Warfarin, No Antiplatelet Upheld in Ischemic HF With AF

May 02, 2014

COPENHAGEN, DENMARK — In a retrospective exploration of antithrombotic therapy in patients at the crossroads of two separate indications, thromboembolic risk went up similarly in either preexisting or incident AF in patients with ischemic heart failure. And with either AF type, treating with a vitamin-K antagonist (VKA) alone, compared with an antiplatelet agent alone, cut that thromboembolic risk, though at a cost of more serious bleeding[1].

But such bleeding was even more likely, without any gain in antithrombotic effect, when giving the antiplatelet (either aspirin or clopidogrel) on top of the VKA (either warfarin or phenprocoumon).

"Our data suggest that monotherapy with vitamin-K antagonists should be the preferred choice when atrial fibrillation is present in heart-failure patients with coexisting vascular disease," lead author Dr Morten Lamberts (Gentofte University Hospital, Hellerup, Denmark) told heartwire by email.

He observed that many clinicians remain uncertain about the specifics of antithrombotic therapy in HF patients with vascular disease (indicating antiplatelet therapy) who also have AF (an indication for anticoagulant therapy). The analysis of 37 464 unselected such patients "showed a very heterogeneous approach concerning selection of patients to vitamin-K antagonist and antiplatelets or both," Lamberts noted. The patients had been hospitalized from 1997 to 2009, before the era of new oral anticoagulants (NOACs), and followed for mean of three years.

"Currently," he said, "these data, although observational, are some of the best evidence supporting monotherapy with a vitamin-K antagonist in real-life patients and also support current guidelines on the management of atrial fibrillation." The analysis was published online April 30, 2014 in the Journal of the American College of Cardiology.

"Despite the large sample in this study, reported confidence intervals are often wide, suggesting underpowering. Nevertheless, it adds to accumulating evidence that optimal risk/benefit balance in some patients with AF and vascular disease may be achieved by VKA alone," states an accompanying editorial from Dr Srijita Sen-Chowdhry (University College London, UK) and Dr Richard J Gordon (Stern Cardiovascular Foundation, Munford, TN)[1].

Prevalent AF was identified in 20.7%, who were followed for 20 691 person-years; 17.2% showed incident AF over a follow-up of 15 758 person-years. The remainder without any AF were followed for 77 317 person-years. The overall rate of thromboembolic events was 11.4% and of "serious" bleeding (requiring hospitalization) was 11.7%

In those with prevalent AF, the rate of thromboembolism was similar for those on VKA plus an antiplatelet vs VKA alone. But the two agents combined showed a hazard ratio (HR) for serious bleeding of 1.31 (95% CI 1.09–1.57) compared with VKA alone. Meanwhile, the bleeding risk went down significantly with antiplatelet therapy vs VKA alone: HR 0.80 (95% CI 0.68–0.95).

In those with incident AF, the rate of thromboembolism wasn't elevated using both agents compared with VKA alone, but it was increased by an antiplatelet alone: HR 1.45 (95% CI 1.13–1.85). And again, the serious bleeding risk went up with VKA plus an antiplatelet (HR 2.71, 95% CI 1.33–2.21), but not with an antiplatelet alone.

In patients without any AF, thromboembolism was similarly likely with VKA alone, antiplatelet alone, or the two combined. But as expected, compared with single-agent antiplatelet therapy, the risk of serious bleeding was HR 2.05 (95% CI 1.73–2.43) for VKA plus antiplatelet and HR 1.69 (95% CI 1.37–2.06) for VKA alone.

Among patients without AF, dual antiplatelet therapy (aspirin plus clopidogrel) cut the risk of thromboembolism (HR 0.82, 95% CI 0.69–0.97) and raised the risk of serious bleeding (HR 1.53 [95% CI 1.33–1.76]) compared with single-antiplatelet therapy.

Not much is yet known in this setting about combination therapy that includes one of the NOACs, Lamberts observed. "Individual assessment of benefit and safety is crucial but, in my practice, most ischemic heart-failure patients with atrial fibrillation will receive an oral anticoagulant only."

Lamberts had no conflicts of interest; disclosures for the coauthors are listed in the report. Sen-Chowdhry had no disclosures; Gordon "is a speaker for Boehringer Ingelheim on Pradaxa."

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