LAUSR

As clinicians, we are very interested in providing care that improves the quality of our patient's lifestyle and decreases cardiovascular events. As such, the results of the Ischemia Trial, recently presented at the 2019 American Heart Association's Scientific Sessions was eagerly awaited. As the culmination of the NIH funded randomized ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial we looked at how it could be incorporated into our daily practice. This trial was focused on addressing a question of whether medical therapy alone or percutaneous intervention with optimal medical therapy should be the initial approach in patients who present with chronic stable angina. The investigators are to be commended in completing this important trial. As in all studies, we as clinicians should decide how to apply this to our individual patient populations. Our first question is which of our patients that we would refer for angiography and revascularization were included. We know that mortality and symptom benefit is related to patient acuity (ACS) and the extent of myocardium at jeopardy. In fact, if there was not a large amount ischemia at baseline, patients were much less like have improved symptoms or survival and we have accepted this premise. In ISCHEMIA, patients were selected for mild chronic stable angina and those with unstable angina/ACS within the 2-month period preceding randomization as well as those with class III-IV congestive heart failure, ejection fraction <35%, low glomerular filtration rate or hemodialysis, history of prior percutaneous coronary intervention (PCI) or coronary artery bypass graft within 1 year were excluded. From the 8,518 patients initially enrolled, 3,339 were subsequently eliminated. Major reasons included insufficient ischemia, no obstructive coronary artery disease (CAD) on Coronary CT angiography (CCTA) or significant Unprotected LM (ULM) disease in 434 patients (5%). This excludes a large percentage of patients that we see in our daily practice. Thus, a total of 5,179 patients were deemed suitable and subsequently randomized in an intention to treat model to either a conservative arm of medical therapy alone or to an invasive arm for cardiac catheterization. Not surprisingly in this trial the recruited patients were younger, had normal left ventricular ejection fraction (LVEF), and included fewer women than other investigations and the patients we see in our practice. Most patients referred to us electively are for management of lifestyle altering angina. In ischemia from the randomized group of patients, 38.9% according to the Seattle Angina Questionnaire had not had any angina in the month preceding randomization and >40% only had angina monthly. This indicates that nearly 80% of the studied patients had no or infrequent angina. Is this the population of patients you would be seeking to perform PCI in your daily practice? Unlikely that we would. Patients were to be selected for baseline moderate to severe ischemia on exercise stress testing and could then be enrolled to undergo baseline CCTA. Notably, to support enrollment, the imaging component for ischemia was altered in 2014 and severely abnormal stress tests alone (exercise tolerance testing [ETT] with >1.5 mm ST depression in >2 leads or >2 mm ST depression in single lead at <7 METS with angina) were accepted. In the randomized group, 14% of the stress imaging and 17% of the exercise electrocardiogram patients had less than severe ischemia, so that roughly one in seven patients with chronic stable infrequent angina. We do not know what their correlation of percent ischemia was in those that were randomized with infrequent angina. Those patients with limited ischemia and limited angina are extraordinarily low-risk population for future cardiovascular disease events. We would not be pursuing interventional therapy for those patients. Further, this study wanted to remove the bias of angiography by using a criteria of >50% stenosis by CCTA if they had not previously undergone catheterization. One needs to ask if this was sufficient, particularly in the population using stress test alone especially as only 75% of the patients underwent CCTA. In those randomized to the PCI arm, 20% did not have significant coronary Received: 11 February 2020 Accepted: 11 February 2020