Vorapaxar in Patients With Diabetes Mellitus and Previous Myocardial Infarction

Background— Vorapaxar reduces cardiovascular death, myocardial infarction (MI), or stroke in patients with previous MI while increasing bleeding. Patients with diabetes mellitus (DM) are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 trial was a randomized, double-blind, placebo-controlled trial of vorapaxar in patients with stable atherosclerosis. Methods and Results— We examined the efficacy of vorapaxar in patients with and without DM who qualified for the trial with a previous MI. Because vorapaxar is contraindicated in patients with a history of stroke or transient ischemic attack, the analysis (n=16 896) excluded such patients. The primary end point of cardiovascular death, MI, or stroke occurred more frequently in patients with DM than in patients without DM (rates in placebo group: 14.3% versus 7.6%; adjusted hazard ratio, 1.47; P<0.001). In patients with DM (n=3623), vorapaxar significantly reduced the primary end point (11.4% versus 14.3%; hazard ratio, 0.73 [95% confidence interval, 0.60–0.89]; P=0.002) with a number needed to treat to avoid 1 major cardiovascular event of 29. The incidence of moderate/severe bleeding was increased with vorapaxar in patients with DM (4.4% versus 2.6%; hazard ratio, 1.60 [95% confidence interval, 1.07–2.40]). However, net clinical outcome integrating these 2 end points (efficacy and safety) was improved with vorapaxar (hazard ratio, 0.79 [95% confidence interval, 0.67–0.93]). Conclusions— In patients with previous MI and DM, the addition of vorapaxar to standard therapy significantly reduced the risk of major vascular events with greater potential for absolute benefit in this group at high risk of recurrent ischemic events. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00526474.

[1]  Masafumi Ueno,et al.  Impaired responsiveness to the platelet P2Y12 receptor antagonist clopidogrel in patients with type 2 diabetes and coronary artery disease. , 2014, Journal of the American College of Cardiology.

[2]  Marc P. Bonaca,et al.  Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2°P-TIMI 50 trial , 2012, The Lancet.

[3]  D. Waters,et al.  Determinants of Residual Risk in Secondary Prevention Patients Treated With High- Versus Low-Dose Statin Therapy: The Treating to New Targets (TNT) Study , 2012, Circulation.

[4]  Marc P. Bonaca,et al.  Vorapaxar in the secondary prevention of atherothrombotic events. , 2012, The New England journal of medicine.

[5]  D. Angiolillo,et al.  Diabetes and Antiplatelet Therapy in Acute Coronary Syndrome , 2011, Circulation.

[6]  Deepak L. Bhatt,et al.  Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. , 2010, JAMA.

[7]  S. Stevens,et al.  Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial , 2010, European heart journal.

[8]  Marc P. Bonaca,et al.  Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P)-TIMI 50 trial. , 2009, American heart journal.

[9]  Sunil V. Rao,et al.  Major bleeding: management and risk reduction in acute coronary syndromes , 2008, Expert opinion on pharmacotherapy.

[10]  E. Antman,et al.  Effect of enoxaparin versus unfractionated heparin in diabetic patients with ST-elevation myocardial infarction in the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction study 25 (ExTRACT-TIMI 25) trial. , 2007, American heart journal.

[11]  Christopher P Cannon,et al.  Diabetes and mortality following acute coronary syndromes. , 2007, JAMA.

[12]  Michael J Pencina,et al.  Increasing Cardiovascular Disease Burden Due to Diabetes Mellitus: The Framingham Heart Study , 2007, Circulation.

[13]  John Robbins,et al.  National cross sectional survey to determine whether the decision to delivery interval is critical in emergency caesarean section , 2004, BMJ : British Medical Journal.

[14]  R. Nesto,et al.  The platelet in diabetes: focus on prevention of ischemic events. , 2003, Diabetes care.

[15]  M. Sabatine,et al.  Will diabetes save the platelet blockers? , 2001, Circulation.

[16]  Deepak L. Bhatt,et al.  Platelet Glycoprotein IIb/IIIa Inhibitors Reduce Mortality in Diabetic Patients With Non–ST-Segment-Elevation Acute Coronary Syndromes , 2001, Circulation.

[17]  Deepak L. Bhatt,et al.  Abciximab reduces mortality in diabetics following percutaneous coronary intervention. , 2000, Journal of the American College of Cardiology.

[18]  G. Moneta.  Comparative Determinants of 4-Year Cardiovascular Event Rates in Stable Outpatients at Risk of or With Atherothrombosis , 2011 .

[19]  Caroline A Milton,et al.  For personal use. Only reproduce with permission from The Lancet Publishing Group. Late cardiopulmonary complication of ventriculo-atrial shunt , 2001 .

[20]  Teven,et al.  MORTALITY FROM CORONARY HEART DISEASE IN SUBJECTS WITH TYPE 2 DIABETES AND IN NONDIABETIC SUBJECTS WITH AND WITHOUT PRIOR MYOCARDIAL INFARCTION , 2000 .

[21]  Ken W. Woodhouse,et al.  The Clinical Perspective , 1994 .