Extended Dual Antiplatelet Therapy After PCI With DES Curbs MI but Boosts Bleeding

Updated meta-analysis supports personalizing antiplatelet strategies

percutaneous coronary intervention

Use of dual antiplatelet therapy (DAPT) for more than 12 months after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is associated with a lower rate of myocardial infarction (MI) than shorter periods of DAPT use. However, the benefit comes at a cost — a higher risk of major bleeding. While shorter DAPT strategies confer similar ischemic protection to each other, DAPT for less than six months followed by P2Y12 inhibitor monotherapy entails the lowest risk of bleeding events.


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Those are the primary conclusions of a large meta-analysis of randomized controlled trials recently published online in Circulation by a multi-institutional team of researchers.

“Our analysis suggests that there is not a single best antiplatelet strategy for all patients following PCI,” says study co-author Ankur Kalra, MD, a Cleveland Clinic cardiologist. “Providers need to consider each patient’s risk of ischemia and bleeding to determine the optimal DAPT intensity and duration.”

DAPT recommendations need reexamining

Recommendations concerning DAPT after PCI continue to evolve as more evidence emerges. Guidelines from the European Society of Cardiology (2017) and the American College of Cardiology/American Heart Association (2016) offer somewhat different recommendations depending on bleeding risk, stent type and presence of acute coronary syndrome.

The European and American guidelines were based on 15 randomized controlled trials; since then, additional clinical trials have been published.

Study design and findings

The new meta-analysis analyzed 24 randomized controlled trials comprising 79,073 patients and with a median follow-up of 18 months. Fourteen of the trials reported outcomes in patients with acute coronary syndrome.

The following strategies after PCI with DES were compared:

  • Short-term DAPT (< 6 months) followed by aspirin or P2Y12 inhibitor monotherapy
  • Mid-term DAPT (6 months)
  • 12-month DAPT
  • Extended DAPT (> 12 months)

The primary endpoints were MI and major bleeding.

The analysis revealed the following outcomes:

  • Extended DAPT had a significantly lower risk of MI than each of the other strategies.
  • Extended DAPT had a significantly higher risk of major bleeding than each of the other strategies, except among patients with acute coronary syndrome.
  • No significant differences in risk of ischemic endpoints were found between 12-month DAPT, mid-term DAPT and short-term DAPT followed by aspirin/P2Y12 inhibitor monotherapy.
  • Short-term DAPT followed by P2Y12 inhibitor monotherapy had a reduced risk of major bleeding and net adverse clinical events compared with 12-month DAPT.
  • Among P2Y12 inhibitors, clopidogrel was associated with the lowest incidence of major bleeding and ticagrelor had the lowest incidence of MI.


Notably, none of the strategies was associated with significant differences in either cardiovascular or overall mortality.

Best strategy? It depends

The investigators point out several study limitations, including that only one-third of the trials were powered to test superiority of different DAPT strategies (the others were powered for noninferiority). Also, studies differed in design and baseline health status of patients, with relatively few patients having acute coronary syndrome.

Still, Dr. Kalra notes that this meta-analysis extends findings from previous analyses by incorporating more recent clinical trials. He highlights the following key takeaways from the new study:

  • Short-term DAPT followed by P2Y12 inhibitor monotherapy appears safe for select patients. For patients without acute coronary syndrome, this strategy showed no excess risk of ischemia. The findings support existing data favoring P2Y12 inhibitor monotherapy over aspirin because of superior safety and efficacy.
  • Extended DAPT may be appropriate for those at high cardiovascular risk and low bleeding risk. This strategy should be considered for patients presenting with acute coronary syndrome or diabetes mellitus, or who are otherwise at high ischemic risk.
  • A multidimensional approach may further optimize benefits. Aggressively managing risk factors and using potent P2Y12 inhibitors, contemporary stents and optimal procedural techniques may allow realization of the benefits of short-term DAPT along with low ischemic complications.

“This study can reassure physicians that for many patients, a short-term DAPT course followed by P2Y12 inhibitor monotherapy is reasonable,” concludes study co-author Samir Kapadia, MD, Chair of Cardiovascular Medicine at Cleveland Clinic. “But high cardiovascular and low bleeding risks could tip the decision to an extended DAPT strategy.”


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