Alteplase can stave off death in stroke patients with AF not undergoing thrombectomy

The thrombolytic drug alteplase appears to confer survival gains in acute ischaemic stroke patients with atrial fibrillation (AF), especially those who are not undergoing mechanical thrombectomy (MT), as shown in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study.

“We found that intravenous alteplase treatment was associated with a reduced 90‐day mortality in patients with acute ischaemic stroke in the setting of AF who were not treated with MT. Among patients undergoing MT, there was a nonsignificantly lower number of passes and mortality in [those who did vs did not receive] intravenous alteplase,” according to the investigators.

“The benefit of intravenous alteplase in acute stroke within 4.5 hours of onset is now well established, but up to 25 percent of eligible patients fail to receive [the said] treatment partially as a consequence of provider bias,” they added. 

This analysis indicates that intravenous alteplase should be given to eligible AF patients with acute ischaemic stroke, despite the slightly higher risk of a haemorrhagic conversion within this subgroup. [Neurology 2016;87:1565-1574]

In IAC, the investigators retrospectively analysed the medical records of 1,889 consecutive patients (mean age 77.2 years, 51.8 percent female) with acute ischaemic stroke diagnosed with AF. Of these, 32.0 percent had a history of stroke or transient ischaemic attack and 35.6 percent were on anticoagulation prior to stroke.

In the group of 1,367 patients (72.4 percent) who did not receive MT, alteplase use increased the likelihood of haemorrhagic transformation by more than twofold (adjusted odds ratio [aOR], 2.14, 95 percent confidence interval [CI], 1.49–3.07; p<0.001) but reduced the risk of 90‐day mortality by 42 percent (aOR, 0.58, 95 percent CI, 0.39–0.87; p=0.009) compared with nonuse. [J Am Heart Assoc 2021;doi:10.1161/JAHA.121.020945]

Meanwhile, in the group of 522 patients (27.6 percent) who underwent MT, those who did vs did not use alteplase had nonsignificantly lower 90‐day mortality (aOR, 0.68, 95 percent CI, 0.45–1.04; p=0.077) but similar odds of haemorrhagic transformation (aOR, 0.82, 95 percent CI, 0.56–1.20; p=0.312).

“Premorbid anticoagulation for AF was more common in patients who did not receive intravenous alteplase, as would be expected. However, recent evidence suggests that the use of warfarin for stroke prevention in AF has become less frequent than the use of direct oral anticoagulants (DOACs),” the investigators noted. [Circ Cardiovasc Qual Outcomes 2017;10:e003476]

Despite the favourable safety profile of DOACs, their disadvantage is that there are no available rapid laboratory tests to measure their therapeutic effect, the investigators pointed out. “As a result, patients with AF taking DOACs are not eligible to receive intravenous alteplase, unless they missed taking their medication within 24 to 48 hours of the index stroke.”

Existing evidence suggests that intravenous thrombolysis in select patients treated with DOAC does not seem to heighten the risk of symptomatic intracerebral haemorrhage. Additionally, those at high risk of stroke, such as extensive atherosclerosis of the cerebrovasculature or CHA₂DS₂‐VASc >5, may be considered for atrial appendage occlusion with subsequent antiplatelet therapy, which has been shown to provide comparable efficacy as anticoagulation in stroke risk reduction in recent studies. 

“This will obviate the need for long‐term anticoagulation and may potentially make these patients alteplase eligible if they were to have an ischaemic stroke,” according to the investigators.

They called for further investigation into the risk vs benefit of the thrombolytic in AF patients on DOAC treatment, considering the mortality benefit for intravenous alteplase in patients with AF found in IAC.

“Future studies are [also] needed to establish whether intravenous thrombolysis before MT is beneficial in cardioembolic stroke,” the investigators said.