Visits to the ED for AEs Related to Hemorrhage in Patients Receiving Dual Antiplatelet Therapy

For patients with cardiovascular disease, standard of care is dual antiplatelet therapy (DAT) with clopidogrel plus aspirin. DAT has demonstrated significant benefits in decreasing in-stent thrombosis and recurrent ischemic events following acute coronary syndrome in patients who have undergone percutaneous coronary intervention as well as those who have not. DAT has also recently gained increased attention as a potential alternative to warfarin in patients with nonvalvular atrial fibrillation who are at increased risk for thromboembolic complications but are not optimal candidates for warfarin therapy.

Hemorrhage is the chief adverse event (AE) of concern with DAT, but there have been few studies that describe the magnitude and nature of hemorrhage-related AEs from DAT. Researchers recently conducted an analysis of nationally representative surveillance data to estimate the frequency, rates, and nature of visits to emergency departments (EDs) for hemorrhagic and other related AEs attributed to clopidogrel plus aspirin therapy compared with those related to warfarin. They reported results in Archives of Internal Medicine [2010;170(21):1926-1933].

The current analysis utilized data from the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance (NEISS-CADES) project; data from 58 participating nonpediatric hospitals in the United States. In the NEISS-CADES project, trained coders reviewed clinical records of every ED visit to identify physician-diagnosed adverse drug events (ADEs) and report up to 2 medications implicated in each ADE as well as any concomitant medications listed in the medical record. An ADE case was defined as an incident ED visit by a patient <17 years of age between January 1, 2006, and December 31, 2008, with the following criteria: (1) clopidogrel, aspirin, or warfarin implicated in the visit; (2) the ED visit the result of an unintentional overdose from an antiplatelet or anticoagulant agent or workup for hemorrhage in a patient receiving an antiplatelet or anticoagulant.

Based on 384 NEISS-CADES cases, an estimated 7654 ED visits (95% confidence interval [CI], 3325-11,983) were made each year for hemorrhage-related AEs by patients receiving clopidogrel plus aspirin, compared with an estimated 60,575 visits to the ED made each year by patients receiving warfarin (95% CI, 36,117-85,033), based on 2926 NEISS-CADES cases. The median age of ED patients taking clopidogrel plus aspirin was 73 years; for patients taking warfarin, the median age was 75 years. For both groups, the number of ED visits related to hemorrhage-related AEs increased with age. Of visits involving clopidogrel plus aspirin, 46.9% were female, compared with 53.6% of those involving warfarin. Among patients taking clopidogrel plus aspirin, nearly 100% of ED visits for AEs related to hemorrhage were for acute hemorrhages, compared with two thirds of ED visits for warfarin complications. The remaining one third of ED visits for warfarin complications were for abnormalities in laboratory coagulation variables with no evidence of hemorrhage, for evaluation of potential hemorrhage from a fall or injury while taking warfarin, and for other toxic effects.

Overall, approximately 60% of ED visits related to DAT consisted of epistaxis, skin, or other minor hemorrhages for patients taking clopidogrel plus aspirin and for patients taking warfarin. When only ED visits for acute hemorrhage were considered, there was no significant difference between clopidogrel plus aspirin and warfarin in the risk of hospitalization for ED visits involving acute hemorrhage. After adjusting for frequency of prescribing, the estimated rate of ED visits for AEs related to hemorrhage was approximately 3 times higher for patients taking warfarin versus patients taking clopidogrel plus aspirin (3.7 vs 1.2 ED visits per 1000 outpatient prescription visits). For ED visits for acute hemorrhage, the rate for patients taking warfarin was 2.5 per 1000 outpatient prescription visits compared with 1.2 per 1000 outpatient prescription visits for patients taking clopidogrel plus aspirin. In summary, the researchers stated: “These findings indicate that the acute hemorrhagic risk with DAT is clinically significant and reinforce the importance of practitioners and patients recognizing and anticipating this risk.”