Clopidogrel monotherapy is preferable to dual antiplatelet therapy prolongation in patients with acute coronary syndromes undergoing percutaneous coronary interventions who are at both high bleeding and ischaemic risks, a new study suggests.

Patients who completed nine to 12 months of DAPT after PCI had 25% less clinically relevant bleeding if they received ongoing treatment with clopidogrel rather than continuing with aspirin and clopidogrel, a randomised controlled trial published in JAMA Cardiology (link here) has shown.

The double-blind placebo-controlled trial included 7758 PCI-treated patients with ACS who were at both high bleeding and ischaemic risks (‘birisk’) after drug-eluting stent implantation.

After receiving up to 12 months of dual antiplatelet therapy (DAPT), patients were randomised either to clopidogrel (75 mg per day ) plus placebo or clopidogrel plus aspirin (100mg per day) for an additional nine months.

At nine months post-randomisation,  there was a significant difference in the primary end point of Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding in favour of clopidogrel only.

Bleeding occurred in 2.5% of patients (95 of 3873) assigned to clopidogrel plus placebo and 3.3% (127 of 3885) of patients assigned to clopidogrel plus aspirin (hazard ratio [HR], 0.75; 95% CI, 0.57-0.97; difference, −0.8%; 95% CI, −1.6% to −0.1%; P = .03).

Similarly, there was a significant difference in favour of clopidogrel monotherapy for the secondary outcome of ischaemic events.

The incidence of major adverse cardiac and cerebral events (MACCE; the composite of all-cause death, myocardial infarction, stroke or clinically driven revascularisation) was 2.6% (101 of 3873 patients) in the clopidogrel plus placebo group and 3.5% (136 of 3885 patients) in the clopidogrel plus aspirin group (HR, 0.74; 95% CI, 0.57-0.96; difference, −0.9%; 95% CI, −1.7% to −0.1%; P < .001 for noninferiority; P = .02 for superiority).

The study investigators said the findings provided important data to inform the management of the difficult-to-treat post-PCI patient population who have not only increased ischemic risk but also increased bleeding risk.

They noted that aspirin monotherapy after DAPT has been the standard of care for PCI patients for many years, but there was emerging evidence to support DAPT followed by P2Y₁₂ inhibitor monotherapy to reduce bleeding after PCI. However until now ischaemic events have been reduced only with ticagrelor monotherapy.

In some studies, DAPT followed by clopidogrel or aspirin monotherapy was associated with an increase in ischaemic events, “underscoring the importance of maintaining DAPT for guideline-recommended durations (eg, 12 months) in most high ischaemic-risk patients unless ticagrelor monotherapy is used,” they wrote.

They observed that studies such as HOST-EXAM had suggested that long-term clopidogrel was a superior monotherapy regimen to aspirin alone in higher risk patients.

“The outcomes from the present study, in concert with the findings from the HOST-EXAM trial and a prior meta-analysis, suggest that chronic clopidogrel monotherapy should be a preferred treatment option after 9 to 12 months of DAPT in appropriate patients with ACS,” they concluded.

An accompanying commentary (link here) welcomed the findings but highlighted the relatively late transition from DAPT to clopidogrel monotherapy  at nine to 12 months.

“This study did not show that clopidogrel monotherapy was a preferable treatment to aspirin and clopidogrel soon after PCI,” the authors said.

Nevertheless the study had identified a patient population in whom the question of DAPT prolongation or monotherapy was relevant, they noted.

“The selection of a P2Y₁₂ inhibitor rather than aspirin and most likely choosing its potency and consistency based on ischaemic vs bleeding risks seems to provide the best compromise between aspirin monotherapy and DAPT,” they wrote.

“Therefore, the real lingering question, even more after this important trial, is when should aspirin be combined with a P2Y₁₂ inhibitor in current practice?”