Editor's Note: Commentary based on Chang M, Lee CW, Ahn JM, et al. Outcomes of coronary artery bypass graft surgery versus drug-eluting stents in older adults. J Am Geriatr Soc 2017;65:625-30.

Rationale for Study/Background: The optimal coronary revascularization strategy (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]) in older adults with multiple chronic conditions (MCC), who have been inadequately represented in clinical trials, is unknown.^1,2

Funding: This study was supported by a research grant from The CardioVascular Research Foundation (CVRF), Seoul, South Korea (2015-09).

Study Design: Individual patient-level data meta-analysis of three prior trials, BEST (Bypass Surgery Versus Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease), PRE-COMBAT (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease), and SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery).

The BEST trial was a non-inferiority trial across 27 centers in Asia recruiting 880 multi-vessel CAD patients randomized to PCI with everolimus-eluting stents or to CABG.

The Korean PRECOMBAT trial randomly assigned 600 patients with unprotected left main coronary artery disease to PCI with sirolimus-eluting stent or CABG.

The SYNTAX trial randomized 1,800 patients in the U.S. and Europe with 3-vessel or left main coronary artery disease (CAD) to paclitaxel eluting stents or to CABG.

For the current analysis the investigators identified 1,079 patients (32.9% of the three cohorts) that were between 70 to 89 years. The merged database included participant age, sex, body weight, height, clinical history such as prior myocardial infarction (MI), etc., angiographic and echocardiographic variables along with medication history.

Outcomes

Primary: Composite of major adverse cardiac and cerebrovascular events (MACCE) (all-cause mortality, MI, stroke, or repeat coronary revascularization)

Secondary individual outcomes: All-cause mortality, cardiac mortality, MI, stroke, repeat revascularization death, or MI.

Statistical Analysis: A one-stage approach using a random-effects meta-analysis and a likelihood ratio test to assess the heterogeneity of the data.

Results: The average age in the CABG cohort (n = 550, 74.7 ± 3.7 years) was similar to the PCI group (n = 529, 74.8 ± 3.7 years, p = 0.68). The balanced with respect to the distribution of all available covariates (individual baseline comorbidities, presence of left ventricular dysfunction, coronary anatomy, SYNTAX score, and EUROSCORE).

The primary composite outcome occurred in 25.6% of CABG patients, and 33.8% in PCI patients, with a HR of 0.75 (95% CI 0.60-0.94) favoring CABG.

Significant secondary outcomes (all favoring CABG) were:

• Cardiovascular death (HR 0.80, 95% CI 0.43-0.98)
• Myocardial infarction (HR 0.48, 95% CI 0.29-0.80)
• Repeat coronary revascularization (HR 0.44, 95% CI 0.31-0.64)
• Death or MI (HR 0.75, 95% CI 0.57-0.98)

Of interest, the investigators reported on the primary outcome stratified by the SYNTAX score:

• Low (<23) SYNTAX score (HR 1.19, 95% CI 0.78-1.83)
• Intermediate (23-32) SYNTAX score (HR 0.76, 95% CI 0.53-1.09)
• High (≥33) SYNTAX score (HR 0.49, 95% CI 0.34-0.72)

Conclusion: This individual patient-level data meta-analysis of three prior randomized trials of PCI (using drug eluting stents) versus CABG in adults between 70-89 years old demonstrated that revascularization with CABG had a 25% lower relative risk of the primary composite MACCE outcome compared to those randomized to PCI.

The investigators noted that the strength of this association varied with SYNTAX score, such that participants in the highest SYNTAX score stratum derived the greatest benefit from CABG.

Limitations of study/perspective: Comparative effectiveness studies of coronary revascularization strategies are critically needed in older adults. Unfortunately, older adults are insufficiently represented in cardiovascular clinical trials. Those that are recruited for clinical trials are most often a healthier cohort. This is in stark contrast to the real world population of older adults with multiple chronic conditions and associated geriatric syndromes such as frailty, disability, polypharmacy, cognitive decline, history of falls, and incontinence. The current individual patient-level data meta-analysis of three prior trials reported that CABG was associated with a lower hazard of the composite MACCE outcome than PCI. However, this decreased risk with CABG was primarily driven not by a reduction in mortality but a reduction in repeat revascularization, which is not a novel finding.

Decreased MACCE with CABG among those with higher SYNTAX scores is again not a new finding. Furthermore, translation of this finding to the management of older adults with multiple chronic conditions and geriatric syndromes cannot and probably should not be done based on the current study. Although the SYNTAX score addresses cardiac specific issues such as completeness of revascularization and reduction of MI risk, it does not include important geriatric-specific variables such as frailty, activities of daily living, and cognitive status that may influence procedural risk and clinical outcomes, including patient centered quality of life. It is also important to note that, as with most cardiovascular trials, patients enrolled in BEST, PRECOMBAT, and SYNTAX were relatively free of major comorbidities and advanced geriatric syndromes, and all patients had to be considered suitable candidates for either PCI or CABG, thereby further restricting patient selection.

In the day-to-day management of older adults with cardiovascular disease, the decision to revascularize and the method of revascularization can perhaps be approached as a value proposition, where value is defined by health outcome/cost.³ The health outcome chosen should be patient-centered and can vary from survival to a specific patient centered goal, such as "Doc, I just want to be able to go places with my grandkids," and the cost can be thought of as the related treatment burden. Discussions using this framework will hopefully improve understanding and shared decision making between patients, families and their physicians in regards to healthcare choices.

In summary, this study provides important data on the relative merits of PCI and CABG in selected older adults with CAD, but it should not be considered the "last word" in choosing the optimal coronary revascularization strategy. Additional high quality research is critically needed in this area, and future studies should target increased recruitment of older adults with MCC and geriatric syndromes in order to ensure that study findings will be applicable to patients typically encountered in routine clinical practice.

References

1. Skolnick AH, Alexander KP. Older adults in clinical research and drug development: closing the geriatric gap. Circ Cardiovasc Qual Outcomes 2015;8:631-3.
2. Rich MW, Chyun DA, Skolnick AH, et al. Knowledge gaps in cardiovascular care of older adults: a scientific statement from the American Heart Association, American College of Cardiology, and American Geriatrics Society: executive summary. J Am Geriatr Soc 2016;64:2185-92.
3. Tinetti ME, Naik AD, Dodson JA. Movign from disease-centered to patient goals-directed care for patients with multiple chronic conditions: patient value-based care. JAMA Cardiol 2016;1:9-10.

Keywords: Drug-Eluting Stents, Coronary Artery Disease, Paclitaxel, Taxus, Sirolimus, Comorbidity, Quality of Life, Percutaneous Coronary Intervention, Myocardial Revascularization, Myocardial Infarction, Angioplasty, Stroke, Ventricular Dysfunction, Left, Coronary Artery Bypass, Aged, Geriatrics

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