Highlight
– In a propensity score–matched, population-based Ontario cohort (2012–2021), women undergoing CABG had lower long-term MACCE (HR 1.81 for PCI vs CABG) and lower all‑cause mortality (HR 1.34) than matched women undergoing PCI.
– Cardiovascular readmissions (MI, HF, or stroke) and repeat revascularization were more frequent after PCI.
– Findings support preferential consideration of CABG for appropriately selected women with chronic severe multivessel coronary artery disease, while recognizing limitations of observational data.
Background: disease burden and clinical context
Coronary artery disease (CAD) remains the leading cause of death and disability worldwide. Women with CAD present later in life, often with more comorbidities and differing coronary anatomy (smaller vessel size, higher prevalence of microvascular disease) than men. Historically, women have been underrepresented in randomized revascularization trials, and sex-specific evidence to guide the choice between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) is limited. Clinical guidelines recommend heart‑team decision‑making that integrates anatomic complexity (e.g., SYNTAX score), comorbidity (including diabetes), and patient preferences, but sex-specific recommendations are not comprehensive due to lack of dedicated data.
Study design and methods
The study by An et al. (Eur Heart J. 2025) is a retrospective, propensity score–matched cohort analysis linking clinical and administrative databases in Ontario, Canada, to compare long‑term outcomes after PCI versus CABG in women with chronic severe CAD who underwent revascularization between 2012 and 2021. Key design elements include:
- Population: Women with chronic severe CAD undergoing first revascularization with PCI or CABG during the study period; initial cohorts comprised 2,469 PCI and 3,721 CABG patients.
- Matching: A 1:1 propensity score match produced 2,033 well‑balanced pairs, with mean age 66.5 ± 8.6 years.
- Endpoints: The primary outcome was MACCE (composite of all‑cause mortality, myocardial infarction [MI], stroke, or repeat revascularization). Secondary endpoints included individual MACCE components and cardiovascular readmission (MI, heart failure, or stroke).
- Analysis: Time‑to‑event outcomes examined using Cox proportional hazards models with hazard ratios (HRs) and 95% confidence intervals (CIs); median follow‑up was 5.1 years (IQR 2.9–7.5).
Key findings
The principal results in propensity‑matched women were:
- MACCE: Significantly higher after PCI compared with CABG (HR 1.81; 95% CI 1.63–2.01; P < .001). This large effect indicates nearly an 80% higher hazard of the composite outcome in the PCI group over long‑term follow‑up.
- All‑cause mortality: Higher after PCI (HR 1.34; 95% CI 1.16–1.54; P < .001), indicating a 34% higher hazard of death compared with CABG.
- Cardiovascular readmission: More common after PCI (HR 1.40; 95% CI 1.32–1.49; P < .001), demonstrating increased burden of recurrent ischemic events or heart failure admissions following PCI.
- Individual components: Although the provided summary does not list all component HRs separately, the composite MACCE excess with PCI is likely driven by higher rates of repeat revascularization and MI; the mortality difference is clinically meaningful.
Overall, these data suggest that, in this real‑world cohort, CABG confers durable protection against major adverse cardiovascular and cerebrovascular events and reduces long‑term mortality compared with PCI in women with chronic severe CAD.
Interpretation and biological plausibility
Several plausible mechanisms can explain superior long‑term outcomes with CABG in patients with complex multivessel CAD, and these may be particularly relevant to women:
- Completeness and durability of revascularization: CABG provides conduit bypasses that can supply ischemic territories beyond focal lesions, reducing the risk of future ischemic events caused by progression of nonstented lesions.
- Bypassing diffuse atherosclerosis: Women often have more diffuse disease and smaller coronary calibers; CABG may better address diffuse lesions not amenable to durable stenting.
- Lower need for repeat procedures: Surgical grafts (especially internal mammary artery grafts) show excellent long‑term patency, which reduces the incidence of repeat revascularization and downstream complications.
Strengths of the study
- Large, population‑based sample from a universal health‑care setting, enhancing generalizability within Canada and potentially similar health systems.
- Contemporary time frame (2012–2021) that captures modern stent technology, surgical techniques, and medical therapy.
- Robust propensity score matching to reduce measured confounding and produce well‑balanced treatment groups.
- Long median follow‑up (5.1 years), enabling assessment of durable outcomes including mortality and repeat events.
Limitations and caveats
Despite careful methods, important limitations inherent to observational studies remain:
- Residual confounding and treatment selection bias: Even with propensity matching, unmeasured differences (frailty, patient anatomy such as SYNTAX score, frailty indices, coronary physiology, patient preferences) may have influenced treatment assignment and outcomes.
- Limited anatomical detail: Administrative and clinical linkage may lack granular angiographic data (extent of left main disease, true multivessel complexity, SYNTAX score, completeness of revascularization), which are key determinants of revascularization strategy and outcomes.
- Heterogeneity of procedures: PCI techniques and stent types, as well as surgical approaches and conduit choices, evolve and vary across centers; subgroup heterogeneity is difficult to fully account for.
- Unrecorded perioperative complications and quality‑of‑life outcomes: The administrative datasets may undercapture procedural complications, neurocognitive or functional outcomes important to patients.
- Generalisability: Findings from Ontario may not generalize to regions with different demographic mix, surgical capacity, or PCI practice patterns.
How this fits with randomized trial evidence and guidelines
Randomized trials comparing PCI and CABG have informed guideline recommendations, but most trials underrepresent women. For example, the SYNTAX trial (Serruys et al., 2009) and FREEDOM (2012) demonstrated CABG benefit for complex multivessel disease and for diabetes, respectively, primarily in mixed‑sex populations. The EXCEL trial compared PCI with CABG for left main disease with mixed findings and controversy around long‑term outcomes. Current guideline frameworks (e.g., 2018 ESC/EACTS myocardial revascularization guideline) emphasize heart‑team decision‑making and individualized selection based on anatomic complexity and clinical factors. The new real‑world evidence from An et al. strengthens the argument that, for women with chronic severe CAD—particularly when anatomy is complex—CABG is a durable option that may confer lower rates of MACCE and death over long‑term follow‑up.
Clinical implications and recommendations
For clinicians managing women with chronic severe CAD, this study suggests the following practical points:
- Heart‑team discussion remains essential; include sex‑specific considerations (body and vessel size, frailty, bleeding risk, patient values) when weighing PCI versus CABG.
- For anatomically complex multivessel disease or left main disease, practitioners should counsel women that CABG was associated with lower long‑term MACCE and mortality in this large real‑world cohort.
- Shared decision‑making should incorporate durable outcomes (repeat revascularization, recurrent ischemia), quality of life, recovery time, and individual surgical risk.
- Optimize guideline‑directed medical therapy irrespective of revascularization strategy, and ensure secondary prevention adherence and cardiac rehabilitation referral—factors that importantly influence long‑term outcomes.
Research implications and future directions
Key research priorities emerging from this work include:
- Prospective randomized trials or well‑designed pragmatic studies that specifically enroll and power analyses for women to define optimal revascularization strategies by sex.
- Registries that capture detailed angiographic complexity (SYNTAX), physiologic lesion assessment (FFR/iFR), completeness of revascularization, frailty metrics, and patient‑reported outcomes to clarify treatment effect heterogeneity.
- Mechanistic and imaging studies to understand sex differences in coronary atherosclerosis (plaque morphology, microvascular disease) and their implications for revascularization durability.
Conclusion
This large, contemporary, propensity‑matched, population‑based study indicates that CABG is associated with significantly lower long‑term MACCE and all‑cause mortality than PCI among women with chronic severe CAD. While these findings support consideration of CABG as the preferred strategy in appropriately selected women—particularly those with complex multivessel disease—they must be interpreted in light of the observational design and potential residual confounding. Individualized, heart‑team shared decision‑making remains essential, and there is a clear need for more sex‑specific randomized evidence and granular registry data to refine recommendations.
Funding and clinicaltrials.gov
This analysis was a retrospective cohort study using linked administrative and clinical databases. Trial registration is not applicable. Funding sources and disclosures should be reviewed in the original publication (An KR et al., Eur Heart J. 2025).
Selected references
1. An KR, Vervoort D, Qiu F, Tam DY, Rocha RV, Harik L, Hirji S, Sandner S, Fremes SE, Wijeysundera HC, Gaudino MFL. Women with chronic coronary artery disease: long‑term outcomes after percutaneous coronary intervention vs coronary artery bypass grafting. Eur Heart J. 2025 Nov 25:ehaf806. doi:10.1093/eurheartj/ehaf806.
2. Serruys PW, Morice M‑C, Kappetein AP, et al.; SYNTAX Investigators. Percutaneous coronary intervention versus coronary‑artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961–972.
3. Farkouh ME, Domanski M, Sleeper LA, et al.; FREEDOM Trial Investigators. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367(25):2375–2384.
4. Stone GW, Sabik JF, Serruys PW, et al.; EXCEL Trial Investigators. Everolimus‑eluting stents or bypass surgery for left main coronary artery disease. N Engl J Med. 2016;375(23):2223–2235.
5. Neumann FJ, Sousa‑Uva M, Ahlsson A, et al.; ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87–165.
