Further Support for Limiting Antiplatelets in AFib: GARFIELD-AF

Patrice Wendling

March 10, 2020

Patients with newly diagnosed atrial fibrillation (AF) at risk for stroke who are treated with an antiplatelet in addition to oral anticoagulation (OAC) have higher risks for stroke and bleeding at 1 year than those given OAC alone, new data from the GARFIELD-AF registry show.

"We very carefully adjusted for 40 baseline factors and all the covariate treatments, and demonstrated there was no improvement in any of the outcomes. In fact, the trend for mortality goes the wrong way and there is a statistically significant increased risk for stroke and for bleeding," said senior study author Keith A.A. Fox, MBChB, a professor of cardiology at the University of Edinburgh, United Kingdom.

"So what this says is that if someone doesn't have a mandated indication for an antiplatelet, they should just get the anticoagulation."

Current guidelines recommend OAC as stroke prophylaxis in patients with nonvalvular AF and a CHA2DS2-VASc score of at least 2 (moderate- to high-stroke risk), regardless of symptoms. Antiplatelet drugs are not advocated for stroke prophylaxis in AF but are still used with OAC in practice.

Commenting to theheart.org | Medscape Cardiology, Christopher Granger, MD, Duke University, Durham, North Carolina, said: "The study adds to the considerable evidence that we should not be using antiplatelets in addition to anticoagulation for most patients who have atrial fibrillation."

He noted that observational studies in Denmark and the United States, as well as analyses from trials such as ARISTOTLE and ROCKET-AF, have shown increased bleeding events with combination OAC and antiplatelet therapy, compared with OAC alone.

The recent Japanese AFIRE trial also provided "particularly compelling" randomized data in support of OAC monotherapy in patients with AF and stable coronary artery disease (CAD), although rivaroxaban was given at a lower dose than is used in much of the world, Granger observed.

The new analysis involved 24,436 patients (55% male; median age, 71 years) prospectively enrolled in the multinational GARFIELD-AF registry, of which 84.4% had a CHA2DS2-VASc score of at least 2.

One in eight patients (12.5%) was prescribed an antiplatelet in addition to OAC, the investigators reported February 28 in JAMA Network Open.

Patients receiving dual therapy were more likely than those receiving OAC alone to have a cardiovascular indication for antiplatelet therapy, including acute coronary syndrome (22.0% vs 4.3%), CAD (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%).

A substantial proportion of these people have some underlying coronary artery disease or prior vascular disease, but a significant proportion of them do not, observed Fox.

"There are what I would call first-line cardiovascular indications," he said. "Somebody with atrial fibrillation who needs a PCI and a stent, they clearly have to be on an antiplatelet. Somebody who just had a myocardial infarction who's got atrial fibrillation, they have to be on for a period of time.

"The remainder are relative indications," he said. "They have some vascular disease and yet there is evidence that anticoagulation alone is effective in that setting."

Over 12 months, patients treated with an antiplatelet plus OAC had higher adjusted rates of stroke (hazard ratio [HR], 1.49; 95% CI, 1.01 - 2.20) and any bleeding event (HR, 1.41; 95% CI, 1.17 - 1.70).

"The surprises were that there was no trend, not even a trend, for improvement in ACS or MI in those who got the combined treatment versus those who got anticoagulation alone (HR, 1.16; 95% CI, 0.70 - 1.94)," Fox said.

Similarly, there was no significant difference in all-cause mortality (HR, 1.22; 95% CI, 0.98 - 1.51).

The GARFIELD-AF risk calculator, which includes clinical data and 16 questions, may help clinicians better assess risk, Fox suggested.

"One of the main reasons we're making the risk calculator available is that there were many people who were very high risk where clinicians were not using an anticoagulant because of fear of bleeding, and when you actually analyze the bleeding risk and stroke risk, the stroke risk was much higher in these older patients," he said. "So there is much to gain in anticoagulation in those patients. And, conversely, there were patients whose stroke risk was very low but they were being anticoagulated."

"So we believe by providing the clinician with a more accurate assessment of both stroke and bleeding risk and mortality, he or she can then make a more informed choice with the patient," Fox said.

As for why so many patients received add-on antiplatelet therapy, Fox said, "clinicians have been so used to using antiplatelets in the past that somehow they feel that it must be better to combine them. And, actually, what we found is, no, it isn't."

As with other aspects of medicine, Granger said it will take measurement, feedback and a concerted effort to change practice. "So many people think of antiplatelet therapy for anybody who's had vascular disease as something you always give, and people don't realize there are some situations where the benefit is outweighed by the risk —  and this is one of them."

Despite the solid dataset, limitations of the study are the lack of granularity on the individual drugs prescribed and whether the findings are consistent for various antiplatelet regimens, Granger said.

AFIRE lead investigator Satoshi Yasuda, MD, PhD, deputy director general and chair of cardiovascular medicine at the National Cerebral and Cardiovascular Center in Osaka, Japan, also noted in an email that the details of combination therapy and its duration were not provided.

The phase 3 AQUATIC trial comparing OAC with or without 100 mg once-daily aspirin in 2000 individuals with AF and stable coronary disease may provide additional insights. "The AQUATIC trial is now ongoing," he said. "This is a similar concept design to AFIRE, with a 'less is more' regimen."

The Garfield-AF Registry is an independent academic research initiative sponsored by the Thrombosis Research Instituted and supported by an unrestricted research grant from Bayer Pharma AG. Fox reports receiving grants and personal fees from Bayer during the conduct of the study, and grants from AstraZeneca and personal fees from Sanofi/Regeneron and Verseon outside the submitted work. Granger reports consulting fees/honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Gilead Sciences, GlaxoSmithKline, Hoffman La Roche, Janssen, Medtronic, Novartis, Pfizer, The Medicines Company, and Verseon; and research grants from Armetheon, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, GlaxoSmithKline, Janssen, Medtronic Foundation, Novartis, Pfizer, and The Medicines Company. Yasuda reports receiving grant support from Takeda Pharmaceutical Company and Abbott Laboratories, and lecture fees from Daiichi Sankyo and Bristol-Myers Squibb.

JAMA Netw Open. 2020;3:e200107. Full text

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