Dual trumps triple therapy in reducing bleeding risk in patients with AF post-PCI

In adults with atrial fibrillation (AF) after percutaneous coronary intervention (PCI), dual therapy (direct oral anticoagulant [DOAC] + P2Y12 inhibitor) reduces the risk of bleeding compared with triple therapy (vitamin K antagonist [VKA] + DAPT* [aspirin and P2Y12 inhibitor]), a meta-analysis has shown. However, its effects on the risks of mortality and ischaemic endpoints** remain unclear.

“The management of AF post-PCI is a common clinical conundrum. Fundamental questions include the timing of aspirin withdrawal, whether aspirin [withdrawal] can compromise any potential cardiovascular benefits, and the choice of DOAC vs VKA for oral anticoagulation,” said the researchers.

Therefore, the team pooled data from four*** randomized controlled trials (RCTs; n=7,953) to determine the most appropriate antithrombotic regimen in this setting. “[Our] two principal findings [are the] reduced risk of bleeding events with DOAC-based dual therapy [vs] VKA-based triple therapy and [the] inconclusive effects of dual vs triple therapy on the risks of death and ischaemic endpoints,” they said.

High-certainty evidence showed that dual therapy was associated with reduced risk of TIMI^# major bleeding (risk difference [RD], –0.013), TIMI major and minor bleeding (RD, –0.031), and trial-defined bleeding (RD, –0.072) vs triple therapy at a median follow-up of 1 year. [Ann Intern Med 2020;doi:10.7326/M19-3763]

Although two trials individually echoed these findings, it remains unclear whether the effect was exclusively driven by using a DOAC instead of a VKA or whether it was due to an aspirin-free strategy. [N Engl J Med 2016;375:2423-2434; N Engl J Med 2017;377:1513-1524]

Nonetheless, another trial addressed this issue by showing a reduction in bleeding events with the DOAC apixaban vs VKA and increased bleeding with the addition of aspirin. [N Engl J Med 2019;380:1509-1524] “[This trial implied] that perhaps both aspects of antithrombotic strategies — early aspirin withdrawal and preference for DOACs over VKAs — offer the optimal balance of safety and efficacy in the management of AF post-PCI,” said the researchers.

Despite the lack of difference between the two regimens in terms of bleeding in one of the studies, the researchers attributed this to the reduced bleeding rates with VKA during the first 2 weeks of treatment. [Lancet 2019;394:1335-1343] “[This was] when a high proportion of patients did not achieve an international normalized ratio of two,” they explained.

Taken together, these findings correlate with studies showing the more favourable risk-benefit profile of DOACs vs VKAs in AF, as well as current American and European guidelines. [Lancet 2014;383:955-962; Ann Intern Med 2012;157:796-807; Eur Heart J 2019;40:87-165]

Death, ischaemic endpoints

Conversely, low-certainty evidence showed inconclusive effects of dual vs triple therapy on the risks of mortality (RDs, 0.004 [all-cause] and 0.001 [cardiovascular]), myocardial infarction (MI; RD, 0.003), stent thrombosis (RD, 0.003), and stroke (RD, –0.003).

While the RCTs reflected a numerical increase in ischaemic endpoints with dual therapy, these should be interpreted with caution considering the individual trial limitations, noted the researchers. The results of future^## RCTs might shed light on this issue.

Aspirin: To withdraw or not?

Aspirin has been the cornerstone of secondary preventive measures post-PCI until a recent shift favouring P2Y12 inhibitor over aspirin monotherapy following DAPT withdrawal. [Nat Rev Cardiol 2018;15:480-496]

The ACC/AHA/HRS^### recommend limiting aspirin use during the preprocedural and hospitalization periods. [J Am Coll Cardiol 2019;74:104-132] However, the 2018 European Society of Cardiology guidelines restrict dual therapy for those with high bleeding risk at baseline and recommend triple therapy for up to 6 months for all other patients depending on bleeding and thrombotic risk assessments, the researchers pointed out.

“Our meta-analysis might promote more consistency between American and European society guidelines regarding the safety of early withdrawal of aspirin from triple therapy,” they said.