Invasive vs conservative strategy did not result in benefit in patients with advanced CKD and SIHD
International Study of Comparative Health Effectiveness With Medical and Invasive Approaches- Chronic Kidney Disease (ISCHEMIA-CKD): Primary Results of Clinical Outcomes
Presented during the AHA Scientific Sessions 2019 by Sripal Bangalore (New York Univ Sch of Med, New York, NY; ISCHEMIA-CKD Research Group.
Quality of Life data were presented by John A. Spertus (Mid America Heart Inst, Kansas City, MO; ISCHEMIA Research Group)
Introduction and methods
This CKD substudy of the ISCHEMIA trial aimed to answer the question whether in stable patients with advanced CKD and at least moderate ischemia on a stress test, is there a benefit of adding cardiac catheterization and, if feasible, revascularization to optimal medical therapy (OMT). In contemporary revascularization vs. medicine stable ischemic heart disease (SIHD), CKD patients are underrepresented or excluded.
Stable patients with moderate or severe ischemia and eGFR <30 mL/min/1.73m² or on dialysis were randomized to an invasive strategy (INV) or a conservative strategy (CON). INV consisted of optimal medical therapy (OMT) plus catheterization plus optimal revascularization (if suitable) and CON of OMT only, with catheterization reserved for OMT failure. The primary endpoint was a composite of death and myocardial infarction (MI). The trial had >80% power to detect 22-24% relative reduction in the primary endpoint, assuming an aggregate 4-year cumulative rate of approximately 41% to 48%.
777 Patients were randomized. Median follow-up for survivors in the INV group was 2.3 (1.9 to 3.2) year, and 99.2% of patients completed follow-up. In the CON group, median duration was 2.5 (1.9 – 3.2) years, and 99.7% completed it. On a stress test, baseline inducible ischemia was severe in 36%, and moderate in 64% of those in the INV group and 39%, and 61%, respectively in the CON group. The treatment groups showed no differences in risk factor management.
Quality of life was assessed at randomization, and throughout the follow-up period of up to 36 months. SAQ Angina Frequency Scale scores were used. A higher score reflects less angina.
- The primary endpoint of death or MI did not differ between treatment strategies (HRadj: 1.01, 95%CI: 0.79 – 1.29, P=0.95). A Bayesian analysis suggested that the probability of having more than 10% benefit with INV vs CON was 19%.
- No effect of INV vs CON was seen on the major secondary end point, a composite of death, MI, hospitalization for unstable angina or HF or rescuscitated cardiac arrest (HRadj: 1.01, 95%CI: 0.79-1.29, P=0.93), with 17% chance of an HR <0.90.
- No significant reductions of secondary endpoints were seen with INV vs. CON. Stroke was seen more often in the INV group (HRadj: 3.76, 95%CI: 1.52-9.32, P=0.004).
- Of safety endpoints, death or new dialysis was seen more often in the INV group (HRadj: 1.46, 95%CI: 1.04-2.11, P=0.02), which appeared to be driven by new dialysis (HRadj: 1.47, 95%CI: 0.88-2.44, P=0.13).
- In subgroup analyses, a significant interaction of degree of baseline ischemia with the treatment effect was seen (P=0.02), favoring INV in those with severe ischemia and favouring CON in those with moderate ischemia, both for the primary and the secondary composite outcomes.
Quality of Life (QoL) outcomes
- At baseline, in both groups, about half of patients had no angina, about 40% had it several times per month and about 11% had daily/weekly angina.
- Given the large proportion of asymptomatic patients at baseline, we cannot exclude the possibility of a small benefit in symptomatic patients for SAQ summary, SAS angina frequency and SAS QoL during follow-up, although findings for all patients were quite similar for INV and CON.
These data show that an initial invasive strategy did not result in a reduced risk of clinical outcomes as compared with an initial conservative strategy in patients with advanced CKD and SIHD. It should be noted that there were also low rates of revascularization in the INV arm, possibly because the sensitivity and specificity of stress testing in CKD patients are poor, and because there was no requirement for CCTA in the trial. The rate of procedural complications (stroke, acute kidney injury) was low, because sites were specifically trained to minimize risk of AKI after cardiac catheterization and revascularization. Thus, these findings may not be generalizable to centers with higher complication rates.
Regarding the QoL outcomes, no substantial improvement in angina control and QoL was seen. Given the large proportion of asymptomatic patients at baseline, we cannot exclude the possibility of a small benefit in symptomatic patients. Indeed, enrolment was very skewed towards less symptomatic patients; we may not have been able to discern a QoL benefit in more symptomatic patients.
- Our reporting is based on the information provided during AHA Scientific Sessions 2019 -