Benefits of statin therapy and compliance in high risk cardiovascular patients

Joel A Lardizabal, Prakash C Deedwania, Joel A Lardizabal, Prakash C Deedwania

Abstract

Cardiovascular disease (CVD) remains the top cause of global mortality. There is considerable evidence that supports the mortality and morbidity benefit of statin therapy in coronary heart disease (CHD) and stroke, both in primary and secondary prevention settings. Data also exist pointing to the advantage of statin treatment in other high-risk CVD conditions, such as diabetes, CKD, CHF, and PVD. National and international clinical guidelines in the management of these CVD conditions all advocate for the utilization of statin therapy in appropriate patients. However, overall compliance to statin therapy remains suboptimal. Patient-, physician-, and economic-related factors all play a role. These factors need to be considered in devising approaches to enhance adherence to guideline-based therapies. To fully reap the benefits of statin therapy, interventions which improve long-term treatment compliance in real-world settings should be encouraged.

Keywords: cardiovascular disease; coronary heart disease; long-term treatment compliance; statin therapy.

Figures

Figure 1
Figure 1
Plotted estimates of outcomes pooled from primary prevention trials on statin therapy. Pooled relative risk with bars representing 95% confidence intervals (CIs). Notes: Adapted with permission from Mills EJ, Rachlis B, Wu P, Devereaux PJ, Arora P, Perri D. Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients. J Am Coll Cardiol. 2008;52(22):1769–1781.
Figure 2
Figure 2
Comparison of relative risks for coronary heart disease mortality and nonfatal myocardial infarction between statin therapy and placebo from the different secondary prevention trials. Notes: Adapted with permission from Wilt TJ, Bloomfield HE, MacDonald R, et al. Effectiveness of statin therapy in adults with coronary heart disease. Arch Intern Med. 2004;164(13):1427–1436.
Figure 3
Figure 3
Plotted estimates of adverse events cancer and rhabdomyolysis pooled from primary prevention trials on statin therapy. Pooled relative risk with bars representing 95% confidence intervals (CIs). Notes: Adapted with permission from Mills EJ, Rachlis B, Wu P, Devereaux PJ, Arora P, Perri D. Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients. J Am Coll Cardiol. 2008;52(22):1769–1781.

References

    1. The global burden of disease: 2004 update. World Health Organization; 2008.
    1. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive Summary: Heart Disease and Stroke Statistics – 2010 Update: a report from the American Heart Association. Circulation. 2010;121(7):948–954.
    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(19):2363–2372.
    1. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2006;113(24):e873–e923.
    1. American Diabetes Association. Standards of medical care in diabetes: 2008. Diabetes Care. 2008;31:S12–S54.
    1. Barr DP, Russ EM, Eder HA. Protein-lipid relationships in human plasma. II. In atherosclerosis and related conditions. Am J Med. 1951;11(4):480–493.
    1. Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ. Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol. 2005;46(6):937–954.
    1. Saiki A, Murano T, Watanabe F, et al. Pitavastatin enhanced lipoprotein lipase expression in 3T3-L1 preadipocytes. J Atheroscler Thromb. 2005;12(3):163–168.
    1. Yano M, Matsumura T, Senokuchi T, et al. Statins activate peroxisome proliferator-activated receptor gamma through extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase- dependent cyclooxygenase-2 expression in macrophages. Circ Res. 2007;100(10):1442–1451.
    1. Ray KK, Cannon CP. The potential relevance of the multiple lipid-independent (pleiotropic) effects of statins in the management of acute coronary syndromes. J Am Coll Cardiol. 2005;46(8):1425–1433.
    1. Lardizabal JA, Deedwania PC. Low levels of high-density lipoprotein cholesterol and increased cardiovascular disease risk. Asia-Pacific J Cardiol. 2010
    1. Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial) Am J Cardiol. 2003;92(2):152–160.
    1. Mills EJ, Rachlis B, Wu P, Devereaux PJ, Arora P, Perri D. Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients. J Am Coll Cardiol. 2008;52(22):1769–1781.
    1. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301–1307.
    1. Nakamura H, Arakawa K, Itakura H, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet. 2006;368(9542):1155–1163.
    1. Furberg CD, Adams HP, Jr, Applegate WB, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Circulation. 1994;90(4):1679–1687.
    1. Sever PS, Dahlöf 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. 2003;361(9364):1149–1158.
    1. Ridker PM, Danielson E, Fonseca FAG, et al. JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–2207.
    1. The Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation. 2004;110:227–239.
    1. The 4S Investigators. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) Lancet. 1994;344(8934):1383–1389.
    1. 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. 1996;335(14):1001–1009.
    1. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339(19):1349–1357.
    1. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22.
    1. Nissen SE, Tuzcu EM, Schoenhagen P, et al. Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) Investigators. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med. 2005;352(1):29–38.
    1. LaRosa JC, Deedwania PC, Shepherd J, et al. TNT Investigators. Comparison of 80 versus 10 mg of atorvastatin on occurrence of cardiovascular events after the first event (from the Treating to New Targets [TNT] trial) Am J Cardiol. 2010;105(3):283–287.
    1. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285(13):1711–17118.
    1. Murphy SA, Cannon CP, Wiviott SD, McCabe CH, Braunwald E. Reduction in recurrent cardiovascular events with intensive lipid-lowering statin therapy compared with moderate lipid-lowering statin therapy after acute coronary syndromes from the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy- Thrombolysis In Myocardial Infarction 22) trial. J Am Coll Cardiol. 2009;54(25):2358–2362.
    1. Wilt TJ, Bloomfield HE, MacDonald R, et al. Effectiveness of statin therapy in adults with coronary heart disease. Arch Intern Med. 2004;164(13):1427–1436.
    1. Smith SC, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update. Circulation. 2006;113:2363–2372.
    1. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, American College of Physicians, Society for Academic Emergency Medicine, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2007;50:e1–e157.
    1. Everett BM, Glynn RJ, MacFadyen JG, Ridker PM. Rosuvastatin in the prevention of stroke among men and women with elevated levels of C-reactive protein: Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) Circulation. 2010;121(1):143–150.
    1. Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. Engl J Med. 2006;355(6):549–559.
    1. Reeves MJ, Gargano JW, Luo Z, et al. Paul Coverdell National Acute Stroke Registry Michigan Prototype Investigators. Effect of pretreatment with statins on ischemic stroke outcomes. Stroke. 2008;39(6):1779–1785.
    1. Byington RP, Davis BR, Plehn JF, et al. Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) Project. Circulation. 2001;103(3):387–392.
    1. Waters DD, Schwartz GG, Olsson AG, et al. Effects of atorvastatin on stroke in patients with unstable angina or non-Q-wave myocardial infarction: a Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) substudy. Circulation. 2002;106(13):1690–1695.
    1. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2006;113(24):e873–e923.
    1. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke. 2006;37(2):577–617.
    1. Deedwania PC, Javed U. Statins in heart failure. Cardiol Clin. 2008;26(4):573–587.
    1. Khush KK, Waters DD, Bittner V, et al. Effect of high-dose atorvastatin on hospitalizations for heart failure: subgroup analysis of the Treating to New targets (TNT) Study. Circulation. 2007;115:576–583.
    1. Vyas AK, Guo H, Moss AJ, et al. Reduction in ventricular tachyarrhythmias with statins in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. J Am Coll Cardiol. 2006;47:769–773.
    1. Goldberger JJ, Subacius H, Schaechter A, et al. Effects of statin therapy on arrhythmic events and survival in patients with nonischemic dilated cardiomyopathy. J Am Coll Cardiol. 2006;48:1228–1233.
    1. The CORONA Investigators. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357:2248–2261.
    1. Gissi-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9645):1231–1239.
    1. Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009;53:e1–e90.
    1. 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. 2007;45(4):645–654.
    1. McDermott MM, Guralnik JM, Greenland P, et al. Statin use and leg functioning in patients with and without lower-extremity peripheral arterial disease. Circulation. 2003;107(5):757–761.
    1. Giri J, McDermott MM, Greenland P, et al. Statin use and functional decline in patients with and without peripheral arterial disease. J Am Coll Cardiol. 2006;47(5):998–1004.
    1. Mondillo S, Ballo P, Barbati R, et al. Effects of simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease. Am J Med. 2003;114(5):359–364.
    1. Aronow WS, Nayak D, Woodworth S, Ahn C. Effect of simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at six months and at one year after treatment. Am J Cardiol. 2003;92(6):711–712.
    1. Mohler ER, Hiatt WR, Creager MA. Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation. 2003;108(12):1481–1486.
    1. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 2006;113(11):e463–e654.
    1. The LIPID Study Group. Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose: results from the LIPID trial. Diabetes Care. 2003;26:2713–2721.
    1. 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. 2003;361:2005–2016.
    1. The CARDS Investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364:685–696.
    1. American Diabetes Association. Standards of medical care in diabetes – 2008. Diabetes Care. 2008;31:S12–S54.
    1. Cholesterol and Recurrent Events (CARE) Trial Investigators. Pravastatin for secondary prevention of cardiovascular events in persons with mild chronic renal insufficiency. Ann Intern Med. 2003;138(2):98–104.
    1. Chonchol M, Cook T, Kjekshus J, et al. Simvastatin for secondary prevention of all-cause mortality and major coronary events in patients with mild chronic renal insufficiency. Am J Kidney Dis. 2007;49(3):373–382.
    1. MEGA Study Group. Pravastatin and cardiovascular risk in moderate chronic kidney disease. Atherosclerosis. 2009;206(2):512–517.
    1. 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. 2009;(2):CD007784.
    1. German Diabetes and Dialysis Study Investigators. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353(3):238–248.
    1. AURORA Study Group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360(14):1395–1407.
    1. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Managing Dyslipidemias in Chronic Kidney Disease. Am J Kidney Dis. 2003;41:S1–S2.
    1. Ford I, Murray H, Packard CJ, et al. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med. 2007;357(15):1477–1486.
    1. Benner JS, Glynn RJ, Mogun H, et al. Long-term persistence in use of statin therapy in elderly patients. JAMA. 2002;288(4):455–461.
    1. 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(4):772–729.
    1. Shah ND, Dunlay SM, Ting HH, et al. Long-term medication adherence after myocardial infarction: experience of a community. Am J Med. 2009;122(10):e7–e13.
    1. Glader EL, Sjölander M, Eriksson M, Lundberg M. Persistent use of secondary preventive drugs declines rapidly during the first 2 years after stroke. Stroke. 2010;41(2):397–401.
    1. Donnelly LA, Doney AS, Morris AD, Palmer CN, Donnan PT. Longterm adherence to statin treatment in diabetes. Diabet Med. 2008;25(7):850–855.
    1. Thompson PD, Clarkson PM, Rosenson RS National Lipid Association Statin Safety Task Force Muscle Safety Expert Panel. An assessment of statin safety by muscle experts. Am J Cardiol. 2006;97:69C–76C.
    1. Yang Y, Thumula V, Pace PF, et al. Predictors of medication nonadherence among patients with diabetes in Medicare Part D programs: a retrospective cohort study. Clin Ther. 2009;31(10):2178–2188.
    1. Chan DC, Shrank WH, Cutler D, et al. Patient, physician, and payment predictors of statin adherence. Med Care. 2010;48(3):196–202.
    1. Mehta JL, Bursac Z, Hauer-Jensen M, Fort C, Fink LM. Comparison of mortality rates in statin users versus nonstatin users in a United States veteran population. Am J Cardiol. 2006;98(7):923–928.
    1. Brookhart MA, Patrick AR, Schneeweiss S, et al. Physician follow-up and provider continuity are associated with long-term medication adherence: a study of the dynamics of statin use. Arch Intern Med. 2007;167(8):847–852.
    1. Yam FK, Akers WS, Ferraris VA, et al. Interventions to improve guideline compliance following coronary artery bypass grafting. Surgery. 2006;140(4):541–547.
    1. Muhlestein JB, Horne BD, Bair TL, et al. Usefulness of in-hospital prescription of statin agents after angiographic diagnosis of coronary artery disease in improving continued compliance and reduced mortality. Am J Cardiol. 2001;87(3):257–261.
    1. Jelinek M, Vale MJ, Liew D, et al. The COACH program produces sustained improvements in cardiovascular risk factors and adherence to recommended medications-two years follow-up. Heart Lung Circ. 2009;18(6):388–392.
    1. Fonarow GC, Gawlinski A, Moughrabi S, Tillisch JH. Improved treatment of coronary heart disease by implementation of a Cardiac Hospitalization Atherosclerosis Management Program (CHAMP) Am J Cardiol. 2001;87(7):819–822.
    1. Eagle KA, Montoye CK, Riba AL, et al. Guideline-based standardized care is associated with substantially lower mortality in medicare patients with acute myocardial infarction: the American College of Cardiology’s Guidelines Applied in Practice (GAP) Projects in Michigan. J Am Coll Cardiol. 2005;46(7):1242–1248.
    1. Heidenreich PA, Lewis WR, LaBresh KA, Schwamm LH, Fonarow GC. Hospital performance recognition with the Get With The Guidelines Program and mortality for acute myocardial infarction and heart failure. Am Heart J. 2009;158(4):546–553.
    1. Lewis WR, Ellrodt AG, Peterson EH, et al. Trends in the use of evidence-based treatments for coronary artery disease among women and the elderly: findings from the get with the guidelines quality-improvement program. Circ Cardiovasc Qual Outcomes. 2009;2(6):633–641.
    1. Cohen MG, Fonarow GC, Peterson ED, et al. Racial and Ethnic Differences in the Treatment of Acute Myocardial Infarction. Findings From the Get With The Guidelines-Coronary Artery Disease Program. Circulation. 2010 May 17; [Epub ahead of print]
    1. Schwamm LH, Reeves MJ, Pan W, et al. Race/ethnicity, quality of care, and outcomes in ischemic stroke. Circulation. 2010;121(13):1492–501.
    1. Xian Y, Pan W, Peterson ED, et al. Are quality improvements associated with the Get With the Guidelines-Coronary Artery Disease (GWTGCAD) program sustained over time? A longitudinal comparison of GWTG-CAD hospitals versus non-GWTG-CAD hospitals. Am Heart J. 2010;159(2):207–214.
    1. Schneeweiss S, Patrick AR, Maclure M, Dormuth CR, Glynn RJ. Adherence to statin therapy under drug cost sharing in patients with and without acute myocardial infarction: a population-based natural experiment. Circulation. 2007;115(16):2128–2135.
    1. Choudhry NK, Patrick AR, Antman EM, Avorn J, Shrank WH. Cost-effectiveness of providing full drug coverage to increase medication adherence in post-myocardial infarction Medicare beneficiaries. Circulation. 2008;117(10):1261–1268.

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