Comparison of Days Alive Out of Hospital With Initial Invasive vs Conservative Management A Prespecified Analysis of the ISCHEMIA Trial

This prespecified analysis of the ISCHEMIA randomized clinical trial compares days alive out of hospital between those receiving invasive management and conservative management, including invasive protocol-assigned stays. Question Is the patient-focused metric days alive out of hospital (DAOH) different in patients randomized to invasive management compared with conservative management in the ISCHEMIA randomized clinical trial? Findings This prespecified analysis of the ISCHEMIA trial analyzed 5179 patients with stable coronary disease and moderate or severe ischemia randomized to invasive or conservative management. Compared with the invasive management group, DAOH was higher in the conservative management group at 1 month (difference, 2.4 days), 1 year (difference, 6.4 days), and 2 years (difference, 6.4 days); at 4 years, DAOH was similar in both groups. Meaning DAOH can inform patient decisions about trade-offs, with higher DAOH earlier with conservative management but similar DAOH to invasive management at 4 years. Importance Traditional time-to-event analyses rate events occurring early as more important than later events, even if later events are more severe, eg, death. Days alive out of hospital (DAOH) adds a patient-focused perspective beyond trial end points. Objective To compare DAOH between invasive management and conservative management, including invasive protocol-assigned stays, in the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) randomized clinical trial. Design, Setting, and Participants In this prespecified analysis of the ISCHEMIA trial, DAOH was compared between 5179 patients with stable coronary disease and moderate or severe ischemia randomized to invasive management or conservative management. Participants were recruited from 320 sites in 37 countries. Stays included overnight stays in hospital or extended care facility (skilled nursing facility, rehabilitation, or nursing home). DAOH was separately analyzed excluding invasive protocol-assigned procedures. Data were collected from July 2012 to June 2019, and data were analyzed from July 2020 to April 2021. Interventions Invasive management with angiography and revascularization if feasible or conservative management, with both groups receiving optimal medical therapy. Main Outcomes and Measures The hypothesis was formulated before data lock in July 2020. The primary end point was mean DAOH per patient between randomization and 4 years. Initial stays for invasive protocol-assigned procedures were prespecified to be excluded. Results Of 5179 included patients, 1168 (22.6%) were female, and the median (interquartile range) age was 64 (58-70) years. The average DAOH was higher in the conservative management group compared with the invasive management group at 1 month (30.8 vs 28.4 days; P < .001), 1 year (362.2 vs 355.9 days; P < .001), and 2 years (718.4 vs 712.1 days; P = .001). At 4 years, the 2 groups' DAOH were not significantly different (1415.0 vs 1412.2 days; P = .65). In the invasive management group, 2434 of 4002 stays (60.8%) were for protocol-assigned procedures. There were no clear differences at any time point in DAOH when protocol-assigned procedures were excluded from the invasive management group. There were more hospital and extended care stays in the invasive management vs conservative management group during follow-up (4002 vs 1897; P < .001). Excluding protocol-assigned procedures, there were fewer stays in the invasive vs conservative group (1568 vs 1897; P = .001). Cardiovascular stays following the initial assigned procedures were lower in the invasive management group (685 of 4002 [17.1%] vs 1095 of 1897 [57.8%]; P < .001) due to decreased spontaneous myocardial infarction stays (65 [1.6%] vs 123 [6.5%]; P < .001) and unstable angina stays (119 [3.0%] vs 216 [11.4%]; P < .001). Conclusions and Relevance DAOH was higher for patients in the conservative management group in the first 2 years but not different at 4 years. DAOH was decreased early in the invasive management group due to protocol-assigned procedures. Hospital stays for myocardial infarction and unstable angina during follow-up were lower in the invasive management group. DAOH provides a patient-focused metric that can be used by clinicians and patients in shared decision-making for management of stable coronary artery disease.

Automated summary

This prespecified analysis of the ISCHEMIA randomized clinical trial found that patients in the conservative management group had higher days alive out of hospital (DAOH) in the first 2 years, but no significant difference at 4 years. Early decrease in DAOH in the invasive management group was attributed to protocol-assigned procedures. Hospital stays for myocardial infarction and unstable angina during follow-up were lower in the invasive management group. DAOH provides a patient-focused metric that can be used by clinicians and patients in shared decision-making for management of stable coronary artery disease.