Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention in Patients Receiving Dialysis: Is CABG Worth the Risk?

Cardiovascular disease is the leading cause of death among dialysis patients, and an estimated 40% of patients receiving dialysis have ischemic heart disease.1Annual Data Report. USRDS. Accessed October 25, 2023. https://adr.usrds.org/Google Scholar,2Cheung A.K. Sarnak M.J. Yan G. et al.Cardiac diseases in maintenance hemodialysis patients: results of the HEMO Study.Kidney Int. 2004; 65: 2380-2389https://doi.org/10.1111/j.1523-1755.2004.00657.xAbstract Full Text Full Text PDF PubMed Scopus (430) Google Scholar While it may seem intuitive that more aggressive coronary interventions would lead to improved outcomes, whether dialysis patients with coronary artery disease benefit from coronary revascularization and which revascularization strategy leads to the best outcomes remain open questions. The most recent American College of Cardiology/American Heart Association guidelines recommend that patients with CKD receive coronary interventions if they present with an acute coronary syndrome while discouraging revascularization in dialysis patients with stable coronary artery disease..3Lawton J.S. Tamis-Holland J.E. Bangalore S. et al.2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Circulation. 2022; 145: e18-e114https://doi.org/10.1161/CIR.0000000000001038Crossref PubMed Scopus (343) Google Scholar Critically these recommendations are backed by a paucity of data, as patients treated by dialysis were almost entirely excluded from all major trials supporting percutaneous coronary revascularization (PCI) and coronary artery bypass grafting (CABG). ISCHEMIA-CKD is the largest trial to examine coronary revascularization in patients with chronic kidney disease (CKD). ISCHEMIA-CKD randomized 777 patients with advanced CKD (including 311 with CKD stage 4, 51 with CKD stage 5, and 411 receiving dialysis) with moderate to severe coronary ischemia to receive coronary angiography plus optimized medical therapy versus optimized medical therapy alone. ISCHEMIA-CKD excluded individuals with acute coronary syndrome within the prior two months. Optimized medical therapy included lifestyle interventions accompanied by hypertension management, lipid lowering therapy and anti-anginal medications.4Bangalore S. Maron D.J. O’Brien S.M. et al.Management of Coronary Disease in Patients with Advanced Kidney Disease.N Engl J Med. 2020; 382: 1608-1618https://doi.org/10.1056/NEJMoa1915925Crossref PubMed Scopus (286) Google Scholar The ISCHEMIA-CKD trial demonstrated no difference in the primary outcome of death or nonfatal myocardial infarction using either strategy [HR 1.01 (95% CI 0.79-1.29), p= 0.95) although there was significant cross-over between groups.4Bangalore S. Maron D.J. O’Brien S.M. et al.Management of Coronary Disease in Patients with Advanced Kidney Disease.N Engl J Med. 2020; 382: 1608-1618https://doi.org/10.1056/NEJMoa1915925Crossref PubMed Scopus (286) Google Scholar Critically, only 50% of the invasive strategy group underwent revascularization, as a high proportion of participants were found to have non-obstructive CAD, while 20% of the strategy group ultimately received a revascularization procedure, potentially biasing the trial towards the null. If revascularization of a patient receiving dialysis is considered, it is also unclear what intervention should be performed.5Sarnak M.J. Amann K. Bangalore S. et al.Chronic Kidney Disease and Coronary Artery Disease: JACC State-of-the-Art Review.J Am Coll Cardiol. 2019; 74: 1823-1838https://doi.org/10.1016/j.jacc.2019.08.1017Crossref PubMed Scopus (349) Google Scholar One older study using data from the US Renal Data System from 1995-1998 demonstrated that CABG was associated with a lower risk of all-cause mortality than PCI among dialysis patients receiving revascularization procedures.6Herzog C.A. Ma J.Z. Collins A.J. Comparative survival of dialysis patients in the United States after coronary angioplasty, coronary artery stenting, and coronary artery bypass surgery and impact of diabetes.Circulation. 2002; 106: 2207-2211https://doi.org/10.1161/01.cir.0000035248.71165.ebCrossref PubMed Scopus (0) Google Scholar Notably, this study evaluated all patients who underwent revascularization, including those with acute coronary syndromes, and predated drug eluting stents. A similar study using USRDS data from 1997-2009 also demonstrated a relative survival advantage to CABG over PCI in dialysis patients with multivessel coronary disease.7Chang T.I. Shilane D. Kazi D.S. Montez-Rath M.E. Hlatky M.A. Winkelmayer W.C. Multivessel coronary artery bypass grafting versus percutaneous coronary intervention in ESRD.J Am Soc Nephrol JASN. 2012; 23: 2042-2049https://doi.org/10.1681/ASN.2012060554Crossref PubMed Scopus (112) Google Scholar Since then, there have been major advances in both drug-eluting stent technology and percutaneous intervention methodologies that require revisiting whether this survival advantage with CABG persists in the dialysis population. In this issue of Kidney Medicine, Pan and colleagues attempt to answer this question in a more modern, national cohort.8Pan S.Y. Yang J.Y. Teng N.C. et al.Percutaneous Coronary Intervention With a Drug-Eluting Stent Versus Coronary Artery Bypass Grafting in Dialysis Patients: A National Study From Taiwan.Kidney Med. 2023; https://doi.org/10.1016/j.xkme.2023.100768Abstract Full Text Full Text PDF PubMed Google Scholar Using data from the Taiwan National Health Insurance Research Database, they examined records from 1840 propensity-matched dialysis patients who received either CABG or PCI with a drug-eluting stent between 2009 and 2015. In contrast to findings from the older USRDS data, all-cause mortality was significantly higher among patients who underwent CABG than those who underwent PCI with stent placement at every time point examined up to 5 years from the time of revascularization. While it is tempting to attribute higher mortality among those who underwent CABG to in-hospital mortality immediately following surgery, when examining the subsets of patients who survived the index hospitalization and were alive 90-days post-revascularization, there was still no mortality benefit to CABG over PCI. Of note, PCI with stenting was associated with higher rates of subsequent acute coronary syndrome, repeat revascularization procedures, and repeat hospitalizations when compared with CABG; in models also accounting for death, only repeat revascularization remained significantly more likely among PCI recipients. There are several limitations to this work. First, given that this is a retrospective study, there are potential biases as to which patients received each revascularization procedure that may not be accounted for in the propensity matching. Second, there are no available data regarding which coronary arteries were treated. It is possible that more patients who underwent PCI received low-risk single-vessel or two-vessel interventions while more patients who underwent CABG were treated for a left-main coronary artery lesion, potentially biasing the results towards demonstrating higher mortality in the CABG group. The authors also note that surgical/operator expertise could also be causing this effect. Third, both acute coronary syndrome and stable angina patients are included, although sensitivity analyses excluding those with acute coronary syndromes demonstrated similar results to the whole cohort. Lastly, there are no data on which type of stent was deployed other than it being drug eluting. Given the multitude of drug-eluting stents available, it would be helpful to know which ones were used in this study. While it may seem that these results contradict prior work demonstrating a survival benefit to CABG over PCI in dialysis patients, it is plausible that these results reflect the improved efficacy of stents and the improved PCI techniques over this time period, although the same result has not reliably been demonstrated in treatment of multivessel disease in the general population.9Head S.J. Milojevic M. Daemen J. et al.Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data.The Lancet. 2018; 391: 939-948https://doi.org/10.1016/S0140-6736(18)30423-9Abstract Full Text Full Text PDF PubMed Scopus (465) Google Scholar Coronary artery disease in individuals with advanced CKD may have different features than that seen in the general population, with a far greater contribution of non-atherosclerotic mechanisms to ischemia, particularly among patients receiving dialysis. Ischemia in advanced CKD is augmented by high rates of endothelial dysfunction, oxidative stress, vascular stiffness, left ventricular hypertrophy and microvascular disease that may make potential benefits of surgical revascularization a fundamentally different prospect than in non-dialysis patients.5Sarnak M.J. Amann K. Bangalore S. et al.Chronic Kidney Disease and Coronary Artery Disease: JACC State-of-the-Art Review.J Am Coll Cardiol. 2019; 74: 1823-1838https://doi.org/10.1016/j.jacc.2019.08.1017Crossref PubMed Scopus (349) Google Scholar Furthermore, given the dramatically higher mortality rates among patients receiving dialysis as compared to general population overall, it is also possible that patients receiving dialysis are not surviving long enough to experience benefits from CABG, although Pan and colleagues present robust data through 5 years of follow-up. It is also unclear if the potential harms associated with CABG as compared to PCI are specific to dialysis patients in Taiwan or if this result is replicable elsewhere. In conclusion, the current report from Pan and colleagues represents a careful analysis of extensive data with multiple sensitivity analyses all demonstrating the same result - there is no benefit and potentially even harm associated with CABG as compared to PCI in patients receiving maintenance dialysis. Given the high rates of early morbidity following CABG as well as the high costs of this procedure, with a $35,000 higher cost per quality-adjusted life-year associated with CABG,10Reynolds M.R. Gong T. Li S. Herzog C.A. Charytan D.M. Cost‐Effectiveness of Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention in Patients With Chronic Kidney Disease and Acute Coronary Syndromes in the US Medicare Program.J Am Heart Assoc Cardiovasc Cerebrovasc Dis. 2021; 10e019391https://doi.org/10.1161/JAHA.120.019391Crossref Scopus (2) Google Scholar the threshold for recommending CABG as compared with PCI should be very high, and potentially limited to cases where there are no PCI options. Critically, this study does not answer the fundamental question raised by ISCHEMIA-CKD - is any revascularization strategy of benefit to the stable dialysis patient with CAD as compared to medical management? While we do not have answers for this question, we can certainly use this knowledge generated by Pan and colleagues to minimize use of CABG in patients receiving dialysis given the potential signal for harm.