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Review of the ISIS-2 Trial by Cardiology Trialsratings:
Length:
11 minutes
Released:
Aug 1, 2024
Format:
Podcast episode
Description
Lancet 1982;320:1173-1180Background: The first coronary artery bypass graft surgery (CABG) was performed in 1964 and by the 1970’s it was commonly used for relief of angina. However, whether it improved survival was unknown. The European Coronary Surgery Study (ECSS) sought to test the hypothesis that CABG compared to medical therapy improved survival at 5 years.Cardiology Trial’s Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Note to readers: Several preliminary reports of ECSS results were published at earlier time points (2 and 3-5 years). We are reporting the 5-year results since this was the prespecified hypothesis the investigators sought to test.Patients: Men under 65 years of age with angina pectoris of more than 3 months duration, a left ventricular ejection fraction >50%, and angiographic obstruction of >/=50% in at least 2 major coronary vessels with at least 1 vessel suitable for grafting. Patients with severe angina that could not be controlled with medical therapy were excluded.Baseline characteristics: No information is provided in the main paper on the number or characteristics of individuals screened to enrolled. There were 768 patients enrolled in the study. They were recruited from September, 1973 to March, 1976. The average age of patients was 50 years and the left ventricular ejection fraction was 65%. Approximately, 46% had a previous heart attack, 43% smoked, 35% had a high cholesterol, 15% had hypertension and 6% had diabetes. In terms of coronary anatomy, 53% had 3-vessel disease, 40% had 2-vessel disease, and 7% had left main disease.Procedures: Patients were randomly assigned to receive medical or surgical treatment. Medical measures varied based on location. The authors reported that strict standardization was not felt to be practical or necessary. Surgical treatment was either with saphenous-vein graft or internal mammary artery and was performed as soon as possible following randomization. The average time from randomization to surgery was approximately 4 months.Follow-up evaluations were performed 6 months after randomization and annually thereafter. Graft angiography was planned at 6 and 12 months after operation.Endpoints: The primary endpoint was all-cause death. The prespecified minimum follow-up time, set at the start of the trial, for all patients was 5 years. At the time of this report, some patients had been followed up to 8 years. A strict hypothesis was not tested (i.e., CABG would reduce death by X% compared to medical therapy). The primary analysis was a traditional intention to treat analysis and medical patients who crossed over to surgery and surgical patients who died prior to receiving surgery or refused surgery after randomization were retained within their original groups.Results: There were 767 patients included in the final analysis; 373 patients in the medical group and 394 in the surgical group (1 patient was lost from the surgical group immediately following randomization and was not counted in the group). At 5 years, 90 patients (24%) of the medical group had crossed over to surgery and 26 (7%) of the surgical patients were not operated on. An average of 1.9 grafts per patient were performed in the 2-vessel disease subgroup and 2.4 grafts per patient in the 3-vessel disease subgroup. The graft patency rate was 90% within 9 months and 77% between 9 and 18 months.Compared to medical therapy, surgery significantly reduced death at 5 years by 53% (7.6% vs 16.4%; p=0.00025). Operative (in-hospital) mortality was 3.6% for a total of 494 operations and 7.7% for 26 reoperations. Seven of 27 prespecified variables recorded at the time of randomization were found to be associated with significant treatment effect heterogeneity. They included: (i) extent of disease; (ii) location of lesion(s) in the proximal third of the left anterior descending artery (proximal LAD); (iii) resting ECG suggestive of
Released:
Aug 1, 2024
Format:
Podcast episode
Titles in the series (94)
- 11 min listen