Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of left ventricular dysfunction (LVD) or heart failure (HF) when ejection fraction is greater than or equal to 35% but less than 45% is unknown. Amongst 5179 participants randomized into ISCHEMIA, all of whom had left ventricular ejection fraction (LVEF) ≥35%, we compared cardiovascular outcomes by treatment strategy in participants with a history of HF/LVD at baseline versus those without HF/LVD.
There were 398 participants with HF/LVD at baseline, of whom 177 had HF/LVEF >45%, 28 HF/LVEF 35% to 45%, and 193 LVEF 35% to 45% but no history of HF. Compared with patients without HF/LVD, participants with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest (22.7% vs. 13.8%; myocardial infarction or cardiovascular death, 12.3% vs. 19.7%; and HF or all-cause death, 6.9% vs. 15%). Participants with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% vs. 29.3%), whereas those without HF/LVD did not (13% vs. 14.6%).
In conclusion, ISCHEMIA participants with stable ischemic heart disease with a history of LVD or HF were at elevated risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35% to 45%. An initial invasive approach was associated with a better event-free survival; this result should be considered hypothesis-generating.