P2Y12 Inhibitor Pre-Treatment in Non-ST-Elevation Acute Coronary Syndrome: A Decision-Analytic Model

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.

Keywords: cardiac catheterization and angiography; non-ST segment myocardial infarction; percutaneous coronary intervention.

Figure 1

Decision tree representing the outcomes in the Monte Carlo model during the 30 day cycle. DAPT = Dual anti-platelet therapy, CABG = Coronary artery bypass graft, PCI = Percutaneous coronary intervention.

Figure 2

Estimated probability of achieving a positive 30 day Net Clinical Benefit (NCB) from pre-treatment with (A) clopidogrel; (B) ticagrelor and (C) prasugrel at varying levels of baseline ischemic and bleeding risk.

Figure 3

Frontier plot with each line representing the estimates of 30 day Net Clinical Benefit at varying levels of baseline ischemic and bleeding risk for clopidogrel, ticagrelor and prasugrel. Area below each line indicates a neutral or positive net clinical benefit from pre-treatment. Using this plot and assuming a 4% 30 day risk of major bleeding, pre-treatment is harmful with any P2Y₁₂ inhibitor at 2% 30 day ischemic risk (Point A), beneficial with clopidogrel only at 8% 30 day ischemic risk (Point B), and beneficial with both ticagrelor and clopidogrel at 13% 30 day ischemic risk (Point C).

Figure 4

Estimated likelihood of deriving a significant clinical benefit from pre-treatment with clopidogrel, ticagrelor and prasugrel at varying levels of baseline ischemic risk. Significant clinically benefit defined as absolute increase in 30 day Net Clinical Benefit by 1% or more (NNT < 100).