DOACs Safe and Effective in Atrial Fibrillation, Review Confirms

By Will Boggs, MD; Reuters Health
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Direct-acting oral anticoagulants (DOACs) are at least as safe and effective as warfarin for preventing thromboembolic events in patients with atrial fibrillation (AF), a new systematic review confirms.

"The choice of the best antithrombotic therapy for a patient remains an individualized decision with discussion between each patient and his or her physician," Dr. Angela Lowenstern from Duke University School of Medicine, in Durham, North Carolina, told Reuters Health by email. "However, as we found in our study, the DOAC medications offer a safe and efficacious treatment option that does not require routine blood monitoring."

White speckled pills. Source

Antithrombotic therapies are the mainstays for preventing thromboembolic events in patients with AF, and numerous individual studies and reviews have shown safety and effectiveness of four DOACs (the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, rivaroxaban, and edoxaban) for stroke prevention in patients with nonvalvular AF.

Dr. Lowenstern and colleagues updated previous reviews, aiming to compare the effectiveness of available medical and procedural therapies in preventing thromboembolic events and bleeding complications in patients with AF. Their review included 220 articles, representing 117 unique studies of 3.9 million patients.

Based on their review, dabigatran and apixaban are superior to warfarin, and rivaroxaban and edoxaban are similar to warfarin in preventing stroke or systemic embolism.

Apixaban and edoxaban are superior to warfarin in reducing the risk for major bleeding, while rivaroxaban and dabigatran have major bleeding risks similar to that of warfarin, the team reports in Annals of Internal Medicine, online October 29.

Consistent treatment effects for the factor Xa inhibitors are evident across many subgroups, including patients with a history of stroke, concomitant aspirin treatment, or heart failure, and in patients with paroxysmal versus persistent AF.

"Additionally, in patients with certain comorbidities the benefit of treatment may be even greater than in the general population," Dr. Lowenstern said. "For example, in patients treated with apixaban, those with renal dysfunction (GFR<50) had the greatest bleeding risk reduction as compared to those treated with warfarin."

Based on two randomized controlled trials, left atrial appendage (LAA) closure devices decrease the risk for major bleeding and show a trend toward a lower risk for stroke but with higher rates of procedural adverse events, such as serious pericardial effusion, major bleeding and device embolization (versus warfarin therapy alone).

"This report provides further confirmation of the results that were observed in the large randomized clinical trials examining the DOAC medications, across a diverse set of patient populations," Dr. Lowenstern said. "However, there are still gaps in our knowledge for the treatment of patients with nonvalvular atrial fibrillation. Data is lacking in the direct comparisons of the DOAC medications, and currently there is only sparse data on the benefits and risks of left atrial appendage closure devices."

Dr. Peter A. Noseworthy from Mayo Clinic, in Rochester, Minnesota, who studies stroke prevention in patients with atrial fibrillation, told Reuters Health by email, "The results are not surprising, but the paper is valuable in summarizing a large body of evidence that has emerged over the past several years. It will give clinicians a useful guide in making treatment choices."

"It's important to note that all the non-vitamin K antagonist oral anticoagulant (NOAC) comparative safety and effectiveness data come from observational studies or indirect comparisons," cautioned Dr. Noseworthy, who was not involved in the review. "Without randomized clinical trials directly comparing the NOACs to each other, our confidence in these comparisons is not a high as it is in the literature comparing each of the NOACs to warfarin."

Dr. Tomas Forslund from Karolinska Institutet, in Stockholm, has also researched stroke prevention and bleeding associated with DOACs and LAA closure versus warfarin. He told Reuters Health by email, "I think that the most important decision is to treat high-risk atrial fibrillation patients with any oral anticoagulant instead of low-dose aspirin. Other important decisions to consider are to reduce bleeding risk if possible, to actively monitor hemoglobin levels, to manage bleeding complications if they occur, and to try to restart anticoagulant treatment after bleeding events if possible."

"In old and frail patients with a high bleeding risk, it is probably most beneficial to choose a treatment that minimizes bleeding risk since treatment interruptions will leave the patients without stroke protection as well," said Dr. Forslund, who also was not part of the review. "In this case, apixaban seems to be the treatment of choice. Apixaban is also the DOAC which is the least dependent on kidney function for elimination, and this is important in the oldest patients."


Ann Intern Med 2018.


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