Efficacy of DOACs

As mentioned above, using warfarin to maintain an INR target range of 2–3 reduces the risk recurrent stroke by 64% in AF patients.7 DOACs further reduce recurrent stroke and systemic embolism by 14% compared with warfarin in non-valvular AF (from 6% to 5%), without increasing the risk of major bleeding.7 When evaluating these results, it is important to bear in mind that most of the original clinical trials comparing warfarin with DOACs were non-inferiority, rather than superiority, studies.46

While the studies investigated the risk of haemorrhage extensively, the definition of bleeding differed. Therefore, comparing the haemorrhage risk with the different DOACs is difficult. Nevertheless, the risk of haemorrhage was consistently comparable to or less than with warfarin.34 Moreover, 30-day mortality after a major bleeding episode was 13% with warfarin and 9% with a DOAC (dabigatran).47

A meta-analysis included 13 randomised controlled trials (RCT) and 27 observational studies, 32 involving AF patients and 8 people with venous thromboembolism. Overall, the results from the RCTs were consistent with the observational studies and showed that DOAC showed similar or superior efficacy and effectiveness to warfarin.43 

Some differences emerged between the DOACs. For example, in AF patients, apixaban, dabigatran and edoxaban – but not rivaroxaban – were associated with a 10% to 71% decreased risk of major bleeding, myocardial infarction, haemorrhagic stroke, all-cause mortality, and intracerebral haemorrhage compared with warfarin (Figure 20).43 

Results of a meta-analysis showing the effectiveness of DOAC in atrial fibrillation and venous thromboembolism

Figure 20. Results of a meta-analysis showing the effectiveness of DOAC in atrial fibrillation and venous thromboembolism.43

The choice of DOAC depends on several factors, including hepatic and renal function, potential for drug interactions, patient preference, cost and tolerability.34 For example, 15–20% of patients with CKD have AF.5 Renal function might influence the choice of DOAC: 85% of a dose of dabigatran is excreted unchanged in urine, compared with 27% and 33% of a dose of apixaban and rivaroxaban, respectively. Indeed, warfarin remains the anticoagulant of choice for patients with non-valvular AF and severe renal dysfunction.34 In addition, the risk of gastrointestinal bleeding may be higher with rivaroxaban, edoxaban and dabigatran compared with warfarin.47

Review direct oral anticoagulants in valvular atrial fibrillation

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