Abstract
Current guidelines recommend initiation of a P2Y12 inhibitor for all patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) at the time of diagnosis (pre-treatment); however, there are no randomized trials directly comparing pre-treatment with initiation at the time of angiography to support this practice. We explore clinical and institutional parameters potentially associated with benefit with this strategy in a decision-analytic model based on available evidence from randomised trials. A decision analysis model was constructed comparing three P2Y12 inhibitors in addition to aspirin in patients with NSTE-ACS. Based on clinical trial data, the cumulative probability of 30 day mortality, myocardial infarction (MI) and major bleeding were determined, and used to calculate the net clinical benefit (NCB) with and without pre-treatment. Sensitivity analysis was performed to assess the relationship between NCB and baseline ischemic risk, bleeding risk, time to angiography and local surgical revascularization rates. Pre-treatment with ticagrelor and clopidogrel was associated with a greater than 50% likelihood of providing a >1% increase in 30 day NCB when baseline estimated ischemic risk exceeds 11% and 14%, respectively. Prasugrel pre-treatment did not achieve a greater than 50% probability of an increase in NCB regardless of baseline ischemic risk. Institutional surgical revascularization rates and time to coronary angiography did not correlate with the likelihood of benefit from P2Y12 pre-treatment. In conclusion, pre-treatment with P2Y12 inhibition is unlikely to be beneficial to the majority of patients presenting with NSTE-ACS. A tailored assessment of each patient’s individual ischemic and bleeding risk may identify those likely to benefit.
Highlights
Pre-treatment with anti-platelet agents, the co-administration of aspirin and a second agent such as P2Y12 or glycoprotein IIb/IIIa inhibitors prior to coronary angiography in patients with acute coronary syndromes without ST elevation, remains a complex and controversial topic in the current era [1,2]
Pre-treatment with P2Y12 inhibition is unlikely to be beneficial to the majority of patients presenting with NSTE-ACS
To estimate the overall benefit of the strategy, we report the net benefit of pre-treatment with each of the P2Y12 inhibitors, calculated as the absolute reduction in a 30 day ischemic event rate minus the absolute increase in bleeding event rate, (i.e., net clinical benefit (NCB))
Summary
Pre-treatment with anti-platelet agents, the co-administration of aspirin and a second agent such as P2Y12 or glycoprotein IIb/IIIa inhibitors prior to coronary angiography in patients with acute coronary syndromes without ST elevation, remains a complex and controversial topic in the current era [1,2]. The net benefit of pre-treatment is a balance between a reduction in ischemic events versus an increase in bleeding complications. The ‘Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention (PCI) or as Pre-treatment at the Time of Diagnosis in Patients with Non-ST Elevation Myocardial Infarction’ (ACCOAST) study is the only contemporary randomised trial of the timing of administration of a second antiplatelet agent in patients with non-ST elevation acute coronary syndromes [11]. Given the evidence gap in this area, we applied a decision-analytic model based on the available evidence from randomised trials to explore the possible clinical and institutional factors that may be associated with greater benefit with a pre-treatment strategy
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