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Association of Strict Versus Lenient Cholesterol Lowering with Cardiac Outcomes, Diabetes Progression and Complications, and Mortality in Patients with Diabetes Treated with Statins: Is Less More?

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Abstract

Introduction

Whereas some guidelines recommend statin use to achieve low-density lipoprotein cholesterol (LDL-C) goal < 70 mg/dL for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in patients at higher risk, others recommend against a target LDL-C level. Achieving a target level < 70 mg/dL commonly requires the use of high intensity statins, which has been associated with higher risk of diabetes progression. The objective of this study is to assess the association of strict (≤ 70 mg/dL) versus lenient (> 70 to100 mg/dL) LDL-C lowering on major adverse cardiovascular events (MACE), diabetes progression, diabetes microvascular complications, and total mortality in patients with diabetes.

Methods

This was a retrospective propensity score (PS)-matched study from a national cohort of, predominantly male, veterans diagnosed with diabetes without prior cardiovascular disease (from fiscal years 2003–2015), who were initiated on a statin. We created PS to match strict (mean LDL-C during follow-up ≤ 70 mg/dL) versus lenient (mean LDL-C during follow up > 70–100 mg/dL) using 65 baseline characteristics including comorbidities, risk scores, medication classes usage, vital signs, and laboratory data. Outcomes included MACE, diabetes progression, microvascular diabetes complications, and total mortality.

Results

From 80,110 eligible patients, we PS-matched 21,294 pairs of statin initiators with strict or lenient LDL-C lowering. The mean (SD) age was 64 (9.5) years and mean (SD) duration of follow-up was 6 (3) years. MACE was similar in the PS-matched groups [6.1% in strict versus 5.8% in lenient; odds ratio (OR): 1.06; 95% confidence interval (95% CI) 0.98–1.15, P = 0.17]. Diabetes progression was higher among the strict vs lenient group (66.7% in strict versus 64.1% in lenient; OR 1.12; 95% CI 1.08–1.17, P < 0.001). There was no difference in microvascular diabetes complications (22.3% in strict versus 21.9% in lenient; OR 1.02; 95% CI 0.98–1.07, P = 0.31) and no difference in total mortality (14.6% in strict versus 15% in lenient; OR 0.97; 95% CI 0.92–1.02, P = 0.20).

Conclusion

Strict compared with lenient lowering of LDL-C with statins in men with diabetes without preexisting ASCVD did not decrease the risk of MACE but was associated with an increased diabetes progression. Clinicians should monitor their patients for diabetes progression upon escalating statins to achieve LDL-C levels ≤ 70 mg/dL.

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Author information

Authors and Affiliations

  1. University of Central Florida HCA Healthcare GME, Greater Orlando, FL, USA

    Victoria Odeleye & Omar Masarweh

  2. Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, USA

    Victoria Odeleye, Omar Masarweh, Jorge Restrepo & Ishak A. Mansi

  3. Education Services, Orlando VA Healthcare System, Orlando, FL, 13400 Veterans Way, Orlando, FL 32827, USA

    Jorge Restrepo & Ishak A. Mansi

  4. Department of Pharmacy Practice, Texas Tech University Health Sciences Center, Dallas, TX, USA

    Carlos A Alvarez

  5. Center of Excellence in Real-world Evidence, Dallas, TX, USA

    Carlos A Alvarez

  6. North Texas VA Health Sciences Center, Dallas, TX, USA

    Carlos A Alvarez

Authors
  1. Victoria Odeleye
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  2. Omar Masarweh
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  3. Jorge Restrepo
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  4. Carlos A Alvarez
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  5. Ishak A. Mansi
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Corresponding author

Correspondence to Ishak A. Mansi.

Ethics declarations

Funding

No funding was provided for this work. Resources of the Orlando VA Medical Center were used to conduct the study.

Conflict of interest/Disclosure

The authors declare that they do not have a financial conflict of interest related to this work. CAA has received research funding from Merck, Boehringer Ingelheim, and Bristol Myers Squibb not related to this project. CAA us supported, in part, by the National Institutes of Health Clinical and Translational Science Award (UL1TR003163)

Ethics approval

This study was approved by the VA North Texas Health Care System (1589775-3), Orlando VA Health Care System (1679434-1), and the Texas Tech University Health Sciences Center (A14-3811).

Consent to participate

Institutional review boards have waived informed consent because the study used only previously collected, deidentified data.

Consent for publication

All authors have reviewed the manuscript and agree on its publication and submission to the Journal.

Data availability

Data are stored in the VA Informatics and Computing Infrastructure (VINCI), the operational platform for health services research at the Veterans Healthcare Administration (VHA). VINCI acts as data steward for VHA Data Systems. Data in VINCI cannot be copied, transferred, or printed. Access to data by other researchers is possible following VINCI protocols, as described in VINCI Central website: http://vaww.vinci.med.va.gov/VinciCentral.

Code availability

Codes used in this study is provided in the Electronic Supplementary Material.

Author contributions

Concept and study design: all authors; data collection and statistical analysis: CA and IM; results’ interpretation: all authors; initial draft of the manuscript: VO and OM; final review and edit of the manuscript: all authors. Dr. Mansi is the overall guarantor for data and study integrity.

Disclaimer

The views expressed herein are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, VA Administration, or the US Government or any of its affiliated entities. This research was supported (in whole or in part) by the resources of the Orlando VA Medical Center. Some of the authors are employees of the US government. This work was prepared as part of their official duties and, as such, there is no copyright to be transferred. This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.

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Odeleye, V., Masarweh, O., Restrepo, J. et al. Association of Strict Versus Lenient Cholesterol Lowering with Cardiac Outcomes, Diabetes Progression and Complications, and Mortality in Patients with Diabetes Treated with Statins: Is Less More?. Drug Saf 46, 1105–1116 (2023). https://doi.org/10.1007/s40264-023-01347-8

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