Bleeding Complications With Dual Antiplatelet Therapy Among Patients With Stable Vascular Disease or Risk Factors for Vascular Disease
- 15 June 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 121 (23), 2575-2583
- https://doi.org/10.1161/circulationaha.109.895342
Abstract
Background— Uncertainty exists about the frequency, correlates, and clinical significance of bleeding with dual antiplatelet therapy (DAPT), particularly over an extended period in a stable population. We sought to determine the frequency and time course of bleeding with DAPT in patients with established vascular disease or risk factors only; identify correlates of bleeding; and determine whether bleeding is associated with mortality. Methods and Results— We analyzed 15 603 patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial, a double-blind, placebo-controlled, randomized trial comparing long-term clopidogrel 75 mg/d versus placebo; all patients received aspirin (75 to 162 mg) daily. Patients had either established stable vascular disease or multiple risk factors for vascular disease without established disease. Median follow-up was 28 months. Bleeding was assessed with the use of the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) criteria. Severe bleeding occurred in 1.7% of the clopidogrel group versus 1.3% on placebo ( P =0.087); moderate bleeding occurred in 2.1% versus 1.3%, respectively ( P P P P Conclusions— In CHARISMA, there was an increased risk of bleeding with long-term clopidogrel. The incremental risk of bleeding was greatest in the first year and similar thereafter. Moderate bleeding was strongly associated with mortality. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00050817.Keywords
This publication has 13 references indexed in Scilit:
- Prasugrel versus Clopidogrel in Patients with Acute Coronary SyndromesNew England Journal of Medicine, 2007
- Variation in the definitions of bleeding in clinical trials of patients with acute coronary syndromes and undergoing percutaneous coronary interventions and its impact on the apparent safety of antithrombotic drugsAmerican Heart Journal, 2007
- Patients With Prior Myocardial Infarction, Stroke, or Symptomatic Peripheral Arterial Disease in the CHARISMA TrialJournal of the American College of Cardiology, 2007
- Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery StentsCirculation, 2007
- Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic EventsNew England Journal of Medicine, 2006
- Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trialThe Lancet, 2005
- Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction with ST-Segment ElevationNew England Journal of Medicine, 2005
- Early and Sustained Dual Oral Antiplatelet Therapy Following Percutaneous Coronary InterventionJAMA, 2002
- Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without ST-Segment ElevationNew England Journal of Medicine, 2001
- An International Randomized Trial Comparing Four Thrombolytic Strategies for Acute Myocardial InfarctionNew England Journal of Medicine, 1993