Acute coronary syndrome (ACS) events in people receiving long-term haemodialysis (HD) are common, present atypically and are associated with poor outcomes.1–3 Diagnosis is challenging, and treatment even more so. The complexity of this population drives their exclusion from clinical trials, resulting in a scarcity of evidence supporting any ‘optimal’ treatment strategy.4 Guidelines are, as a result, vague and, to a degree, contradictory.5–7 These are some of the reasons that the combination of cardiac and renal disease strike fear into even the most seasoned clinicians. Is it this fear that underlies the observed conservatism in treatment of those with advanced chronic kidney disease (CKD), and are we, therefore, contributing inadvertently to the adverse outcomes we are simultaneously striving to avoid? I commend Muhammad Haider and colleagues for tackling this challenging area, and attempting to summarise our knowledge in their review: “Diagnosis and management of ACS in patients with ESRD on haemodialysis: a comprehensive review”.8
Cardiovascular disease is the primary cause of premature mortality and morbidity in people with CKD.9,10 The risk of cardiovascular disease increases as kidney function declines, but also notably with an increase in proteinuria;11 those with kidney failure (the relatively new term proposed by the Kidney Disease Improving Global Outcomes [KDIGO] group to encompass all individuals with an estimated glomerular filtration rate [eGFR] <15 ml/min/1.73 m2) experience the greatest risk. It is this association between kidney and cardiac disease that explains the high prevalence of CKD among individuals hospitalised with ACS; the population prevalence of moderate-to-severe CKD (eGFR <60 ml/min/1.73 m2) is just 6%, but this rises to 30–40% of those with ACS.2,12,13 Respective figures for people who use HD are approximately 0.04% and 0.8%.2 This equates to an estimate of 1,000 people per year in the UK. This number is likely an underestimation given the diagnostic challenges and elevated prevalence of silent myocardial infarction (MI) in those with advanced CKD.14
Somewhat ironically, those with the worst kidney function not only have the highest risk of development of cardiovascular events, but also the worst outcomes.12,13 At 30 days post-ACS, 98% of those with normal kidney function remain alive. Among those with an eGFR <30 ml/min/1.73 m2, this falls to 80% following non-ST-elevation MI (NSTEMI) and 70% after ST-elevation MI (STEMI).2 People receiving HD at the time of their ACS event have just a 40% chance of surviving their first year.15,16 Not only are those with reduced kidney function more likely to die following an acute cardiovascular event, but they spend longer in hospital, are less likely to return to work on discharge,17,18 and risk resulting poor cardiac function, precluding them from either receiving a kidney transplant or tolerating ongoing dialysis.
Are outcomes modifiable?
What is unclear regarding these morbidity and mortality outcomes, is to what degree they are modifiable. Most analyses performed within observational cohorts have compared outcomes after ACS in a CKD or HD population to those of people without kidney impairment.2,19 We know, however, that the baseline mortality rate of people with CKD is elevated compared with those without.20 Estimated survival for an individual starting HD aged 80 years is just 2–2.4 years. Mortality, however, decreases in line with age,21 and for many, including those who are remarkably elderly, dialysis may exist as a bridge to kidney transplantation. It is unlikely, therefore, that we will ever improve outcomes to the degree that we see in our non-CKD population. A nihilistic view would be to believe that there is little point in investing resources in research designed to further our understanding of ACS or its management in this population.22 The counter argument of course, is that the heightened incidence of ACS, together with the staggeringly high absolute rates of mortality and morbidity, suggest that a small improvement in care could have a significant impact on, not only clinical outcomes, but quality of life.
Current management of ACS in people receiving HD is conservative, compared with those without kidney disease. A wealth of observational data from across the globe demonstrates that, despite a trend towards reducing disparities (at least in the US),19 utilisation of invasive management and guideline-directed cardioprotective medical therapies declines with worsening kidney function.2,12,19,23 Data from the UK show that coronary angiography is undertaken in just 40% of those with an eGFR <30 ml/min/1.73 m2 following NSTEMI, versus 70% of those with normal kidney function.2 Respective figures after STEMI are 64% versus 92%. These trends persist after adjustment for measurable demographics and comorbidities, to the extent that can be achieved within observational data.1,2,12,19,24
Why are we so conservative?
Why are we so conservative in our management of ACS in individuals with advanced kidney impairment? There likely exist a multitude of contributory factors. Frailty and multi-morbidity are common in those with advanced kidney disease, and, for these individuals, avoidance of invasive management and polypharmacy may be appropriate. Furthermore, as described by Haider and colleagues, there exists a dearth of high-quality clinical trials providing evidence of the optimal treatment regimens in this population. As a result, previous editions of international guidelines contained vague advice, such as to “consider the use of invasive management”.5 In the absence of clear direction, clinicians appear biased towards adoption of conservative treatment strategies, particularly for patients considered to be at higher risk of adverse outcomes.25,26 Findings from qualitative research suggest this may result from our perception that patient harm occurring secondary to active treatment decisions is more ‘blameworthy’ than harm occurring as the result of undertreatment.27–30 Time-pressured decision-making, insufficient inter-disciplinary working and lack of available follow-up to identify potential treatment complications, may also drive us towards conservatism.30
Although we continue to lack clinical trial data, the body of observational research in this field continues to grow. These studies consistently demonstrate that the benefits of early invasive management (for high-risk ACS events) and cardioprotective medications exist independent of kidney function.12,13,31 Evidence is weakest for those with advanced CKD, as small numbers preclude many studies from obtaining sufficient power. This is especially pertinent with regards to those receiving HD. Nevertheless, taken together, this body of evidence was sufficient for the European Society of Cardiology (2023) to update their recommendations relating to the CKD population: “It is recommended to apply the same diagnostic and therapeutic strategies in patients with CKD … as in patients with normal kidney function”.6 No exception is made within these guidelines for individuals receiving HD.
Diagnostic challenges
As Haider et al. describe, the diagnosis of ACS in those with advanced CKD is complicated. People receiving HD frequently have baseline abnormalities in their electrocardiogram (ECG) and cardiac troponins (cTns), and rarely present with symptoms that we are taught to be ‘typical’ of ACS.3,32–34 Standard hospital protocols recommending 0/1 hour ‘rule in/out’ strategies are, as a result, of little use. Fortunately, the Standardised Outcomes in Nephrology Group (SONG)-HD brought together a multi-national working group to address the challenges of applying the fourth universal definition of MI to this patient cohort.35,36 While developed primarily for the purpose of clinical trials, their recommendations appear sufficiently pragmatic for use in clinical practice. Key advice includes obtaining ‘baseline’ ECGs in HD populations and assuming a dynamic change of >20% in high-sensitivity (hs)-cTn as evidence of myocardial injury in those with an initial presentation over the 99th centile upper reference limit (URL)*.
*(A note of caution is added regarding the timing of cTn tests: delayed presentations are common in those with advanced CKD and serial troponins may be required given the potential for cTn to have reached the plateau stage of its excretory curve at presentation.)
In stark contrast to many of the non-invasive tests used in the diagnosis of ACS, kidney function affects neither the specificity nor the sensitivity of coronary angiography. It is noticeable, therefore, that despite the challenges of diagnosis of ACS in people receiving HD, angiography is used infrequently in this population.2,13,19 Perhaps this relates to the belief that subsequent revascularisation will either not be feasible or of benefit to the patient. As mentioned previously, many of those receiving HD are not only elderly and multi-morbid, but already experience a poor quality of life. Alternatively, are we reluctant to undertake coronary artery intervention due to associated technical challenges and risks? The incidence of bleeding, embolisation, arrythmias, and, in the non-HD populations, contrast-associated acute kidney injury (for those that believe in its existence) are all considered to be increased in those with advanced kidney disease.37 However, in restricting our use of coronary angiography, is there a chance that we could be unnecessarily prescribing antiplatelet agents (and thus increasing bleeding risk) to individuals in whom we could have otherwise excluded ACS?
Optimising outcomes
To optimise ACS outcomes for those receiving HD, it is likely that we will need to address both the lack of (robust) research, and the translation of these findings into clinical practice. Not only have people with advanced CKD been excluded from clinical trials in cardiovascular medicine, insufficient attention has been paid to subgroup analysis by degree of kidney impairment, and relevant outcomes often overlooked. The recently published, and otherwise excellent, SENIOR-RITA trial (wherein individuals >75 years were randomised to invasive versus optimal medical care for NSTEMI) is a prime example of a missed opportunity to advance our understanding of care for people with CKD.38 An inadvertent bias in recruitment led to undersampling of those with CKD (20.7% vs. an expected 40%), the binary subgroup analysis of eGFR <60 versus >60 ml/min/1.73 m2 missed the intricacies of the relationship between kidney function and outcome, and long-term change in eGFR was not assessed.
Even if these limitations could be addressed, a single pooled-trial result may remain inadequate to direct ACS care for those with advanced CKD. First, because the extent of the clinical and demographic heterogeneity within this population could make it impossible to know where on the spectrum of benefit and risk around this single result a single patient lies. A 42-year-old using dialysis as a temporary bridge to kidney transplantation is vastly different to a multi-morbid 78-year-old for whom the purpose of HD is to survive to see her son married in two months’ time. Second, because sadly in practice there are few populations less likely to receive the ‘optimal medical management’, utilised in trials such as SENIOR-RITA, as those with severe kidney impairment.19
Which leads to a second, and perhaps even more important barrier: the translation of evidence and guidelines into practice. The purpose of clinical guidelines is to summarise an evidence base, reduce unwarranted variation in care and optimise health and quality of life for patients. However, there is a wealth of data demonstrating that clinical care varies significantly from what such guidelines recommend. Focusing our efforts on addressing the many inter-related factors that prevent clinicians from managing those with advanced CKD in line with clinical guidelines will ensure that the efforts of future research are not wasted. Not only will this require ensuring clinical guidelines adequately cover the complexity of the patient populations we see in clinical practice, but that they offer pragmatic treatment solutions. Heterogeneity among those who receive HD may, however, prevent this population from ever being sufficiently described by protocols or guidelines. For these individuals, optimal outcomes are likely to require personalised collaborative treatment decision-making between cardiologist and nephrologist, and clear continuity of treatment into the community. To deliver such time-consuming care has never been more challenging than under the pressures of the NHS, as it currently stands.
Conflicts of interest
None.
Funding
JS is funded by an NIHR Clinical Doctoral Research Fellowship (NIHR300906). The views expressed in this publication are those of the author and not necessarily those of the NIHR, NHS or the UK Department of Health and Social Care.
Editors’ note
Please also see the article by Haider et al. which can be found at: https://doi.org/10.5837/bjc.2025.011
References
1. Khan MZ, Syed M, Osman M et al. Contemporary trends and outcomes in patients with ST-segment elevation myocardial infarction and end-stage renal disease on dialysis: insight from the national inpatient sample. Cardiovasc Revasc Med 2020;21:1474–81. https://doi.org/10.1016/j.carrev.2020.05.004
2. Scott JK, Johnson T, Caskey FJ et al. Association between kidney function, frailty and receipt of invasive management after acute coronary syndrome. Open Heart 2024;11:e002875. https://doi.org/10.1136/openhrt-2024-002875
3. Charytan DM, Setoguchi S, Solomon DH, Avorn J, Winkelmayer WC. Clinical presentation of myocardial infarction contributes to lower use of coronary angiography in patients with chronic kidney disease. Kidney Int 2007;71:938–45. https://doi.org/10.1038/sj.ki.5002159
4. Colombijn JMT, Idema DL, van Beem S et al. Representation of patients with chronic kidney disease in clinical trials of cardiovascular disease medications: a systematic review. JAMA Netw Open 2024;7:e240427. https://doi.org/10.1001/jamanetworkopen.2024.0427
5. Amsterdam EA, Wenger NK, Brindis RG et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary. A report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation 2014;130:2354–94. https://doi.org/10.1161/CIR.0000000000000133
6. Byrne RA, Rossello X, Coughlan JJ et al. 2023 ESC guidelines for the management of acute coronary syndromes. Eur Heart J Acute Cardiovasc Care 2024;13:55–161. https://doi.org/10.1093/ehjacc/zuad107
7. Lawton JS, Tamis-Holland JE, 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. J Am Coll Cardiol 2022;79:e21–e129. https://doi.org/10.1016/j.jacc.2021.09.006
8. Haider MA, Shah MU, Kassianides X, Hazara A, Ali N, Feldman DN. Diagnosis and management of ACS in patients with ESRD on haemodialysis: a comprehensive review. Br J Cardiol 2025;32:7–11. https://doi.org/10.5837/bjc.2025.011
9. Drey N, Roderick P, Mullee M, Rogerson M. A population-based study of the incidence and outcomes of diagnosed chronic kidney disease. Am J Kidney Dis 2003;42:677–84. https://doi.org/10.1016/S0272-6386(03)00916-8
10. John R, Webb M, Young A, Stevens PE. Unreferred chronic kidney disease: a longitudinal study. Am J Kidney Dis 2004;43:825–35. https://doi.org/10.1053/j.ajkd.2003.12.046
11. Herzog CA, Asinger RW, Berger AK et al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2011;80:572–86. https://doi.org/10.1038/ki.2011.223
12. Bhatia S, Arora S, Bhatia SM et al. Non-ST-segment-elevation myocardial infarction among patients with chronic kidney disease: a propensity score-matched comparison of percutaneous coronary intervention versus conservative management. J Am Heart Assoc 2018;7:e007920. https://doi.org/10.1161/JAHA.117.007920
13. Shaw C, Nitsch D, Steenkamp R et al. Inpatient coronary angiography and revascularisation following non-ST-elevation acute coronary syndrome in patients with renal impairment: a cohort study using the Myocardial Ischaemia National Audit Project. PloS One 2014;9:e99925. https://doi.org/10.1371/journal.pone.0099925
14. Rizk DV, Gutierrez O, Levitan EB et al. Prevalence and prognosis of unrecognized myocardial infarctions in chronic kidney disease. Nephrol Dial Transplant 2012;27:3482–8. https://doi.org/10.1093/ndt/gfr684
15. Montalescot G, Dallongeville J, Van Belle E et al. STEMI and NSTEMI: are they so different? 1 year outcomes in acute myocardial infarction as defined by the ESC/ACC definition (the OPERA registry). Eur Heart J 2007;28:1409–17. https://doi.org/10.1093/eurheartj/ehm031
16. Charytan D, Mauri L, Agarwal A, Servoss S, Scirica B, Kuntz RE. The use of invasive cardiac procedures after acute myocardial infarction in long-term dialysis patients. Am Heart J 2006;152:558–64. https://doi.org/10.1016/j.ahj.2006.02.021
17. Sederholm Lawesson S, Alfredsson J, Szummer K, Fredrikson M, Swahn E. Prevalence and prognostic impact of chronic kidney disease in STEMI from a gender perspective: data from the SWEDEHEART register, a large Swedish prospective cohort. BMJ Open 2015;5:e008188. https://doi.org/10.1136/bmjopen-2015-008188
18. Vasaiwala S, Cannon CP, Fonarow GC et al. Quality of care and outcomes among patients with acute myocardial infarction by level of kidney function at admission: report from the get with the guidelines coronary artery disease program. Clin Cardiol 2012;35:541–7. https://doi.org/10.1002/clc.22021
19. Bagai A, Lu D, Lucas J et al. Temporal trends in utilization of cardiac therapies and outcomes for myocardial infarction by degree of chronic kidney disease: a report from the NCDR Chest Pain-MI registry. J Am Heart Assoc 2018;7:e010394. https://doi.org/10.1161/JAHA.118.010394
20. Neovius M, Jacobson SH, Eriksson JK, Elinder CG, Hylander B. Mortality in chronic kidney disease and renal replacement therapy: a population-based cohort study. BMJ Open 2014;4:e004251. https://doi.org/10.1136/bmjopen-2013-004251
21. UK Kidney Association. UK Renal Registry: 25th annual report – data to 31/12/2021. Bristol: UKRR, 2023. Available from: https://ukkidney.org/audit-research/annual-report
22. Chertow GM, Normand SL, McNeil BJ. “Renalism”: inappropriately low rates of coronary angiography in elderly individuals with renal insufficiency. J Am Soc Nephrol 2004;15:2462–8. https://doi.org/10.1097/01.ASN.0000135969.33773.0B
23. Gallacher PJ, Miller-Hodges E, Shah ASV et al. High-sensitivity cardiac troponin and the diagnosis of myocardial infarction in patients with kidney impairment. Kidney Int 2022;102:149–59. https://doi.org/10.1016/j.kint.2022.02.019
24. Fox CS, Muntner P, Chen AY et al. Use of evidence-based therapies in short-term outcomes of ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction in patients with chronic kidney disease: a report from the National Cardiovascular Data Acute Coronary Treatment and Intervention Outcomes Network registry. Circulation 2010;121:357–65. https://doi.org/10.1161/CIRCULATIONAHA.109.865352
25. Rothnie KJ, Smeeth L, Herrett E et al. Closing the mortality gap after a myocardial infarction in people with and without chronic obstructive pulmonary disease. Heart 2015;101:1103–10. https://doi.org/10.1136/heartjnl-2014-307251
26. van der Sangen NMR, Azzahhafi J, Chan Pin Yin D et al. External validation of the GRACE risk score and the risk-treatment paradox in patients with acute coronary syndrome. Open Heart 2022;9:e001984. https://doi.org/10.1136/openhrt-2022-001984
27. Ritov I, Baron J. Reluctance to vaccinate: omission bias and ambiguity. J Behav Decis Mak 1990;3:263–77. https://doi.org/10.1002/bdm.3960030404
28. Arutyunova KR, Bakhchina AV, Sozinova IM, Alexandrov YI. Complexity of heart rate variability during moral judgement of actions and omissions. Heliyon 2020;6:e05394. https://doi.org/10.1016/j.heliyon.2020.e05394
29. Webster CS, Taylor S, Weller JM. Cognitive biases in diagnosis and decision making during anaesthesia and intensive care. BJA Educ 2021;21:420–5. https://doi.org/10.1016/j.bjae.2021.07.004
30. Scott J, Selman LE, Caskey FJ, Johnson T, Ben-Shlomo Y. Qualitative study of treatment decision-making for myocardial infarction in people with advanced kidney disease. Unpublished manuscript from Department of Population Health Sciences, University of Bristol, 2024.
31. Fong KY, Low CHX, Chan YH et al. Role of invasive strategy for non-ST-elevation myocardial infarction in patients with chronic kidney disease: a systematic review and meta-analysis. Am J Cardiol 2023;205:369–78. https://doi.org/10.1016/j.amjcard.2023.07.178
32. Canto JG, Shlipak MG, Rogers WJ et al. Prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain. JAMA 2000;283:3223–9. https://doi.org/10.1001/jama.283.24.3223
33. Shafi S, Saleem M, Anjum R, Abdullah W, Shafi T. ECG abnormalities in patients with chronic kidney disease. J Ayub Med Coll Abbottabad 2017;29:61–4. https://doi.org/10.4103/1319-2442.229270
34. Needham DM, Shufelt KA, Tomlinson G, Scholey JW, Newton GE. Troponin I and T levels in renal failure patients without acute coronary syndrome: a systematic review of the literature. Can J Cardiol 2004;20:1212–18. https://pubmed.ncbi.nlm.nih.gov/15494773/
35. Thygesen K, Alpert JS, Jaffe AS et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019;40:237–69. https://doi.org/10.1093/eurheartj/ehy462
36. O’Lone E, Apple FS, Burton JO et al. Defining myocardial infarction in trials of people receiving hemodialysis: consensus report from the SONG-HD MI Expert Working Group. Kidney Int 2023;103:1028–37. https://doi.org/10.1016/j.kint.2023.02.033
37. Tavakol M, Ashraf S, Brener SJ. Risks and complications of coronary angiography: a comprehensive review. Glob J Health Sci 2012;4:65–93. https://doi.org/10.5539/gjhs.v4n1p65
38. Kunadian V, Mossop H, Shields C et al. Invasive treatment strategy for older patients with myocardial infarction. N Engl J Med 2024;391:1673–84. https://doi.org/10.1056/NEJMoa2407791
