Clopidogrel in-laboratory versus outpatient preloading in chronic coronary syndrome patients undergoing diagnostic coronary angiography with potential ad-hoc percutaneous coronary intervention

Background In chronic coronary syndrome (CCS) patients undergoing diagnostic coronary angiography (CAG), angiographic findings guide the decision to perform an ad-hoc percutaneous coronary intervention (PCI). In contemporary practice, clopidogrel is initiated either several days before CAG (outpatient preloading) or administered as a loading dose in the catheterization laboratory directly before PCI. Currently, no clear consensus exists regarding the optimal timing for clopidogrel initiation for CCS patients undergoing a diagnostic CAG. Purpose To evaluate whether in-laboratory clopidogrel loading is noninferior to outpatient preloading of clopidogrel at -3 days in CCS patients who are planned to undergo diagnostic CAG with optional ad-hoc PCI. Methods In this prospective monthly cluster randomization trial, the rates of net adverse clinical events (NACE, a composite of all-cause mortality, myocardial infarction, definite/probable stent thrombosis, stroke and bleeding academic research consortium type 2, 3 or 5 bleeding) within 30 days were compared between patients with an outpatient preloading strategy vs an in-laboratory loading strategy. In-laboratory loading consisted of a 600mg clopidogrel loading dose in the catheterization laboratory in case of an ad-hoc PCI. Preloading was defined as a 300mg clopidogrel loading dose on day -3, followed by 75mg clopidogrel daily until the day of CAG (day 0). Secondary endpoints included NACE at 30 days in the overall cohort and a pre-specified interaction analysis for high bleeding risk (HBR), as defined as an Academic Research Consortium HBR score ≥2. We determined that inclusion of 1462 patients would be needed to demonstrate noninferiority (80% power, margin 4%). The study was prematurely terminated after 2.5 years and the inclusion of 768 patients due to slow recruitment. Results Of 768 patients included (in-laboratory loading n=408, preloading n=360, mean age 66 years, 32% female), 98% completed the 30-day follow-up. HBR was observed in 17% (in-laboratory 19% vs preloading 15%). Rates of performed PCI were similar (in-laboratory 36% vs preloading 34%, p=0.53). At 30-day follow-up, the incidence of NACE was comparable between the in-hospital and the preloading group in patients who underwent PCI (Fig A). Similarly, NACE, as well as its individual endpoint rates did not differ significantly in the overall cohort undergoing diagnostic CAG (in-laboratory 7% vs preloading 10%, OR 0.69 [0.40–1.16 95% CI], p=0.16). No significant interaction was observed between HBR status and clopidogrel loading strategy (p-interaction 0.74). Conclusions Among CCS patients undergoing diagnostic CAG with potential ad-hoc PCI, in-laboratory loading was not associated with an increased incidence of NACE, as compared to outpatient preloading of clopidogrel. These findings suggest that in-laboratory loading of clopidogrel may represent a safe and more selective alternative to routine outpatient preloading.