In 5,179 patients with chronic coronary disease and moderate or severe ischemia, ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) compared an initial invasive treatment plan (INV) with an initial conservative strategy. A thorough quality-of-life (QOL) substudy was included in the ISCHEMIA research program. Researchers gathered a battery of disease-specific and general QOL measures from 1,819 individuals (907 INV, 912 conservative approaches) via structured interviews at baseline, 3, 12, 24, and 36 months post-randomization, and at study closeout. Angina-related QOL (19-item Seattle Angina Questionnaire), generic health status (EQ-5D), depressive symptoms (Patient Health Questionnaire-8), and cardiac functional status (for North American patients) were also assessed (Duke Activity Status Index). The median age was 67, 19.2% were female, and 15.9% were non-White. Over the whole follow-up period, the estimated mean difference for the 19-item Seattle Angina Questionnaire Summary score supported INV (1.4 points [95% CI, 0.2–2.5]). In individuals with rare/absent baseline angina (SAQ Angina Frequency score >80), no changes were detected. Among patients with more frequent angina at baseline (SAQ Angina Frequency score 80, 744 patients, 41%), those randomly assigned to INV had a 3.7-point higher 19-item Seattle Angina Questionnaire Summary score than the conservative strategy (95% CI, 1.6–5.7), with consistent effects across SAQ subscales: Physical Limitations Angina Frequency 3.2 points (95% CI, 1.2–5.1), Quality of Life/Health Perceptions 5.3 points (95% CI, 2.8–7.8). There was no overall difference estimated by treatment for the Duke Activity Status Index, but in patients with baseline SAQ Angina Frequency scores of 80, Duke Activity Status Index scores were higher for INV (3.2 points [95% CI, 0.6–5.7]), whereas patients with rare/absent baseline angina showed no treatment-related differences. At randomization, moderate to severe depression was uncommon (11.5%–12.8%) and was unaffected by treatment assignment.

Patients with more frequent baseline angina reported greater improvements in the symptom, physical functioning, and psychological well-being dimensions of QOL when treated with an invasive strategy in the ISCHEMIA comprehensive QOL substudy, whereas patients with rare/absent angina at baseline reported no consistent treatment-related QOL differences.