Re-evaluating Safety and Effectiveness of Dabigatran Versus Warfarin in a Nationwide Data Environment: A Prevalent New-User Design Study

Abstract

Introduction The new user cohort design is widely used to assess the effects of a new drug, such as dabigatran, but inherently excludes some users due to prior use of the comparator drug, for example warfarin. The prevalent new-user design offers a solution that includes all eligible users of the new drug. Objective To evaluate the safety and effectiveness of dabigatran versus warfarin in non-valvular atrial fibrillation (NVAF) patients with prevalent new-user design. Methods Taiwan National Health Insurance and mortality data from 2011 through 2015 were utilized. From an incident NVAF cohort, we identified dabigatran initiators as either incident or prevalent (switchers from warfarin) new users. Time- and prescription-based exposure sets were formed for dabigatran initiators to account for prior warfarin prescriptions. A comparable warfarin user was matched on the time-conditional propensity score to the dabigatran initiator in each set. The matched patients were followed for clinical outcomes, with Cox proportional hazards model used to estimate hazard ratios (HRs). Results There were 10,811 dabigatran initiators, including 22% prevalent new users (switchers), who formed the exposure sets and were matched 1:1 to warfarin users. Dabigatran use was associated with lower risks of intracranial hemorrhage (HR 0.51; 95% confidence interval [CI] 0.39, 0.66) and gastrointestinal bleeding (HR 0.81; 95% CI 0.70, 0.92), compared with warfarin use. These effects were similar between the incident and prevalent new users. Conclusion Using a design that includes both incident and prevalent new users of dabigatran, the use of dabigatran is associated with lower major bleeding risk than warfarin use among patients with incident NVAF. Electronic supplementary material The online version of this article (10.1007/s40801-019-0156-2) contains supplementary material, which is available to authorized users.

Switching of oral anticoagulants in patients with nonvalvular atrial fibrillation: A narrative review

“…Of these, 36 reported the rate of OAC switching, 27,32–66 13 of which also conducted predictor analysis for switching 32,34–36,42,44,48,53,55,57,62,63,65 . Five studies assessed clinical outcomes of switching, 27,37,67–69 while three investigated reasons for switching 46,47,66 . The sample size ranged between 233 66 and 486 215 55 NVAF patients.…”

The Risk of Gastrointestinal Bleeding between Non-Vitamin K Antagonist Oral Anticoagulants and Vitamin K Antagonists in the Asian Atrial Fibrillation Patients: A Meta-Analysis

“…Then sixty-four articles without GIB data or using inappropriate statistical methods were ruled out. Fifteen articles probably extracted from the identical database or the same population were not applied [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Sixteen articles investigating non-Asians or not fully Asians were not enrolled [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ].…”

Comparison of the outcomes of the prolonged antianginal therapy use in stable coronary artery disease patients according to the data of randomized and observational studies

“…Nevertheless, OS helps to clarify how data from RCT on effectiveness and safety of drugs are realized in clinical practice. Thus, for example, it was found that effectiveness of direct oral anticoagulants (DOAC) in prevention of stroke, according to RCT, exceeded warfarin and in conditions of RCP was true only for new users of DOAC, but not for patients who have previously taken warfarin [ 5 , 17 ].…”

“…On the other hand, there is evidence that in real clinical practice (RCP) efficiency of medications proved by the results of RCT was less pronounced and convincing [ 5 , 6 ]. This can be explained by the difference of conditions and characteristics of different study designs – RCT and observational studies (OS), for example, strict inclusion and exclusion criteria, which usually limit participation in RCT of some patient categories (elderly, patients with severe comorbidities, multicomponent concomitant therapy, etc) [ [7] , [8] , [9] ].…”