No Benefit Seen with Adding Blood Thinners to r-TPA for Ischemic Stroke Treatment

The addition of blood thinners to standard thrombolytic therapy for ischemic stroke did not significantly improve patient physical function compared with the use of thrombolysis alone, according to results of a large clinical trial presented at the American Stroke Association’s International Stroke Conference 2024. The blood thinners assessed in the study were Integrilin (eptifibatide; Millennium Pharmaceuticals, Cambridge, MA) and argatroban. Researchers reported no increase in bleeding into the brain associated with the use of blood thinners along with clot-busting medication.

The MOST clinical trial (NCT03735979) was a multi-arm single blinded, randomized study that enrolled 514 participants with acute ischemic stroke (National Institutes of Health Stroke Severity Scale score of 6 or higher) from 57 hospitals. All participants received standard thrombolytic therapy (within 3 hours of stroke onset) and were then randomized to receive either argatroban, Integrilin, or placebo by intravenous (IV) infusion within 75 minutes of thrombolysis. The primary outcome was physical function assessed by modified Rankin score (mRS) measured 90 days after randomization which was then translated into a utility-weighted mRS score using validated ratings of functional outcomes by patients and physicians. The utility-weighted mRS is a 0 to 10 point scale, with higher scores designating greater benefit from treatment. According to the results on this utility-weighted mRS:

• Participants who received a placebo had an average score of 6.8
• Participants who received Integrilin had an average score of 6.3
• Participants who received argatroban had an average score of 5.2

In addition to medical treatment, 44% of the patients across all 3 groups were treated with thrombectomy to remove clots. The study was planned to include 1200 participants, but the independent Data and Safety Monitoring Board (DSMB) halted the trial at 514 participants after analysis of interim results suggested that the addition of blood thinners to thrombolysis was unlikely to be beneficial.

“When we began the trial, we believed the medications would improve outcomes, so we were surprised with the negative results,” said lead study author Opeolu M. Adeoye, MD, MS. “However, we designed the trial to allow us to efficiently answer the question for two blood-thinning medications in one trial. We have definitely done that and are pleased with the ability to answer this question.”

The authors of this study are affiliated with Washington University, the University of Cincinnati, the University of Iowa, Memorial Herman Hospital TMC, and University of Texas Health Science Center Houston.