Tirofiban on Top of Endovascular Therapy for Acute Stroke Tied to Fatal Hemorrhage

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Patients who undergo endovascular stroke therapy in combination with the glycoprotein IIb/IIIa inhibitor (GPI) tirofiban see a sharp increase in the risk of fatal intracerebral hemorrhage and have poorer functional outcome at 3 months. The findings, from an observational single-center study, were published online March 5, 2013, ahead of print in Stroke.

Lars Kellert, MD of the University of Heidelberg (Heidelberg, Germany), and colleagues prospectively collected data on 162 patients with acute ischemic stroke who underwent mechanical thrombectomy between 2006 and 2011. Tirofiban was given to 30 of 128 patients with anterior circulation stroke and 20 of 34 patients with posterior circulation stroke.

Patients who received permanent stents were more than 5 times more likely to receive tirofiban compared with nonstented patients (44.0% vs. 8.0%; P = 0.001). Within the anterior circulation stroke group, tirofiban use also was associated with lower National Institutes of Health Stroke Scale (NIHSS) score (P = 0.04) and shorter time to treatment (P = 0.03).

Patients treated with tirofiban were more likely to experience fatal intracranial hemorrhage and, at 3 months, had worse functional outcome as defined by modified Rankin Scale (mRS) score. Though the difference was not significant, the rate of parenchymal hematoma type 2 was more than doubled in the tirofiban group (table 1).

Table 1. Bleeding Events and 3-Month Functional Outcome

Abbreviation: mRS, modified Rankin Scale.

Logistic regression modeling identified patient age (OR 1.17; 95% CI 1.00-1.37; P = 0.05) and tirofiban (OR 3.03; 95% CI 1.50-4.05; P= 0.04) as independent predictors of fatal intracranial hemorrhage, while NIHSS score (OR 1.08; 95% CI 1.00-1.17; P < 0.05) and tirofiban (OR 6.60; 95% CI 1.06-41.52; P < 0.04) both predicted poor outcome.

According to the authors, “tirofiban is administered in acute stroke patients undergoing mechanical thrombectomy and stenting to avert the risks of thromboembolic complications caused by endothelial damage.”

Dr. Kellert and colleagues acknowledge that the “higher rate of stenting in tirofiban-treated patients might be a confounder regarding bleeding complications,” though stent implantation was not shown to predict fatal intracranial hemorrhage.

“Future studies may evaluate oral antiplatelet agents or lower doses of tirofiban for reduction of bleeding complications,” they conclude, noting that a randomized controlled trial on this issue is unlikely and, as such, single centers should continue to publish data.

Tirofiban Not Entirely to Blame

Joseph P. Broderick, MD, of the University of Cincinnati (Cincinnati, OH), emphasized that the tirofiban use seen here is center specific.

“The study is interesting, but you have to understand the context,” Dr. Broderick said to TCTMD in a telephone interview. In particular, the paper “may be a little bit overstating tirofiban’s risk and understating the procedural risk of permanent stenting,” he noted, adding that an analysis of bleeding in the stented vs. nonstented patients would have been helpful.

“The bottom line,” he stressed, “is that the patients in the tirofiban group were more difficult, challenging patients who resisted primary therapy and probably had longer time to reopening of the artery as well, and they got a permanent stent—and they got tirofiban.” Moreover, tirofiban is typically administered over at least an entire day, a time period during which the risk of intracranial hemorrhage can accumulate, and many patients also received tPA, Dr. Broderick stressed.

Although it is unsurprising to hear that tirofiban is associated with hemorrhage, the paper offers a welcome cautionary tale both about GPIs and about stenting for stroke more generally, Philip M. Meyers, MD, of Columbia University Medical Center (New York, NY), told TCTMD in a telephone interview.

“There’s actually a fair amount of [evidence] out there to suggest that [GPIs] are a bad idea in acute stroke, but we don’t have anything better. . . . I’m glad they tried it and they went ahead and were brave enough to publish their results,” Dr. Meyers commented.

Source:

Kellert L, Hametner C, Rohde S, et al. Endovascular stroke therapy: Tirofiban is associated with risk of fatal intracerebral hemorrhage and poor outcome. Stroke. 2013;Epub ahead of print.

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