Effect of Apixaban on all-cause death in patients with atrial fibrillation: a meta-analysis based on imputed placebo effect

Purpose: Vitamin K antagonists (VKAs) are the standard of care for stroke prevention in patients with atrial fibrillation (AF); therefore, there is not equipoise when comparing newer oral anticoagulants with placebo in this setting. Methods: To explore the effect of apixaban on mortality in patients with AF, we performed a meta-analysis of apixaban versus placebo using a putative placebo analysis based on randomized controlled clinical trials that compared warfarin, aspirin, and no antithrombotic control. We used data from two prospective randomized controlled trials for our comparison of apixaban versus warfarin (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) and apixaban versus aspirin (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment). Using meta-analysis approaches, we indirectly compared apixaban with an imputed placebo with respect to the risk of death in patients with AF. We used results from meta-analyses of randomized trials as our reference for the comparison between warfarin and placebo/no treatment, and aspirin and placebo/no treatment. Results: In these meta-analyses, a lower rate of death was seen both with warfarin (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.57–0.97) and aspirin (OR 0.86, 95% CI 0.69–1.07) versus placebo/no treatment. Using data from ARISTOTLE and AVERROES, apixaban reduced the risk of death by 34% (95% CI 12–50%; p = 0.004) and 33% (95% CI 6–52%; p = 0.02), respectively, when compared with an imputed placebo. The pooled reduction in all-cause death with apixaban compared with an imputed placebo was 34% (95% CI 18–47%; p = 0.0002). Conclusions: In patients with AF, indirect comparisons suggest that apixaban reduces all-cause death by approximately one third compared with an imputed placebo

Ticagrelor as an Alternative for Clopidogrel-Associated Acute Arthritis

A 65-year-old Caucasian man was hospitalized for a non-ST-elevation myocardial infarction. On discharge, the patient was started on multiple new medications, including clopidogrel and atorvastatin. Twenty-six days after discharge, he presented to the Emergency Department (ED) with polyarthralgias. He was instructed to stop atorvastatin and to follow up with rheumatology and cardiology clinic. At cardiology clinic follow-up 43 days after ED discharge, clopidogrel was discontinued and patient was switched to ticagrelor. On follow-up one month later, his symptoms had completely resolved. During the next 4 months, patient had routine follow-up due to participation in Cardiopulmonary Rehab and he had no cardiac events or recurrence of joint symptoms. Our patient had no history of arthritis. Because he initially presented with 2 medication classes associated with arthritis, each was withdrawn separately. The temporal association of patient’s symptomatic improvement strongly suggests that the arthritis was caused by clopidogrel. Our patient was able to tolerate ticagrelor with complete resolution of his arthritis and no cardiac events. Clopidogrel-induced arthritis is a rare adverse drug event. For patients with a recent drug-eluting stent, alternative antiplatelet therapy with ticagrelor may provide positive cardiac outcomes without similar adverse effects