Randomized Comparison of Intensified and Standard P2Y ₁₂ -Receptor-Inhibition Before Elective Percutaneous Coronary Intervention

Abstract

Background: Even among biomarker-negative patients undergoing elective percutaneous coronary intervention (PCI), periprocedural thrombotic and bleeding complications can lead to increased morbidity and mortality. Whether stronger platelet inhibition by an intensified oral loading strategy (ILS) before PCI impacts on outcomes among these patients in contemporary practice remains unclear. Methods: This multicenter, randomized, assessor-blinded trial tested the hypothesis that in elective PCI prasugrel 60 mg (ILS) is superior to standard loading strategy with clopidogrel 600 mg regarding a composite primary end point of all-cause death, any myocardial infarction, definite/probable stent thrombosis, stroke, or urgent vessel revascularization. After PCI, all patients were on clopidogrel 75 mg/day and aspirin. The trial was terminated prematurely because of slower-than-expected recruitment and funding discontinuation. Results: Of 781 patients included in the final analysis, 382 were assigned to ILS and 399 to standard loading strategy. At 30 days, the primary end point occurred in 66 patients (17.3%) assigned to ILS and 74 patients (18.6%) assigned to standard loading strategy (odds ratio, 0.92 [95% CI, 0.63–1.32]; P =0.64). Any myocardial infarction and Bleeding Academic Research Consortium ≥2 bleeding rates were similar among ILS and standard loading strategy groups 16.2% versus 17.5%, odds ratio, 0.91 (95% CI, 0.62–1.32), P =0.62 and 4.2% versus 4.8%, odds ratio 0.87 (95% CI, 0.44–1.73), P =0.70, respectively. Conclusions: In biomarker-negative stable and unstable angina patients undergoing elective PCI, the trial did not find a conclusive difference in efficacy or safety. This observation should be interpreted in the context of wide CIs and premature termination of the trial. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02548611.

Prognostically relevant periprocedural myocardial injury and infarction associated with percutaneous coronary interventions: a Consensus Document of the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI)

“…The 2017 ESC focused update on dual anti-platelet therapy (DAPT) in CAD recommends clopidogrel (600 mg loading dose, 75 mg daily dose) in addition to aspirin in CCS patients undergoing planned PCI (IA recommendation). 94 This is supported by recent studies in CCS patients undergoing PCI reporting that pre-treatment with the potent platelet P2Y 12 inhibitors ticagrelor (pre-PCI and daily for 30 days) 95 or prasugrel (pre-PCI only), 96 did not reduce periprocedural myocardial injury or MI, with ticagrelor being associated with an increased risk of minor bleeding at 30 days, when compared with clopidogrel. For DAPT-naïve CCS patients who require PCI following diagnostic coronary angiography, it is probably advisable to delay PCI by >2 h or even to the next day, given that a 600 mg loading dose of clopidogrel acts in ∼2 h. However, in those rare instances where ad-hoc PCI is urgently required in DAPT-naïve CCS patients, oral loading with soluble aspirin and ticagrelor or crushed prasugrel may be considered given their faster onset of action (30 min), with clopidogrel given thereafter (600 mg loading dose, 75 mg daily dose).…”

Ticagrelor vs. Clopidogrel After Complex Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease

“…The increased risk of bleeding remains an important concern for patients treated with DAPT after stent implantation (26), especially in east Asian patients who have a higher risk of severe bleeding risk than the western population (27,28). In several previous studies enrolling east Asians, the benefits of stronger P2Y12 inhibitors were partly counterbalanced by an increased risk of bleeding events, which was related to a higher risk of mortality (29)(30)(31). The recommendations for use of ticagrelor over clopidogrel in patients with ACS are based on the clinical trials from western countries and need to be further validated in east Asians.…”

Periprocedural Antithrombotic Treatment in Complex Percutaneous Coronary Intervention

“…Interestingly, the authors proceeded to a pooled analysis of the available randomized trials of using a potent P2Y 12 inhibitors in elective PCI, the aforementioned ALPHEUS trial, and the SASSICAIA (Strategies of Loading With Prasugrel vs. Clopidogrel in PCI-Treated Bio-marker Negative Angina) trial, which concluded that the use of stronger ADP inhibitor was not translated to better ischemic outcomes (OR 1.01, 95% CI, 0.80-1.28, P = 0.94). 54,55 In aggregate, with the available data so far, it seems that clopidogrel remains the standard of care in patients undergoing elective PCI, even in those with a more complex feature. 54,56 Cangrelor, an intravenous reversible antagonist of the platelet P2Y 12 receptor, with a fast onset and offset of action, has been recommended as class IIb across the spectrum of patients with CAD who are naïve of P2Y 12 inhibitor undergoing PCI.…”