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MI risk lower with direct oral anticoagulants vs. vitamin K antagonists
Compared with vitamin K antagonists such as warfarin, direct oral anticoagulants were associated with lower risk for MI in patients with nonvalvular atrial fibrillation, according to a retrospective cohort study.
There was no difference in MI risk among the direct oral anticoagulants, researchers reported.
The researchers analyzed 31,739 patients (median age, 74 years; 47% women) with nonvalvular AF from Danish health care registers who began a prescription for a vitamin K antagonist (28%), apixaban (Eliquis, Bristol-Myers Squibb/Pfizer; 27%), dabigatran (Pradaxa, Boehringer Ingelheim; 23%) or rivaroxaban (Xarelto, Janssen; 22%) between January 2013 and June 2016.
The outcome of interest was standardized 1-year risk for MI.
The standardized 1-year risk for MI was higher in patients taking a vitamin K antagonist (1.6%; 95% CI, 1.3-1.8) than in patients taking apixaban (1.2%; 95% CI, 0.9-1.4), dabigatran (1.2%; 95% CI, 1-1.5) or rivaroxaban (1.1%; 95% CI, 0.8-1.3), Christina Ji-Young Lee, MD, from the department of health science and technology at Aalborg University and unit of epidemiology and biostatistics at Aalborg University Hospital in Denmark, and colleagues wrote.
The risk differences for all three direct oral anticoagulants vs. vitamin K antagonists were significant (apixaban, –0.4%; 95% CI, –0.7 to –0.1; dabigatran, –0.4%; 95% CI, –0.7 to –0.03; rivaroxaban; –0.5%; 95% CI, –0.8 to –0.2), according to the researchers.
However, the risk differences between the direct oral anticoagulants were not significant (dabigatran vs. apixaban, 0.04%; 95% CI, –0.3 to 0.4; rivaroxaban vs. apixaban, 0.1%; 95% CI, –0.4 to 0.3; rivaroxaban vs. dabigatran, –0.1%; 95% CI, –0.5 to 0.2), they wrote.
“Furthermore, the results were consistent for patients with and without prior ischemic heart disease and concomitant antiplatelet therapy,” Lee and colleagues wrote.
In a related editorial, Stefan H. Hohnloser, MD, professor of medicine and cardiology and head of the department of electrophysiology at Johann Wolfgang Goethe University in Frankfurt, Germany, and John W. Eikelboom, MD, MBBS, MSc, associate professor of medicine at McMaster University in Hamilton, Ontario, Canada, wrote that the study “helps to settle the dust around an 8-year-old debate concerning the risk of MI in patients receiving [direct oral anticoagulant] therapy (and specifically dabigatran) for stroke prevention in AF. Based on the large and consistent body of evidence now available, clinicians can use dabigatran with even greater confidence in AF patients, including those with a history of coronary artery disease and prior MI.” – by Erik Swain
Disclosures: Lee reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Eikelboom and Hohnloser report they have financial ties with multiple pharmaceutical and device companies.
Perspective
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We know that direct oral anticoagulants appear to be superior to vitamin K antagonists in almost every possible way they can be measured except for cost. Combined data from the pivotal trials of all the direct oral anticoagulants showed that compared with warfarin, they were associated with lower risk for intracranial hemorrhage and all-cause death.
These are highly effective anticoagulants that are much safer than warfarin. There was early concern about a slight increase in risk for MI with some of the direct oral anticoagulants, particularly in the RE-LY trial of dabigatran, but when aggregate data from additional follow-up were collected, there was no increase in risk. Therefore, when you have a safer anticoagulant, it is not surprising to see lower rates of MI. These findings also fit in with what we have seen in trials of direct oral anticoagulants in vascular disease and ACS.
I would hope that for most practitioners, this study does not change their practice. I would hope that, if cost is not a concern and there are no contraindications, a clinician who has a patient with AF who is at high risk for stroke is treating that patient with a direct oral anticoagulant. Assuming the patient has adequate renal function and appropriate prescription coverage, why wouldn’t you pick a medication with better outcomes? When direct oral anticoagulants were first introduced, there were a large number of clinicians who preferred to maintain use of vitamin K antagonists, but that number has grown much smaller as we’ve attained more evidence regarding the direct oral anticoagulants. Patients with mechanical valves or advanced chronic kidney disease need vitamin K antagonists, but absent those relatively uncommon conditions, the evidence supports that direct oral anticoagulants yield a safer and more effective treatment.
While the authors were careful to adjust for everything they could adjust for, the present study has some limitations. Some variables associated with MI, including cholesterol levels and family history, were not available to the authors. Also, it was unclear if they had access to precise renal function levels. These are important influencers of patient risk.
For patients with AF who are stable, we have excellent information as to what medication they should be on: a direct oral anticoagulant dosed appropriately for them. Where we have few definitive answers is for patients with AF and ongoing active vascular disease or a recent MI. These are what general cardiologists, interventional cardiologists and electrophysiologists struggle with on patient consults. The good news is that ongoing clinical trials are going to help with this, and that pharmaceutical companies are developing next-generation anticoagulants.