New Anticoagulation Medications for Atrials Fibrillation

Abstract

year; RR 1.5; 95% CI: 1.19-1.89; p<0.001). The warfarin group had 64% in the mean time in therapeutic range and based on the findings, the FDA approved the 150 mg BID dosing regimen. Dabigatran was well tolerated except dyspepsia was more common associated with it versus warfarin (11.3% vs. 5.8% respectively; p <0.001). Note that additionally analysis of RE-LY raised concerns of increased rate of myocardial infarction (MI) was seen with dabigatran compared to warfarin (0.74% per year vs. 0.53% per year; RR 1.38, 95% CI, 1.001.91; p=0.048). Twenty-eight more cases of silent MI were identified during the reanalysis period, that changed the statistically significant difference between dabigatran and warfarin for this outcome (0.81% per year vs. 0.64% per year; RR 1.27; 95% CI, 0.94-1.71; p=0.12) [5,6]. Also, Boehringer Ingelheim confirmed serious cases and potentially life-threatening bleeding associated with dabigatran between March 2008 and October 2011 [7,8]. There were 260 fatal bleeding events worldwide that triggered safety concerns and the need for regular assessment of kidney function and dabigatran use. Rivaroxaban was compared to warfarin in the ROCKET AF trial. The study was a multicentered, randomized, double-blind, doubledummy, event-driven trial, which enrolled 14,264 NAF patients at moderate to high risk for stroke. In contrast to the RE-LY trial, patients who were on warfarin for the ROCKET AF had therapeutic International Normalized Ratio 55% of the time. For the per protocol patient population, rivaroxaban was proven to be noninferior to warfarin in the primary efficacy composite endpoint of stroke and systemic embolism (Hazard Ratio [HR]: 0.79, 95% CI: 0.66-0.96, p<0.001). As for the intention to treat population, rivaroxaban was also noninferior to warfarin, but it fails to show superiority over warfarin (HR: 0.88, 95% CI: 0.74 to 1.03, p<0.001 for noninferiority, and p=0.12 for superiority). Mortality rates were similar between the treatment groups for the as treated population (HR: 0.85, 95% CI: 0.70 to 1.02, p=0.07) and in the intention to treat population (HR: 0.92, 95% CI: 0.82 to 1.03, p=0.15). Patients in the rivaroxaban group had lower rates of critical bleeding, fatal bleedings, and intracranial hemorrhages (p=0.007, p=0.003, p=0.02, respectively) [9]. Advantages of rivaroxaban over dabigatran are that rivaroxaban is the once daily dosing, and can be crushed and mixed with applesauce in patients who are unable to swallow tablets. For patients with nasogastric tube or feeding tube, rivaroxaban can be crushed and suspended in water. In addition to NAF, rivaroxaban is indicated for the treatment and prevention of deep vein thrombosis and pulmonary embolism. One specific dose is approved for each indication so healthcare professionals need to be extremely cautious when prescribing rivaroxaban [10]. The ARISTOTLE compared apixaban with warfarin in a multicentered, randomized, double-blinded, double dummy study. Eighteen-thousand two hundred patients with NAF and at least 1 risk factor for stroke were enrolled. Patients on warfarin had a therapeutic INR 62.2% of the time. Patients in the apixaban group has lower rates of stroke or systemic embolism (HR: 0.79, 95% CI: 0.66 to 0.95, p<0.001 for noninferiority and p=0.01 for superiority), and lower mortality rates (HR: 0.89, 95% CI: 0.80 to 0.99, p=0.047). Additionally, less patients in the apixaban group experienced intracranial bleeding (HR: 0.42, 95% CI: 0.30-0.58, p<0.001) or major or clinically relevant non-major bleeding (HR: 0.68, 95%CI 0.61-0.75, p<0.001) [11]. Advantages of apixaban are that doses do not need to be adjusted unless patients have at least 2 factors: age of 80 years or greater, serum creatinine of 1.5 mg/dl or greater, or body weight less than 60 kg. Disadvantages include the twice daily dosing, not recommended for CLcr<15 mL/min or hemodialysis, and no information available on crush or administration through feeding tube [11]. All of the new anticoagulants have the advantage of having a predictable drug effect, faster onset of action, and less need for monitoring as compared to warfarin. The decision of selecting one anticoagulant over another may be difficult. Although all of the new anticoagulants were noninferior in preventing stroke or systemic embolism, apixaban is the only one proven to be superior as compared to warfarin, and is the only one shown to reduce risk of death from any cause [4,9,12]. While dabigatran does not reduce risks of death, it reduces risks of death from vascular causes (p=0.04). Based on the