Dual therapy with an oral anticoagulant (OAC) and clopidogrel appears to be at least as effective and safe as triple therapy, including aspirin, in patients with atrial fibrillation (AF) after MI or percutaneous coronary intervention (PCI), a study from Denmark has found.

A total of 12,165 AF patients hospitalised with MI and/or undergoing PCI were identified from nationwide registries in Denmark between 2001 and 2009. Mean age was 75.6 years and 60.7% of the patients were men.

Nearly two thirds were treated with multiple antithrombotic drugs at baseline, and 38.3% received OAC therapy. Risk of MI/coronary death, ischaemic stroke, and bleeding according to antithrombotic treatment regimen was estimated by Cox regression models.

MI or coronary death, ischaemic stroke, and bleeding events occurred in 2,255 (18.5%), 680 (5.6%), and 769 (6.3%) patients, respectively, within a year.

There was no increased risk of MI or coronary death with an OAC and a single antiplatelet agent compared with triple therapy; OAC + aspirin hazard ratio (HR) 0.96 (95% CI:0.77-1.19); OAC + clopidogrel HR 0.69 (95% CI:0.48-1.00).

There was a significant reduction in the rate of bleeding with OAC + aspirin; HR 0.69 (95% CI:0.53-0.90) and a non significant reduction with OAC + clopidogrel; HR 0.78 (95% CI:0.55-1.12) when compared with triple therapy.

Furthermore, the authors found that dual antiplatelet therapy alone (aspirin + clopidogrel) was just as effective as triple therapy in terms of the risk of MI or coronary death; HR 1.17 (95% CI:0.96-1.42) but led to a significant increase in the risk of ischaemic stroke; HR 1.50 (95% CI:1.03-2.20) compared with triple therapy.

One final interesting point related to all cause mortality with OAC + aspirin and aspirin + clopidogrel associated with a significant increased risk of all-cause death; HR 1.52 (95% CI:1.17-1.99) and HR 1.60 (95% CI:1.25-2.05) respectively.

This study was carried out before the introduction of the newer oral anticoagulants and as such the results cannot be extrapolated from warfarin to these newer agents.

Although this was a registry-based study the findings are consistent with those of a recent albeit small prospective randomised trial (WOEST with 573 patients).¹ This trial showed that those who received oral anticoagulation plus clopidogrel after PCI with stents had significantly fewer bleeds than those also receiving aspirin. They also may have had fewer clinical events, although the trial was underpowered for those outcomes.

Patients with AF present a therapeutic challenge when they have an MI or a coronary stent inserted. These patients may already be on warfarin and the standard recommendation of dual antiplatelet therapy post MI or PCI exposes them to a significant risk of bleeding-related complications, particularly from the upper gastrointestinal tract. This study suggests that triple therapy is probably not necessary in these patients.

A combination of warfarin with clopidogrel is probably a safer and equally effective strategy compared with triple therapy in such patients. Undoubtedly, further studies will be forthcoming to inform clinical decision making and guideline development more conclusively.

Dr Peter Savill