Clopidogrel

Comparative studies

The combination of clopidogrel + aspirin has been explored in the management of atherothrombosis with clopidogrel in high-risk patients trial, and compared with clopidogrel alone for secondary prevention in patients with transient ischemic attacks and strokes in a population with a high prevalence of other vascular risk factors. There was a non-significant trend towards a reduction in the combined end-point of ischemic stroke, myocardial infarction, vascular death, and rehospitalization in the combination therapy group [ ]. However, the frequency of life-threatening bleeding was almost doubled in the combination arm.

Drug-combination studies

The use of the combination of aspirin plus a thienopyridine and warfarin has been subjected to systematic review [ ]. One randomized clinical trial has evaluated the safety and efficacy of adding warfarin to dual antiplatelet therapy; other published data are from case series, observational studies, and case–control studies, primarily of patients undergoing percutaneous coronary intervention with intracoronary stenting. Four of 12 studies reported no increased risk of major bleeding events. In the other eight studies, there was a 3- to 6-fold increase in bleeding events with triple antithrombotic therapy. Ischemic events were reported in only six of the studies. In only two studies was there additional benefit from a reduced incidence of ischemic events; in one study there were worse ischemic outcomes with the triple regimen compared with dual therapy. The authors concluded that there is little evidence to support the combined use of aspirin, a thienopyridine, and warfarin.

Sensory systems

Psychiatric

Hallucinations have been attributed to clopidogrel [ ].

• A 58-year-old-man who underwent coronary angiography was treated with a stent and was given a loading dose of clopidogrel 600 mg followed by 75 mg/day. His other medications included atorvastatin, bisoprolol, furosemide, gabapentin, insulin, isosorbide mononitrate, metformin, and ramipril. Within 48 hours of the start of clopidogrel therapy he reported visual hallucinations, described as visions of ghostly apparitions walking past him. He stopped taking the clopidogrel and within 24 hours the hallucinations resolved. Ticlopidine was given instead and the hallucinations did not recur.

Hematologic

The adverse effects of clopidogrel have been reviewed [ ], and it has been suggested that the risks of aplastic anemia, thrombocytopenia, and neutropenia have been underestimated [ ]. Anecdotal reports of these adverse effects continue to appear [ ].

Thrombotic thrombocytopenic purpura has been attributed to clopidogrel in an 80-year-old woman who had taken clopidogrel for 4 days [ ].