Antiplatelets Add Risk in Newly Diagnosed A-fib Patients: GARFIELD-AF

Patients with newly diagnosed atrial fibrillation who take not only an oral anticoagulant (OAC) but also an antiplatelet face increased risks of stroke and bleeding at 1 year, according to an analysis of data derived from nearly 25,000 patients enrolled in the prospective GARFIELD-AF registry. Moreover, there were no reductions in mortality or acute coronary syndromes with the added antiplatelet therapy.

Given the added risk, clinicians should only prescribe an antiplatelet on top of an anticoagulant for A-fib patients when there is a very good reason to do so, Keith A. A. Fox, MBChB (University of Edinburgh, Scotland), the study’s lead investigator, emphasized to TCTMD.

“We found that one in eight patients get antiplatelets newly prescribed along with their anticoagulant. And only some of those have a coronary indication for the prescription,” he pointed out.

Benjamin A. Steinberg, MD (University of Utah, Salt Lake City), asked to comment on the study, told TCTMD that “the big picture is that it adds to the evidence for us as a clinical community to be more and more thoughtful about antiplatelet therapy,” especially for primary prevention.

In the GARFIELD-AF report, “the signals are impressively consistent. Obviously it suffers from all of the usual limitations of an observational analysis, . . . but I think the strength is the power and consistency of the outcomes,” Steinberg said, noting that even though not all comparisons were statistically significant, the hazard ratios all were higher when antiplatelet therapy was used.

“I think it’s eye-opening and adds to our building hesitancy about the perhaps lackadaisical approach to antiplatelets we’ve taken historically,” Steinberg said.

Stroke and Bleeding

Fox and colleagues analyzed clinical outcomes at 3 and 12 months, adjusting for 40 covariates, including medication use and comorbidities. Among the total of 24,436 patients with newly diagnosed A-fib, 55% were men, the median age was 71 years, and 84.4% had a moderate-to-high risk of stroke (CHA₂DS₂-VASc score ≥ 2).

Fully 12.5% were taking an antiplatelet in addition to an oral anticoagulant. Those taking dual therapy were more likely to have a cardiovascular indication for antiplatelet therapy than those on anticoagulation alone: ACS (22.0% vs 4.3%), CAD (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%).

At 3 months, dual therapy was associated with worse clinical outcomes. By 1 year, patients receiving antiplatelets were more apt to have experienced stroke or bleeding than those prescribed anticoagulation alone. There was no difference in death or ACS risk.

Anticoagulant With vs Without Aspirin: Outcomes at 1 Year

Steinberg confirmed that, in real-world practice, a slice of patients with A-fib are indeed receiving antiplatelet on top of anticoagulant therapy, sometimes even in the absence of cardiovascular indications.

The reason why this occurs, though, is uncertain, he stressed. “Is it happening because people believe it’s helpful to add [an antiplatelet]? Or is it happening because they’re on aspirin and then they are diagnosed with A-fib and get started on [an anticoagulant] and it’s just inertia of treatment? Or [is it] because there are multiple different subspecialties and generalists managing the patients, between the cardiologist and maybe an electrophysiologist, the primary care physician, and possibly a neurologist?”

In the midst of these various scenarios, Steinberg said, “the important question is: what is the appropriate combination of treatment?”

Steinberg said that for him, in his practice as an electrophysiologist rather than a general cardiologist, “I tend to stop more antiplatelets and aspirin than I start, largely due to these types of data and others.”

Unknowns in the GARFIELD-AF analysis are discontinuation rates as well as the breakdown of which specific drugs were taken.

The latter is a relevant question “because we know warfarin has a higher risk of bleeding than the [direct oral anticoagulants] and we know that the newer antiplatelets—ADP inhibitors, particularly prasugrel and ticagrelor compared with clopidogrel—[confer a] higher risk of bleeding,” Steinberg noted. Further complicating matters is that “aspirin [use] is notoriously difficult to ascertain, in terms of what patients are taking. That’s another problem in clinical practice: often patients do not report over-the-counter medications that they are taking, importantly including aspirin.”

Still the results make sense and should influence practice, Steinberg said.

ORBIT-AF, as described in a 2013 Circulation paper for which he was lead author, found increased bleeding in more than 7,000 A-fib patients when aspirin was given on top of anticoagulation, for example. Unlike the current GARFIELD-AF analysis, that population included not only newly diagnosed patients but also those with longstanding knowledge that they had the arrhythmia.

Moreover, data have shown oral anticoagulants in and of themselves can reduce atherosclerotic or atherothrombotic events, Steinberg said. “And so the question remains: what is the role for antiplatelet therapy in those patients, particularly when we know that antiplatelet therapy alone is not good enough for stroke prevention in A-fib?”