ISCHEMIA Trial Potential Impacts

ASNC leaders will continue sharing perspectives on the ISCHEMIA trial as findings are published and secondary analyses are presented. Continue reading for the letter that then-President Rob Beanlands, MD, MASNC, sent to members in November. 
November 22, 2019

Dear ASNC Members, 

As I'm sure you know, the abstracts for the landmark ISCHEMIA trial, quality of life (QoL) outcomes and the ancillary ISCHEMIA-CKD trial were presented at the American Heart Association (AHA.19) meeting this past weekend. The results have generated substantive discussion; extensive media coverage; and a long list of questions, only some of which will be answered when the studies are published.

I'd like to share the perspective of the ASNC leadership on the trial and how it might impact your practice.

Top-level Findings

A well-designed, randomized clinical trial, ISCHEMIA showed that, at 4 years, optimal medical therapy (OMT) alone was equivalent to OMT and invasive strategy, when feasible, for the primary outcome of cardiovascular death, myocardial infarction, and hospitalization for unstable angina, heart failure or resuscitation due to cardiac arrest in patients with stable moderate-to-severe coronary artery disease. The interventional strategy improved QoL and reduced angina compared to medical therapy, and patients in the invasive strategy arm required fewer medications.

Although there are several criticisms and questions about this so far unpublished study, the main findings are consistent with prior trials and do not change the conversations that most of us have been having with our patients for years, namely that, in non-emergent situations, revascularization does not prolong your life but may alleviate your symptoms and improve QoL.

What Does ISCHEMIA Mean Today?

ISCHEMIA used a variety of tests to assess ischemia as an initial entry criterion. Patients with moderate-to-severe ischemia, and meeting all other study criteria, underwent CT angiography to rule out left main disease (except in patients with known disease or where the likelihood of left main disease was considered low). Patients whose CTAs found left main disease were excluded from the trial.

This protocol means that the results of ISCHEMIA are based on patients who had a functional-first strategy—performed to determine if a patient's symptoms were due to angina from ischemic heart disease and/or to risk-stratify the patient for no or mild ischemia versus moderate-to-severe ischemia. Given the current guidelines and the ISCHEMIA results presented to date, this strategy of functional testing to determine the cause of chest pain and/or for risk stratification should continue as a mainstay for clinical practice.

It is important to interpret the findings of ISCHEMIA in its context. One should not extrapolate the results to patients that were excluded from the trial, including those with recent acute coronary syndrome within two months, PCI within one year, left ventricular ejection fraction less than 35%, prior CABG and, most importantly, uncontrolled or unstable symptoms despite maximal medical therapy. We should limit our interpretations to what the evidence that ISCHEMIA clearly shows and not draw any conclusions that are not supported by the important data this trial provides.

It is also important to remember that the value of myocardial perfusion imaging extends beyond that of treadmill testing and beyond the identification of the extent of ischemic burden. It also provides additional information that identifies high-risk patients, including those with elevated lung-to-heart ratio, transient ischemic dilation of the left ventricle, transient visualization of the right ventricle, left ventricular dysfunction, and, in the case of PET, impaired coronary flow reserve.

Another key takeaway from the ISCHEMIA presentation at AHA.19 reinforces the value of shared decision making—making time and, where possible, using tools to help patients examine their own health goals and trajectory and inform their treatment choices. Ultimately, this approach will help our patients make informed decisions about whether to undergo revascularization and may encourage them to be more compliant with optimal medical therapy and lifestyle recommendations.

Future Follow-up

We will learn much more when the ISCHEMIA trial, the QoL, and CKD studies are published. Of course, extended follow-up, subsequent analyses and future studies will support our field's ongoing effort to deliver the highest-quality, evidence-based care for all of our patients. I look forward to these developments and to your thoughts. You can reach me at

Rob Beanlands, MD, MASNC
2019 President