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Long-Term Survival After Initial Invasive or Conservative Management of Stable Coronary Disease in Patients With Advanced Chronic Kidney Disease: ISCHEMIA-CKD EXTEND
What happened
Initial invasive strategy undergoes evaluation against conservative management for long-term survival in stable CAD and CKD.
- HR 1.05
- 95% CI 0.87-1.28
- n=777
Key points
- Context & question: Although the ISCHEMIA-CKD trial found similar rates of death or nonfatal myocardial infarction between initial invasive and initial conservative strategies at a median of 2.2 years in patients with moderate or severe myocardial ischemia and advanced chronic kidney disease, the long-term outcomes comparing these two approaches remained unknown.
- Methods & population: Study design, patient population, and sample size are not yet reported.
- Finding & limits: In patients with advanced chronic kidney disease and moderate or severe ischemia, an initial invasive strategy did not significantly reduce the primary outcome of all-cause mortality at 8 years compared with an initial conservative strategy (57.4% vs. 56.8%; adjusted HR 1.05, 95% CI 0.87–1.28). Experts name an urgent need for therapies that reduce the very high death rate in these patients, which neither strategy addressed.
Discussion
Expert perspectives 6
Expert perspective
Sripal Bangalore19h ago
Interventional · NYU Langone Health
In this five year follow up of patients from the ISCHEMIA-CKD trial, an initial invasive management strategy did not improve survival when added to guideline directed medical therapy in patients with advanced chronic kidney disease and chronic coronary disease. Similarly, there were no significant differences in cardiovascular death or non-cardiovascular death with an invasive versus conservative strategy. Further analyses showed no significant heterogeneity of treatment effect for any subgroup. Of note, the death rate was very high with close to 40% mortality at five years indicating a very high risk group of patients who are in urgent need of therapies to reduce this risk.
ISCHEMIA-CKD EXTEND co-authorExpert perspective
Sripal Bangalore19h ago
Interventional · NYU Langone Health
What we showed in the trial, at least, is that an invasive strategy is safe. If patients have an indication for revascularization — for example, if they come in with ACS — if you follow protocol and strategies to minimize risk, you can safely go ahead and do it. What this study also shows, is that in patients who have stable CAD, routine revascularization may not have significant benefit.
ISCHEMIA-CKD EXTEND co-authorExpert perspective
Mauricio Soto V17h ago
LIVE from #ScientificSessions26 @AHAScience: ISCHEMIA-CKD EXTEND: in advanced CKD, invasive-first did not improve survival at 8 years (HR 1.05). More than half of patients died. My take: in advanced CKD, the kidney sets the prognosis, not the stenosis. @ACCinTouch @JACCJournals
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Expert perspective
Janet Wei19h ago
Cardiac Imaging
When combined with guideline-directed medical therapy, an initial invasive management strategy did not reduce the high mortality risk in patients with advanced CKD and myocardial ischemia. This emphasizes that optimal medical management should be the main cardioprotective strategy patients with advanced CKD.
ISCHEMIA-CKD EXTENDExpert perspective
Deepak L. Bhatt19h ago
The main message here, really, is don't just go looking for ischemia, at least with the modalities used in this trial, in your CKD patients as a routine practice, and then try to stomp out that ischemia with revascularization. The right thing to do in these high-risk patients is to focus on lifestyle modification and intensive medical therapy.
ISCHEMIA-CKD EXTENDExpert perspective
PulseMD19h ago
@CircAHA @AHAScience @SripalBangalore For boards, advanced CKD + moderate ischemia still lands on "optimize GDMT first" — ISCHEMIA-CKD EXTEND extending the null long-term invasive signal is the stem answer when the question tempts early cath without a compelling ACS indication.
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Full evidence
Why the trial, key points, tables, limitations, PICO, abstract, media & sources
Full evidence
Why the trial, key points, tables, limitations, PICO, abstract, media & sources
Why the trial?
Although the ISCHEMIA-CKD trial found similar rates of death or nonfatal myocardial infarction between initial invasive and initial conservative strategies at a median of 2.2 years in patients with moderate or severe myocardial ischemia and advanced chronic kidney disease, the long-term outcomes comparing these two approaches remained unknown.
Does an initial invasive strategy reduce long-term all-cause mortality compared with an initial conservative strategy in patients with stable coronary disease, moderate or severe myocardial ischemia, and advanced chronic kidney disease?
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Key Points
- To determine whether an initial invasive strategy improves long-term survival compared with an initial conservative strategy in patients with advanced chronic kidney disease and stable coronary disease.
- Extended follow-up (median 8 years) of the ISCHEMIA-CKD randomized trial (NCT01985360), which assigned 777 participants with advanced kidney disease and ischemia to an initial invasive strategy (n=388) or conservative management (n=389) alongside guideline-directed medical therapy.
- Primary outcome was all-cause mortality tracked via site contact and health databases, achieving 95% vital status retention among survivors, with cause-specific mortality as secondary outcomes.
- Cumulative all-cause mortality over a median of 8 years was 57.4% in the invasive arm versus 56.8% in the conservative arm (adjusted HR, 1.05 [95% CI, 0.87–1.28]), encompassing 429 total deaths.
- Cardiovascular mortality did not significantly differ between groups, occurring in 40.3% of the invasive arm versus 38.4% of the conservative arm (adjusted HR, 1.06 [95% CI, 0.84–1.34]).
- Restricted mean survival time reached 1941 days (95% CI, 1834–2047) with an invasive strategy versus 1990 days (95% CI, 1885–2094) with conservative therapy (adjusted difference, −99 days [95% CI, −245 to 46]).
Structured PICO
Does an initial invasive strategy reduce long-term all-cause mortality compared with an initial conservative strategy in patients with stable coronary disease, moderate or severe myocardial ischemia, and advanced chronic kidney disease?
Population
777 patients with stable coronary disease, moderate or severe myocardial ischemia, and advanced chronic kidney disease, followed for a median of 8 years.
Intervention
Initial invasive strategy (INV), involving coronary angiography and revascularization when feasible, added to guideline-directed medical therapy
Comparator
Initial conservative strategy (CON) with guideline-directed medical therapy alone and invasive procedures reserved for failure of guideline-directed medical therapy
Outcome
All-cause mortality over a median of 8 years of extended follow-uphard clinical endpoint
Main Result
Hazard Ratio1.05 (95% CI 0.87–1.28)
Absolute Event Rate57.4% vs 56.8%
In patients with stable coronary disease, moderate or severe ischemia, and advanced chronic kidney disease, an initial invasive strategy offers no long-term survival benefit over initial conservative medical management at 8 years.
Where experts stand
Coronary artery disease evidence still formingExperts read this as a clear null result: in advanced kidney disease with stable coronary disease, going straight to the cath lab did not help patients live longer, so medical therapy stays the foundation.
Clinicians commenting agree that an invasive-first approach gave no long-term survival gain over medical therapy in this group. They also stress how many of these patients died regardless of strategy, which points to the kidney disease itself driving outcomes. The open question is what could actually lower this very high death risk.
Agreement
Clinicians agree that adding an initial invasive strategy to guideline-directed medical therapy did not improve survival in advanced chronic kidney disease, and that mortality stayed very high in both arms.
2 clinicians say this directly
What they’re arguing about
supportiveneutralcautiouscritical
Counts are expert takes we classified by axis. Tap a row to see the takes behind its count.
Still unclear
Experts name an urgent need for therapies that reduce the very high death rate in these patients, which neither strategy addressed.
Where verified peers stand
No verified votes yet. Vote to see where peers land.Vote to reveal
Peer votes count verified clinicians only (n=0).
Implication
Conservative management remains appropriate for advanced CKD with stable CAD; extends 2-year null findings to confirm no 8-year mortality benefit.
Abstract
BACKGROUND: In the ISCHEMIA-CKD trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches–Chronic Kidney Disease), at a median follow-up of 2.2 years, the primary composite outcome of death or nonfatal myocardial infarction was similar between an initial invasive strategy (INV) compared with an initial conservative strategy (CON) in patients with moderate or severe myocardial ischemia and advanced chronic kidney disease. However, the long-term outcomes comparing the 2 strategies are unknown. METHODS: Participants in the ISCHEMIA-CKD trial were randomly assigned to either INV, involving coronary angiography and revascularization when feasible, added to guideline-directed medical therapy or to CON with guideline-directed medical therapy alone and invasive procedures reserved for failure of guideline-directed medical therapy. After the active intervention trial phase, long-term vital status follow-up was conducted through participant contact by participating sites and by health record and centralized death database searches. The primary outcome for the extended follow-up phase was all-cause mortality. Secondary outcomes were cause-specific mortality, including cardiovascular and noncardiovascular mortality. RESULTS: Among the 777 participants randomized (388 to INV and 389 to CON), over a median of 8 years of follow-up, vital status retention among survivors was 95%. There was a total of 429 deaths (55%). Cumulative all-cause mortality (57.4% versus 56.8%; adjusted hazard ratio, 1.05 [95% CI, 0.87–1.28]) or cardiovascular mortality (40.3% versus 38.4%; adjusted hazard ratio, 1.06 [95% CI, 0.84–1.34]) at 8 years did not differ between INV and CON. The restricted mean survival time was 1941 days (1834–2047 days) for INV versus 1990 days (1885–2094 days) for CON, with an adjusted estimated difference of −99 days (−245 to 46). The posterior probability of at least a 1 percentage point lower or higher death with INV at the 8-year median follow-up was 28% and 52%, respectively. Similarly, the posterior probability of at least a 1 percentage point lower or higher cardiovascular mortality with INV was 23% and 56%, respectively. CONCLUSIONS: In patients with at least moderate ischemia and advanced chronic kidney disease, there was no significant long-term benefit of an initial INV at reducing the risk of all-cause or cardiovascular mortality compared with an initial conservative strategy. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01985360
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Bangalore et al. (2026) conducted an RCT in Stable coronary disease with moderate or severe myocardial ischemia and advanced chronic kidney disease (n=777). Initial invasive strategy (coronary angiography and revascularization when feasible, added to guideline-directed medical therapy) vs. Initial conservative strategy (guideline-directed medical therapy alone with invasive procedures reserved for failure of guideline-directed medical therapy) was evaluated on All-cause mortality (HR 1.05, 95% CI 0.87-1.28). An initial invasive strategy did not reduce 8-year all-cause mortality vs conservative management in advanced CKD and ischemia (57.4% vs 56.8%; aHR 1.05; 95% CI 0.87-1.28).