Initial Invasive Strategy Not Linked to Recurrent CV Event Prevention in Stable CAD

Coronary Artery Spasm
Net recurrent cardiovascular events were not prevented by an initial invasive treatment strategy in the ISCHEMIA trial.

An initial invasive (INV) strategy was no more effective than a conservative (COV) strategy for the management of stable coronary artery disease (CAD). These findings, from a large randomized trial, were published in the European Heart Journal.

The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial ( Identifier: NCT01471522) recruited 5179 patients with stable CAD and moderate-to-severe ischemia. The primary outcome was a composite endpoint of cardiovascular death; myocardial infarction; and hospitalization for unstable angina, heart failure, or cardiac arrest.

Patients were randomized to receive symptom management with INV (optimal medical therapy plus catheterization, angiography, and revascularization if feasible) or COV (optimal therapy alone or with catheterization if optimal therapy failed) strategies. After a median follow-up of 3.2 years, the rate of the composite endpoint was assessed.

Most patients (87.1%) did not present with any of the endpoint events. A total of 10.3% had 1 event, 12.9% had 1 or more events, and 2.6% had 2 or more events. Patients who experienced more events were older and had higher rates of most comorbid conditions. Specifically, patients with recurrent events had a higher prevalence of diabetes, hypertension, and multivessel disease; and patients with multiple events had a higher prevalence of peripheral vascular or cerebrovascular disease and a higher prevalence of prior CABG surgery.

There were 873 primary endpoint events. Among the 670 total index events, 318 occurred among the INV recipients and 352 occurred among the CON recipients. Among the 203 recurrent events, there were 102 in the INV group and 101 in the CON group.

Significant differences were not observed overall for the composite event. However, hospitalization for heart failure was reduced in the CON cohort (difference, 1.3; 95% CI, 0.2-2.4; P =.021) and hospitalization for unstable angina was reduced in the INV group (difference, -0.8; 95% CI, -1.5 to -0.1; P =.020).

This study was limited by power. Although this was a large CAD trial, the numbers of events associated with each of the composite outcome components were low, which may have decreased the investigators’ ability to detect significant differences.

However, it is notable that patients with stable CAD who received more invasive therapies were not more likely to have superior outcomes than patients managed using a conservative approach.

The investigators concluded that “this report adds important new evidence to the ISCHEMIA primary publication that from a clinical events perspective, the [2] strategies tested provide equivalent outcomes for at least the first 4 years after randomization.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of authors’ disclosures.


Lopez-Sendon JL, Cyr DD, Mark DB, et al, for the ISCHEMIA Research Group. Effects of initial invasive vs initial conservative treatment strategies on recurrent and total cardiovascular events in the ISCHEMIA trial. Eur Heart J. Published online September 13, 2021. doi:10.1093/eurheartj/ehab509