Risks of Overinterpreting Interim Data
Lessons From the TOTAL Trial (Thrombectomy With PCI Versus PCI Alone in Patients With STEMI)
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Thrombus aspiration in ST-segment–elevation myocardial infarction has been an area of intense debate among interventional cardiologists. A prior single-center trial (n=1071) observed an unexpected nearly 50% reduction in mortality with routine thrombus aspiration.1 These findings led to the development of the randomized trial of routine aspiration TOTAL (Thrombectomy With PCI Versus PCI Alone in Patients With STEMI; n=10 732).2 During the conduct of the TOTAL trial, thrombus aspiration was recommended by guidelines and was commonly used in clinical practice and believed to improve patient outcomes.
In the TOTAL trial, thrombus aspiration did not reduce the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure at 180 days but was associated with a significant increase in stroke at 30 days.
The objective of this research letter is to show the importance of a data monitoring committee (DMC) continuing a trial despite emerging treatment findings.
A Cox proportional hazards model was used to compare patients randomized to thrombus aspiration with percutaneous coronary intervention (PCI) and PCI alone. A modified intent-to-treat analysis was prespecified to include only patients who underwent PCI because patients were randomized before angiography. Outcomes presented are at 30 days given that during early analyses data at longer-term follow-up had few patients and were not reliable. The data were compiled from actual DMC reports. The outcomes analyzed for this article include the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure), death, and stroke. The stopping guidelines for efficacy were exceeding a difference of 4 …