Outcomes associated with combined antiplatelet and anticoagulant therapy.
BACKGROUND
The use of antiplatelet therapy in combination with oral anticoagulants remains controversial. The objective of this study was to estimate and compare the incidence of adverse and coronary event rates between patients receiving warfarin monotherapy or warfarin and antiplatelet combination therapy.


METHODS
This was a retrospective, longitudinal, pharmacoepidemiologic analysis. Adult patients receiving warfarin managed by an anticoagulation service who had documented the use of antiplatelet agents (eg, aspirin, clopidogrel, and/or dipyridamole) [ie, the combination-therapy cohort] or their nonuse (ie, the monotherapy cohort) were identified as of September 30, 2005. Utilizing integrated, electronic medical records, anticoagulation-related adverse events (eg, death, hemorrhage, or thrombosis) and coronary events were identified during a 6-month follow-up period (October 2005 through March 2006). The proportions of events were compared between cohorts. Independent associations between the cohorts and the outcomes were assessed with adjustment for potential confounding factors.


RESULTS
Data from 2,560 patients in the monotherapy cohort and 1,623 patients in the combination-therapy cohort were analyzed. Patients in the combination-therapy cohort were more likely to have had anticoagulation-related hemorrhages (4.2% vs 2.0%, respectively; unadjusted p < 0.001) and coronary events (0.9% vs 0.3%, respectively; p = 0.009), but not death (0.1% vs 0.2%, respectively; unadjusted p = 0.186) or thrombotic events (0.3% vs 0.4%, respectively; unadjusted p = 0.812). With adjustment, combined warfarin and antiplatelet use was independently associated with hemorrhagic events (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.44 to 5.28), but not with coronary events (OR, 0.99; 95% CI, 0.37 to 2.62).


CONCLUSIONS
At the population level, the hemorrhagic risk associated with warfarin therapy combined with antiplatelet therapy appears to outweigh the benefits. These findings suggest that clinicians should carefully consider the risks and benefits when recommending combined antiplatelet therapy for patients receiving warfarin who do not meet the evidence-based criteria for such therapy.
Johnson
Samuel G
SG
Kaiser Permanente Colorado Region, Clinical Pharmacy Services, Aurora, CO 80011, USA. samuel.g.johnson@kp.org
Rogers
Kristina
K
Delate
Thomas
T
Witt
Daniel M
DM
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D000077144:Clopidogrel; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004176:Dipyridamole / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D013923:Thromboembolism / Q000139:chemically induced*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D004176:Dipyridamole; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin