Efficacy and safety of ezetimibe plus atorvastatin therapy

References

• Baigent C, Blackwell L, Emberson J et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376(9753), 1670–1681 (2010). •• Largest meta-analysis of 26 randomized controlled statin trials, including intensive treatment, showing that the magnitude of LDL lowering is related to the reduction of cardiovascular events.
   Google Scholar
• Baigent C, Keech A, Kearney PM et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366(9493), 1267–1278 (2005).
   Google Scholar
• Robinson JG, Smith B, Maheshwari N, Schrott H. Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. J. Am. Coll. Cardiol. 46(10), 1855–1862 (2005). • Meta-analysis of 18 intervention trials showing the relationship between statin and nonstatin lipid-lowering therapies with cardiovascular risk reduction.
   Google Scholar
• Anderson TJ, Gregoire J, Hegele RA et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can. J. Cardiol. 29(2), 151–167 (2013).
   Google Scholar
• Teramoto T, Sasaki J, Ishibashi S et al. Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan: 2012 Version. J. Atheroscler. Thromb. 20(6), 517–523 (2013).
   Google Scholar
• Jellinger PS, Smith DA, Mehta AE et al. American Association of Clinical Endocrinologists’ guidelines for management of dyslipidemia and prevention of atherosclerosis. Endocr. Pract. 18(Suppl. 1), 1–78 (2012).
   Google Scholar
• Cooper A, Nherera L, Calvert N et al. Clinical Guidelines and Evidence Review for Lipid Modification: cardiovascular risk assessment and the primary and secondary prevention of cardiovascular disease. London National Collaborating Centre for Primary Care and Royal College of General Practitioners. NICE Publications, London, UK (2008).
   Google Scholar
• International Atherosclerosis Society. An International Atherosclerosis Society position paper: global recommendations for the management of dyslipidemia (2014). www.athero.org/IASPositionPaper.asp
   Google Scholar
• Catapano AL, Reiner Z, De Backer G 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). Atherosclerosis 217(1), 3–46 (2011).
   Google Scholar
• National Cholesterol Education Program. Second report of the expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II). Circulation 89(3), 1333–1445 (1994).
   Google Scholar
• Report of the National Cholesterol Education Program Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults. Expert Panel. Arch. Intern. Med. 148(1), 36–69 (1988).
   Google Scholar
• 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) final report. Circulation 106(25), 3143–3421 (2002).
   Google Scholar
• Grundy SM, Cleeman JI, Merz CN et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J. Am. Coll. Cardiol. 44(3), 720–732 (2004).
   Google Scholar
• Smith SC Jr, Allen J, Blair SN et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation 113(19), 2363–2372 (2006).
   Google Scholar
• Grundy SM. Low-density lipoprotein, non-high-density lipoprotein, and apolipoprotein B as targets of lipid-lowering therapy. Circulation 106(20), 2526–2529 (2002).
   Google Scholar
• Brunzell JD, Davidson M, Furberg CD et al. Lipoprotein management in patients with cardiometabolic risk. Diabetes Care 31(4), 811–822 (2008).
   Google Scholar
• Stone NJ, Robinson J, Lichtenstein AH et al. 2013 ACC/ AHA Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 129(25 Suppl. 2), S1–S45 (2014).
   Google Scholar
• Besseling J, van Capelleveen J, Kastelein JJ, Hovingh GK. LDL cholesterol goals in high-risk patients: how low do we go and how do we get there? Drugs 73(4), 293–301 (2013).
   Google Scholar
• Mihaylova B, Emberson J, Blackwell L et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 380(9841), 581–590 (2012). •• Meta-analysis of 27 randomized, controlled statin trials showing the relationship between LDL-C lowering and reduction of cardiovascular events in patients with lower cvd risk; the clinical benefit outweighed the risk.
   Google Scholar
• Nicholls SJ, Ballantyne CM, Barter PJ et al. Effect of two intensive statin regimens on progression of coronary disease. N. Engl. J. Med. 365(22), 2078–2087 (2011).
   Google Scholar
• Downs JR, 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. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 279(20), 1615–1622 (1998).
   Google Scholar
• Sever PS, Dahlof B, Poulter NR et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 361(9364), 1149–1158 (2003).
   Google Scholar
• Sacks FM, Pfeffer MA, Moye LA et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N. Engl. J. Med. 335(14), 1001–1009 (1996).
   Google Scholar
• Heart Protection Study Collaborative Group. Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions. J. Vasc. Surg. 45(4), 645–654 (2007).
   Google Scholar
• Pedersen TR, Faergeman O, Kastelein JJ et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 294(19), 2437–2445 (2005).
   Google Scholar
• Shepherd J, Blauw GJ, Murphy MB et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360(9346), 1623–1630 (2002).
   Google Scholar
• Cannon CP, Braunwald E, McCabe CH et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N. Engl. J. Med. 350(15), 1495–1504 (2004).
   Google Scholar
• LaRosa JC, Grundy SM, Waters DD et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N. Engl. J. Med. 352(14), 1425–1435 (2005).
   Google Scholar
• Shepherd J, Cobbe SM, Ford I et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N. Engl. J. Med. 333(20), 1301–1307 (1995).
   Google Scholar
• Foody JM, Sajjan SG, Hu XH et al. Loss of early gains in low-density lipoprotein cholesterol goal attainment among high-risk patients. J. Clin. Lipidol. 4(2), 126–132 (2010).
   Google Scholar
• Jukema JW, Chiang CW, Ferrieres J et al. Lipid goals among patients with diabetes or metabolic syndrome: Lipid Treatment Assessment Project (L-TAP) 2. Curr. Med. Res. Opin. 26(11), 2589–2597 (2010).
   Google Scholar
• Chiang CW, Santos RD, Waters DD et al. Reaching C-reactive protein and low-density lipoprotein cholesterol goals in dyslipidemic patients (from the Lipid Treatment Assessment Project [L-TAP] 2). Am. J. Cardiol. 107(11), 1639–1643 (2011).
   Google Scholar
• Rodriguez F, Santos RD, Messig M et al. Comparison of lipid profiles and attainment of lipid goals in patients <65 years versus patients >/=65 years (from the Lipid Treatment Assessment Project [L-TAP] 2). Am. J. Cardiol. 109(12), 1738–1742 (2012).
   Google Scholar
• Rublee DA, Burke JP. LDL-C goal attainment in patients who remain on atorvastatin or switch to equivalent or nonequivalent doses of simvastatin: a retrospective matched cohort study in clinical practice. Postgrad. Med. 122(2), 16–24 (2010).
   Google Scholar
• Willey VJ, Bullano MF, Shoetan NN, Gandhi SK. Therapy modifications and low-density lipoprotein cholesterol goal attainment rates associated with the initiation of generic simvastatin. Curr. Med. Res. Opin. 26(1), 121–128 (2010).
   Google Scholar
• Nichols GA, Nag S, Chan W. Intensity of lipid-lowering therapy and low-density lipoprotein cholesterol goal attainment among the elderly before and after the 2004 National Cholesterol Education Program Adult Treatment Panel III update. Am. Heart J. 154(3), 554–560 (2007).
   Google Scholar
• Waters DD, Brotons C, Chiang CW et al. Lipid treatment assessment project 2: a multinational survey to evaluate the proportion of patients achieving low-density lipoprotein cholesterol goals. Circulation 120(1), 28–34 (2009).
   Google Scholar
• Cullen MW, Stein JH, Gangnon R, McBride PE, Keevil JG. National improvements in low-density lipoprotein cholesterol management of individuals at high coronary risk: National Health and Nutrition Examination Survey, 1999 to 2002. Am. Heart J. 156(2), 284–291 (2008).
   Google Scholar
• Karalis DG, Victor B, Ahedor L, Liu L. Use of lipid-lowering medications and the likelihood of achieving optimal LDL-cholesterol goals in coronary artery disease patients. Cholesterol 2012, 861924 (2012).
   Google Scholar
• Kauffman AB, Olson KL, Youngblood ML, Zadvorny EB, Delate T, Merenich JA. Attainment of low-density lipoprotein cholesterol goals in coronary artery disease. J. Clin. Lipidol. 4(3), 173–180 (2010).
   Google Scholar
• Kotseva K, Wood D, De Backer G, De Bacquer D, Pyorala K, Keil U. Cardiovascular prevention guidelines in daily practice: a comparison of EUROASPIRE I, II, and III surveys in eight European countries. Lancet 373(9667), 929–940 (2009).
   Google Scholar
• Steinberg BA, Bhatt DL, Mehta S et al. Nine-year trends in achievement of risk factor goals in the US and European outpatients with cardiovascular disease. Am. Heart J. 156(4), 719–727 (2008).
   Google Scholar
• Roberts WC. The rule of 5 and the rule of 7 in lipid-lowering by statin drugs. Am. J. Cardiol. 80(1), 106–107 (1997).
   Google Scholar
• Atar D, Carmena R, Clemmensen P et al. Clinical review: impact of statin substitution policies on patient outcomes. Ann. Med. 41(4), 242–256 (2009).
   Google Scholar
• Lipitor® (atorvastatin calcium trihydrate), package insert. Pfizer, NY, USA (2014).
   Google Scholar
• Boden WE, Probstfield JL, Anderson T et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N. Engl. J. Med. 365(24), 2255–2267 (2011). •• Randomized, controlled trial of the effect of combination niacin plus simvastatin therapy versus simvastatin on high-density lipoprotein cholesterol-raising and cardiovascular risk in patients with low-density lipoprotein cholesterol (LDL-C) <70 mg/dl.
   Google Scholar
• Landray MJ, Haynes R, Hopewell JC et al. Effects of extended-release niacin with laropiprant in high-risk patients. N. Engl. J. Med. 371(3), 203–212 (2014).
   Google Scholar
• Ginsberg HN, Elam MB, Lovato LC et al. Effects of combination lipid therapy in Type 2 diabetes mellitus. N. Engl. J. Med. 362(17), 1563–1574 (2010). •• Randomized, controlled trial that assessed the effect of combination fibrate plus stain therapy versus statin monotherapy on cardiovascular disease risk in patients with type 2 diabetes mellitus at high cardiovascular disease risk.
   Google Scholar
• The Lipid Research Clinics Coronary Primary Prevention Trial. Results of 6 years of post-trial follow-up. The Lipid Research Clinics Investigators. Arch. Intern. Med. 152(7), 1399–1410 (1992).
   Google Scholar
• Morrone D, Weintraub WS, Toth PP, et al. Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: a pooled analysis of over 21,000 subjects from 27 clinical trials. Atherosclerosis 223(2), 251–261 (2012).
   Google Scholar
• Catapano AL, Toth PP, Tomassini JE, Tershakovec AM. The efficacy and safety of ezetimibe co-administered with statin therapy in various patient groups. Clin. Lipidol. 8(1), 13–41 (2013). • Most recent updated review of the efficacy and safety of ezetimibe plus statin combination therapy in various patient populations.
   Google Scholar
• Toth PP, Catapano A, Tomassini JE, Tershakovec AM. Update on the efficacy and safety of combination ezetimibe plus statin therapy. Clin. Lipidol. 5(5), 655–684 (2010).
   Google Scholar
• Toth PP, Morrone D, Weintraub WS et al. Safety profile of statins alone or combined with ezetimibe: a pooled analysis of 27 studies including over 22,000 patients treated for 6–24 weeks. Int. J. Clin. Pract. 66(8), 800–812 (2012). • Pooled analysis of safety data from 27 randomized controlled clinical trials of ezetimibe plus statin combination therapy.
   Google Scholar
• Baigent C, Landray MJ, Reith C et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 377(9784), 2181–2192 (2011). •• Large, randomized controlled sharp trial of the effect of simvastatin plus ezetimibe versus placebo in patients with chronic kidney disease.
   Google Scholar
• Rossebo AB, Pedersen TR, Boman K et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N. Engl. J. Med. 359(13), 1343–1356 (2008).
   Google Scholar
• Holme I, Boman K, Brudi P et al. Observed and predicted reduction of ischemic cardiovascular events in the Simvastatin and Ezetimibe in Aortic Stenosis trial. Am. J. Cardiol. 105(12), 1802–1808 (2010). • Substudy of the seas trial that assessed the relationship between lipid-lowering and ischemic risk.
   Google Scholar
• Califf RM, Lokhnygina Y, Cannon CP et al. An update on the IMProved reduction of outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) design. Am. Heart J. 159(5), 705–709 (2010). •• Update on the ongoing improve-it trial evaluating the effect of ezetimibe plus simvastatin versus simvastatin on cardiovascular disease events.
   Google Scholar
• Blazing MA,, Giugliano RP, Cannon CP, et al. Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: final baseline characteristics of the IMPROVE-IT study population. Am. Heart J. 168(2), 205–212 (2014).
   Google Scholar
• Conard SE, Bays HE, Leiter LA et al. Efficacy and safety of ezetimibe added on to atorvastatin (20 mg) versus uptitration of atorvastatin (to 40 mg) in hypercholesterolemic patients at moderately high risk for coronary heart disease. Am. J. Cardiol. 102(11), 1489–1494 (2008).
   Google Scholar
• Bays HE, Averna M, Majul C et al. Efficacy and safety of ezetimibe added to atorvastatin versus atorvastatin uptitration or switching to rosuvastatin in patients with primary hypercholesterolemia. Am. J. Cardiol. 112(12), 1885–1895 (2013). • Randomized, controlled trial evaluating the LDL-C lowering efficacy of ezetimibe added to atorvastatin therapy versus uptitration and switching to more potent statin in patients with LDL-C >100 mg/dl.
   Google Scholar
• Leiter LA, Bays H, Conard S et al. Efficacy and safety of ezetimibe added on to atorvastatin (40 mg) compared with uptitration of atorvastatin (to 80 mg) in hypercholesterolemic patients at high risk of coronary heart disease. Am. J. Cardiol. 102(11), 1495–1501 (2008).
   Google Scholar
• Zieve F, Wenger NK, Ben Yehuda O et al. Safety and efficacy of ezetimibe added to atorvastatin versus up titration of atorvastatin to 40 mg in Patients > or = 65 years of age (from the ZETia in the ELDerly [ZETELD] study). Am. J. Cardiol. 105(5), 656–663 (2010).
   Google Scholar
• Vargo R, Adewale A, Behm MO, Mandeema J, Kerbusch T. Leveraging literature meta-analysis for statins to predict clinical equivalence for ezetimibe+atorvastatin fixed-dose combination and confirm with optimized trial design. Clin. Pharmacol. Ther. doi:10.1038/clpt.66 (2014) (Epub ahead of print). • Describes a dose-response model that predicted the clinical equivalence of a fixed dose combination of ezetimibe plus atorvastatin versus coadministration of these agents individually.
   Google Scholar
• Bays HE, Chen E, Tomassini JE, McPeters G, Polis AB, Triscari J et al. Fixed dose combinationezetimibe+atorvastat in lowers LDL-C equivalent to coadministered components inrandomized trials: use of a dose response model.. Fundam. Clin. Pharmacol.(2014) (In Press).
   Google Scholar
• Liptruzet® (ezetimibe/atrovastatin), package insert. Merck & Co. Inc., Whitehouse Station, NJ, USA (2014).
   Google Scholar
• Merck & Co. Inc. Whitehouse Station NJ, USA FDA approves Merck’s LIPTRUZET™ (ezetimibe and atorvastatin), a new product that can help powerfully lower LDL cholesterol. www.mercknewsroom.com/press-release/research-and-development-news/fda-approves-mercks-liptruzet-ezetimibe-and-atorvastatin
   Google Scholar
• Brown MS, Goldstein JL A receptor-mediated pathway for cholesterol homeostasis. Science 232(4746), 34–47 (1986).
   Google Scholar
• Weng TC, Yang YH, Lin SJ, Tai SH. A systematic review and meta-analysis on the therapeutic equivalence of statins. J. Clin. Pharm. Ther. 35(2), 139–151 (2010).
   Google Scholar
• Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344(8934), 1383–1389 (1994).
   Google Scholar
• MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360(9326), 7–22 (2002).
   Google Scholar
• Ridker PM, Danielson E, Fonseca FA et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N. Engl. J. Med. 359(21), 2195–2207 (2008).
   Google Scholar
• Herd JA, Ballantyne CM, Farmer JA et al. Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]). Am. J. Cardiol. 80(3), 278–286 (1997).
   Google Scholar
• Nasu K, Tsuchikane E, Katoh O et al. Effect of fluvastatin on progression of coronary atherosclerotic plaque evaluated by virtual histology intravascular ultra-sound. JACC Cardiovasc. Interv. 2(7), 689–696 (2009).
   Google Scholar
• Serruys PW, de Feyter P, Macaya C et al. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. JAMA 287(24), 3215–3222 (2002).
   Google Scholar
• Istvan E. Statin inhibition of HMG-CoA reductase: a 3-dimensional view. Atheroscler. .Suppl. 4(1), 3–8 (2003).
   Google Scholar
• Jones PH. Comparing HMG-CoA reductase inhibitors. Clin. Cardiol. 26(Suppl. 1), I15–I20 (2003).
   Google Scholar
• Zhou SF. Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr. Drug Metab. 9(4), 310–322 (2008).
   Google Scholar
• Abd TT, Jacobson TA. Statin-induced myopathy: a review and update. Expert Opin. Drug Saf. 10(3), 373–387 (2011).
   Google Scholar
• Bruckert E, Hayem G, Dejager S, Yau C, Begaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients-the PRIMO study. Cardiovasc. Drugs Ther. 19(6), 403–414 (2005).
   Google Scholar
• Perk J, De Backer G, Gohlke H 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 (constituted by representatives of nine societies and by invited experts) * Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur. Heart J. 33(13), 1635–1701 (2012).
   Google Scholar
• Alexander KP, Blazing MA, Rosenson RS et al. Management of hyperlipidemia in older adults. J. Cardiovasc. Pharmacol. Ther. 14(1), 49–58 (2009).
   Google Scholar
• Davidson MH, Robinson JG. Safety of aggressive lipid management. J. Am. Coll. Cardiol. 49(17), 1753–1762 (2007).
   Google Scholar
• Venero CV, Thompson PD. Managing statin myopathy. Endocrinol. Metab. Clin. North Am. 38(1), 121–136 (2009).
   Google Scholar
• Blaier O, Lishner M, Elis A. Managing statin-induced muscle toxicity in a lipid clinic. J. Clin. Pharm. Ther. 36(3), 336–341 (2011).
   Google Scholar
• Harper CR, Jacobson TA. Evidence-based management of statin myopathy. Curr. Atheroscler. Rep. 12(5), 322–330 (2010).
   Google Scholar
• Sattar N, Preiss D, Murray HM et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 375(9716), 735–742 (2010).
   Google Scholar
• Preiss D, Seshasai SR, Welsh P et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 305(24), 2556–2564 (2011).
   Google Scholar
• U.S. Food and Drug Administration: FDA Drug Safety Communication: important safety label changes to cholesterol-lowering statin drugs. www.fda.gov/Drugs/DrugSafety/ucm293101.htm
   Google Scholar
• Brugts JJ, Yetgin T, Hoeks SE et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ 338, b2376 (2009).
   Google Scholar
• Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet 380(9841), 565–571 (2012).
   Google Scholar
• Waters DD, Ho JE, Demicco DA et al. Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J. Am. Coll. Cardiol. 57(14), 1535–1545 (2011).
   Google Scholar
• IMS Health. Top 20 Global Products 2012 (2012). www.imshealth.com/deployedfiles/ims/Global/Content/Corporate/Press%20Room/Top-Line%20Market%20Data%20&%20Trends/Top_20_Global_Products_2012_2.pdf
   Google Scholar
• Adams SP, Tsang M, Wright JM. Lipid lowering efficacy of atorvastatin. Cochrane Database Syst. Rev. 12, CD008226 (2012).
   Google Scholar
• Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam. Clin. Pharmacol. 19(1), 117–125 (2005).
   Google Scholar
• Jacobsen W, Kuhn B, Soldner A et al. Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab. Dispos. 28(11), 1369–1378 (2000).
   Google Scholar
• Ballantyne CM, Corsini A, Davidson MH et al. Risk for myopathy with statin therapy in high-risk patients. Arch. Intern. Med. 163(5), 553–564 (2003).
   Google Scholar
• Harper CR, Jacobson TA. Managing dyslipidemia in chronic kidney disease. J. Am. Coll. Cardiol. 51(25), 2375–2384 (2008).
   Google Scholar
• Holdaas H, Fellstrom B, Jardine AG et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet 361(9374), 2024–2031 (2003).
   Google Scholar
• Smilde TJ, van Wissen S, Wollersheim H, Trip MD, Kastelein JJ, Stalenhoef AF Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial. Lancet 357(9256), 577–581 (2001).
   Google Scholar
• van Wissen S, Smilde TJ, Trip MD, Stalenhoef AF, Kastelein JJ. Long-term safety and efficacy of high-dose atorvastatin treatment in patients with familial hypercholesterolemia. Am. J. Cardiol. 95(2), 264–266 (2005).
   Google Scholar
• Taylor AJ, Kent SM, Flaherty PJ, Coyle LC, Markwood TT, Vernalis MN. 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 106, 2055–2060 (2002).
   Google Scholar
• Standards of medical care in diabetes--2012. Diabetes Care 35(Suppl. 1), S11–S63 (2012).
   Google Scholar
• Colhoun HM, Betteridge DJ, Durrington PN 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 364(9435), 685–696 (2004).
   Google Scholar
• Schwartz GG, Olsson AG, Ezekowitz MD et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 285(13), 1711–1718 (2001).
   Google Scholar
• Koren MJ, Hunninghake DB Clinical outcomes in managedcare patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the alliance study. J. Am. Coll. Cardiol. 44(9), 1772–1779 (2004).
   Google Scholar
• Amarenco P, Bogousslavsky J, Callahan A, III et al. High-dose atorvastatin after stroke or transient ischemic attack. N. Engl. J. Med. 355(6), 549–559 (2006).
   Google Scholar
• Goldstein LB, Amarenco P, Szarek M et al. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology 70(24 Pt 2), 2364–2370 (2008).
   Google Scholar
• Knopp RH, d’Emden M, Smilde JG, Pocock SJ. 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 29(7), 1478–1485 (2006).
   Google Scholar
• Hey-Hadavi JH, Kuntze E, Luo D, Silverman P, Pittman D, Lepetri B. Tolerability of atorvastatin in a population aged > or =65 years: a retrospective pooled analysis of results from fifty randomized clinical trials. Am. J. Geriatr. Pharmacother. 4(2), 112–122 (2006).
   Google Scholar
• Wenger NK, Lewis SJ, Herrington DM, Bittner V, Welty FK. Outcomes of using high- or low-dose atorvastatin in patients 65 years of age or older with stable coronary heart disease. Ann. Intern. Med. 147(1), 1–9 (2007).
   Google Scholar
• Athyros VG, Papageorgiou AA, Symeonidis AN et al. Early benefit from structured care with atorvastatin in patients with coronary heart disease and diabetes mellitus. Angiology 54(6), 679–690 (2003).
   Google Scholar
• Shepherd J, Kastelein JJ, Bittner V et al. Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study. J. Am. Coll. Cardiol. 51(15), 1448–1454 (2008).
   Google Scholar
• Newman CB, Palmer G, Silbershatz H, Szarek M. Safety of atorvastatin derived from analysis of 44 completed trials in 9,416 patients. Am. J. Cardiol. 92(6), 670–676 (2003).
   Google Scholar
• Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Atorvastatin: safety and tolerability. Expert Opin. Drug Saf. 9(4), 667–674 (2010).
   Google Scholar
• Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Shin EK. Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. J. Am. Coll. Cardiol. 55(12), 1209–1216 (2010).
   Google Scholar
• Navarese EP, Buffon A, Andreotti F et al. Meta-analysis of impact of different types and doses of statins on new-onset diabetes mellitus. Am. J. Cardiol. 111(8), 1123–1130 (2013).
   Google Scholar
• Waters DD, Ho JE, Boekholdt SM et al. Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes. J. Am. Coll. Cardiol. 61(2), 148–152 (2013).
   Google Scholar
• US Food and Drug Administration. FDA Drug Safety Communication: important safety label changes to cholesterol-lowering statin drugs (2012). www.fda.gov/Drugs/DrugSafety/ucm293101.htm
   Google Scholar
• Phan BA, Dayspring TD, Toth PP Ezetimibe therapy: mechanism of action and clinical update. Vasc. Health Risk Manag. 8, 415–427 (2012).
   Google Scholar
• Davis HR Jr, Tershakovec AM, Tomassini JE, Musliner T. Intestinal sterol transporters and cholesterol absorption inhibition. Curr. Opin. Lipidol. 22(6), 467–478 (2011).
   Google Scholar
• Jia L, Betters JL, Yu L. Niemann-Pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport. Annu. Rev. Physiol. 73, 239–259 (2011).
   Google Scholar
• Bays HE, Neff D, Tomassini JE, Tershakovec AM. Ezetimibe: cholesterol lowering and beyond. Expert Rev. Cardiovasc. Ther. 6(4), 447–470 (2008).
   Google Scholar
• Clader JW. The discovery of ezetimibe: a view from outside the receptor. J. Med. Chem. 47(1), 1–9 (2004).
   Google Scholar
• Halleck M, Davis HR, Kirschmeier P et al. An assessment of the carcinogenic potential of ezetimibe using nonclinical data in a weight-of-evidence approach. Toxicology 258(2–3), 116–130 (2009).
   Google Scholar
• Davis HR Jr, Halleck MA. Ezetimibe. Mechanism of action update and recent controversies. In: The Year in Lipid Disorders. Toth P (Ed.). Atlas Medical Publishing Ltd, Oxford, UK. 81–96 (2010).
   Google Scholar
• Zetia® (ezetimibe and atorvastatin), package insert. Merck & Co. Inc., Whitehouse Station NJ, USA (2013)
   Google Scholar
• Pandor A, Ara RM, Tumur I et al. Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J. Intern. Med. 265(5), 568–580 (2009).
   Google Scholar
• Athyros VG, Tziomalos K, Kakafika AI, Koumaras H, Karagiannis A, Mikhailidis DP Effectiveness of ezetimibe alone or in combination with twice a week Atorvastatin (10 mg) for statin intolerant high-risk patients. Am. J. Cardiol. 101(4), 483–485 (2008).
   Google Scholar
• Gazi IF, Daskalopoulou SS, Nair DR, Mikhailidis DP Effect of ezetimibe in patients who cannot tolerate statins or cannot get to the low density lipoprotein cholesterol target despite taking a statin. Curr. Med. Res. Opin. 23(9), 2183–2192 (2007).
   Google Scholar
• Wierzbicki AS, Doherty E, Lumb PJ, Chik G, Crook MA Efficacy of ezetimibe in patients with statin-resistant and statin-intolerant familial hyperlipidaemias. Curr. Med. Res. Opin. 21(3), 333–338 (2005).
   Google Scholar
• Ballantyne CM, Houri J, Notarbartolo A et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation 107(19), 2409–2415 (2003).
   Google Scholar
• Davidson MH, McGarry T, Bettis R et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J. Am. Coll. Cardiol. 40(12), 2125–2134 (2002).
   Google Scholar
• Goldberg AC, Capece R, Sapre A, Liu J, Mitchel Y. Efficacy of ezetimibe-10 mg/day coadministered with multiple doses of simvastatin in patients with primary hypercholesterolemia. J. Am. Coll. Cardiol. 43(5 Suppl. A), 480A–480A (2004).
   Google Scholar
• Kerzner B, Corbelli J, Sharp S et al. Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia. Am. J. Cardiol. 91(4), 418–424 (2003).
   Google Scholar
• Melani L, Mills R, Hassman D et al. Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Eur. Heart J. 24(8), 717–728 (2003).
   Google Scholar
• Gaudiani L, Lewin A, Meneghini L et al. Efficacy and safety of ezetimibe coadministered with simvastatin versus simvastatin alone in thiazolidinedione-treated patients with Type 2 diabetes mellitus. J. Am. Coll. Cardiol. 43(5 Suppl. A), 479A–479A (2004).
   Google Scholar
• Stein E, Stender S, Mata P et al. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am. Heart J. 148(3), 447–455 (2004).
   Google Scholar
• Stein EA, Ose L, Retterstol K et al. Further reduction of low-density lipoprotein cholesterol and C-reactive protein with the addition of ezetimibe to maximum-dose rosuvastatin in patients with severe hypercholesterotemia. J. Clin. Lipidol. 1(4), 280–286 (2007).
   Google Scholar
• Hamilton-Craig I, Kostner K, Colquhoun D, Woodhouse S. Combination therapy of statin and ezetimibe for the treatment of familial hypercholesterolemia. Vasc. Health Risk Manag. 6, 1023–1037 (2010).
   Google Scholar
• Gagne C, Gaudet D, Bruckert E. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation 105(21), 2469–2475 (2002).
   Google Scholar
• Kastelein JJ, Akdim F, Stroes ES et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N. Engl. J. Med. 358(14), 1431–1443 (2008).
   Google Scholar
• Conard S, Bays H, Leiter LA et al. Ezetimibe added to atorvastatin compared with doubling the atorvastatin dose in patients at high risk for coronary heart disease with diabetes mellitus, metabolic syndrome or neither. Diabetes Obes. Metab. 12(3), 210–218 (2010).
   Google Scholar
• Denke M, Pearson T, McBride P, Gazzara RA, Brady WE, Tershakovec AM. Ezetimibe added to ongoing statin therapy improves LDL-C goal attainment and lipid profile in patients with diabetes or metabolic syndrome. Diab. Vasc. Dis. Res. 3(2), 93–102 (2006).
   Google Scholar
• Leiter LA, Betteridge DJ, Farnier M et al. Lipid-altering efficacy and safety profile of combination therapy with ezetimibe/statin vs statin monotherapy in patients with and without diabetes: an analysis of pooled data from 27 clinical trials. Diabetes Obes. Metab 13(7), 615–628 (2011).
   Google Scholar
• Simons L, Tonkon M, Masana L et al. Effects of ezetimibe added to on-going statin therapy on the lipid profile of hypercholesterolemic patients with diabetes mellitus or metabolic syndrome. Curr. Med. Res. Opin. 20(9), 1437–1445 (2004).
   Google Scholar
• Averna M, Missault L, Vaverkova H et al. Lipid-altering efficacy of switching to ezetimibe/simvastatin 10/20 mg versus rosuvastatin 10 mg in high-risk patients with and without metabolic syndrome. Diab. Vasc. Dis. Res. 8(4), 262–270 (2011).
   Google Scholar
• Robinson JG, Ballantyne CM, Grundy SM et al. Lipid-altering efficacy and safety of ezetimibe/simvastatin versus atorvastatin in patients with hypercholesterolemia and the metabolic syndrome (from the VYMET study). Am. J. Cardiol. 103(12), 1694–1702 (2009).
   Google Scholar
• Robinson JG, Ballantyne CM, Hsueh W et al. Achievement of specified low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol apolipoprotein B, and high-sensitivity C-reactive protein levels with ezetimibe/ simvastatin or atorvastatin in metabolic syndrome patients with and without atherosclerotic vascular disease (from the VYMET study). J. Clin. Lipidol. 5(6), 474–482 (2011).
   Google Scholar
• Park H, Shima T, Yamaguchi K et al. Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease. J. Gastroenterol. 46(1), 101–107 (2011).
   Google Scholar
• SHARP Collaborative Group: Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease. Am. Heart J. 160(5), 785–794 (2010).
   Google Scholar
• Nakamura T, Sato E, Fujiwara N et al. Co-administration of ezetimibe enhances proteinuria-lowering effects of pitavastatin in chronic kidney disease patients partly via a cholesterol-independent manner. Pharmacol. Res. 61(1), 58–61 (2010).
   Google Scholar
• Farnier M, Volpe M, Massaad R, Davies MJ, Allen C. Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease. Int. J. Cardiol. 102(2), 327–332 (2005).
   Google Scholar
• Derosa G, D’Angelo A, Franzetti IG et al. Efficacy and safety of ezetimibe/simvastatin association on non-diabetic and diabetic patients with polygenic hypercholesterolemia or combined hyperlipidemia and previously intolerant to standard statin treatment. J. Clin. Pharm. Ther. 34(3), 267–276 (2009).
   Google Scholar
• Gagne C, Bays HE, Weiss SR et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am. J. Cardiol. 90(10), 1084–1091 (2002).
   Google Scholar
• Pearson TA, Denke MA, McBride PE, Battisti WP, Brady WE, Palmisano J. A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the ezetimibe add-on to statin for effectiveness (EASE) trial. Mayo Clin. Proc. 80(5), 587–595 (2005).
   Google Scholar
• Cruz-Fernandez JM, Bedarida GV, Adgey J, Allen C, Johnson-Levonas AO, Massaad R. Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease. Int. J. Clin. Pract. 59(6), 619–627 (2005).
   Google Scholar
• Chapman RH, Pelletier EM, Smith PJ, Roberts CS. Can adherence to antihypertensive therapy be used to promote adherence to statin therapy? Patient Prefer. Adherence 3, 265–275 (2009).
   Google Scholar
• Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension 55(2), 399–407 (2010).
   Google Scholar
• Thom S, Poulter N, Field J et al. Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial. JAMA 310(9), 918–929 (2013).
   Google Scholar
• Chapman RH, Yeaw J, Roberts CS. Association between adherence to calcium-channel blocker and statin medications and likelihood of cardiovascular events among US managed care enrollees. BMC. Cardiovasc. Disord. 10, 29 (2010).
   Google Scholar
• Hussein MA, Chapman RH, Benner JS et al. Does a single-pill antihypertensive/lipid-lowering regimen improve adherence in US managed care enrolees? A non-randomized, observational, retrospective study. Am. J. Cardiovasc. Drugs 10(3), 193–202 (2010).
   Google Scholar
• Carotid atorvastatin study in hyperlipidemia postmenopausal women: a randomized evaluation of atorvastatin versus placebo (Cashmere). NCT#00163163. Pfizer PhRMA Web Synopsis Protocol A2581051. Final Report. www.clinicalstudy.org
   Google Scholar
• Kastelein JJ, van Leuven SI, Burgess L et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N. Engl. J. Med. 356(16), 1620–1630 (2007).
   Google Scholar
• Fleg JL, Mete M, Howard BV et al. Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in Type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial. J. Am. Coll. Cardiol. 52(25), 2198–2205 (2008).
   Google Scholar
• Howard BV, Roman MJ, Devereux RB et al. Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: the SANDS randomized trial. JAMA 299(14), 1678–1689 (2008).
   Google Scholar
• Meaney A, Ceballos G, Asbun J et al. The VYtorin on Carotid intima-media thickness and overall arterial rigidity (VYCTOR) study. J. Clin. Pharmacol. 49(7), 838–847 (2009).
   Google Scholar
• Farmer J. The Vytorin on Carotid-Media Thickness and Overall Arterial Rigidity (VYCTOR) study. Expert Rev. Cardiovasc. Ther. 7(9), 1057–1060 (2009).
   Google Scholar
• Costanzo P, Perrone-Filardi P, Vassallo E et al. Does carotid intima-media thickness regression predict reduction of cardiovascular events? A meta-analysis of 41 randomized trials. J. Am. Coll. Cardiol. 56(24), 2006–2020 (2010).
   Google Scholar
• Vergeer M, Zhou R, Bots ML et al. Carotid atherosclerosis progression in familial hypercholesterolemia patients: a pooled analysis of the ASAP, ENHANCE, RADIANCE 1, and CAPTIVATE studies. Circ. Cardiovasc. Imaging 3(4), 398–404 (2010).
   Google Scholar
• Savarese G, Musella F, Volpe M, Paneni F, Perrone-Filardi P. Effects of atorvastatin and rosuvastatin on renal function: a meta-analysis. Int. J. Cardiol167(6), 2482–2489 (2012).
   Google Scholar
• Wu Y, Wang Y, An C et al. Effects of rosuvastatin and atorvastatin on renal function: meta-analysis. Circ. J. 76(5), 1259–1266 (2012).
   Google Scholar
• Fellstrom BC, Jardine AG, Schmieder RE et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N. Engl. J. Med. 360(14), 1395–1407 (2009).
   Google Scholar
• Wanner C, Krane V, Marz W et al. Atorvastatin in patients with Type 2 diabetes mellitus undergoing hemodialysis. N. Engl. J. Med. 353(3), 238–248 (2005).
   Google Scholar
• Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 361(9374), 2005–2016 (2003).
   Google Scholar
• Navaneethan SD, Pansini F, Perkovic V et al. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane. Database. Syst. Rev.(2), CD007784 (2009).
   Google Scholar
• Strippoli GF, Navaneethan SD, Johnson DW et al. Effects of statins in patients with chronic kidney disease: meta-analysis and meta-regression of randomised controlled trials. BMJ 336(7645), 645–651 (2008).
   Google Scholar
• Tonelli M, Keech A, Shepherd J et al. Effect of pravastatin in people with diabetes and chronic kidney disease. J. Am. Soc. Nephrol. 16(12), 3748–3754 (2005).
   Google Scholar
• Cowell SJ, Newby DE, Prescott RJ et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N. Engl. J. Med. 352(23), 2389–2397 (2005).
   Google Scholar
• Chan KL, Teo K, Dumesnil JG, Ni A, Tam J. Effect of lipid lowering with rosuvastatin on progression of aortic stenosis results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial. Circulation 121(2), 306–314 (2010).
   Google Scholar
• Cannon CP, Giugliano RP, Blazing MA et al. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am. Heart J. 156(5), 826–832 (2008).
   Google Scholar
• Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J. Am. Coll. Cardiol. 48(3), 438–445 (2006).
   Google Scholar
• Vytorin [product insert]. Merck & Co. Inc., Whitehouse Station. NJ, USA (2014).
   Google Scholar
• Abramson BL, Benlian P, Hanson ME, Lin J, Shah A, Tershakovec AM. Response by sex to statin plus ezetimibe or statin monotherapy: a pooled analysis of 22,231 hyperlipidemic patients. Lipids Health Dis. 10, 146- (2011).
   Google Scholar
• Kashani A, Sallam T, Bheemreddy S, Mann DL, Wang Y, Foody JM. Review of side-effect profile of combination ezetimibe and statin therapy in randomized clinical trials. Am. J. Cardiol. 101(11), 1606–1613 (2008).
   Google Scholar
• Robinson JG, Davidson MH, Shah A et al. Efficacy and safety of ezetimibe and ezetimibe+statin therapy in patients aged <65, 65–74, and 75 years and older. Aging Health 3(6), 691–705 (2007).
   Google Scholar
• Ballantyne CM, Lipka LJ, Sager PT et al. Long-term safety and tolerability profile of ezetimibe and atorvastatin coadministration therapy in patients with primary hypercholesterolaemia. Int. J. Clin. Pract. 58(7), 653–658 (2004).
   Google Scholar
• Morrone D, Weintraub WS, Toth PP, et al. Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: A pooled analysis of over 21,000 subjects from 27 clinical trials.. Atherosclerosis. 223(2), 251–261 (2012).
   Google Scholar
• Link E, Parish S, Armitage J et al. SLCO1B1 variants and statin-induced myopathy--a genomewide study. N. Engl. J. Med. 359(8), 789–799 (2008).
   Google Scholar
• Peto R, Emberson J, Landray M et al. Analyses of cancer data from three ezetimibe trials. N. Engl. J. Med. 359(13), 1357–1366 (2008). • Meta-analysis of safety data from the then ongoing improve-it trial and the reported seas trial.
   Google Scholar
• Emberson JR, Kearney PM, Blackwell L et al. Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy. PLoS One. 7(1), e29849 (2012). • Analysis of 27 randomized controlled statin trials, including intensive therapy assessing the LDL-C lowering effect of therapy on the incidence of or mortality from any type of cancer.
   Google Scholar
• Kuoppala J, Lamminpaa A, Pukkala E. Statins and cancer: asystematic review and meta-analysis. Eur. J. Cancer 44(15), 2122–2132 (2008).
   Google Scholar
• Alsheikh-Ali AA, Karas RH. Ezetimibe, and the combination of ezetimibe/simvastatin, and risk of cancer: a post-marketing analysis. J. Clin. Lipidol. 3(2), 138–142 (2009).
   Google Scholar
• Aronow HD, Hess G, Hill J, Kuznik A, Liu LZ. Switching from atorvastatin to simvastatin in patients at high cardiovascular risk: effects on low-density lipoprotein cholesterol. Am. J. Ther. 17(2), 167–175 (2010).
   Google Scholar
• Butler R, Wainwright J. Cholesterol lowering in patients with CHD and metabolic syndrome. Lancet 369(9555), 27 (2007).
   Google Scholar
• Colivicchi F, Tubaro M, Santini M. Clinical implications of switching from intensive to moderate statin therapy after acute coronary syndromes. Int. J. Cardiol. 152(1), 56–60 (2011).
   Google Scholar
• Phillips B, Roberts C, Rudolph AE, Morant S, Aziz F, O’Regan C. Switching statins: the impact on patient outcomes. Br. J. Cardiol. 14, 280–285 (2007).
   Google Scholar
• Tunceli K, Sajjan SG, Ramey DR et al. Switching from high-efficacy lipid-lowering therapies to simvastatin and low-density lipoprotein cholesterol goal attainment in coronary heart disease/coronary heart disease-equivalent patients. J. Clin. Lipidol. 4(6), 491–500 (2010).
   Google Scholar
• Niaspan ®, package insert. AbbVie Inc, IL, USA.
   Google Scholar
• TRicor ® (fenofibrate), package insert. Abbott Laboratories, IL, USA.
   Google Scholar
• Welchol® (colesevelam hydrochloride), package insert. Daiichi Sankyo, Inc, NJ, USA.
   Google Scholar
• Roth EM, McKenney JM, Hanotin C, Asset G, Stein EA Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N. Engl. J. Med. 367(20), 1891–1900 (2012).
   Google Scholar
• US Food and Drug Administration. FDA approves new orphan drug for rare cholesterol disorder. (2012). www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333285.htm
   Google Scholar
• Cuchel M, Meagher EA, du Toit TH et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, Phase 3 study. Lancet 381(9860), 40–46 (2013).
   Google Scholar
• Visser ME, Wagener G, Baker BF et al. Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial. Eur. Heart J. 33(9), 1142–1149 (2012).
   Google Scholar
• Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354(12), 1264–1272 (2006).
   Google Scholar
• Abifadel M, Rabes JP, Devillers M et al. Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum. Mutat. 30(4), 520–529 (2009).
   Google Scholar
• Giugliano RP, Desai NR, Kohli P et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, Phase 2 study. Lancet 380(9858), 2007–2017 (2012).
   Google Scholar
• Koren MJ, Scott R, Kim JB et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, Phase 2 study. Lancet 380(9858), 1995–2006 (2012).
   Google Scholar
• McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein EA. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J. Am. Coll. Cardiol. 59(25), 2344–2353 (2012).
   Google Scholar
• Raal F, Scott R, Somaratne R et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the reduction of LDL-C with PCSK9 inhibition in heterozygous familial hypercholesterolemia disorder (RUTHERFORD) randomized trial. Circulation 126(20), 2408–2417 (2012).
   Google Scholar
• Stein EA, Gipe D, Bergeron J et al. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a Phase 2 randomised controlled trial. Lancet 380(9836), 29–36 (2012).
   Google Scholar
• Sullivan D, Olsson AG, Scott R et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA 308(23), 2497–2506 (2012).
   Google Scholar
• ClinicalTrials.gov. NCT01663402. www.clinicaltrials.gov/show/NCT01663402
   Google Scholar
• ClinicalTrials.gov. NCT01764633. www.clinicaltrials.gov/ct2/show/NCT01764633
   Google Scholar
• ClinicalTrials.gov. NCT01975376. www.clinicaltrials.gov/show/NCT01975376
   Google Scholar
• ClinicalTrials.gov. NCT01975389. www.clinicaltrials.gov/show/NCT01975389
   Google Scholar
• US Food and Drug Administration. FDA approves new orphan drug Kynamro to treat inherited cholesterol disorder (2013). www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm337195.htm
   Google Scholar
• Raal FJ, Santos RD, Blom DJ et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet 375(9719), 998–1006 (2010).
   Google Scholar
• McGowan MP, Tardif J-C, Ceska R et al. Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. PLOS ONE 7(11), e49006 (2012).
   Google Scholar
• Stein EA, Dufour R, Gagne C et al. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. Circulation 126(19), 2283–2292 (2012).
   Google Scholar