Cardiovascular outcomes trials with statins in diabetes
DOI:
https://doi.org/10.15277/bjd.2018.161Keywords:
diabetes, hypercholesterolaemia, lipids, statins, cardiovascular diseaseAbstract
Treatment with statins is one of the most effective ways of reducing cardiovascular events in those with diabetes. Many studies containing thousands of subjects with diabetes have demonstrated that statins reduce cardiovascular events when there is no known cardiovascular disease (primary prevention) and in those with confirmed atherosclerotic disease (secondary prevention). High-dose statins appear to be even more effective in established cardiovascular disease, but at the expense of increased drug side effects. In this paper we review the evidence for the benefits of statins in diabetes. In a second review we will examine the evidence for possible benefits of other lipid-lowering therapies when these are added to background statin therapy in diabetes.
References
Verges B. Pathophysiology of diabetic dyslipidaemia: where are we? Diabetologia 2015;58:886–99. http://dx.doi.org/10.1007/s00125-015-3525-8
Verges B. Lipid disorders in type 1 diabetes. Diabetes Metab 2009; 35:353–60. http://dx.doi.org/10.1016/j.diabet.2009.04.004
Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010;375:2215–22. http://dx.doi.org/10.1016/S0140-6736(10)60484-9.
Colhoun HM, Betteridge DJ, Durrington PN, et al, on behalf of 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;364:685–96.
Knopp RH, d’Emden M, Smilde JG, Pocock SJ, on behalf of the ASPEN Study Group. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care 2006;29: 1478–85. http://dx.doi.org/10.2337/dc05-2415
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;360:7–22.
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;361:2005–16.
ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLA). JAMA 2002;288:2998–3007.
Sever PS, Dahlöf B, Poulter NR, et al, for the ASCOT Investigators. 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;361:1149–58.
Sever PS, Poulter NR, Dahlöf B, et al, for the ASCOT Investigators. Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes. Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA). Diabetes Care 2005;28:1151–7.
Nakamura H, Arakawa K, Itakura H, et al, for the MEGA Study Group. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet 2006;368:1155–63. http://dx.doi.org/10.1016/S0140-6736(06)69472-5
Nishimura R, Sone H, Nakagami T, Tajima N. Importance of high-density lipoprotein cholesterol control during pravastatin treatment in hypercholesterolemic Japanese with type 2 diabetes: a post hoc analysis of MEGA study. Diabetes Res Clin Pract 2013;100:e31–3. http://dx.doi.org/10.1016/j.diabres.2013.02.003.
Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease : the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–9.
Pyörälä K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care 1997; 20:614–20.
Haffner SM, Alexander CM, Cook TJ, et al, for the Scandinavian Simvastatin Survival Study Group. Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels. Arch Intern Med 1999;159:2661–7.
Sacks FM, Pfeffer MA, Moye LA, et al, for the Cholesterol And Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001–09.
Goldberg RB, Mellies MJ, Sacks FM, et al, for the CARE Investigators. Cardiovascular events and their reduction with pravastatin in diabetic and glucose intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the Cholesterol And Recurrent Events (CARE) trial. Circulation 1998;98:2513–19.
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;339:1349–57.
Keech A, Colquhoun D, Best J, et al, for the LIPID Study Group. Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasing glucose: results from the LIPID trial. Diabetes Care 2003;26:2713–21.
Mark PB, Winocour P, Day C. Management of lipids in adults with diabetes mellitus and nephropathy and/or chronic kidney disease: summary of joint guidance from the Association of British Clinical Diabetologists (ABCD) and the Renal Association (RA). Br J Diabetes 2017;17:64–72. http://dx.doi.org/10.15277/bjd.2017.125
Wanner C, Krane V, Marz W, et al, for the German Diabetes and Dialysis Study Investigators. Atorvastatin in patients with type 2 diabetes undergoing hemodialysis. N Engl J Med 2005;353:238–48. http://dx.doi.org/10.1056/NEJMoa043545
Krane V, Schmidt K-R, Gatjahr-Lengsfled LJ, et al, for the 4D study investigators (the German Diabetes and Dialysis Study investigators). Long-term effects following 4 years of randomized treatment with atorvastatin in patients with type 2 diabetes on hemodialysis. Kidney Int 2016;89:1380–7. http://dx.doi.org/10.1016/j.kint.2015.12.033
The Stoke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549–59.
Callahan A, Amerenco P, Goldstein LB, et al, for the SPARCL Investigators. Risk of stroke and cardiovascular events after ischemic stroke or transient ischemic attack in patients with type 2 diabetes or metabolic syndrome. Arch Neurol 2011;68:1245–51. http://dx.doi.org/10.1001/archneurol.2011.146
Cannon CP, Braunwald E, McCabe CH, et al, for the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus conventional lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350:1495–504. http://dx.doi.org/10.1056/NEJMoa040583
Ahmed S, Cannon CP, Murphy SA, Braunwald E. Acute coronary syndromes and diabetes: is intensive lipid lowering beneficial? Results of PROVE IT-TIMI 22. Eur Heart J 2006;27:2323–9. http://dx.doi.org/10.1093/eurheartj/ehl220
LaRosa JC, Grundy SM, Waters DD, et al. for the Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425–35. http://dx.doi.org/10.1056/NEJMoa050461
Shepherd J, Barter P, Carmena R, et al, for the Treating to New Targets Investigators. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating To New Targets (TNT) study. Diabetes Care 2006;29:1220–6. http://dx.doi.org/10.2337/dc05-2465
de Lemos JA, Blazing MA, Wiviott SD, et al, for the A to Z Investigators. Early intensive vs delayed conservative simvastatin strategy in patients with acute conronary syndromes: phase Z of the A to Z trial. JAMA 2004;292:1307–16.
Pedersen TR, Faergeman O, Kastelein JJP, et al, for the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Study Group. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction. The IDEAL study: a randmized controlled trial. JAMA 2005;294:2437–45.
Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction: a double-blind randomised trial. Lancet 2010;376:1658–69. http://dx.doi.org/10.1016/S0140-6736(10)60310-8.
Cholesterol Treatment Trialists' (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005; 366:1267–78. http://dx.doi.org/10.1016/S0140-6736(05)67394-1
Downs JR, Clearfield M, Weis S, et al, for the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA 1998;279:1615–22.
Shepherd J, Blauw GJ, Murphy MB, et al, on behalf of the PROSPER Study Group. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623–30.
Shepherd J, Cobbe CM, Ford I, et al, for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333:1301–07.
GISSI Prevenzione Investigators. Results of the low-dose (20 mg) pravastain GISSI Prevenzione trial in 4271 patients with recent myocardial infarction: do stopped trials contribute to overall knowledge? Ital Heart J 2000;1:810–20.
Serruys PW, de Feyter P, Macaya C, et al, for the Lescol Intervention Prevention Study (LIPS) Investigators. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;287:3215–22.
The Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary bypass grafts. N Engl J Med 1997;336:153–62.
Holdaas H, Fellstrom B, Jardine AJ, et al, on behalf of the Assessment of Lescol in Renal Trnasplantation (ALERT) Study Investigators. Effect of fluvastatin on cardiac outcomes in renal transplant receipients: a multicentre, randomised, placebo-controlled trial. Lancet 2003;361:2024–31. http://dx.doi.org/10.1016/S0140-6736(03)13638-0
Cholesterol Treatment Trialists' (CTT) Collaborators. Efficacy of cholesterol-lowering therapy in 18 686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008;371:117–25. http://dx.doi.org/10.1016/S0140-6736(08)60104-X
Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet 2010;376: 1670–81. http://dx.doi.org/10.1016/S0140-6736(10)61350-5
Chen Y-H, Feng B, Chen Z-W. Statins for primary prevention of cardiovascular and cerebrovascular events in diabetic patients without established cardiovascular disease: a meta-analysis. Exp Clin Endocrinol Diabetes 2012;120:116–20. http://dx.doi.org/10.1055/s-0031-1297968
Chang Y-H, Hsieh M-C, Wang C-Y, Lin K-C, Lee Y-J. Reassessing the benefits of statins in the prevention of cardiovascular disease in diabetic patients: a systemetic review and meta-analysis. Rev Diabet Studies 2013;10:157–70. http://dx.doi.org/10.1900/RDS.2013.10.157
de Vries FM, Kolthof J, Postma MJ, Denig P, Hak E. Efficacy of standard and intensive statin treatment for the secondary prevention of cardiovascular and cerebrovascular events in diabetes patients: a meta-analysis. Plos One 2014;9:e111247. http://dx.doi.org/10.1371/journal.pone.0111247
Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010;375:735–42. http://dx.doi.org/10.1016/S0140-6736(09)61965-6
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 2011;305:2556–64. http://dx.doi.org/10.1001/jama.2011.860
Erqou S, Lee CC, Adler AI. Statins and glycaemic control in individuals with diabetes: a systematic review and meta-analysis. Diabetologia 2014;57:2444–52. http://dx.doi.org/10.1007/s00125-014-3374-x.
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