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Which NOAC for which Patient with Nonvalvular AF?

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Dr Srinivasa Rao Maddury, Hyderabad    06 January 2018

  1. Rivaroxaban and edoxaban are given once-daily; apixaban and dabigatran given twice-daily. Rivaroxaban needs to be given with food to facilitate gut absorption. Renal clearance for dabigatran is 80%, adaxoban 50%, rivaroxaban 33% and apixaban 25%.
  2. Dose reductions for NOACs is needed in renal dysfunction. Dabigatran is not recommended with CrCl <30, apixaban <15 mL. Although rivaroxaban and edoxaban are not recommended below CrCl of 15 mL, caution should be exercised if CrCl <30 mL.
  3. Patients with AF have other comorbidities: HT (70-80%), HF (40%), coronary disease (30%), diabetes (25%); hence they are already taking many pills. If they want to reduce their pill burden, rivaroxaban and edoxaban taken once-daily would be the preferred choices.
  4. Dabigatran is a prodrug, highly acidic in nature and tends to get activated in GI wall. It produces more GI irritation and may enhance GI bleed in those patients with tendency to GI bleed. So, it may be given with food to minimize the gastric irritation. Dabigatran may not be right choice in these subset of patients.
  5. Although there is no head-to-head trial comparing different NOACs with each other, from the individual clinical trials with each of the NOAC, dabigatran 150 mg b.i.d. was far superior in preventing ischemic stroke. In RE-LY trial, dabigatran has shown a 34% risk reduction (rivaroxaban and edoxaban 22%, apixaban 22% in ROCKET, ARISTOTEL and ENGAGE AF trials, respectively). Hence, dabigatran may be preferred choice in those who have highest risk ischemic stroke.
  6. GI absorption of NOACs is influenced by P-glycoprotein(P-gp) in GI tract. Concomitant administration of known P-gp inhibitors e.g., quinidine, verapamil, ketoconazole, cyclosporine, dronedarone, amiodarone and certain macrolide antibiotics influences the plasma levels of NOACS; hence, dose reduction is needed. In the presence of reduced renal function with a NOAC like dabigatran, which has 80% excretion through renal route, a concomitant administration of above drugs is likely to increase plasma levels of dabigatran. Hence, in these situations apixaban which has least renal clearance may be a better choice.c

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