Editors' Note: Safety and Efficacy of Dual Antiplatelet Pretreatment in Patients With Ischemic Stroke Treated With IV Thrombolysis: A Systematic Review and Meta-analysis

Abstract

To date, intravenous alteplase remains the only FDA-approved pharmacologic agent for the treatment of acute ischemic stroke. Among the contraindications to systemic thrombolysis with alteplase is therapeutic anticoagulation (or the use of warfarin with an INR >1.7), but not combination antiplatelet therapy. The most feared complication of treatment, symptomatic intracranial hemorrhage (sICH), may be more common in patients on dual antiplatelet pretreatment (DAPP) as shown in several studies and one previous meta-analysis. However, these data have not been consistently replicated. In their updated meta-analysis of 9 studies, including one randomized controlled clinical trial, 2 prospective registries, and 6 retrospective registries, Dr. Malhotra et al. observed that DAPP was associated with a two-fold higher odds of sICH in unadjusted regression (OR 2.26, 95% CI 1.39–3.67). This negative effect remained despite the use of varying definitions of sICH (SITS-MOST, ECASS II, and National Institute of Neurological Disorders and Stroke). However, after adjustment for confounders, the relationship no longer achieved statistical significance (ORadj 2.03, 95% CI 0.75–5.52, p = 0.16). Drs. Xu and Hu believed the analysis may have been confounded by overlapping patients between some of the included studies in this meta-analysis. Drs. Katsanos and Tsivgoulis confirmed—and we have independently verified—that there are no overlapping patients in this meta-analysis. Furthermore, the authors report the prospective TRISP registry corroborate the lack of a statistically significant, independent relationship between DAPP and sICH after thrombolysis (ORadj 1.29, 95% CI 0.82–2.05, p = 0.27). Although this information may provide us with greater reassurance regarding the safety of intravenous alteplase in patients on DAPP, these data highlight the importance of a priori significance thresholds. We believe readers should not be discouraged from using this FDA-approved acute treatment in patients prescribed DAPP but that does not mean one should not be cautious with it. To date, intravenous alteplase remains the only FDA-approved pharmacologic agent for the treatment of acute ischemic stroke. Among the contraindications to systemic thrombolysis with alteplase is therapeutic anticoagulation (or the use of warfarin with an INR >1.7), but not combination antiplatelet therapy. The most feared complication of treatment, symptomatic intracranial hemorrhage (sICH), may be more common in patients on dual antiplatelet pretreatment (DAPP) as shown in several studies and one previous meta-analysis. However, these data have not been consistently replicated. In their updated meta-analysis of 9 studies, including one randomized controlled clinical trial, 2 prospective registries, and 6 retrospective registries, Dr. Malhotra et al. observed that DAPP was associated with a two-fold higher odds of sICH in unadjusted regression (OR 2.26, 95% CI 1.39–3.67). This negative effect remained despite the use of varying definitions of sICH (SITS-MOST, ECASS II, and National Institute of Neurological Disorders and Stroke). However, after adjustment for confounders, the relationship no longer achieved statistical significance (ORadj 2.03, 95% CI 0.75–5.52, p = 0.16). Drs. Xu and Hu believed the analysis may have been confounded by overlapping patients between some of the included studies in this meta-analysis. Drs. Katsanos and Tsivgoulis confirmed—and we have independently verified—that there are no overlapping patients in this meta-analysis. Furthermore, the authors report the prospective TRISP registry corroborate the lack of a statistically significant, independent relationship between DAPP and sICH after thrombolysis (ORadj 1.29, 95% CI 0.82–2.05, p = 0.27). Although this information may provide us with greater reassurance regarding the safety of intravenous alteplase in patients on DAPP, these data highlight the importance of a priori significance thresholds. We believe readers should not be discouraged from using this FDA-approved acute treatment in patients prescribed DAPP but that does not mean one should not be cautious with it.