Background

Patients with chronic kidney disease (CKD), including those with end-stage renal disease (ESRD) on dialysis, are at high risk of developing cardiovascular disease (CVD). The results of the Alberta Kidney Disease Network and Atherosclerosis Risk in Communities studies showed that the number of CVD events attributed to CKD were comparable with those attributed to diabetes mellitus.^1,2

Whereas the 2019 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of CVD recommends the initiation of statin therapy for all patients with diabetes mellitus, the evidence in favor of statin therapy in patients with CKD is less compelling. CKD is considered a risk-enhancing factor, and the decision to initiate statin therapy for CVD risk reduction in patients with CKD should be based on a clinician–patient risk discussion.³

In the specific population of patients on hemodialysis, the primary analyses of both the 4D (Die Deutsche Diabetes Dialyse)  and AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Ηеmοԁialуѕiѕ: An Assessment of Survival and Cardiovascular Events) trials showed in their primary analyses that statin therapy had no clear benefit in the prevention of atherosclerotic CVD events.^4,5 In contrast, the SHARP (Study of Heart and Renal Protection) trial showed a reduction in events with simvastatin/ezetimibe in patients with CKD, with no difference in effect when patients were stratified according to dialysis status.⁶

Study Design and Findings

Yeh et al. recently studied the association of statin therapy with all-cause mortality in patients on dialysis who underwent a percutaneous coronary intervention (PCI) for acute myocardial infarction (MI).⁷ The authors leveraged claims data from 2000-2016 from the National Health Insurance Research Database (NHIRD) of Taiwan, which captures data from nearly 99% of the Taiwanese population. The study included participants who were hyperlipidemic and on dialysis with an MI/PCI. The primary analysis compared all-cause mortality with those treated with statin therapy versus those not treated.

Each cohort was comprised of 2,642 patients and propensity score matching was used to compare outcomes between the two cohorts. The statistical models were adjusted for age, sex, diabetes mellitus, hypertension, peripheral arterial disease, stroke, heart failure, chronic hepatitis B and C infection, cancers, urbanization, and income. Clinical diagnoses (including hyperlipidemia) were derived using International Classification of Diseases Ninth Revision codes.

All-cause mortality was 23% lower in the cohort receiving statin therapy compared with the nonstatin treated cohort (hazard ratio, 0.77; 95% confidence interval, 0.71-0.84). The authors also found that the patients who derived the most benefit in the statin-treated cohort were those with a history of diabetes mellitus, hypertension, and heart failure. In a nested case-control study in the cohort receiving statin therapy, subgroups that were at increased risk of mortality were women, the elderly, and patients with occlusive peripheral arterial disease. The authors concluded that statin therapy may be considered to decrease mortality risk in patients on dialysis with MI/PCI, particularly for those with diabetes mellitus, hypertension, or heart failure.

Discussion

This study shows a mortality benefit with statin therapy in patients who were hyperlipidemic and on dialysis who had an acute MI with PCI. While the 4D and AURORA trials showed no benefit for statin initiation in patients on dialysis, this study specifically focused on patients diagnosed with hyperlipidemia and who suffered an MI. Thus, this study shines a light on a high-risk population that may specifically benefit from statin therapy and that may have been overlooked in the past.

The population studied by Yeh et al. remains quite distinct from the populations of the 4D, AURORA, and SHARP trials. First, this study focused on a select subset of patients with a very high risk for atherosclerotic CVD as documented by the presence of MI/PCI. Thus, the significant mortality reduction attributed to statins could have been driven by the high burden of atherosclerotic CVD in this cohort. Second, the population in the current study had an MI with PCI, which assumes an acute coronary process. Whether patients on dialysis with acute CVD events may derive more benefit from a statin compared with those on dialysis with more chronic CVD remains an important question.

The study limitations include its retrospective design and the challenge regarding the timing of statin therapy initiation. It remains unclear whether statin therapy was started after the acute MI necessitating PCI or if patients were receiving a statin for their hyperlipidemia prior to their MI. Additionally, no data was available regarding the specific type of statins used (lipophilic vs. hydrophilic), the intensity of statin therapy, the degree of adherence to statin therapy, or the extent of low-density lipoprotein cholesterol (LDL-C) lowering achieved in the statin-treated group. This limits knowledge regarding the role of different statins or the efficacy of more aggressive LDL-C lowering in this patient population.

Independent of the timing of statin initiation (i.e., whether for primary vs. secondary prevention of CVD), this study found an all-cause mortality benefit with statin therapy in patients on dialysis who had a very high risk for CVD or established CVD. Further prospective, interventional, well-powered studies that address statin type (lipophilic vs. hydrophilic), intensity, adherence, and impact on LDL-C are needed to understand if and how statin therapy may have a mortality benefit in certain subgroups of patients with ESRD on dialysis (Figure 1).

Figure 1: Overview of Previous Studies of Statins in Dialysis and Future Research Needed

Created in BioRender. Gharios, C. (2025) https://BioRender.com/f74p511.
4D = Die Deutsche Diabetes Dialyse; ASCVD = atherosclerotic cardiovascular disease; AURORA = A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Ηеmοԁialуѕiѕ: An Assessment of Survival and Cardiovascular Events; CAD = coronary artery disease; CVD = cardiovascular disease; DM = diabetes mellitus; HF = heart failure; HTN = hypertension; MI = myocardial infarction; PCI = percutaneous coronary intervention; SHARP = Study of Heart and Renal Protection.

References

1. Weiner DE, Tighiouart H, Griffith JL, et al. Kidney disease, Framingham risk scores, and cardiac and mortality outcomes. Am J Med 2007;120:552.e1-8.
2. Tonelli M, Muntner P, Lloyd A, et al. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet 2012;380:807-14.
3. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;74:e177-e232.
4. Wanner C, Krane V, Marz W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005;353:238-48.
5. Fellstrom BC, Jardine AG, Schmieder RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009;360:1395-407.
6. Baigent C, Landray MJ, Reith C, et al.; SHARP Investigators. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011;377:2181-92.
7. Yeh YT, Sung FC, Tsai CF, Hsu CC, Tsai WC, Hsu YH. Statin therapy associated mortality in hyperlipidemic dialysis patients with percutaneous coronary intervention for acute myocardial infarction, a retrospective cohort study. Heliyon 2024;10:[ePub ahead of print].