Aspirin, clopidogrel, and warfarin: is the combination appropriate and effective or inappropriate and too dangerous?
OBJECTIVE
To review the rationale, clinical practice guideline recommendations, and clinical trial data describing bleeding and clinical outcomes associated with the use of the combination of aspirin, a thienopyridine, and warfarin.


METHODS
An English-language literature search was conducted using MEDLINE (1966-March 2008) and the search terms aspirin, clopidogrel, ticlopidine, thienopyridine, warfarin, antiplatelet, anticoagulant, myocardial infarction, atrial fibrillation, and percutaneous coronary intervention (PCI). Additional references were identified by reviewing reference citations of articles retrieved.


METHODS
Applicable data were extracted from published reports and studies that included either clinical outcomes or adverse events.


RESULTS
Clinical guidelines recommend the combination of antiplatelets and anticoagulants based largely on writing committee consensus. To date, only one randomized clinical trial has evaluated the safety and efficacy of adding warfarin to dual antiplatelet therapy (ie, triple antithrombotic therapy). Other published data are from case series, observational studies, and case-controlled studies primarily of patients undergoing PCI with intracoronary stent placement. Four of 12 studies reported no increased risk of major bleeding events. In the other 8 studies, a 3- to 6-fold increase in bleeding events was reported with triple antithrombotic therapy. Ischemic events were reported in only 6 of the studies. Only 2 studies observed an additional benefit in the reduction of ischemic events, and 1 study reported worsened ischemic outcomes with the triple antithrombotic regimen compared with dual antithrombotic therapy.


CONCLUSIONS
Available guidelines pertaining to the concomitant administration of aspirin, a thienopyridine, and warfarin are based on limited trial data and consensus judgment. Overall, selection of triple antithrombotic therapy for patients with vascular disease is considered a matter of clinical judgment for an individual patient based on the prescriber's perceived balance between the patient's risk for recurrent ischemic events, expected duration of treatment, and patient's risk for bleeding.
Hermosillo
A Janelle
AJ
Department of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA.
Spinler
Sarah A
SA
D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000077144:Clopidogrel; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007511:Ischemia / Q000209:etiology / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D014652:Vascular Diseases / Q000188:drug therapy*; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin