Cardiovascular disease (CVD) is the leading cause of death among individuals with chronic kidney disease (CKD), which is defined as an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m².¹ Cardiovascular mortality is inversely related to the glomerular filtration rate, with the risk increasing as renal function declines.²

Patients undergoing dialysis due to end-stage renal disease (ESRD) face the highest mortality risk within this population. In the United States, the mortality rate among dialysis patients was 173 per 1,000 individuals in 2019, and the prevalence of coronary artery disease (CAD) reached 22% among younger patients and 41% in those over 45 years of age in 2020.³

In patients with CKD, the pathophysiology of CAD involves traditional risk factors such as smoking, hypertension (HTN), and diabetes mellitus (DM).⁴ However, CKD-specific factors also play a significant role. These include marked vascular medial calcification due to the transformation of smooth muscle cells into osteoblast-like cells, driven by hyperphosphatemia and hypercalcemia, as well as the accumulation of uremic toxins such as asymmetric dimethylarginine, which impairs nitric oxide synthase activity.⁵ Elevated levels of interleukin-6 and C-reactive protein in CKD indicate a pro-inflammatory state characterized by endothelial dysfunction and increased production of free radicals. A hypercoagulable state is also present, resulting from elevated platelet-derived procoagulant factors, although platelet activation response is typically reduced.^5,6

Patients with CKD are often excluded from acute coronary syndrome (ACS) trials because they represent a higher-risk group, making treatment evaluation more challenging.^7,8 Those with ESRD undergoing dialysis are less likely to receive invasive treatments, with only 12% undergoing percutaneous coronary intervention (PCI) and 3% undergoing coronary artery bypass grafting (CABG).⁹

There are discrepancies in literature regarding the optimal treatment for CAD in the CKD population.^10-12 Since the well-documented prevalence of ischemic events among individuals with CKD, the present study aims to analyze both the epidemiology and the most effective therapeutic approach for reducing mortality and complications related to ACS in patients with ESRD undergoing dialysis in the studied population.

This article is based on an observational, analytical, and retrospective study with a cohort epidemiological design. Data collection began after approval from the Human Research Ethics Committee at Centro Universitário para o Desenvolvimento do Alto Vale do Itajaí under opinion no. 6.552.015.

Data were collected from electronic medical records at a tertiary hospital in southern Brazil, in partnership with the regional dialysis center, by using a standardized data collection instrument.

The study population consisted of patients undergoing chronic dialysis who were diagnosed with and treated for ACS. Inclusion criteria were (1) undergoing chronic dialysis; (2) presenting symptoms attributable to CAD; and (3) undergoing invasive stratification through coronary angiography. Exclusion criteria were (1) individuals under 18 years of age; (2) lack of follow-up at the same health care facility; (3) having received a kidney transplant prior to the cardiac event; and (4) experiencing the cardiac event before starting dialysis.

A total of 753 patients undergoing chronic dialysis between January 1, 2013, and December 31, 2023, were identified. Next, we identified patients who underwent invasive cardiac stratification through coronary angiography during the same period, totaling 97 individuals. The exclusion criteria were then applied (Figure 1).

After defining the study population, data were collected and stored in a database using Google Sheets. The information was organized into the following sections: (1) population characteristics and lifestyle habits; (2) clinical aspects, including dialysis and ACS characteristics; (3) medications used; (4) therapeutic approaches; and (5) outcomes and mortality.

In the present study, the incidence of CAD among patients with ESRD on dialysis was 9.0% — almost five times higher than the CAD rate in the general Brazilian population, which was 1.85% in 2019.¹³ The literature shows that the incidence of CAD in the population with CKD increases with age, particularly in individuals over 65 years old.¹⁴ The mean age found in this study was 60.2±13.1 years, with women experiencing coronary events at a younger age (56.6±12.7 years).

Patients with CKD have an elevated risk of developing CAD, which increases further once dialysis is initiated.¹⁵ Our findings revealed a mortality rate of 60.3% among patients who developed an ACS.

HTN, DM, and smoking are well-known shared risk factors for both CKD and CAD.^1,13,16 In our study, the prevalence of DM was 48.5%, dyslipidemia was observed in 63.2%, and HTN was present in 91.2% of patients. However, the prevalence of smoking was low, though this may be underestimated due to incomplete documentation in medical records.

According to the 2022 Brazilian Dialysis Census, the main etiologies of CKD among dialysis patients were HTN, DM, glomerulonephritis, and PKD.¹⁷ In our study, 33.8% of patients had diabetic nephropathy, 20.6% had hypertensive nephropathy, 13.2% had PKD, and 5.9% had glomerular diseases.

STEACS is not commonly seen in patients with ESRD, who often present with atypical or silent symptoms.¹⁸ Consistent with this, only 2 patients (2.9%) in our study presented with STEACS.

Therapeutic decisions vary depending on the angiographic profile, type of ACS, and surgical risk factors of the patient. In line with precious research, we observed a predominance of MTA in patients with no significant atheromatosis and in those with single-vessel disease.^1,8,9 Among patients with two-vessel disease, PCI was the most common approach, while CABG was predominantly used in those with multi-vessel involvement. However, patients with contraindications to surgery remained on MTA.

The currently recommended treatment for HTN in dialysis patients begins with beta-blockers, which have shown superiority over ACE inhibitors. This is followed by CCBs, whose benefits compared to other antihypertensives remain uncertain.^19,20 In our study, the use of CCBs was associated with significantly increased mortality (p = 0.02). The use of antiplatelet agents should be individualized, as they reduce the incidence of myocardial infarction but increase bleeding risk and do not impact overall mortality.²¹ The use of statins in dialysis patients is recommended if already initiated before dialysis, particularly in the presence of established CVD.²² In our study, patients not using statins had a markedly higher mortality rate (82.6%).

The main trial that evaluated patients with CKD in the context of stable CAD outcomes was the ISCHEMIA-CKD trial, which concluded that interventional strategies were not superior to MTA in terms of mortality over 2.2 years.²³ However, the invasive strategy was associated with a lower incidence of recurrent cardiac events.¹²

In our study, there was also no statistically significant difference in mortality between the MTA, PCI, and CABG groups. However, among patients with multivessel disease, those who received conservative treatment had a higher mortality rate (75.0%) compared to those who underwent CABG (45.5%).

The main complications of ACS in dialysis patients include recurrent cardiac events, strokes, and bleeding episodes.^24,25 In our population, MTA was protective against rehospitalization for coronary events and the need for repeat coronary angiography. In contrast, PCI was associated with a higher risk of rehospitalization, affecting 33.3% of patients (p = 0.05).

There is significant underrepresentation of patients with ESRD in clinical trials, which limits the evidence available to support recommendations for optimal therapeutic strategies in this group.²⁶ This highlights the need for studies that include a larger number of patients from this population.

This study faced limitations in effective analysis due to the small sample size and heterogeneity across treatment groups. The retrospective design and inconsistency of medical record documentation also hindered the evaluation of certain variables.

In our study, patients with ESRD on dialysis showed an incidence of CAD approximately five times higher than that of the general Brazilian population, along with an elevated mortality rate. DM, HTN, and dyslipidemia were prevalent risk factors in this population. The absence of statin use among patients undergoing chronic dialysis was associated with increased CAD-related mortality.

Our data did not reveal a statistically significant difference in mortality among the groups treated with MTA, PCI, or CABG. However, MTA proved to be a protective factor against rehospitalization for ACS and repeat coronary angiography over the 10-year study period. In contrast, PCI was associated with a higher risk of rehospitalization for ACS. These findings highlight the need for multicenter studies with larger patient populations to allow for broader analysis and more robust conclusions on the subject.