ISCHEMIA trial 11-year data confirms no survival gain from invasive strategy
Extended follow-up from the ISCHEMIA and COURAGE trials shows no mortality benefit for an initial invasive strategy over optimal medical therapy alone in stable coronary artery disease, with data now spanning up to 25 years.
New 11-year follow-up data from the ISCHEMIA trial provides the most mature evidence yet, confirming that an invasive strategy offers no survival advantage over conservative medical management for stable coronary artery disease. This aligns with the 25-year follow-up of the COURAGE trial, which also showed no difference in death or myocardial infarction between patients receiving upfront PCI plus optimal medical therapy versus optimal medical therapy alone.
In the COURAGE trial, the median age at baseline was 62.7 years, fewer than 2% were women, about 40% had diabetes, and mean left ventricular ejection fraction was just over 59%. The ISCHEMIA trial population had a median age of 64 years, with 23% women, 42% with diabetes, and a median LVEF of 60%. A separate cohort, ISCHEMIA-CKD, focused on patients with chronic kidney disease, where the median age was 63 years, 31% were women, 57% had diabetes, 53% were on dialysis, and median LVEF was 59%. In COURAGE, nearly half of patients randomized to optimal medical therapy alone never required a revascularization procedure during follow-up.
Long-term mortality and MI outcomes
Extended follow-up from both major trials shows consistently neutral outcomes for the invasive approach. In the COURAGE trial's 25-year analysis, the cumulative incidence of combined death or myocardial infarction was 93.3% for patients who received added PCI and 91.0% for those on optimal medical therapy alone. The hazard ratio was 1.01.
| Trial | Follow-up | Endpoint | Invasive Strategy | Conservative Strategy | Hazard Ratio (95% CI) |
|---|---|---|---|---|---|
| COURAGE | 25-year | Death or MI | 93.3% | 91.0% | 1.01 (0.88-1.15) |
| ISCHEMIA | 11-year | All-cause Mortality | 25.8% | 26.9% | 0.97 (0.86-1.09) |
| ISCHEMIA | 11-year | CV Mortality | 15.8% | 17.1% | 0.88 (0.75-1.02) |
A post hoc analysis of 959 veterans from 15 Department of Veterans Affairs hospitals, followed for a median of 15 years, reinforced that upfront PCI added to optimal medical therapy did not reduce long-term death or myocardial infarction. More than half of the veterans in each group underwent a revascularization procedure at some point during the extended follow-up period. In the ISCHEMIA-EXTEND analysis, median follow-up reached 9 years with no significant outcome differences between the strategy groups.
Findings in specific sub-groups
Patients with chronic kidney disease, a high-risk subgroup, also derived no mortality benefit from an initial invasive strategy. In the ISCHEMIA-CKD cohort, cumulative all-cause mortality was 57.4% with an invasive strategy and 56.8% with conservative management. Cardiovascular mortality was 40.3% versus 38.4%, respectively.
| Cohort | Endpoint | Invasive Strategy | Conservative Strategy | Adjusted HR (95% CI) |
|---|---|---|---|---|
| ISCHEMIA-CKD | All-cause Mortality | 57.4% | 56.8% | 1.05 (0.87-1.28) |
| ISCHEMIA-CKD | CV Mortality | 40.3% | 38.4% | 1.06 (0.84-1.34) |
Commenting on the collective evidence, Donald Cutlip, MD, and Robert Yeh, MD, MSc said: "A conservative strategy is a safe initial approach in most cases of chronic stable coronary artery disease." They added, "A conservative strategy has a slightly higher risk for spontaneous MI that should be considered and balanced against initial procedural risks."
In the COURAGE trial, individual components of the primary endpoint were neutral, with death occurring in 83.9% of the PCI group versus 82.2% with medical therapy alone. Myocardial infarction rates were 54.6% versus 54.0%, and revascularization rates were 50.4% versus 53.5%. Clinicians will continue to weigh the risks of procedural intervention against the established safety of optimal medical therapy as the default initial approach.
