Non‐vitamin K Oral Anticoagulants Versus Warfarin for Patients with Atrial Fibrillation: Absolute Benefit and Harm Assessments Yield Novel Insights

Abstract

SUMMARYBackground and Objectives: Benefits and/or harms (including costs) of non-vitamin K oral anticoagulants (NOACs) versus warfarin therapy need appreciation in relative and absolute terms. Methods: Accordingly, we derived clinically relevant relative and absolute benefit/harm parameters for NOACs (apixaban, dabigatran, rivaroxaban, edoxaban) compared to warfarin from four clinical trials involving atrial fibrillation (AF) patients. For each trial, we tabulated patient numbers enduring four important outcomes and calculated unadjusted relative risk reduction (RRR) and number needed to treat (NNT)/year values (and 95% confidence intervals) for the NAOC compared to warfarin. These outcomes were as follows: stroke/systemic embolism (primary endpoint), hemorrhagic stroke, major bleeds, and death. We also addressed drug acquisition costs. Results: Each NOAC was noninferior to warfarin for primary-outcome prevention; RRRs were 12-33% and NNT/year values were 182-481, and all but one indicated statistically significant superiority. All the NOACs yielded statistically significant reductions in hemorrhagic stroke risk; RRRs were 42-74% and NNT/year values were 364-528. Major bleeding risk was comparable in both groups. Apixaban yielded a lower NNT/year for preventing death than for primary-outcome prevention. Compared to warfarin, NOAC acquisition costs were 70-to 140-fold greater. Conclusions: For the primary outcome, the absolute benefits of NOACs were modest (NNT/year values being large). Reduced hemorrhagic stroke rates with NOACs could be due to superior embolic infarct prevention and fewer consequential hemorrhagic transformations. Among apixaban recipients, the absolute mortality benefit exceeded that for the primary outcome, indicating prevention of additional unrelated deaths. The substantially greater NOAC acquisition costs need viewing against probable greater safety and the avoidance of monitoring bleeding risks.

Pharmacogenetic studies with oral anticoagulants. Genome-wide association studies in vitamin K antagonist and direct oral anticoagulants

“…However, DOACs have greater acquisition costs. Thus, greater cost versus greater efficacy/safety profile and avoidance of monitoring have to be balanced [ 112 ]. A review of the use of DOACs in an elderly population with non-valvular AF demonstrated that they are beneficial and lead to a reduction of stroke risk in this population [ 76 ].…”

Trends of ambulatory oral anticoagulant prescription in five major cities of China, 2012–2017

“…In China, three NOACs (rivaroxaban, dabigatran and apixaban) were approved sequentially for clinical use since 2009. Considering the high price of NOACs in China, the costutility of NOACs should be carefully re-evaluated [8]. It can be foreseen that there is a great demand of NOACs in China due to the high burden of diseases needing anticoagulation therapy [9,10].…”

<p>Using non-vitamin K oral anticoagulants in specific patient populations: a study of Korean cases</p>

“…Therefore, patients with a high risk of relapse, such as those with cancer, must pay the cost of NOACs by themselves after the first 6 months and the actual prescription rate of NOACs after the first 6 months cannot be identified using the Korean Health Insurance Review and Assessment Service (HIRA) databases. 12 Absolute benefits and harms of NOACs in NVAF patients using the number needed to treat (NNT) and/or number needed to harm (NNH) were addressed in several reports including a study conducted by Kumana et al 122 Kumana et al showed absolute benefits of NOACs for primary-outcome prevention were modest in terms of NNT/year value (eg, 182-481, Table 3) with greater acquisition costs compared to warfarin. 122 However, these findings should be considered with benefits from avoidance of INR monitoring and its impact on the quality of life, etc.…”

“…12 Absolute benefits and harms of NOACs in NVAF patients using the number needed to treat (NNT) and/or number needed to harm (NNH) were addressed in several reports including a study conducted by Kumana et al 122 Kumana et al showed absolute benefits of NOACs for primary-outcome prevention were modest in terms of NNT/year value (eg, 182-481, Table 3) with greater acquisition costs compared to warfarin. 122 However, these findings should be considered with benefits from avoidance of INR monitoring and its impact on the quality of life, etc. 122 Therefore, we need to focus on the long-term cost-effectiveness of NOACs.…”

“…122 However, these findings should be considered with benefits from avoidance of INR monitoring and its impact on the quality of life, etc. 122 Therefore, we need to focus on the long-term cost-effectiveness of NOACs. To our knowledge, three studies assessed the costeffectiveness of NOACs compared to warfarin in Korean patients as shown in Table 7.…”