ISCHEMIA trial: Is there enough evidence to drive a change in clinical practice? A critical appraisal

Abstract

Recently, ISCHEMIA trial was published in order to determine the effect of adding cardiac catheterization and revascularization when feasible to medical therapy in patients with stable CAD and moderate or severe ischemia. Over a median of 3.2 years of follow-up, among patients with stable CAD who had moderate or severe ischemia on stress testing, an initial invasive strategy, as compared with an initial conservative strategy, did not reduce the rates of the primary or key secondary composite outcomes. The primary outcome was the composite of death from cardiovascular causes, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. The key secondary outcomes were the composite of death from cardiovascular causes or MI and angina-related quality of life. Patients in the invasive-strategy group had more procedural myocardial MIs, and they had fewer spontaneous infarctions during follow-up. The incidence of death from any cause was low and similar in the two groups. However, the ISCHEMIA trial was challenging to implement, event rates were low and enrollment fell behind initial milestones. Furthermore, power of the study was compromised, composite end-point definition as well as definitions of crucial individual components were changed amid study progression. There was a “heterobaric” combined end-point with procedural MIs favoring the conservative arm and spontaneous MIs favoring the invasive arm. Finally, the duration of reported follow-up showed signals that findings may shift in favor of invasive treatment and results were sensitive to definition and type of MIs. Therefore, we believe that it is premature to change clinical practice in view of the results of ISCHEMIA trial. As stable CAD patients is a vastly heterogenous patient group, it may be prudent to apply common clinical judgement and individual decision-making according to current guidelines before changing our management strategies.

Keywords

• ISCHEMIA trial
• invasive therapy
• optimal medical therapy
• clinical trial