ligand system.
        Proc. Natl. Acad. Sci. 2000; 97: 6930-6932
        • Schönbeck U.
        • Gerdes N.
        • Varo N.
        • Reynolds R.S.
        • Horton D.B.
        • et al.
        Oxidized low-density lipoprotein augments and 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors limit CD40 and CD40L expression in human vascular cells.
        Circulation. 2002; 106: 2888-2893
        • Massy Z.A.
        • Kim Y.
        • Guijarro C.
        • Kasiske B.L.
        • Keane W.F.
        • et al.
        Low-density lipoprotein-induced expression of interleukin-6, a marker of human mesangial cell inflammation: effects of oxidation and modulation by lovastatin.
        Biochem. Biophys. Res. Commun. 2000; 267: 536-540
        • Bieleckadabrowa A.
        • Goch J.H.
        • Mikhailidis D.P.
        • Rysz J.
        • Maciejewski M.
        • et al.
        The influence of atorvastatin on parameters of inflammation and function of the left ventricle in patients with dilated cardiomyopathy.
        Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2009; 15
        • Mahajan N.
        • Dhawan V.
        In vitro modulation of peroxisome proliferator-activated receptor-γ and its genes by c-reactive protein. role of atorvastatin.
        Arch. Med. Res. 2010; 41: 154-161
        • Vondrakova D.
        • Ostadal P.
        • Kruger A.
        Immediate effect of intensive atorvastatin therapy on lipid parameters in patients with acute coronary syndrome.
        Lipids Health & Dis. 2010; 9: 1-5
        • Amin K.A.
        • Abd ElTwab T.M.
        Oxidative markers, nitric oxide and homocysteine alteration in hypercholesterolimic rats: role of atorvastatin and cinnamon.
        Int. J. Clin. Exp. Med. 2009; 2: 254-265