tPA for Stroke: Reassuring Results for Patients on Antiplatelets

November 18, 2015

A new study — which represents the largest clinical experience of thrombolysis for stroke in patients taking antiplatelet therapy — suggests that the overall benefits of thrombolytic therapy may outweigh the risks in this population.

The study, published online in JAMA Neurology on November 9, was conducted by a team led by Ying Xian, MD, Duke Clinical Research Institute, Durham, North Carolina.

The only approved medical therapy for acute ischemic stroke is intravenous tissue plasminogen activator (tPA), Dr Xian explained to Medscape Medical News. "But there is always the concern about intracranial hemorrhage (ICH), especially if the patient is already taking aspirin or clopidogrel."

Dr Xian said that whether to give tPA to acute stroke patients who had antiplatelet agents on board has long been a thorny issue.

"We know tPA improves functional outcomes but we also know it increases the risk of ICH, a catastrophic adverse effect. Patients taking antiplatelet agents will be at a higher bleeding risk. There is no good data on the risk benefit of giving tPA to these patients. Subgroup analysis from the major randomized trials has shown conflicting results and there is much confusion as to what to do."

For the current study, Dr Xian and colleagues analyzed data on more than 85,000 stroke patients who had received tPA, approximately half of whom were taking antiplatelet medication at the time of their stroke.

"Our results showed that the patients on antiplatelets were at a higher risk of ICH after tPA than those not taking antiplatelet agents, but this increased risk was small," he commented. "Specifically, there was one additional ICH associated with tPA for every 147 patients taking an antiplatelet agent."

But these patients also showed better functional outcomes — in particular they were more likely to walk independently at discharge and to have better scores on the modified Rankin Scale (mRS), he added. "The number needed to treat for benefit was 39 to 50, depending on which outcome is measured, so the benefit appears to outweigh the risk."

"Our bottom-line message is that taking antiplatelet agents before stroke should not be a contraindication for tPA treatment," he concluded. "Our results are reassuring in that they will give doctors more confidence to use tPA in the large population of patients taking antiplatelet agents."

The study used data from the American Heart Association and American Stroke Association Get With the Guidelines–Stroke registry, which included 85,072 adult patients with ischemic stroke who received tPA in 1545 registry hospitals between 2009 and 2015.

Of the 85,072 registry patients, 38,844 (45.7%) were receiving antiplatelet therapy before admission. Patients receiving antiplatelet therapy were older and had a higher prevalence of cardiovascular risk factors.

The unadjusted rate of symptomatic ICH was higher in patients receiving antiplatelet therapy (5.0% vs 3.7%). After risk adjustment, the odds ratio was 1.18, with a number need to harm (NNH) of 147.

The risk was higher in patients receiving dual antiplatelet therapy (odds ratio, 1.47; NNH, 60), but in neither case did this translate into an increase in in-hospital mortality.

In terms of benefit, patients receiving antiplatelet therapy had a greater likelihood of independent ambulation and better functional outcomes (mRS score, 0 to 1) at discharge.

Adjusted Odds Ratio for Benefit and Harm With tPA in Patients Taking Antiplatelets vs Those Not Taking Antiplatelets

Endpoint Adjusted Odds Ratio (95% Confidence Interval) NNT or NNH
Symptomatic ICH 1.18 (1.10 - 1.28) NNH, 147
In-hospital mortality 1.00 (0.94 - 1.06)
Independent ambulation 1.13 (1.08 - 1.17) NNT, 43
mRS score, 0 - 1 1.14 (1.07 - 1.22) NNT, 50
mRS score, 0 - 2 1.16 (1.09 - 1.24) NNT, 39

NNT, number needed to treat.

 

Subgroup analysis showed similar association for each clinically relevant group including patents given tPA at 3.0 to 4.5 hours, those aged 80 years or older, women, and those with a medical history of coronary artery disease or a prior stroke.

Dr Xian reports receiving research funding directed to the Duke Clinical Research Institute from the American Heart Association, Daiichi Sankyo, Janssen Pharmaceutical Companies, and Genentech.

JAMA Neurol. Published online November 9, 2015. Abstract

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