Meta-Analysis Compares Effects of DAPT Durations After PCI with DES

A new systematic review and network meta-analysis from investigators at leading institutions across the US is providing clinicians with an updated overview of appropriate duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents.

Led by Deepak Bhatt, MD, MPH, and a team of investigators representing institutions including the Cleveland Clinic, West Virginia University, and Johns Hopkins University, results of the network meta-analysis concluded short-term DAPT was associated with reductions in major bleeding compared to 12-month DAPT, but also found extended-term DAPT was associated with reductions of myocardial infarction.

“Compared with 12-month DAPT, the net clinical benefit appears to favor short-term DAPT followed by P2Y12 inhibitor monotherapy in patients similar to the ones included in these trials,” wrote study investigators. “However, extended-term DAPT in patients with ACS or at a higher risk of recurrent ischemic MACE is still warranted in patients selected to be at low bleeding risk.”

With no clear consensus among guidelines from major international organizations, investigators sought to provide a more definitive determination of outcomes associated with different durations of DAPT in patients undergoing PCI with drug-eluting stents. To do so, they designed the current study as using randomized clinical trials comparing durations of DAPT followed by aspirin or P2Y12 monotherapy in the aforementioned population published in the Medline, Embase, Cochrane library, and online databases through September 2019.

The co-primary end points for the study were myocardial infarction (MI) and major bleeding, which was used to calculate net clinical benefit for each respective approach. For the purpose of the analysis, short-term DAPT was defined as 6 months or less, mid-term DAPT was defined as 6 months, and extended-term DAPT was defined as more than 12 months. Outcomes for these respective durations were compared to 12-month DAPT using a random effects model.

Additional criteria for trials to be included study were having a sample size of 500 or more patients and follow-up of at least 6 months and reporting on cardiovascular and bleeding outcomes. Investigators noted pharmacokinetic and pharmacodynamic studies, those with a cross-over design, or those where a minority of patients included received PCI or drug-eluting stents.

In total, 24 trials with data related to 79,073 patients and 112,387 patient-years of follow-up were identified for inclusion in the network meta-analysis. Of the 24 included in the study, 95% had a low risk of bias for sequence generation and 75% had low risk of bias for allocation concealment. Additionally, 33% had a high risk of bias for blinding and 21% had high risk of detection bias.

For MI, results indicated extended-term DAPTwas associated with a reduction in risk of MI when compared to 12-month DAPT (absolute risk difference [ARD], -3.8 incident cases per 1000 person-years; relative risk [RR], 0.68; 95% CI, 0.54-0.87). Conversely, no significant difference was found when comparing mid-term DAPT (ARD, -4.6 incident cases per 1000 person-years; RR, 0.61; 0.45-0.83) and short-term DAPT followed by aspirin (ARD, -6.1 incident cases per 1000 person-years; RR, 0.55; 0.37-0.83) or P2Y12 monotherapy (ARD, -0.3 incident cases per 1000 person-years; RR, 0.97; 0.78-1.22) to 12-month DAPT for MI.

When compared against extended-term DAPT, 12-month DAPT, mid-term DAPT, and short-term DAPT followed by aspirin monotherapy or P2Y12 inhibitor monotherapy were associated with significantly higher risk of MI.

For major bleeding, results indicated extended-term DAPT was associated with an increased risk of major bleeding compared to 12-month DAPT (ARD, 4.9 incident cases per 1000 person-years; RR, 1.63; 1.15-2.30). Investigators highlighted short-term DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduction in risk of major bleeding (ARD, -3.7 incident cases per 1000 person-years; RR, 0.69; 0.50-0.96).

Of note, the analysis indicated no significant differences in major bleeding when comparing mid-term DAPT and short-term DAPT followed by aspirin monotherapy to 12-month DAPT. Additionally, results of the analysis suggested all other approaches were associated with a reduced risk of major bleeding when compared to extended-term DAPT.

When assessing net clinical benefit, results of the analysis favored short-term APT followed by P2Y12 monotherapy in the entire cohort. However, the net clinical benefit favored extended-term DAPT for patients with acute coronary syndrome, which investigators attribute to a reduced risk of MI and a non-significant risk of major bleeding compared to a 12-month DAPT strategy.

This study, “Dual Antiplatelet Therapy After Percutaneous Coronary Intervention and Drug-Eluting Stents: A Systematic Review and Network Meta-Analysis,” was published in Circulation.