Recurrent stroke prevention: Continuing same DOAC more effective than switching in nonvalvular AF

In patients with nonvalvular atrial fibrillation (NVAF) who experience ischaemic stroke (IS) while on a direct oral anticoagulant (DOAC), continuing treatment with the same DOAC is more effective at preventing recurrent IS than switching to a different DOAC or warfarin, a Hong Kong population-based retrospective cohort study has shown.

“IS despite DOAC use is increasingly common and portends a high risk of subsequent IS,” wrote the researchers from the Chinese University of Hong Kong (CUHK). “[As] the efficacy and safety of antithrombotic regimens after IS are unclear, we aimed to compare the outcomes of patients with IS despite DOAC treatment with and without an alternative antithrombotic regimen.” [Neurology 2023;101:e358-e369]

The study included all patients who were admitted to Hong Kong’s public hospitals from 1 January 2015 to 31 December 2020 with IS despite DOAC use. A total of 2,337 patients with NVAF were included in the final analyses, of whom 1,652 patients (70.7 percent) remained on the same DOAC regimen (DOAC_same), 477 patients (20.4 percent) received an alternative DOAC (DOAC_switch), 122 patients (5.2 percent) were prescribed warfarin, and 86 patients (3.7 percent) stepped up from dabigatran 110 mg BID to 150 mg BID. Over a median follow-up of 16.5 months, 315 patients (13.4 percent) experienced another episode of IS.

“Compared with DOAC_same, warfarin [adjusted hazard ratio (aHR), 1.96; 95 percent confidence interval (CI), 1.29–3.02; p=0.002) and DOAC_switch [aHR, 1.62; 95 percent CI, 1.25–2.11; p<0.001] were associated with an increased risk of recurrent IS,” reported the researchers. “[S]witching to warfarin after a recurrent thrombotic episode while on DOACs is popular, but our study results caution against such practice unless strong indications, such as renal insufficiency, antiphospholipid syndrome or valvular AF, are present.” [Ir J Med Sci 2018;187:719-721; Europace 2021;23:1612-1676; J Thromb Thrombolysis 2017;44:435-441; Blood 2018;132:1365-1371]

“IS despite DOAC treatment is a common clinical conundrum faced by emergency, internal medicine, and stroke physicians worldwide. Our study provides the important insight that change isn’t always better, especially from the original DOAC to warfarin,” emphasized first author, Dr Bonaventure Ip of the Department of Medicine and Therapeutics at CUHK.

While DOAC_switch was associated with an increased risk of acute coronary syndrome (ACS; aHR, 2.18; 95 percent CI, 1.29–6.67; p=0.003), DOAC_switch and warfarin use were not associated with intracranial haemorrhage (ICH) or death. The researchers noted that although the incidence of ICH was numerically higher in the warfarin vs DOAC_same group, the sample size was not sufficient to detect statistical significance.

Of patients in the DOAC_same group, 15.1 percent were started on antiplatelet agents within 8 weeks of the first IS, in addition to their DOAC. Compared with patients in the DOAC_same group who did not receive any antiplatelet therapy, adjunctive antiplatelet treatment did not reduce the risk of recurrent IS, ICH, ACS, or death. “Although prior studies showed efficacy of aspirin in combination with rivaroxaban for cardiovascular protection in atherosclerotic diseases, our study suggests that this dual pathway inhibition strategy may not be similarly effective in a population purely consisting of patients with NVAF,” commented the researchers. [N Engl J Med 2017;377:1319-1330; Lancet 2018;391:219-229]

“Our study provides evidence-based guidance for antithrombotic management of NVAF patients after IS despite DOAC treatment,” concluded Professor Thomas Leung of the Division of Neurology at CUHK. “We also encourage patients with AF to seek regular medical follow-up and adhere to their DOAC regimen, which is of paramount importance to reduce the risk of recurrent IS.”