Clopidogrel reloading in patients undergoing percutaneous coronary intervention on chronic clopidogrel therapy: results of the ARMYDA-4 RELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) randomized trial†

To evaluate safety and effectiveness of clopidogrel reloading in patients on chronic clopidogrel therapy undergoing percutaneous coronary intervention (PCI). Five hundred and three patients on > 10 days clopidogrel therapy (41% with non-ST-segment elevation acute coronary syndrome, ACS) randomly received 600 mg clopidogrel loading 4-8 h before PCI (n = 252) or placebo (n = 251). Primary endpoint was 30-day incidence of major adverse cardiac events (MACE). In the overall population primary endpoint occurred in 6.7% of patients in the reload vs. 8.8% in the placebo arm [odds ratios (OR) 0.75, 95% confidence intervals (CI) 0.37-1.52; P = 0.50]. In stable angina patients, 1-month MACE were not significantly different (7.0 vs. 3.9%; OR 1.84, 0.60-5.88; P = 0.36), whereas ACS patients had significant clinical benefit with reloading (6.4 vs. 16.3%; OR 0.34, 95% CI 0.32-0.90, P = 0.033 at multivariable analysis; interaction test: P = 0.01). There was no excess bleeding in the reload arm (6% in both groups). ARMYDA-4 RELOAD reveals no overall benefit from reloading patients on chronic clopidogrel therapy prior to PCI; the benefit observed in ACS patients is a hypothesis-generating finding that needs to be confirmed by larger studies.