Jennifer Harris, MD

Altavilla R, Caso V, Bandini F, Agnelli G, Tsivgoulis G, Yaghi S, et al. Anticoagulation After Stroke in Patients With Atrial Fibrillation: To Bridge or Not With Low-Molecular-Weight Heparin? Stroke. 2019; 50:2093–2100

Despite evidence that it might be harmful, some clinicians still use bridging therapy with low-molecular-weight heparin (LWMH) to prevent early recurrent stroke in patient with acute stroke and history of atrial fibrillation. In the August issue of Stroke, Altavilla et al. report the results of pooled observational data from RAF (Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation) and RAF NOAC (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non–Vitamin K Oral Anticoagulants) to shed some light on the clinical characteristics and differences in outcomes of patients who received or did not receive bridging therapy.

The primary outcome was a composite of ischemic stroke, TIA, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after acute ischemic stroke.

Out of a total of 1780 patients, 561 patients (31%) were initiated on vitamin K antagonists, and 1219 patients (68%) were initiated on NOAC. Out of those, 20% had bridging with LMWH before oral anticoagulation (44.7% on vitamin K antagonists and 9.8% on an NOAC). There was no difference in initiation of therapy in between the bridging group versus the nonbridging group, median of 7 and 8 days, respectively. There was also no difference in NIHSS admission score between the bridging and nonbridging groups, mean 7.2 +/-6.3 and 7.7+/- 6.2, respectively. However, patients undergoing bridging therapy were more likely to be younger, male sex, had a lower CHA2 DS2 -VASc score, more likely to have medium sized infarcts and less likely to have large anterior circulation infarcts or leukokaraiosis. Within the bridging group, 41 of 371 patients (11%) were taking an antiplatelet agent (aspirin 100mg daily or Plavix 75mg daily), compared to 200 out of 1439 patients (13.9%) in the nonbridging group, which was not statistically significant.

The study found that more patients in the bridging group experienced the combined outcome compared to the nonbridging group (11% vs 5.1%, p=0.0001). Patients in the bridging group also had higher events of major bleeding compared to the nonbridging group (5% vs2.3% p=0.008), which is in line with results of previous studies. Interestingly, patients in the bridging group also had a higher risk of ischemic events compared to the nonbridging group (7.8% vs 3.1% p=0.0001). This association was still significant even after multivariable analysis and propensity score matching.

Why ischemic events occurred more frequently in the bridging versus the nonbridging group is somewhat unclear. The authors offered several explanations, including possible underdosing of heparin, as well as possible confounding by unmeasured variables. Furthermore, it is possible that patients selected for a bridging had a higher risk of recurrent embolism to begin with.   

There was also an increase in ischemic events in the nonbridging group in patients treated with vitamin K antagonists, compared to patients in the nonbridging group treated with a NOAC (5.5% vs 2.5% p=0.015), which is thought to be due to the immediate anticoagulation achieved by NOAC’s, as compared to vitamin K antagonists, and further supports the notion that NOAC’s should be preferred over warfarin for poststroke nonvalvular AF patients.

Although this might suggest that there were more ischemic events in the bridging group, because NOAC was less frequently used, this appears to be not the case since there was no statistical difference found in within each group according to type of anticoagulation used. Why bridging was used in the first place for the NOAC-treated patients in this study is also unclear since effective anticoagulation is achieved within a few hours.

Importantly, the study found that there was no difference in the rate of ischemic events when comparing bridging vs nonbridging restricted to vitamin K antagonists only (8.4% vs 6.8%, respectively), suggesting that bridging with LMWH followed by vitamin K antagonists has no role in the management of acute stroke in patients with atrial fibrillation. 

Despite several limitations, including observational trial design and its inherent inability to completely exclude the possibility of residual confounding, as well as differences in patient characteristics in the two groups, the data from this study adds to the evidence that there is no benefit and even possible harm in bridging with LMWH, and that NOACs should be the preferred treatment approach.