Long-term follow-up after invasive or conservative management of stable coronary disease: the ISCHEMIA-EXTEND study

The ISCHEMIA trial found no statistical difference in the primary endpoint between initial invasive and conservative management of patients with chronic coronary disease and moderate-to-severe ischaemia on stress testing. However, an invasive strategy increased peri-procedural myocardial infarction (MI) but decreased spontaneous MI with continued separation of curves over time. Thus, in order to assess the long-term effect of invasive management strategy on mortality, the ISCHEMIA-EXTEND observational study was planned including surviving participants from the initial phase of the ISCHEMIA trial with a projected median follow-up of nearly 10 years. Recently, an interim report of 7-year all-cause, cardiovascular (CV), and non-CV mortality rates has been published showing no difference in all-cause mortality between the two strategies, but with a lower risk of CV mortality and higher risk of non-CV mortality with an initial invasive strategy over a median follow-up of 5.7 years. The trade-offs in CV and non-CV mortality observed in ISCHEMIA-EXTEND raise many important questions regarding the heterogeneity of treatment effect, the drivers of mortality, and the relative importance and reliability of CV vs. all-cause mortality. Overall, findings from ISCHEMIA and ISCHEMIA-EXTEND trials might help physicians in shared decision-making as to whether to add invasive management to guideline-directed medical management in selected patients with chronic coronary artery disease and moderate or severe ischaemia.