ABSTRACT
Aims: There is a paucity of randomized diagnostic studies in women with suspected coronary artery disease (CAD). This study sought to assess the relative value of exercise stress echocardiography (ESE) compared with exercise electrocardiography (Ex-ECG) in women with CAD. Methods and results: Accordingly, 416 women with no prior CAD and intermediate probability of CAD (mean pre-test probability 41%), were randomized to undergo either Ex-ECG or ESE. The primary endpoints were the positive predictive value (PPV) for the detection of significant CAD and downstream resource utilization. The PPV of ESE and Ex-ECG were 33% and 30% (P = 0.87), respectively for the detection of CAD. There were similar clinic visits (36 vs. 29, P = 0.44) and emergency visits with chest pain (28 vs. 25, P = 0.55) in the Ex-ECG and ESE arms, respectively. At 2.9 years, cardiac events were 6 Ex-ECG vs. 3 ESE, P = 0.31. Although initial diagnosis costs were higher for ESE, more women underwent further CAD testing in the Ex-ECG arm compared to the ESE arm (37 vs. 17, P = 0.003). Overall, there was higher downstream resource utilization (hospital attendances and investigations) in the Ex-ECG arm (P = 0.002). Using National Health Service tariffs 2020/21 (British pounds) the cumulative diagnostic costs were 7.4% lower for Ex-ECG compared with ESE, but this finding is sensitive to the cost differential between ESE and Ex-ECG. Conclusion: In intermediate-risk women who are able to exercise, Ex-ECG had similar efficacy to an ESE strategy, with higher resource utilization whilst providing cost savings.
ABSTRACT
BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. METHODS: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. RESULTS: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85-1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63-0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08-1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. CONCLUSIONS: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04894877.
