When statin therapy stops: Implications for the patient

Current Opinion in Cardiology

Volumn 24, Issue 5, 2009, Pages 454-460

  Daskalopoulou, Stella S ^a  

^a MONTREAL GENERAL HOSPITAL   (Canada)

Author keywords

Adherence; Cardiovascular risk; Compliance; Discontinuation; Statin

Indexed keywords

ACETYLSALICYLIC ACID; ATORVASTATIN; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; C REACTIVE PROTEIN; CALCIUM CHANNEL BLOCKING AGENT; FLUINDOSTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; PRAVASTATIN; PROTON PUMP INHIBITOR; ROSUVASTATIN; SIMVASTATIN; HYPOCHOLESTEROLEMIC AGENT;

ACUTE HEART INFARCTION; ANTIINFLAMMATORY ACTIVITY; BRAIN INFARCTION; CARDIAC PATIENT; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; CLINICAL PRACTICE; CLINICAL TRIAL; CORONARY ARTERY DISEASE; COST CONTROL; COST EFFECTIVENESS ANALYSIS; DRUG EFFECT; DRUG EFFICACY; DRUG WITHDRAWAL; ENDOTHELIAL DYSFUNCTION; FUNCTIONAL STATUS; HEART FAILURE; HUMAN; HYPERCHOLESTEROLEMIA; ISCHEMIC HEART DISEASE; LOW FAT DIET; MORTALITY; PATIENT COMPLIANCE; PATIENT COUNSELING; PERCUTANEOUS CORONARY INTERVENTION; PRACTICE GUIDELINE; PRESCRIPTION; PRIMARY PREVENTION; PRIORITY JOURNAL; REBOUND; REVIEW; RISK REDUCTION; SECONDARY PREVENTION; ST SEGMENT ELEVATION; STROKE; SUSTAINED RELEASE FORMULATION; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT WITHDRAWAL; DRUG EFFECTS; INFLAMMATION; MEDICATION COMPLIANCE; RISK FACTOR; VASCULAR ENDOTHELIUM;

ANTICHOLESTEREMIC AGENTS; CORONARY ARTERY DISEASE; ENDOTHELIUM, VASCULAR; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INFLAMMATION; MEDICATION ADHERENCE; RISK FACTORS; SECONDARY PREVENTION;

EID: 69749097819     PISSN: 02684705     EISSN: None     Source Type: Journal    
DOI: 10.1097/HCO.0b013e32832ebf92     Document Type: Review

References (77)

1. 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 2006; 113:2363-2372.
2. 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 2002; 106:3143-3421.
3. Graham I, Atar D, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Eur Heart J 2007; 28:2375-2414.
4. Dembowski E, Davidson MH. A review of lipid management in primary and secondary prevention. J Cardiopulm Rehabil Prev 2009; 29:2-12.
5. Betteridge DJ. Lipid lowering in diabetes mellitus. Curr Opin Lipidol 2008; 19:579-584.
6. Brown WV. Safety of statins. Curr Opin Lipidol 2008; 19:558-562.
7. Deedwania PC, Javed U. Statins in heart failure. Cardiol Clin 2008; 26:573-587.
8. Bersano A, Ballabio E, Lanfranconi S, et al. Statins and stroke. Curr Med Chem 2008; 15:2380-2392.
9. Biria M, Howard PA, Vacek J. Do statins have a role in the management of diastolic dysfunction? Am J Cardiovasc Drugs 2008; 8:297-303.
10. Silva VS, Martin LC, Franco RJ, et al. Pleiotropic effects of statins may improve outcomes in atherosclerotic renovascular disease. Am J Hypertens 2008; 21:1163-1168.
11. El HK, Akdim F, Stroes ES, et al. Current and future pharmacologic options for the management of patients unable to achieve low-density lipoprotein-cholesterol goals with statins. Am J Cardiovasc Drugs 2008; 8:233-242.
12. Maroo BP, Lavie CJ, Milani RV. Secondary prevention of coronary heart disease in elderly patients following myocardial infarction: are all HMG-CoA reductase inhibitors alike? Drugs Aging 2008; 25:649-664.
13. Chan YC, Cheng SW, Irwin MG. Perioperative use of statins in noncardiac surgery. Vasc Health Risk Manag 2008; 4:75-81.
14. Kapur NK, Musunuru K. Clinical efficacy and safety of statins in managing cardiovascular risk. Vasc Health Risk Manag 2008; 4:341-353. (Pubitemid 351711963)
15. Peters B, Maitland-van der Zee AH. Pharmacogenomic importance of pravastatin. Pharmacogenomics 2008; 9:1207-1210.
16. Arshad A, Mandava A, Kamath G, Musat D. Sudden cardiac death and the role of medical therapy. Prog Cardiovasc Dis 2008; 50:420-438. (Pubitemid 351649368)
17. O'Regan C, Wu P, Arora P, et al. Statin therapy in stroke prevention: a meta-analysis involving 121,000 patients. Am J Med 2008; 121:24-33.
18. Kamal-Bahl SJ, Burke T, Watson D, Wentworth C. Discontinuation of lipid modifying drugs among commercially insured United States patients in recent clinical practice. Am J Cardiol 2007; 99:530-534. (Pubitemid 46215558)
19. Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 2002; 288:462-467. (Pubitemid 34787477)
20. Daskalopoulou SS, Delaney JA, Filion KB, et al. Discontinuation of statin therapy following an acute myocardial infarction: a population-based study. Eur Heart J 2008; 29:2083-2091. This study showed, in a large population-based cohort with excellent follow-up, that statin discontinuation after an AMI is associated with higher 1-year mortality than in those who never received statins. This is the first study to look at long-term mortality reflecting the actual clinical practice as it includes data from the general population of all ages, and, therefore, the results are more generalizable than most studies.
21. Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA 2007; 297:177-186. (Pubitemid 46089734)
22. Heeschen C, Hamm CW, Laufs U, et al. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation 2002; 105:1446-1452. (Pubitemid 34263276)
23. Blanco M, Nombela F, Castellanos M, et al. Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology 2007; 69:904-910. (Pubitemid 47329591)
24. Vrtovec B, Okrajsek R, Golicnik A, et al. Atorvastatin therapy may reduce the incidence of sudden cardiac death in patients with advanced chronic heart failure. J Card Fail 2008; 14:140-144. (Pubitemid 351312881)
25. Aronson D, Mutlak D, Lessick J, et al. Relation of statin therapy to risk of heart failure after acute myocardial infarction. Am J Cardiol 2008; 102:1706-1710.
26. Lev EI, Kornowski R, Vaknin-Assa H, et al. Effect of previous treatment with statins on outcome of patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Am J Cardiol 2009; 103:165-169.
27. Westphal S, Abletshauser C, Luley C. Fluvastatin treatment and withdrawal: effects on endothelial function. Angiology 2008; 59:613-618. This study showed that 4 weeks of fluvastatin treatment improved FMD, and this effect was lost after only 24 withdrawals. This provides support for the biological rebound phenomenon after statin discontinuation.
28. Vergouwen MD, de Haan RJ, Vermeulen M, Roos YB. Statin treatment and the occurrence of hemorrhagic stroke in patients with a history of cerebrovascular disease. Stroke 2008; 39:497-502. (Pubitemid 351619482)
29. Reeves MJ, Gargano JW, Luo Z, et al. Effect of pretreatment with statins on ischemic stroke outcomes. Stroke 2008; 39:1779-1785.
30. FitzMaurice E, Wendell L, Snider R, et al. Effect of statins on intracerebral hemorrhage outcome and recurrence. Stroke 2008; 39:2151-2154.
31. Tabata M, Khalpey Z, Cohn LH, et al. Effect of preoperative statins in patients without coronary artery disease who undergo cardiac surgery. J Thorac Cardiovasc Surg 2008; 136:1510-1513.
32. Papathanasiou A, Toumpoulis IK, Milionis HJ, et al. Statin therapy is associated with reduced total and cardiovascular mortality after coronary artery bypass grafting surgery. Coron Artery Dis 2008; 19:619-625.
33. Liakopoulos OJ, Choi YH, Haldenwang PL, et al. Impact of preoperative statin therapy on adverse postoperative outcomes in patients undergoing cardiac surgery: a meta-analysis of over 30,000 patients. Eur Heart J 2008; 29:1548-1559.
34. Kulik A, Brookhart MA, Levin R, et al. Impact of statin use on outcomes after coronary artery bypass graft surgery. Circulation 2008; 118:1785-1792.
35. Takagi H, Kawai N, Umemoto T. Preoperative statin therapy reduces post-operative all-cause mortality in cardiac surgery: a meta-analysis of controlled studies. J Thorac Cardiovasc Surg 2009; 137:e52-e53.
36. Kushiro T, Mizuno K, Nakaya N, et al. Pravastatin for cardiovascular event primary prevention in patients with mild-to-moderate hypertension in the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study. Hypertension 2009; 53:135-141.
37. 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 2008; 359:2195-2207. This is a large primary prevention randomized clinical trial that provided strong evidence for the beneficial anti-inflammatory effects of statins, independently of the reduction in cholesterol. A significant decrease in cardiovascular events and mortality was noted in the rosuvastatin group when compared with the placebo group.
38. Foody JM, Joyce AT, Rudolph AE, et al. Cardiovascular outcomes among patients newly initiating atorvastatin or simvastatin therapy: a large database analysis of managed care plans in the United States. Clin Ther 2008; 30:195-205.
39. Kadota S, Matsuda M, Izuhara M, et al. Long-term effects of early statin therapy for patients with acute myocardial infarction treated with stent implantation. J Cardiol 2008; 51:171-178. (Pubitemid 351718488)
40. Zhang M, Que B, Nie SP, et al. The effect of prehospital statins therapy on incidence of in-hospital death and total MACCE in patients with PCI. J Clin Pharm Ther 2008; 33:613-617.
41. Sadek MM, Haddad T, Haddad H. The role of statins in chronic heart failure. Curr Opin Cardiol 2009; 24:167-171.
42. Gissi-HF Investigators, Tavazzi L, Maggioni AP, 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.
43. Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007; 357:2248-2261. (Pubitemid 350190755)
44. Afilalo J, Duque G, Steele R, et al. Statins for secondary prevention in elderly patients: a hierarchical bayesian meta-analysis. J Am Coll Cardiol 2008; 51:37-45.
45. Kashani A, Sallam T, Bheemreddy S, et al. Review of side-effect profile of combination ezetimibe and statin therapy in randomized clinical trials. Am J Cardiol 2008; 101:1606-1613.
46. Harper CR, Jacobson TA. The broad spectrum of statin myopathy: from myalgia to rhabdomyolysis. Curr Opin Lipidol 2007; 18:401-408.
47. Armitage J. The safety of statins in clinical practice. Lancet 2007; 370:1781-1790.
48. Herrler T, Bohm M, Heeschen C. More good reasons for adherence to statin therapy during acute coronary syndromes. Eur Heart J 2008; 29:2061-2063.
49. Tziomalos K, Athyros VG, Mikhailidis DP. Statin discontinuation: an underestimated risk? Curr Med Res Opin 2008; 24:3059-3062.
50. Jackevicius CA, Li P, Tu JV. Prevalence, predictors, and outcomes of primary nonadherence after acute myocardial infarction. Circulation 2008; 117:1028-1036. This is a population-based study that investigated the association of filling discharge medications postacute myocardial infarction with 1-year mortality. The study showed a continuum effect of filling prescriptions and underscored the importance of taking discharge medication. Filling none, some, and all prescriptions was associated with increasing chance of survival.
51. Shalev V, Chodick G, Silber H, et al. Continuation of statin treatment and all-cause mortality: a population-based cohort study. Arch Intern Med 2009; 169:260-268. This is a very large population-based prospective study demonstrating a strong and independent association between adherence to statin therapy and the improved survival of patients with and without known CHD.
52. Perreault S, Dragomir A, Blais L, et al. Impact of adherence to statins on chronic heart failure in primary prevention. Br J Clin Pharmacol 2008; 66:706-716. This is a large population-based primary prevention study. It is the first study that examined the association of adherence to statin therapy and the risk of developing congestive heart failure.
53. Ho PM, Magid DJ, Shetterly SM, et al. Medication nonadherence is associated with a broad range of adverse outcomes in patients with coronary artery disease. Am Heart J 2008; 155:772-779. This is a retrospective study that showed that nonadherence to statins and other cardioprotective medications is common in clinical practice and is associated with a broad range of adverse outcomes.
54. Wei L, Fahey T, MacDonald TM. Adherence to statin or aspirin or both in patients with established cardiovascular disease: exploring healthy behaviour vs. drug effects and 10-year follow-up of outcome. Br J Clin Pharmacol 2008; 66:110-116. This study was the first to examine the effects of prolonged adherence to statins and aspirin in a primary care setting. The study showed that the healthy behavior associated with medication adherence is not the cause of decreased mortality in statin users; adherence to statins, but not adherence to aspirin, was associated with decreased mortality. (Pubitemid 351822170)
55. Chen H, Ren JY, Xing Y, et al. Short-term withdrawal of simvastatin induces endothelial dysfunction in patients with coronary artery disease: a dose-response effect dependent on endothelial nitric oxide synthase. Int J Cardiol 2009; 131:313-320. This study showed that abrupt discontinuation of statin therapy results in a drastic decrease in endothelial function to lower than pretreatment levels. This provides evidence for the rapid biological rebound phenomenon after statin discontinuation.
56. Colivicchi F, Bassi A, Santini M, Caltagirone C. Discontinuation of statin therapy and clinical outcome after ischemic stroke. Stroke 2007; 38:2652-2657. (Pubitemid 47493999)
57. Wei L, Wang J, Thompson P, et al. Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study. Heart 2002; 88:229-233. (Pubitemid 34913500)
58. Spencer FA, Allegrone J, Goldberg RJ, et al. Association of statin therapy with outcomes of acute coronary syndromes: the GRACE study. Ann Intern Med 2004; 140:857-866. (Pubitemid 38685266)
59. Compliance and adverse event withdrawal: their impact on the West of Scotland Coronary Prevention Study. Eur Heart J 1997; 18:1718-1724. (Pubitemid 27477921)
60. Spencer FA, Fonarow GC, Frederick PD, et al. Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction: national registry of myocardial infarction. Arch Intern Med 2004; 164:2162-2168. (Pubitemid 39410807)
61. Fonarow GC, Wright RS, Spencer FA, et al. Effect of statin use within the first 24 h of admission for acute myocardial infarction on early morbidity and mortality. Am J Cardiol 2005; 96:611-616.
62. Bouchard MH, Dragomir A, Blais L, et al. Impact of adherence to statins on coronary artery disease in primary prevention. Br J Clin Pharmacol 2007; 63:698-708. (Pubitemid 46753568)
63. Collard CD, Body SC, Shernan SK, et al. Preoperative statin therapy is associated with reduced cardiac mortality after coronary artery bypass graft surgery. J Thorac Cardiovasc Surg 2006; 132:392-400. (Pubitemid 44092868)
64. Lee KT, Lai WT, Chu CS, et al. Effect of withdrawal of statin on C-reactive protein. Cardiology 2004; 102:166-170. (Pubitemid 39370270)
65. Laufs U, Endres M, Custodis F, et al. Suppression of endothelial nitric oxide production after withdrawal of statin treatment is mediated by negative feedback regulation of rho GTPase gene transcription. Circulation 2000; 102:3104-3110.
66. Bryson CL, Au DH, Sun H, et al. Alcohol screening scores and medication nonadherence. Ann Intern Med 2008; 149:795-804.
67. Lummis HL, Sketris IS, Gubitz GJ, et al. Medication persistence rates and factors associated with persistence in patients following stroke: a cohort study. BMC Neurol 2008; 8:25.
68. Choudhry NK, Setoguchi S, Levin R, et al. Trends in adherence to secondary prevention medications in elderly postmyocardial infarction patients. Pharmacoepidemiol Drug Saf 2008; 17:1189-1196.
69. Ko DT, Mamdani M, Alter DA. Lipid-lowering therapy with statins in high-risk elderly patients: the treatment-risk paradox. JAMA 2004; 291:1864-1870. (Pubitemid 38509499)
70. Lee DS, Tu JV, Juurlink DN, et al. Risk-treatment mismatch in the pharmacotherapy of heart failure. JAMA 2005; 294:1240-1247. (Pubitemid 41352112)
71. Gaw A. The care gap: underuse of statin therapy in the elderly. Int J Clin Pract 2004; 58:777-785. (Pubitemid 39232323)
72. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360:1623-1630. (Pubitemid 35379733)
73. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360:7-22. (Pubitemid 34756487)
74. Kalantzi KJ, Milionis HJ, Mikhailidis DP, Goudevenos JA. Lipid lowering therapy in the elderly: is there a benefit? Curr Pharm Des 2006; 12:3945-3960.
75. Caldwell PH. Review: intensified patient care may improve adherence to lipid-lowering medication in primary or secondary prevention of CV disease. Evid Based Nurs 2008; 11:51.
76. Pletcher MJ, Lazar L, Bibbins-Domingo K, et al. Comparing impact and cost-effectiveness of primary prevention strategies for lipid-lowering. Ann Intern Med 2009; 150:243-254.
77. Choudhry NK, Patrick AR, Antman EM, et al. Cost-effectiveness of providing full drug coverage to increase medication adherence in postmyocardial infarction Medicare beneficiaries. Circulation 2008; 117:1261-1268.