European Journal of Cardiovascular Medicine

Cardiovascular disease is the leading cause of death among individuals with type 2 diabetes mellitus (T2DM). Statins, as HMG-CoA reductase inhibitors, lower LDL-C and have demonstrated benefits in both primary and secondary prevention of CVD. While randomized clinical trials support their use, there remains a need for real-world evidence assessing long-term outcomes of statin therapy in diverse diabetic populations.

This study aims to examine the association between statin use and cardiovascular outcomes in patients with T2DM using real-world retrospective data across a multi-hospital network.

Study Design and Data Source

This retrospective cohort study used de-identified electronic health records (EHR) from 10 tertiary hospitals in the United States between 2015 and 2021. Data included demographics, diagnoses, medications, laboratory values, and clinical outcomes.

Population

Inclusion criteria:

• Adults (≥40 years) with T2DM
• At least one year of follow-up data
• No history of CVD at baseline

Exclusion criteria:

• Type 1 diabetes
• Active malignancy
• End-stage renal disease

Patients were classified as statin users (≥90 days continuous prescription) or non-users (no statin prescription within first 6 months after T2DM diagnosis).

Outcomes

The primary outcome was major adverse cardiovascular events (MACE), defined as:

• Nonfatal myocardial infarction
• Nonfatal stroke
• Cardiovascular death

Secondary outcomes included all-cause mortality and individual components of MACE.

Statistical Analysis

Baseline characteristics were compared using t-tests and chi-square tests.

Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).

Covariates included age, sex, baseline HbA1c, LDL-C, hypertension, and smoking status.

Baseline Characteristics

A total of 8,053 patients met inclusion criteria: 4,132 statin users and 3,921 non-users. Baseline characteristics were generally balanced after propensity score matching.

Table 1: Baseline Characteristics

Table 2: Incidence of Cardiovascular Events

Table 3: Subgroup Analysis - MACE Event Rates

Table 4: Adverse Effects in Statin Users

Cardiovascular Outcomes

Over a median follow-up of 5.2 years:

• MACE occurred in:
• Statin group: 8.4% (347 events)
• Non-statin group: 13.1% (514 events)
• HR: 0.61 (95% CI 0.55–0.68), p<0.001
• All-Cause Mortality:
• Statin group: 5.2%
• Non-statin group: 8.0%
• HR: 0.66 (95% CI 0.58–0.75), p<0.001
• Reduction consistent across subgroups (see Tables)

Adverse Events

• Elevated liver enzymes and myopathy occurred in <2% of statin users.
• No significant increase in new-onset diabetes or rhabdomyolysis observed.

This large real-world study demonstrates a significant benefit of statin therapy in reducing major cardiovascular events among patients with type 2 diabetes, even in the absence of established CVD. Our results align with clinical trials such as CARDS and HOPE-3 and further validate guideline-based recommendations for statin use in primary prevention.

Limitations include potential residual confounding, reliance on prescription data (vs actual adherence), and limited racial/ethnic diversity in the cohort. Nonetheless, the findings offer robust support for statin use in routine diabetic care.

This large real-world cohort study reinforces the role of statin therapy in significantly reducing cardiovascular morbidity and mortality among patients with type 2 diabetes. Our findings showed a 39% relative risk reduction in major adverse cardiovascular events (MACE) in the statin group compared to non-users. These results align with previous randomized controlled trials, including the CARDS trial, which demonstrated the benefit of atorvastatin in primary prevention among diabetic patients without prior cardiovascular disease (1). Similarly, the HOPE-3 trial established the effectiveness of statins in intermediate-risk populations regardless of baseline LDL-C levels (2).

The observed reduction in MACE and all-cause mortality also supports guideline-based recommendations from the American Diabetes Association and the American College of Cardiology, which advocate for statin use in nearly all patients with diabetes aged over 40 years (3,4). Our findings are further supported by meta-analyses indicating that each 1 mmol/L reduction in LDL-C with statins translates to approximately 20–25% reduction in major vascular events (5,6).

Unlike some prior studies, our cohort did not observe a significant increase in adverse events such as statin-induced diabetes or rhabdomyolysis, suggesting that statins are largely safe in real-world clinical practice (7). Although observational in nature, the study included propensity score matching to reduce confounding, and results remained consistent across key subgroups, including age, sex, LDL levels, and hypertension status (8).

However, certain limitations should be noted. Medication adherence was inferred from prescription data, not confirmed intake. Residual confounding due to lifestyle variables (e.g., diet, exercise) may still exist despite multivariable adjustment. Additionally, this cohort had limited racial diversity, and findings may not generalize to broader populations (9,10).

Nonetheless, this study provides compelling real-world evidence that supports current clinical practice and strengthens the rationale for aggressive lipid-lowering strategies in patients with diabetes.

1. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes: the CARDS trial. Lancet. 2004;364(9435):685–96.
2. Yusuf S, Bosch J, Dagenais G, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374(21):2021–31.
3. American Diabetes Association. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2024. Diabetes Care. 2024;47(Suppl 1):S144–68.
4. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC Guidelines on the Management of Blood Cholesterol. Circulation. 2019;139(25):e1082–143.
5. Ray KK, Seshasai SR, Erqou S, et al. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis. Lancet. 2010;376(9753):653–61.
6. Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532–61.
7. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis. Lancet. 2010;375(9716):735–42.
8. Pencina MJ, Navar-Boggan AM, D’Agostino RB Sr, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med. 2014;370(15):1422–31.
9. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2020;41(1):111–88.
10. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: meta-analysis. Lancet. 2010;376(9753):1670–81.