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Optimal Antiplatelet Therapy After PCI
Quick Takes
- The current analysis was an in-depth review of existing literature of randomized trials comparing de-escalation from DAPT to ticagrelor monotherapy vs. continuing on standard 12 months of DAPT after PCI. Patients in the de-escalation group were transitioned to ticagrelor after a median of 78 days of DAPT.
- Ticagrelor monotherapy was noninferior to standard DAPT for ischemic outcomes (death, MI, stroke: 2.8% vs. 3.3%; HR, 0.89; 95% CI, 0.74-1.06; p = 0.0039 for noninferiority).
- Ticagrelor monotherapy was superior to standard DAPT for bleeding events (0.9% vs. 2.1%; HR, 0.43; 95% CI, 0.34–0.54; p < 0.0001 for superiority).
- The benefits of de-escalation were only seen in the ACS cohort.
Study Questions:
What is the evidence comparing dual antiplatelet therapy (DAPT) de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation?
Methods:
A systematic review and individual patient data (IPD)-level meta-analysis of randomized trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention (PCI) with a coronary drug-eluting stent. Randomized trials comparing P2Y12 inhibitor monotherapy with DAPT after coronary revascularization were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymized electronic data set.
The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for noninferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan–Meier estimates. The noninferiority was tested using a one-sided α of 0.025 with the prespecified noninferiority margin of 1.15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0.05.
Results:
A total of 8,361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (interquartile range, 31–92) after intervention, with a median duration of treatment of 334 days (329−365). Among 23,256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan–Meier estimate 2.8%) with ticagrelor monotherapy and 332 (Kaplan–Meier estimate 3.2%) with DAPT (HR, 0.91; 95% confidence interval [CI], 0.78–1.07; p = 0.0039 for noninferiority; τ2 < 0.0001). Among 24,407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan–Meier estimate 0.9% vs. 2.1%; HR, 0.43; 95% CI 0.34–0.54; p < 0.0001 for superiority; τ2 = 0.079) and all-cause death (Kaplan–Meier estimate 0.9% vs. 1.2%; 0.76; 95% CI, 0.59–0.98; p = 0.034 for superiority; τ2 < 0.0001) were lower with ticagrelor monotherapy.
Trial sequential analysis showed strong evidence of noninferiority for MACCE and superiority for bleeding among the overall and acute coronary syndrome (ACS) populations (the z-curve crossed the monitoring boundaries or the required information size without crossing the futility boundaries or approaching the null). The treatment effects were heterogeneous by sex for MACCE (p for interaction = 0.041) and all-cause death (p for interaction = 0.050), indicating a possible benefit in women with ticagrelor monotherapy, and by clinical presentation for bleeding (p for interaction = 0.022), indicating a benefit in ACS with ticagrelor monotherapy.
Conclusions:
The study found robust evidence that, compared with 12 months of DAPT, de-escalation to ticagrelor monotherapy does not increase ischemic risk and reduces the risk of major bleeding, especially in patients with ACS. Ticagrelor monotherapy might also be associated with a mortality benefit, particularly among women, which warrants further investigation.
Perspective:
There remains lack of consensus regarding type and duration of optimal antiplatelet therapy after PCI. The current analysis was an in-depth review of existing literature of randomized trials comparing de-escalation from DAPT to ticagrelor monotherapy vs. continuing on standard DAPT after PCI. Patients in the de-escalation group were transitioned to ticagrelor after a median of 78 days of DAPT. Ticagrelor monotherapy was noninferior for ischemic outcomes (death, MI, stroke: 2.8% vs. 3.3%; HR, 0.89; 95% CI, 0.74-1.06; p = 0.0039 for noninferiority) and superior for bleeding outcomes (0.9% vs. 2.1%; HR, 0.43; 95% CI, 0.34–0.54; p < 0.0001 for superiority) compared to standard DAPT. The benefits of de-escalation were not seen in the stable coronary syndrome patients. Other notable findings include a signal for mortality benefit for de-escalation among women but this finding needs further study.
Clinical Topics: Invasive Cardiovascular Angiography and Intervention
Keywords: Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors
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