Results of a pivotal trial comparing prasugrel with clopidogrel demonstrated a reduced rate of ischemic events in patients who received prasugrel after percutaneous coronary intervention (PCI). The prasugreltreated group experienced higher rates of bleeding, however, including fatal bleeding.
The study of 13,608 moderate-tohigh risk patients scheduled for PCI compared a regimen of prasugrel (60-mg loading dose and 10-mg daily maintenance dose) with clopidogrel (300-mg loading dose and 75-mg daily maintenance dose) given for 6 to 15 months. The primary efficacy end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The key safety end point was major bleeding.
The primary efficacy end point occurred in 12.1% of patients receiving clopidogrel and 9.9% of patients receiving prasugrel. Significant reductions occured in the prasugrel group in the rates of secondary end points. Major bleeding was observed in 2.4% of patients receiving prasugrel and in 1.8% of patients receiving clopidogrel. Also greater in the prasugrel group was the rate of lifethreatening bleeding.
Publication of these results comes on the heels of the suspension of 2 small, early-phase clinical trials of prasugrel because of concerns related to the need for dosing adjustments in certain populations. The manufacturer, Eli Lilly and Co, expects patient enrollment to resume once the protocols are amended and approved by institutional review boards.
Twenty-three trials (n = 113,494 participants) were identified. Overall, compared with placebo, aspirin reduced the risk of nonfatal MI but not fatal MI. A total of 27% of the variation in the nonfatal MI results could be accounted for by considering the gender mix of the trials. Trials that recruited predominantly men demonstrated the largest risk reduction in nonfatal MI, whereas trials that contained predominantly women failed to demonstrate a significant risk reduction in nonfatal MI. The authors concluded that gender accounts for a substantial proportion of the variability in the efficacy of aspirin in reducing MI rates across these trials.
Temporary interruption of warfarin therapy for invasive procedures does not appear to pose a significant risk of thromboembolism. In a recent study of 1024 patients, warfarin was withheld for varying periods (usually .5 days). Perioperative bridging therapy with heparin or low-molecular-weight heparin was used in 8.3% of cases.
Seven of 1024 patients, none of whom received bridging therapy, experienced a thromboembolic event within 30 days of their procedure. Six patients experienced major bleeding, whereas an additional 17 patients experienced clinically significant, nonmajor bleeding. Of these 23 patients, 14 received periprocedural heparin or lowmolecular- weight heparin. The authors concluded that the risk of thromboembolism is low with warfarin interruption and that this risk should be weighed against the risk of bleeding before administration of bridging therapy.
A decrease in anticoagulation control was observed on transition to physician-managed care. Prior to the transition, 76% of all INRs were in target range, versus 48% after transition. The number of INRs obtained that were >4.5 and <1.5 also was significantly higher. The number of emergency department (ED) or office visits related to anticoagulation while under a pharmacist's care was very low (2) but increased to 13 (7 office visits, 6 ED visits) after patients were discharged back to their physician. None of the episodes resulted in hospitalization. Patient satisfaction with clinical care provided by the anticoagulation clinic was significantly higher before transition.