Statin non-adherence and residual cardiovascular risk: There is need for substantial improvement

International Journal of Cardiology

Volumn 225, Issue , 2016, Pages 184-196

  Banach, Maciej ^a,b   Stulc, Tomas ^c   Dent, Ricardo ^d   Toth, Peter P ^e,f  

^a MEDICAL UNIVERSITY OF LODZ   (Poland)

^b POLISH MOTHER S MEMORIAL HOSPITAL RESEARCH INSTITUTE   (Poland)

^c 1st Department of Medicine   (Czech Republic)

^d AMGEN INC   (United States)

^e CGH MEDICAL CENTER   (United States)

^f JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cardiovascular risk; Discontinuation; HDL C; Non adherence; PCSK9; Statin; Statin associated muscle symptoms

Indexed keywords

ALIROCUMAB; ANACETRAPIB; APOLIPOPROTEIN B; ASTAXANTHIN; ATORVASTATIN; BOCOCIZUMAB; BREAST CANCER RESISTANCE PROTEIN; CERIVASTATIN; DALCETRAPIB; EVACETRAPIB; EVOLOCUMAB; EZETIMIBE; FENOFIBRATE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LIVER ENZYME; LOMITAPIDE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR; MIPOMERSEN; MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 2; MULTIDRUG RESISTANCE PROTEIN; MULTIDRUG RESISTANCE PROTEIN 1; PLACEBO; PRAVASTATIN; PROSTAGLANDIN TRANSPORTER; RHO KINASE; ROSUVASTATIN; SIMVASTATIN; UNINDEXED DRUG; PCSK9 PROTEIN, HUMAN; PROPROTEIN CONVERTASE 9;

ACUTE KIDNEY FAILURE; ALOPECIA; AMNESIA; ARTHRALGIA; ARTHRITIS; ASTHENIA; BACKACHE; BRAIN HEMORRHAGE; BRONCHITIS; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; CATARACT; CHRONIC URTICARIA; CLINICAL EFFECTIVENESS; COGNITIVE DEFECT; CONFUSION; CONSTIPATION; CORONARY ARTERY DISEASE; COUGHING; DIABETES MELLITUS; DIARRHEA; DIET SUPPLEMENTATION; DIET THERAPY; DIPLOPIA; DIZZINESS; DRUG TOLERABILITY; DYSLIPIDEMIA; DYSPEPSIA; ERECTILE DYSFUNCTION; EVIDENCE BASED MEDICINE; FATIGUE; FLATULENCE; GASTROINTESTINAL DISEASE; GYNECOMASTIA; HAIR LOSS; HALLUCINATION; HEADACHE; HEARTBURN; HIGH RISK PATIENT; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; HYPERTRIGLYCERIDEMIA; INFLUENZA; INJECTION SITE REACTION; INSOMNIA; INTERSTITIAL LUNG DISEASE; ISCHEMIC HEART DISEASE; LIBIDO DISORDER; LICHENOID ERUPTION; LIPID METABOLISM; LIVER TOXICITY; LUPUS VULGARIS; MALIGNANT NEOPLASTIC DISEASE; MEDICATION COMPLIANCE; MUSCLE DISEASE; MUSCLE SPASM; MYALGIA; NAUSEA; NEUROLOGIC DISEASE; NIGHTMARE; OPHTHALMOPLEGIA; PATIENT EDUCATION; PHARYNGITIS; PRACTICE GUIDELINE; PRIORITY JOURNAL; PROTEINURIA; PTOSIS; RACE DIFFERENCE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RESTLESSNESS; REVIEW; RHEUMATIC POLYMYALGIA; RHINITIS; RHINOPHARYNGITIS; RISK ASSESSMENT; RISK FACTOR; SIDE EFFECT; SINUSITIS; SLEEP DISORDER; SOMNOLENCE; SUICIDE; TENDINITIS; THROMBOTIC THROMBOCYTOPENIC PURPURA; TREATMENT OUTCOME; TREATMENT WITHDRAWAL; UPPER RESPIRATORY TRACT INFECTION; VOMITING; ANTAGONISTS AND INHIBITORS; BLOOD; CARDIOVASCULAR DISEASES; CHEMICALLY INDUCED; PROCEDURES;

CARDIOVASCULAR DISEASES; CHOLESTEROL, HDL; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERCHOLESTEROLEMIA; MEDICATION ADHERENCE; MYALGIA; PROPROTEIN CONVERTASE 9; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RISK FACTORS; SLEEP WAKE DISORDERS;

EID: 84990196360     PISSN: 01675273     EISSN: 18741754     Source Type: Journal    
DOI: 10.1016/j.ijcard.2016.09.075     Document Type: Review

References (168)

1. [1] Stone, N.J., Robinson, J.G., Lichtenstein, A.H., 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. J. Am. Coll. Cardiol. 63:25 Pt B (2014), 2889–2934.
2. [2] Reiner, Z., Catapano, A.L., De Backer, G., et al. [ESC/EAS guidelines for the management of dyslipidaemias]. Rev. Esp. Cardiol. 64:12 (2011), 1168.e1–1168.e60.
3. [3] Thavendiranathan, P., Bagai, A., Brookhart, M.A., Choudhry, N.K., Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch. Intern. Med. 166:21 (2006), 2307–2313.
4. [4] Cheung, B.M., Lauder, I.J., Lau, C.P., Kumana, C.R., Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes. Br. J. Clin. Pharmacol. 57:5 (2004), 640–651.
5. [5] Cholesterol Treatment Trialists, C., Baigent, C., Blackwell, L., 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 (2010), 1670–1681.
6. [6] Cholesterol Treatment Trialists, C., Mihaylova, B., Emberson, J., 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 (2012), 581–590.
7. [7] Cholesterol Treatment Trialists, C., Fulcher, J., O'Connell, R., et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 385:9976 (2015), 1397–1405.
8. [8] Bittner, V., Deng, L., Rosenson, R.S., et al. Trends in the use of nonstatin lipid-lowering therapy among patients with coronary heart disease: a retrospective cohort study in the Medicare population 2007 to 2011. J. Am. Coll. Cardiol. 66:17 (2015), 1864–1872.
9. [9] Rosenson, R.S., Kent, S.T., Brown, T.M., et al. Underutilization of high-intensity statin therapy after hospitalization for coronary heart disease. J. Am. Coll. Cardiol. 65:3 (2015), 270–277.
10. [10] Simons, L.A., Levis, G., Simons, J., Apparent discontinuation rates in patients prescribed lipid-lowering drugs. Med. J. Aust. 164:4 (1996), 208–211.
11. [11] Avorn, J., Monette, J., Lacour, A., et al. Persistence of use of lipid-lowering medications: a cross-national study. JAMA 279:18 (1998), 1458–1462.
12. [12] Blackburn, D.F., Dobson, R.T., Blackburn, J.L., Wilson, T.W., Stang, M.R., Semchuk, W.M., Adherence to statins, beta-blockers and angiotensin-converting enzyme inhibitors following a first cardiovascular event: a retrospective cohort study. Can. J. Cardiol. 21:6 (2005), 485–488.
13. [13] Schultz, J.S., O'Donnell, J.C., McDonough, K.L., Sasane, R., Meyer, J., Determinants of compliance with statin therapy and low-density lipoprotein cholesterol goal attainment in a managed care population. Am. J. Manag. Care 11:5 (2005), 306–312.
14. [14] Chapman, R.H., Benner, J.S., Petrilla, A.A., et al. Predictors of adherence with antihypertensive and lipid-lowering therapy. Arch. Intern. Med. 165:10 (2005), 1147–1152.
15. [15] Svarstad, B.L., Chewning, B.A., Sleath, B.L., Claesson, C., The Brief Medication Questionnaire: a tool for screening patient adherence and barriers to adherence. Patient Educ. Couns. 37:2 (1999), 113–124.
16. [16] McGinnis, B., Olson, K.L., Magid, D., et al. Factors related to adherence to statin therapy. Ann. Pharmacother. 41:11 (2007), 1805–1811.
17. [17] Banach, M., Rizzo, M., Toth, P.P., et al. Statin intolerance — an attempt at a unified definition. Position paper from an international lipid expert panel. Arch. Med. Sci. 11:1 (2015), 1–23.
18. [18] Stulc, T., Ceska, R., Gotto, A.M. Jr., Statin intolerance: the clinician's perspective. Curr. Atheroscler. Rep., 17(12), 2015, 69.
19. [19] Jacobson, T.A., NLA task force on statin safety—2014 update. J. Clin. Lipidol. 8:3 Suppl. (2014), S1–S4.
20. [20] Reiner, Z., Resistance and intolerance to statins. Nutr. Metab. Cardiovasc. Dis. 24:10 (2014), 1057–1066.
21. [21] Fitchett, D.H., Hegele, R.A., Verma, S., Cardiology patient page. Statin intolerance. Circulation 131:13 (2015), e389–e391.
22. [22] Hovingh, G.K., Gandra, S.R., McKendrick, J., et al. Identification and management of patients with statin-associated symptoms in clinical practice: a clinician survey. Atherosclerosis 245 (2016), 111–117.
23. [23] Rasmussen, J.N., Chong, A., Alter, D.A., Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA 297:2 (2007), 177–186.
24. [24] Bouchard, M.H., Dragomir, A., Blais, L., Berard, A., Pilon, D., Perreault, S., Impact of adherence to statins on coronary artery disease in primary prevention. Br. J. Clin. Pharmacol. 63:6 (2007), 698–708.
25. [25] Mann, D.M., Woodward, M., Muntner, P., Falzon, L., Kronish, I., Predictors of nonadherence to statins: a systematic review and meta-analysis. Ann. Pharmacother. 44:9 (2010), 1410–1421.
26. [26] Henk, H.J., Paoli, C.J., Gandra, S.R., A retrospective study to examine healthcare costs related to cardiovascular events in individuals with hyperlipidemia. Adv. Ther. 32:11 (2015), 1104–1116.
27. [27] Toth, P.P., Ezetimibe provides incremental reduction in risk for cardiovascular events and need for revascularisation following an acute coronary syndrome. Evid. Based Med., 20(5), 2015, 176.
28. [28] Gamboa, C.M., Safford, M.M., Levitan, E.B., et al. Statin underuse and low prevalence of LDL-C control among U.S. adults at high risk of coronary heart disease. Am. J. Med. Sci. 348:2 (2014), 108–114.
29. [29] Reiner, Z., De Backer, G., Fras, Z., et al. Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries — findings from the EUROASPIRE IV survey. Atherosclerosis 246 (2016), 243–250.
30. [30] Lazaro, P., Murga, N., Aguilar, D., Hernandez-Presa, M.A., Investigators, I.S., Therapeutic inertia in the outpatient management of dyslipidemia in patients with ischemic heart disease. The inertia study. Rev. Esp. Cardiol. 63:12 (2010), 1428–1437.
31. [31] Phillips, L.S., Branch, W.T., Cook, C.B., et al. Clinical inertia. Ann. Intern. Med. 135:9 (2001), 825–834.
32. [32] Okonofua, E.C., Simpson, K.N., Jesri, A., Rehman, S.U., Durkalski, V.L., Egan, B.M., Therapeutic inertia is an impediment to achieving the Healthy People 2010 blood pressure control goals. Hypertension 47:3 (2006), 345–351.
33. [33] Shah, B.R., Hux, J.E., Laupacis, A., Zinman, B., van Walraven, C., Clinical inertia in response to inadequate glycemic control: do specialists differ from primary care physicians?. Diabetes Care 28:3 (2005), 600–606.
34. [34] Aujoulat, I., Jacquemin, P., Hermans, M.P., et al. Clinical inertia in general practice, a matter of debate: a qualitative study with 114 general practitioners in Belgium. BMC Fam. Pract., 16, 2015, 13.
35. [35] Zafar, A., Stone, M.A., Davies, M.J., Khunti, K., Acknowledging and allocating responsibility for clinical inertia in the management of type 2 diabetes in primary care: a qualitative study. Diabet. Med. 32:3 (2015), 407–413.
36. [36] Krempf, M., Simpson, R.J. Jr., Ramey, D.R., et al. Patient and physician factors influence decision-making in hypercholesterolemia: a questionnaire-based survey. Lipids Health Dis., 14, 2015, 45.
37. [37] Reiner, Z., Sonicki, Z., Tedeschi-Reiner, E., Physicians’ perception, knowledge and awareness of cardiovascular risk factors and adherence to prevention guidelines: the PERCRO-DOC survey. Atherosclerosis 213:2 (2010), 598–603.
38. [38] Stroes, E.S., Thompson, P.D., Corsini, A., et al. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur. Heart J. 36:17 (2015), 1012–1022.
39. [39] Fung, V., Sinclair, F., Wang, H., Dailey, D., Hsu, J., Shaber, R., Patients’ perspectives on nonadherence to statin therapy: a focus-group study. Perm. J. 14:1 (2010), 4–10.
40. [40] Kopecky, S., Baum, S., Foody, J.M., et al. Insights into statin intolerance. Clin. Cardiol. 38:9 (2015), 520–526.
41. [41] Banach, M., Aronow, W.S., Serban, M.C., Rysz, J., Voroneanu, L., Covic, A., Lipids, blood pressure and kidney update 2015. Lipids Health Dis., 14(1), 2015, 167.
42. [42] Goldacre, B., Meta-analysis of side effects of statins shows need for trial transparency. BMJ, 348, 2014, g2940.
43. [43] Tobert, J.A., Newman, C.B., Statin tolerability: in defence of placebo-controlled trials. Eur. J. Prev. Cardiol., 2015.
44. [44] Anderson, T.J., Gregoire, J., Hegele, R.A., 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 (2013), 151–167.
45. [45] Serban, M.C., Sahebkar, A., Dragan, S., et al. A systematic review and meta-analysis of the impact of spirulina supplementation on plasma lipid concentrations. Clin. Nutr. 35:4 (2016), 842–851.
46. [46] Ursoniu, S., Sahebkar, A., Serban, M.C., Banach, M., Lipid profile and glucose changes after supplementation with astaxanthin: a systematic review and meta-analysis of randomized controlled trials. Arch. Med. Sci. 11:2 (2015), 253–266.
47. [47] Sahebkar, A., Serban, C., Ursoniu, S., Banach, M., Effect of garlic on plasma lipoprotein(a) concentrations: a systematic review and meta-analysis of randomized controlled clinical trials. Nutrition 32:1 (2016), 33–40.
48. [48] Arca, M., Pigna, G., Treating statin-intolerant patients. Diabetes Metab. Syndr. Obes. 4 (2011), 155–166.
49. [49] 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). Atherosclerosis 223:1 (2012), 1–68.
50. [50] Krauss, R.M., Mangravite, L.M., Smith, J.D., et al. Variation in the 3-hydroxyl-3-methylglutaryl coenzyme a reductase gene is associated with racial differences in low-density lipoprotein cholesterol response to simvastatin treatment. Circulation 117:12 (2008), 1537–1544.
51. [51] Baigent, C., Keech, A., Kearney, P.M., 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 (2005), 1267–1278.
52. [52] Superko, H.R., Momary, K.M., Li, Y., Statins personalized. Med. Clin. N. Am. 96:1 (2012), 123–139.
53. [53] Stone, N.J., Reducing residual risk in secondary prevention of cardiovascular disease. Circulation 125:16 (2012), 1958–1960.
54. [54] Jackevicius, C.A., Mamdani, M., Tu, J.V., Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 288:4 (2002), 462–467.
55. [55] Maningat, P., Gordon, B.R., Breslow, J.L., How do we improve patient compliance and adherence to long-term statin therapy?. Curr. Atheroscler. Rep., 15(1), 2013, 291.
56. [56] Degli Esposti, L., Saragoni, S., Batacchi, P., et al. Adherence to statin treatment and health outcomes in an Italian cohort of newly treated patients: results from an administrative database analysis. Clin. Ther. 34:1 (2012), 190–199.
57. [57] Penning-van Beest, F.J., Termorshuizen, F., Goettsch, W.G., Klungel, O.H., Kastelein, J.J., Herings, R.M., Adherence to evidence-based statin guidelines reduces the risk of hospitalizations for acute myocardial infarction by 40%: a cohort study. Eur. Heart J. 28:2 (2007), 154–159.
58. [58] Chan, D.C., Shrank, W.H., Cutler, D., et al. Patient, physician, and payment predictors of statin adherence. Med. Care 48:3 (2010), 196–202.
59. [59] Brown, M.T., Bussell, J.K., Medication adherence: WHO cares?. Mayo Clin. Proc. 86:4 (2011), 304–314.
60. [60] Markovic, B.B., Kranjcevic, K., Reiner, Z., Blazekovic, S.M., Spehar, S.S., Drug therapy of cardiovascular risk factors: guidelines versus reality in primary health care service. Croat. Med. J. 46:6 (2005), 984–989.
61. [61] Jankowski, P., Czarnecka, D., Wolfshaut-Wolak, R., et al. Secondary prevention of coronary artery disease in contemporary clinical practice. Cardiol. J. 22:2 (2015), 219–226.
62. [62] Casebeer, L., Huber, C., Bennett, N., et al. Improving the physician–patient cardiovascular risk dialogue to improve statin adherence. BMC Fam. Pract., 10, 2009, 48.
63. [63] Izadpanah, R., Schachtele, D.J., Pfnur, A.B., et al. The impact of statins on biological characteristics of stem cells provides a novel explanation for their pleiotropic beneficial and adverse clinical effects. Am. J. Phys. Cell Physiol. 309:8 (2015), C522–C531.
64. [64] Banach, M., Serban, C., Sahebkar, A., et al. Impact of statin therapy on coronary plaque composition: a systematic review and meta-analysis of virtual histology intravascular ultrasound studies. BMC Med., 13, 2015, 229.
65. [65] Aranibar, N., Vassallo, J.D., Rathmacher, J., et al. Identification of 1- and 3-methylhistidine as biomarkers of skeletal muscle toxicity by nuclear magnetic resonance-based metabolic profiling. Anal. Biochem. 410:1 (2011), 84–91.
66. [66] Skottheim, I.B., Bogsrud, M.P., Hermann, M., Retterstol, K., Asberg, A., Atorvastatin metabolite measurements as a diagnostic tool for statin-induced myopathy. Mol. Diagn. Ther. 15:4 (2011), 221–227.
67. [67] Gee, R.H., Spinks, J.N., Malia, J.M., Johnston, J.D., Plant, N.J., Plant, K.E., Inhibition of prenyltransferase activity by statins in both liver and muscle cell lines is not causative of cytotoxicity. Toxicology 329 (2015), 40–48.
68. [68] Hinschberger, O., Lohmann, C., Lannes, B., et al. Immune-mediated necrotizing myopathy associated with antibodies to hydroxy-methyl-glutaryl-coenzyme A reductase. Rev. Med. Interne 35:8 (2014), 546–549.
69. [69] Toth, P.P., Harper, C.R., Jacobson, T.A., Clinical characterization and molecular mechanisms of statin myopathy. Expert. Rev. Cardiovasc. Ther. 6:7 (2008), 955–969.
70. [70] Hattori, T., Saito, K., Takemura, M., et al. Statin-induced Ca(2 +) release was increased in B lymphocytes in patients who showed elevated serum creatine kinase during statin treatment. J. Atheroscler. Thromb. 16:6 (2009), 870–877.
71. [71] Dube, M.P., Zetler, R., Barhdadi, A., et al. CKM and LILRB5 are associated with serum levels of creatine kinase. Circ. Cardiovasc. Genet. 7:6 (2014), 880–886.
72. [72] Cohen, J.D., Brinton, E.A., Ito, M.K., Jacobson, T.A., Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users. J. Clin. Lipidol. 6:3 (2012), 208–215.
73. [73] Wei, M.Y., Ito, M.K., Cohen, J.D., Brinton, E.A., Jacobson, T.A., Predictors of statin adherence, switching, and discontinuation in the USAGE survey: understanding the use of statins in America and gaps in patient education. J. Clin. Lipidol. 7:5 (2013), 472–483.
74. [74] 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 (2005), 403–414.
75. [75] Parker, B.A., Capizzi, J.A., Grimaldi, A.S., et al. Effect of statins on skeletal muscle function. Circulation 127:1 (2013), 96–103.
76. [76] Bays, H., Statin safety: an overview and assessment of the data — 2005. Am. J. Cardiol. 97:8A (2006), 6C–26C.
77. [77] Joy, T.R., Hegele, R.A., Narrative review: statin-related myopathy. Ann. Intern. Med. 150:12 (2009), 858–868.
78. [78] Grundy, S.M., Can statins cause chronic low-grade myopathy?. Ann. Intern. Med. 137:7 (2002), 617–618.
79. [79] Jacobson, T.A., Toward “pain-free” statin prescribing: clinical algorithm for diagnosis and management of myalgia. Mayo Clin. Proc. 83:6 (2008), 687–700.
80. [80] Bitzur, R., Cohen, H., Kamari, Y., Harats, D., Intolerance to statins: mechanisms and management. Diabetes Care 36:Suppl. 2 (2013), S325–S330.
81. [81] Heart Protection Study Collaborative G. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360:9326 (2002), 7–22.
82. [82] McKenney, J.M., Davidson, M.H., Jacobson, T.A., Guyton, J.R., National Lipid Association Statin Safety Assessment Task F. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am. J. Cardiol. 97:8A (2006), 89C–94C.
83. [83] McFarland, A.J., Anoopkumar-Dukie, S., Arora, D.S., et al. Molecular mechanisms underlying the effects of statins in the central nervous system. Int. J. Mol. Sci. 15:11 (2014), 20607–20637.
84. [84] Singh-Manoux, A., Kivimaki, M., Glymour, M.M., et al. Timing of onset of cognitive decline: results from Whitehall II prospective cohort study. BMJ, 344, 2012, d7622.
85. [85] Trompet, S., van Vliet, P., de Craen, A.J., et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J. Neurol. 257:1 (2010), 85–90.
86. [86] Swiger, K.J., Manalac, R.J., Blumenthal, R.S., Blaha, M.J., Martin, S.S., Statins and cognition: a systematic review and meta-analysis of short- and long-term cognitive effects. Mayo Clin. Proc. 88:11 (2013), 1213–1221.
87. [87] Ott, B.R., Daiello, L.A., Dahabreh, I.J., et al. Do statins impair cognition? A systematic review and meta-analysis of randomized controlled trials. J. Gen. Intern. Med. 30:3 (2015), 348–358.
88. [88] Lakey, W.C., Greyshock, N.G., Kelley, C.E. et al., Statin intolerance in a referral lipid clinic. J. Clin. Lipidol, 10(4), 2016 870–879.e3.
89. [89] Sampson, U.K., Fazio, S., Linton, M.F., Residual cardiovascular risk despite optimal LDL cholesterol reduction with statins: the evidence, etiology, and therapeutic challenges. Curr. Atheroscler. Rep. 14:1 (2012), 1–10.
90. [90] Keech, A., Simes, R.J., Barter, P., et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366:9500 (2005), 1849–1861.
91. [91] Group, A.S., Ginsberg, H.N., Elam, M.B., et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N. Engl. J. Med. 362:17 (2010), 1563–1574.
92. [92] Barter, P.J., Caulfield, M., Eriksson, M., et al. Effects of torcetrapib in patients at high risk for coronary events. N. Engl. J. Med. 357:21 (2007), 2109–2122.
93. [93] Schwartz, G.G., Olsson, A.G., Abt, M., et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N. Engl. J. Med. 367:22 (2012), 2089–2099.
94. [94] Nicholls, S.J., Lincoff, A.M., Barter, P.J., et al. Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: rationale and design of the ACCELERATE trial. Am. Heart J. 170:6 (2015), 1061–1069.
95. [95] Investigators, A.-H., Boden, W.E., Probstfield, J.L., et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N. Engl. J. Med. 365:24 (2011), 2255–2267.
96. [96] Group, H.T.C., Landray, M.J., Haynes, R., et al. Effects of extended-release niacin with laropiprant in high-risk patients. N. Engl. J. Med. 371:3 (2014), 203–212.
97. [97] Katsiki, N., Nikolic, D., Montalto, G., Banach, M., Mikhailidis, D.P., Rizzo, M., The role of fibrate treatment in dyslipidemia: an overview. Curr. Pharm. Des. 19:17 (2013), 3124–3131.
98. [98] Chruschiel, P., Toth, P.P., Rysz, J., Banach, M., Statins and fibrates: should they be recommended?. Banach, M., (eds.) Combination Therapy in Dyslipidemia, 2015, Springer International Publishing, Switzerland, 11–24.
99. [99] Guyton, J.R., Slee, A.E., Anderson, T., et al. Relationship of lipoproteins to cardiovascular events: the AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes). J. Am. Coll. Cardiol. 62:17 (2013), 1580–1584.
100. [100] Sacks, F.M., Pfeffer, M.A., Moye, L.A., 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 (1996), 1001–1009.
101. [101] Sacks, F.M., Tonkin, A.M., Shepherd, J., et al. Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the prospective pravastatin pooling project. Circulation 102:16 (2000), 1893–1900.
102. [102] Boekholdt, S.M., Hovingh, G.K., Mora, S., et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J. Am. Coll. Cardiol. 64:5 (2014), 485–494.
103. [103] Cannon, C.P., Blazing, M.A., Giugliano, R.P., et al. Ezetimibe added to statin therapy after acute coronary syndromes. N. Engl. J. Med. 372:25 (2015), 2387–2397.
104. [104] Kastelein, J.J., Robinson, J.G., Farnier, M., et al. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies. Cardiovasc. Drugs Ther. 28:3 (2014), 281–289.
105. [105] Serban, M.C., Banach, M., Mikhailidis, D.P., Clinical implications of the IMPROVE-IT trial in the light of current and future lipid-lowering treatment options. Expert. Opin. Pharmacother. 17:3 (2016), 369–380.
106. [106] Hassan, M., OSLER and ODYSSEY LONG TERM: PCSK9 inhibitors on the right track of reducing cardiovascular events. Glob. Cardiol. Sci. Pract., 2015(2), 2015, 20.
107. [107] Dragan, S., Serban, M.C., Banach, M., Proprotein convertase subtilisin/kexin 9 inhibitors: an emerging lipid-lowering therapy?. J. Cardiovasc. Pharmacol. Ther. 20:2 (2015), 157–168.
108. [108] Sabatine, M.S., Giugliano, R.P., Wiviott, S.D., et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N. Engl. J. Med. 372:16 (2015), 1500–1509.
109. [109] Robinson, J.G., Farnier, M., Krempf, M., et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N. Engl. J. Med. 372:16 (2015), 1489–1499.
110. [110] Kereiakes, D.J., Robinson, J.G., Cannon, C.P., et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study. Am. Heart J. 169:6 (2015), 906–915.e13.
111. [111] Cannon, C.P., Cariou, B., Blom, D., et al. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur. Heart J. 36:19 (2015), 1186–1194.
112. [112] Gencer, B., Mach, F., Sweetless'n low LDL-C targets for PCSK9 treatment. Eur. Heart J. 36:19 (2015), 1146–1148.
113. [113] Stoekenbroek, R.M., Kastelein, J.J., Huijgen, R., PCSK9 inhibition: the way forward in the treatment of dyslipidemia. BMC Med., 13, 2015, 258.
114. [114] Chapman, M.J., Stock, J.K., Ginsberg, H.N., Forum, P., PCSK9 inhibitors and cardiovascular disease: heralding a new therapeutic era. Curr. Opin. Lipidol. 26:6 (2015), 511–520.
115. [115] Zimmerman, M.P., How do PCSK9 inhibitors stack up to statins for low-density lipoprotein cholesterol control?. Am. Health Drug Benefits 8:8 (2015), 436–442.
116. [116] Dadu, R.T., Ballantyne, C.M., Lipid lowering with PCSK9 inhibitors. Nat. Rev. Cardiol. 11:10 (2014), 563–575.
117. [117] Evolocumab SmPC. Available from: http://www.medicines.org.uk/emc/medicine/30627.
118. [118] Alirocumab SmPC. Available from: http://www.medicines.org.uk/emc/medicine/30965.
119. [119] Avis, H.J., Hutten, B.A., Gagne, C., et al. Efficacy and safety of rosuvastatin therapy for children with familial hypercholesterolemia. J. Am. Coll. Cardiol. 55:11 (2010), 1121–1126.
120. [120] Nissen, S.E., Stroes, E., Dent-Acosta, R.E., et al. Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial. JAMA, 2016.
121. [121] Sattar, N., Efficacy and safety of the PCSK9 inhibitor evolocumab (AMG 145) in patients with type 2 diabetes. 75th Annual Scientific Sessions of the American Diabetes Association Boston, MA, United States, 2015.
122. [122] Preiss, D., Should we worry about raised triglycerides: the controversy continues. 51st EASD Annual Meeting; Stockholm, Sweden, 2015.
123. [123] Sattar, N., Preiss, D., Blom, D., et al. Evaluation of the one-year efficacy, safety and glycaemic effects of evolocumab (AMG 145) in 4802 subjects with, at high risk for, or at low risk for, diabetes mellitus. 51st EASD Annual Meeting; Stockholm, Sweden, 2015.
124. [124] Colhoun, H.M., Ginsberg, H.N., Leiter, L.A., et al. Efficacy and safety of alirocumab in individuals with diabetes: analyses from the ODYSSEY LONG TERM study. 51st EASD Annual Meeting; Stockholm, Sweden, 2015.
125. [125] Poirier, S., Mayer, G., Benjannet, S., et al. The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2. J. Biol. Chem. 283:4 (2008), 2363–2372.
126. [126] Postmus, I., Trompet, S., de Craen, A.J., et al. PCSK9 SNP rs11591147 is associated with low cholesterol levels but not with cognitive performance or noncardiovascular clinical events in an elderly population. J. Lipid Res. 54:2 (2013), 561–566.
127. [127] Rader, D.J., Kastelein, J.J., Lomitapide and mipomersen: two first-in-class drugs for reducing low-density lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia. Circulation 129:9 (2014), 1022–1032.
128. [128] Turner, T., Stein, E.A., Non-statin treatments for managing LDL cholesterol and their outcomes. Clin. Ther. 37:12 (2015), 2751–2769.
129. [129] Nikolic, D., Mikhailidis, D.P., Davidson, M.H., Rizzo, M., Banach, M., ETC-1002: a future option for lipid disorders?. Atherosclerosis 237:2 (2014), 705–710.
130. [130] Fernandez, A.B., Karas, R.H., Alsheikh-Ali, A.A., Thompson, P.D., Statins and interstitial lung disease: a systematic review of the literature and of food and drug administration adverse event reports. Chest 134:4 (2008), 824–830.
131. [131] Mlodinow, S.G., Onysko, M.K., Vandiver, J.W., Hunter, M.L., Mahvan, T.D., Statin adverse effects: sorting out the evidence. J. Fam. Pract. 63:9 (2014), 497–506.
132. [132] Zureik, M., Courbon, D., Ducimetiere, P., Serum cholesterol concentration and death from suicide in men: Paris prospective study I. BMJ 313:7058 (1996), 649–651.
133. [133] Olson, M.B., Kelsey, S.F., Matthews, K.A., et al. Lipid-lowering medication use and aggression scores in women: a report from the NHLBI-sponsored WISE study. J. Women's Health (Larchmt) 17:2 (2008), 187–194.
134. [134] Kang, J.H., Kao, L.T., Lin, H.C., Tsai, M.C., Chung, S.D., Statin use increases the risk of depressive disorder in stroke patients: a population-based study. J. Neurol. Sci. 348:1–2 (2015), 89–93.
135. [135] Amarenco, P., Bogousslavsky, J., Callahan, A. III, et al. High-dose atorvastatin after stroke or transient ischemic attack. N. Engl. J. Med. 355:6 (2006), 549–559.
136. [136] Golomb, B.A., Kane, T., Dimsdale, J.E., Severe irritability associated with statin cholesterol-lowering drugs. QJM 97:4 (2004), 229–235.
137. [137] Tuccori, M., Lapi, F., Testi, A., et al. Statin-associated psychiatric adverse events: a case/non-case evaluation of an Italian database of spontaneous adverse drug reaction reporting. Drug Saf. 31:12 (2008), 1115–1123.
138. [138] Boriani, G., Biffi, M., Strocchi, E., Branzi, A., Nightmares and sleep disturbances with simvastatin and metoprolol. Ann. Pharmacother., 35(10), 2001, 1292.
139. [139] Sattar, N., Preiss, D., Murray, H.M., et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 375:9716 (2010), 735–742.
140. [140] Preiss, D., Seshasai, S.R., Welsh, P., et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 305:24 (2011), 2556–2564.
141. [141] Ridker, P.M., Pradhan, A., MacFadyen, J.G., Libby, P., Glynn, R.J., Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet 380:9841 (2012), 565–571.
142. [142] Carter, A.A., Gomes, T., Camacho, X., Juurlink, D.N., Shah, B.R., Mamdani, M.M., Risk of incident diabetes among patients treated with statins: population based study. BMJ, 346, 2013, f2610.
143. [143] Bjornsson, E., Jacobsen, E.I., Kalaitzakis, E., Hepatotoxicity associated with statins: reports of idiosyncratic liver injury post-marketing. J. Hepatol. 56:2 (2012), 374–380.
144. [144] Segal, A.S., Alopecia associated with atorvastatin. Am. J. Med., 113(2), 2002, 171.
145. [145] Pua, V.S., Scolyer, R.A., Barnetson, R.S., Pravastatin-induced lichenoid drug eruption. Australas. J. Dermatol. 47:1 (2006), 57–59.
146. [146] Adcock, B.B., Hornsby, L.B., Jenkins, K., Dermographism: an adverse effect of atorvastatin. J. Am. Board Fam. Pract. 14:2 (2001), 148–151.
147. [147] Anliker, M.D., Wuthrich, B., Chronic urticaria to atorvastatin. Allergy, 57(4), 2002, 366.
148. [148] Pfeiffer, C.M., Kazenoff, S., Rothberg, H.D., Toxic epidermal necrolysis from atorvastatin. JAMA 279:20 (1998), 1613–1614.
149. [149] Krasovec, M., Elsner, P., Burg, G., Generalized eczematous skin rash possibly due to HMG-CoA reductase inhibitors. Dermatology 186:4 (1993), 248–252.
150. [150] Leuschen, J., Mortensen, E.M., Frei, C.R., Mansi, E.A., Panday, V., Mansi, I., Association of statin use with cataracts: a propensity score-matched analysis. JAMA Ophthalmol. 131:11 (2013), 1427–1434.
151. [151] Fraunfelder, F.W., Richards, A.B., Diplopia, blepharoptosis, and ophthalmoplegia and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor use. Ophthalmology 115:12 (2008), 2282–2285.
152. [152] Athyros, V.G., Elisaf, M., Papageorgiou, A.A., et al. Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Am. J. Kidney Dis. 43:4 (2004), 589–599.
153. [153] Hippisley-Cox, J., Coupland, C., Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ, 340, 2010, c2197.
154. [154] Stroes, E., Colquhoun, D., Sullivan, D., et al. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J. Am. Coll. Cardiol. 63:23 (2014), 2541–2548.
155. [155] Raal, F.J., Stein, E.A., Dufour, R., et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet 385:9965 (2015), 331–340.
156. [156] Raal, F.J., Honarpour, N., Blom, D.J., et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA part B): a randomised, double-blind, placebo-controlled trial. Lancet 385:9965 (2015), 341–350.
157. [157] Blom, D.J., Djedjos, C.S., Monsalvo, M.L., et al. Effects of evolocumab on vitamin E and steroid hormone levels: results from the 52-week, phase 3, double-blind, randomized, placebo-controlled DESCARTES study. Circ. Res. 117:8 (2015), 731–741.
158. [158] Robinson, J.G., Nedergaard, B.S., Rogers, W.J., et al. Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. JAMA 311:18 (2014), 1870–1882.
159. [159] Koren, M.J., Lundqvist, P., Bolognese, M., et al. Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J. Am. Coll. Cardiol. 63:23 (2014), 2531–2540.
160. [160] Raal, F.H.K., Kees Hovingh, G., Santos, R., et al. Long-term treatment with evolocumab in patients with homozygous familial hypercholesterolaemia (HoFH): interim results from the trial assessing long-term use of PCSK9 inhibition in subjects with genetic LDL disorder (TAUSSIG) study. [Abstract No. 255]. 17th International Symposium on Atherosclerosis; Amsterdam, The Netherlands, 2015.
161. [161] Kiyosue, A., Honarpour, N., Kurtz, C., Xue, A., Wasserman, S.M., Hirayama, A., A phase 3 study of evolocumab (AMG 145) in statin-treated Japanese patients at high cardiovascular risk. Am. J. Cardiol. 117:1 (2016), 40–47.
162. [162] Kastelein, J.J., Ginsberg, H.N., Langslet, G., et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur. Heart J. 36:43 (2015), 2996–3003.
163. [163] Ginsberg, H.R., Rader, D.J., Raal, F.J., et al. ODYSSEY HIGH FH: efficacy and safety of alirocumab in patients with severe heterozygous familial hypercholesterolemia. Circulation, 130, 2014, 2119.
164. [164] Bays, H., Gaudet, D., Weiss, R., et al. Alirocumab as add-on to atorvastatin versus other lipid treatment strategies: ODYSSEY OPTIONS I randomized trial. J. Clin. Endocrinol. Metab. 100:8 (2015), 3140–3148.
165. [165] Farnier, M., Jones, P., Severance, R., et al. Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: the ODYSSEY OPTIONS II randomized trial. Atherosclerosis 244 (2016), 138–146.
166. [166] Moriarty, P.M., Jacobson, T.A., Bruckert, E., et al. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J. Clin. Lipidol. 8:6 (2014), 554–561.
167. [167] Roth, E.R.D., Moriarty, P., Phase 3 randomized trial evaluating alirocumab every four weeks dosing as add-on to statin or as monotherapy: ODYSSEY CHOICE I [Abstract No. 0254]. 17th International Symposium on Atherosclerosis; Amsterdam, The Netherlands, 2015.
168. [168] Stroes, E.G.J., Farnier, M., Alirocumab in patients with hypercholesterolemia not on statin therapy: the ODYSSEY CHOICE II study [Abstract No. 0269]. 17th International Symposium on Atherosclerosis; Amsterdam, The Netherlands, 2015.