Oral anticoagulants prevent stroke in patients with atrial fibrillation

In patients with atrial fibrillation, direct-acting oral anticoagulants lowered the risk for stroke, systemic embolism and all-cause mortality while also reducing the risk for major and intracranial bleeding, compared with warfarin, according to research published in BMJ.

Atrial fibrillation increases the risk of thromboembolic stroke fivefold,” José A López-López, BSc, MSc, PhD, from the department of population health sciences at the University of Bristol, and colleagues wrote.

“The oral anticoagulant warfarin ... is effective for prevention of stroke in patients with atrial fibrillation,” they added. “However, bleeding associated with warfarin is among the top five reasons for hospital stays, secondary to adverse drug effects, in England.”

López-López and colleagues performed a systematic review and network meta-analysis of 23 randomized trials comprising 94,656 patients to determine the efficacy, safety and cost-effectiveness of five direct-acting oral anticoagulants (DOACs), including Eliquis (apixaban, Bristol-Myers Squibb), Bevyxxa (betrixaban, Portola Pharmaceuticals), Savaysa (edoxaban, Daiichi-Sankyo), Xarelto (rivaroxaban, Janssen) and Pradaxa (dabigatran, Boehringer Ingelheim), for the prevention of stroke in patients with atrial fibrillation in comparison to warfarin. Of the included studies, 13 compared a DOAC with warfarin.

The researchers found that compared with warfarin, the risk for stroke or systemic embolism decreased with 5 mg of apixaban twice daily (OR = 0.79; 95% CI, 0.66-0.94), 150 mg of dabigatran twice daily (OR = 0.65; 95% CI, 0.52-0.81), 60 mg of edoxaban once daily (OR = 0.86; 95% CI, 0.74-1.01) and 20 mg of rivaroxaban once daily (OR = 0.88; 95% CI, 0.74-1.03).

Patients treated with 60 mg of edoxaban once daily (OR = 1.33; 95% CI, 1.02-1.75) or 20 mg of rivaroxaban once daily (OR = 1.35; 95% CI, 1.03-1.78) had a higher risk for stroke or systemic embolism than those treated with 150 mg of dabigatran twice daily. All DOACs studied lowered the all-cause mortality risk compared with warfarin.

The risk for major bleeding decreased with use of 5 mg of apixaban twice daily (OR = 0.71; 95% CI, 0.61-0.81), 110 mg of dabigatran twice daily (OR = 0.8; 95% CI, 0.69-0.93), 30 mg of edoxaban once daily (OR = 0.46; 95% CI, 0.4-0.54) and 60 mg of edoxaban once daily (OR = 0.78; 95% CI, 0.69-0.9), compared with warfarin.

Patients were more likely to experience major bleeding when treated with 150 mg of dabigatran twice daily vs. 5 mg of apixaban twice daily (OR = 1.33; 95% CI, 1.09-1.62), 20 mg of rivaroxaban twice daily vs. 5 mg of apixaban twice daily (OR = 1.45; 95% CI, 1.19-1.78) and 20 mg of rivaroxaban twice daily vs. 60 mg of edoxaban once daily (OR = 1.31; 95% CI, 1.07-1.59).

Compared with warfarin, most DOACs substantially reduced the risk for intracranial bleeding, but some increased the risk of gastrointestinal bleeding. Use of 5 mg of apixaban twice daily showed the highest net benefit, followed by 20 mg of rivaroxaban once daily, 60 mg of edoxaban once daily and 150 mg of dabigatran twice daily, according to the researchers.

“DOACs appear to be at least equivalent to warfarin at preventing stroke in patients with atrial fibrillation and to carry a reduced risk of bleeding,” López-López and colleagues concluded. “They overcome some of the limitations associated with warfarin and may lead to increased use by patients with atrial fibrillation. The cost of anticoagulation may be greatly reduced once generic DOACs become available.”

“Further long-term data may bring other insights with respect to safety, and it is important to identify patient groups that may not benefit from DOACs, as well as to develop drugs to reverse the anticoagulant effects of each DOAC,” they added. – by Alaina Tedesco

Disclosure: López-López reports no relevant financial disclosures. Please see study for all other authors’ relevant financial disclosures.

In patients with atrial fibrillation, direct-acting oral anticoagulants lowered the risk for stroke, systemic embolism and all-cause mortality while also reducing the risk for major and intracranial bleeding, compared with warfarin, according to research published in BMJ.

Atrial fibrillation increases the risk of thromboembolic stroke fivefold,” José A López-López, BSc, MSc, PhD, from the department of population health sciences at the University of Bristol, and colleagues wrote.

“The oral anticoagulant warfarin ... is effective for prevention of stroke in patients with atrial fibrillation,” they added. “However, bleeding associated with warfarin is among the top five reasons for hospital stays, secondary to adverse drug effects, in England.”

López-López and colleagues performed a systematic review and network meta-analysis of 23 randomized trials comprising 94,656 patients to determine the efficacy, safety and cost-effectiveness of five direct-acting oral anticoagulants (DOACs), including Eliquis (apixaban, Bristol-Myers Squibb), Bevyxxa (betrixaban, Portola Pharmaceuticals), Savaysa (edoxaban, Daiichi-Sankyo), Xarelto (rivaroxaban, Janssen) and Pradaxa (dabigatran, Boehringer Ingelheim), for the prevention of stroke in patients with atrial fibrillation in comparison to warfarin. Of the included studies, 13 compared a DOAC with warfarin.

The researchers found that compared with warfarin, the risk for stroke or systemic embolism decreased with 5 mg of apixaban twice daily (OR = 0.79; 95% CI, 0.66-0.94), 150 mg of dabigatran twice daily (OR = 0.65; 95% CI, 0.52-0.81), 60 mg of edoxaban once daily (OR = 0.86; 95% CI, 0.74-1.01) and 20 mg of rivaroxaban once daily (OR = 0.88; 95% CI, 0.74-1.03).

Patients treated with 60 mg of edoxaban once daily (OR = 1.33; 95% CI, 1.02-1.75) or 20 mg of rivaroxaban once daily (OR = 1.35; 95% CI, 1.03-1.78) had a higher risk for stroke or systemic embolism than those treated with 150 mg of dabigatran twice daily. All DOACs studied lowered the all-cause mortality risk compared with warfarin.

The risk for major bleeding decreased with use of 5 mg of apixaban twice daily (OR = 0.71; 95% CI, 0.61-0.81), 110 mg of dabigatran twice daily (OR = 0.8; 95% CI, 0.69-0.93), 30 mg of edoxaban once daily (OR = 0.46; 95% CI, 0.4-0.54) and 60 mg of edoxaban once daily (OR = 0.78; 95% CI, 0.69-0.9), compared with warfarin.

Patients were more likely to experience major bleeding when treated with 150 mg of dabigatran twice daily vs. 5 mg of apixaban twice daily (OR = 1.33; 95% CI, 1.09-1.62), 20 mg of rivaroxaban twice daily vs. 5 mg of apixaban twice daily (OR = 1.45; 95% CI, 1.19-1.78) and 20 mg of rivaroxaban twice daily vs. 60 mg of edoxaban once daily (OR = 1.31; 95% CI, 1.07-1.59).

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Compared with warfarin, most DOACs substantially reduced the risk for intracranial bleeding, but some increased the risk of gastrointestinal bleeding. Use of 5 mg of apixaban twice daily showed the highest net benefit, followed by 20 mg of rivaroxaban once daily, 60 mg of edoxaban once daily and 150 mg of dabigatran twice daily, according to the researchers.

“DOACs appear to be at least equivalent to warfarin at preventing stroke in patients with atrial fibrillation and to carry a reduced risk of bleeding,” López-López and colleagues concluded. “They overcome some of the limitations associated with warfarin and may lead to increased use by patients with atrial fibrillation. The cost of anticoagulation may be greatly reduced once generic DOACs become available.”

“Further long-term data may bring other insights with respect to safety, and it is important to identify patient groups that may not benefit from DOACs, as well as to develop drugs to reverse the anticoagulant effects of each DOAC,” they added. – by Alaina Tedesco

Disclosure: López-López reports no relevant financial disclosures. Please see study for all other authors’ relevant financial disclosures.