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Acute coronary syndrome (ACS) patients may better optimize their ischemic and bleeding risks after angioplasty depending on their individual needs, according to a network meta-analysis comparing two dual antiplatelet therapy (DAPT) modulation strategies.

Across 29 randomized trials directly comparing short DAPT and DAPT de-escalation against standard 12-month DAPT but not one against the other, de-escalation was indirectly associated with:

• Reduction in net adverse cardiovascular events (NACE; RR 0.87, 95% CI 0.70-0.94)
• Increase in major bleeding (RR 1.54, 95% CI 1.07-2.21)
• No difference in all-cause death (RR 0.98, 95% CI 0.68-1.43)

Results were consistent in Bayesian analysis and multiple sensitivity analyses, reported Davide Capodanno, MD, PhD, of Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco in Catania, Italy,and colleagues, in .

Investigators noted that all ischemic outcomes were directionally in favor of de-escalation over short DAPT. This finding failed to reach statistical significance, however, likely due to the relatively low power of the analysis.

Downgrading the prasugrel (Effient) or ticagrelor (Brilinta) component of DAPT to either clopidogrel (Plavix) or a lower dose may therefore work better for patients at greater thrombotic risk, whereas short DAPT -- the withdrawal of the P2Y12 inhibitor or aspirin at 1-6 months -- appeared to be better for patients at higher risk for bleeding.

European guidelines for ACS currently assign short DAPT and de-escalation class IIa and IIb recommendations, respectively, after percutaneous coronary intervention (PCI).

"Our results challenge this ranking, as DAPT de-escalation showed a similar risk for death and a reduced risk for NACE -- two measures of overall net benefit -- compared with short DAPT. On this basis, our study suggests that the class of recommendation for these two options should be, if anything, at least the same," Capodanno's group argued.

Both short DAPT and de-escalation can be considered viable alternative strategies to standard DAPT, agreed Dean Kereiakes, MD, of Christ Hospital Heart and Vascular Center in Cincinnati, and Robert Yeh, MD, MSc, of Beth Israel Deaconess Medical Center and Harvard Medical School, in an .

Kereiakes and Yeh suggested de-escalation strategies as "an important intermediate path between standard DAPT regimens and very short DAPT durations."

"The time may have arrived to formally incorporate ischemic/bleeding risk stratification tools into current practice guidelines and to elevate both short DAPT and de-escalation to Class I status for patients who present with ACS and are treated with coronary stents," according to the editorialists.

The meta-analysis comprised randomized trials with clinical outcomes reported at least 6 months after PCI with drug-eluting stents (n=50,602). These studies were split between 19 trials of short DAPT and 10 trials of de-escalation.

Within the broader strategy of DAPT de-escalation, the choice to transition the patient to a halved dose of the P2Y12 inhibitor (rather than clopidogrel) appeared most promising with respect to multiple clinical outcomes, Capodanno and colleagues found.

On the other hand, the risk of stent thrombosis appeared highest after a short DAPT regimen with extended aspirin monotherapy.

Subgroup analyses "suggest that the designations 'short DAPT' and 'de-escalation' are overly simplistic, and that not all short DAPT or deescalation strategies are created 'equal,'" according to Kereiakes and Yeh.

"[I]t remains entirely possible that a short DAPT regimen with extended aspirin single-agent antiplatelet therapy could be associated with significant ischemic hazard (if adequately powered) in patients with intermediate or greater ischemic risk," the duo noted.

Capodanno's group warned of the small samples in these subgroups, however, and acknowledged that the reliance on indirect evidence was another major study limitation.

"In the absence of direct randomized comparisons, these data may inform clinicians on the relative merits of two contemporary DAPT strategies and allow personalized treatment decisions on the basis of treatment objectives and the balance between the risks for thrombosis and bleeding," the authors concluded.

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