Safety and Efficacy of Direct Oral Anticoagulants (DOACs) versus Warfarin for Valvular Atrial Fibrillation

Safety and Efficacy of Direct Oral Anticoagulants (DOACs) versus Warfarin for Valvular Atrial Fibrillation
Anna Insley, PharmD, Welia Health

BackgroundThe 2018 CHEST Guidelines for Antithrombotic Therapy for Atrial Fibrillation set forth a framework for anticoagulant therapy for stroke prevention in patients with atrial fibrillation. The majority of the evidence and guidance contained in this document centers around atrial fibrillation secondary to nonvalvular causes. These guidelines do, however, address the ambiguity in the definition and recommendations for pharmacologic therapy in patients with valvular atrial fibrillation.

There has previously been large variability in the definitions of valvular atrial fibrillation and in the exclusion criteria within primary evidence. The CHEST guidelines define the necessity of a vitamin K antagonist for patients with moderate-to-severe mitral stenosis of rheumatic origin and mechanical prosthetic heart valve replacement. They define therapy with either a vitamin K antagonist or a direct oral anticoagulant (DOAC), also considering CHADS2VASC risk factors, for patients with mitral regurgitation, mitral valve repair, aortic stenosis, aortic regurgitation, tricuspid regurgitation, tricuspid stenosis, pulmonary regurgitation, pulmonic stenosis, bioprosthetic valve replacement and trans-aortic valve intervention. Evidence for the safety and efficacy of DOACs for atrial fibrillation with valvular heart disease has also been ambiguous. Recent evidence has emerged to further suggest safety and efficacy of DOACs for patients with valvular atrial fibrillation.

Evidence: Evidence for the safety and efficacy of DOACs over warfarin in patients with valvular atrial fibrillation, contained in the publication by Dawwas et al, was recently published. This was a new-user, retrospective, propensity score-matched, cohort study that evaluated commercial healthcare claims data for patients newly started on warfarin versus a DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) between January 1, 2010 through June 30, 2019. Their primary outcome related to effectiveness was to evaluate the composite of ischemic stroke or systemic embolism through evaluation of ICD-9 and ICD-10 codes. Their primary outcome related to safety was to evaluate a composite of intracranial or gastrointestinal bleeding through evaluation of ICD-9 and ICD-10 codes.

Eligible participants included those that were over the age of 18 years with a diagnosis of atrial fibrillation and valvular heart disease (aortic, mitral, tricuspid, or pulmonary valve) that was documented in at least one inpatient or two outpatient visits. Those excluded had end-stage renal disease, were status post hip or knee replacement, had a history of ischemic stroke or systemic embolism, or had a bioprosthetic or mechanical valve replacement. Participants were followed until the end of the study period or until they were censored (treatment discontinuation, gap in care, switch in therapy, outcome occurrence or disenrollment). Death of a participant was considered disenrollment.

Participants were matched in a 1:1 ratio based on propensity score to account for confounding variables. The study included 28,168 newly started DOAC patients and 28,168 newly started warfarin patients. The mean age among study participants was 81 years with nearly 50% being male. 55% of participants had a diagnosis of mitral valve disease, 41% had aortic valve disease and 18.5% had tricuspid valve disease. Comorbid conditions were most commonly hypertension, hyperlipidemia and heart failure. 

The authors found that DOACs decreased the risk of ischemic stroke or systemic embolism in comparison to warfarin (HR 0.64 [95% CI 0.59 – 0.70]). The absolute reduction in the probability of stroke or systemic embolism with DOACs versus warfarin was 0.015 within 6 months and 0.026 within one year. These results were consistent across individual DOACs. Additionally, they found a decrease in the risk of major bleeding with DOACs in comparison to warfarin (HR 0.67 [95% CI 0.63 – 0.72]). The absolute reduction in probability of a major bleed with DOACs versus warfarin was 0.019 within six months and 0.035 within one year. This was also found to be consistent among individual DOACs. 

Discussion and Clinical Impact: This study adds to a limited body of evidence for the safe and effective use of DOACs for patients with valvular heart disease. It provides a large amount of longitudinal data that examines patient outcomes over a relatively long time period. The study also included patients with different types of valvular heart disease, stroke and bleed risk. Per the authors, they did not have access to lifestyle variables, over-the counter medication-use or severity of valvular disease. Additionally, the 2018 CHEST guidelines state that patients with bioprosthetic valve replacements may receive either a DOAC or warfarin while patients with mechanical prosthetic heart valves and moderate-to-severe mitral stenosis of a rheumatic origin must receive warfarin. Patients with bioprosthetic or mechanical heart valves were excluded from this study and we do not know the severity of valvular disease for participants included. Therefore, this may not provide strong new evidence for specific valvular heart diseases. There are certainly cases in which this data would not be applicable, however, this data does contribute to our overall knowledge of the safety and efficacy of DOACs for atrial fibrillation patients with valvular heart disease. This data should most certainly be considered when thinking of patient-specific factors (such as convenience) as well as the risk versus benefit of starting specific anticoagulants in patients with valvular heart disease. This is an area that requires further study.

 

References:

  1. Dawwas GK, Dietrich E, Cuker A, et al. Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Valvular Atrial Fibrillation. [published online March 30, 2021] Ann Intern Med. doi:10.7326/m20-6194 

  2. Lip GY, Banerjee A, Boriani G, et al. Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest. 2018;154(5):1121-1201. doi: 10.1016/j.chest.2018.07.040