A Closer Look at the Updated 2018 Chest Guidelines Expert Panel on Atrial Fibrillation

Sarah Medina Pharm.D., West Side Community Health Services - St. Paul, MN

Background: In 2012, authors of the CHEST guidelines recommended vitamin K antagonists (VKAs) as the mainstay treatment for atrial fibrillation (AF). In 2018, the CHEST guidelines were updated to include direct oral anticoagulants (DOACs) as the preferred treatment option in patients with AF in valvular heart disease (VHD),excluding those with mechanical heart valves and those with significant mitral stenosis.Now, there is more evidence showing DOACs are better at preventing hemorrhagic stroke and embolic events compared to VKAs. In addition, patients should be stratified for risk of stroke by calculating their CHA2DS2-VASc. When considering VKAs, a validity tool known as the SAME-TT2R2 should be calculated.

Evidence: A subanalysis of the ROCKET-AF study examined outcomes for patients based on valve disease location, specifically comparing aortic stenosis to mitral regurgitation or aortic regurgitation. Although stroke or side effects occurred twice as often in the aortic stenosis group (4.21 events/100 patient-years) compared to the mitral regurgitation group, the aortic regurgitation group, and the non-VHD group (2.01 events/100 patient-years; P<0.05 and 2.09 events/100 patient-years; P<0.05 respectively), the efficacy of rivaroxaban was consistent among those with or without VHD.

The ARISTOTLE trial excluded patients with moderate or severe mitral stenosis and those with mechanical prosthetic heart valves. For subanalysis comparison, 4,808 (26%) patients had a history of moderate or severe VHD, the majority being mitral regurgitation. Patients with VHD were older (71 vs 69 years; P < 0.0001), more likely to have heart failure (48.6% vs 30.7%; P<0.0001), and less likely to have hypertension (85.3% vs 88.2%; P < 0.0001) and diabetes (22.6% vs 25.8%; P < 0.0001) when compared to the warfarin group. Apixaban efficacy was similar in prevention of stroke or side effects in those with VHD (1.46% apixaban vs 2.08% warfarin; HR 0.70 [95% CI 0.51-0.97] compared with those without VHD (apixaban 1.20% vs 1.43% warfarin; HR 0.79 [95% CI 0.67-1.04].

In the ENGAGE AF-TIMI 48 trial, a limited number of patients with other types of VHD were included. Of the 21,105 patients enrolled, 2824 (13%) of patients had a history of moderate or severe VHD, the most common being mitral regurgitation. Patients with VHD who received edoxaban 60 mg had similar rates of stroke or systemic embolism compared to those without VHD; HR 0.69 [95% CI 0.44-1.07] vs HR 0.91 [95% CI 0.53-1.02].

With ongoing use of VKAs, a validated tool called SAME-TT2R2 allows providers the ability to predict the likelihood of patients to succeed with this therapy. The formulation of SAME-TT2R2 is based on many clinical factors that impact a patient’s time within therapeutic range. A score of less than 2 correlates to a high likelihood of remaining within therapeutic range while on VKA treatment.

Discussion: Overall, each subanalysis of the DOAC trials indicated that efficacy did not differ between patients with or without VHD. In terms of safety, bleeding risk was about the same in dabigatran and apixaban, but rivaroxaban was associated with a higher risk of bleeding. Although the results are promising, the findings should be interpreted with caution as these were not prespecified subgroup analyses.

Clinical Thought: DOACs should be considered first line treatment in place of warfarin for patients with a history of atrial fibrillation and valvular heart disease (in the absence of significant mitral stenosis or mechanical heart valve) as these patients were just as effectively managed compared to those without valvular heart disease. Calculations such as CHA2DS2-VASc and SAME-TT2R2 can help identify which patients are at higher risk for stroke and those who are appropriate candidates for VKAs.

References:

  1. Guyatt, Gordon et al. Antithrombotic therapy and prevention of thrombosis 9th Ed. american college of chest physicians evidence-based practice guidelines. CHEST. 2012;141(2):7S-47S.

  2. Lip G, Freedman B, de Caterina R, et al. Stroke prevention in atrial fibrillation: Past, present and future. Thrombosis and Haemostasis. 2017;1230-1240.

  3. Czuprynska J, Patel, J, Arya R, et al. Current challenges and future prospects in oral anticoagulant therapy. Br J Haematol. 2017 Sep;178(6):838-851. doi: 10.1111/bjh.14714.

  4. Anderson S, Marrs J. Direct oral anticoagulant use in valvular heart disease. Clinical Medicine Insights: Therapeutics. 2017;10:1-6.