Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study

Abstract

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Recurrent Ischemic Stroke and Cardiovascular Outcomes in Patients With Atrial Fibrillation With Ischemic Stroke Despite Direct Oral Anticoagulants

“…Our data also supported that the switch from original DOACs to another DOACs may not lead to a significant benefit in reducing the risk of recurrent IS. [1][2][3][4] However, a benefit may be exhibited if we broaden the outcomes to MACEs since a higher incidence of cardiovascular events may be noted in stroke patients with atrial fibrillation. Further investigation may be warranted to develop an exact algorithm for DOAC failure.…”

New score for predicting thromboembolic events in patients with atrial fibrillation using direct oral anticoagulants

“…et al [19] showed that recurrent thromboembolic events in patients with atrial fibrillation who suffered an acute stroke while on treatment with DOACs were associated with hypertension. Carlisle et al [20] also found that hypertension (hazard ratio 1.50; 95% CI 1.09-2.06; P ¼ 0 0.01) was significantly associated with thromboembolic events in a multivariate Cox proportional risk analysis of 18 955 atrial fibrillation patients taking DOACs in the ORBIT-AF I and II registries.…”

Stroke Prevention in Atrial Fibrillation: Our Current Failures and Required Research

“…The recently published RENO-EXTEND Study showed a recurrent IS and SE rate of 9.7 per 100 patient-years in patients with NVAF who suffered an acute IS while on treatment with DOACs. 45 Overall, the risk of recurrent IS among patients with NVAF who survived an IS while using warfarin or DOAC can be up to 10× higher when compared with IS risk in DOAC RCTs that enrolled low-risk patient populations. 5,48 IS on OAC, that is, OAC failure, is a particularly difficult problem as there does not seem to be a simple medical management strategy that could reduce the high recurrence risk.…”

“…The recently published RENO-EXTEND Study showed a recurrent IS and SE rate of 9.7 per 100 patient-years in patients with NVAF who suffered an acute IS while on treatment with DOACs. 45…”

“…PDLs (including the smallest ones) have been reported in up to 32% of LAAC series with previous generation devices. 59 A PDL ≤5 mm was considered to be acceptable per FDA both at the time of implantation and at the 45 echocardiography, and discontinuation of anticoagulation was allowed per study protocols. Larger PDLs have been reported in 0.7% of over 50 000 LAAC procedures.…”