In Reply In T-TIME, we confirmed that low-dose intracoronary alteplase administered early during primary PCI did not reduce microvascular obstruction. Drs Sezer and Umman suggest a different agent may have been more effective, based on their trial of intracoronary streptokinase vs no additional therapy administered at the end of primary PCI. They recorded improvements in some surrogate outcomes measured during coronary angiography at 2 days and left ventricular volumes and infarct size at 6 months. We view these intriguing results with caution. The final sample size was 41 (17 receiving streptokinase vs 15 receiving no additional therapy in the final analysis), implying a high level of statistical fragility. The intervention was open-label. There was no placebo. The acquisition and analysis of outcomes were mainly performed by unblinded investigators. An interim efficacy analysis disclosed positive findings, and enrollment was then discontinued. However, since only half of the prespecified sample size had been recruited, the possibility of a type 1 (false-positive) error is greatly enhanced. None of these limitations applied to T-TIME.
