Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study

Eric Yuk Fai Wan; Wanchun Xu; Anna Hoi Ying Mok; Weng Yee Chin; Esther Yee Tak Yu; Celine Sze Ling Chui; Esther Wai Yin Chan; Ian Chi Kei Wong; Cindy Lo Kuen Lam; Goodarz Danaei

doi:10.1111/dom.15503

Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study

Eric Yuk Fai Wan^*, Wanchun Xu, Anna Hoi Ying Mok, Weng Yee Chin, Esther Yee Tak Yu, Celine Sze Ling Chui, Esther Wai Yin Chan, Ian Chi Kei Wong, Cindy Lo Kuen Lam, Goodarz Danaei^*

^*Corresponding author for this work

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Abstract

Aim: The present study aimed to evaluate the effect of statin therapy for primary prevention of cardiovascular diseases (CVDs) when initiating therapy at different baseline low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of trials on patients with T2DM with elevated LDL-C levels in every calendar month from January 2008 to December 2014. Pooled logistic regression was applied to obtain the hazard ratios for the major CVDs (stroke, myocardial infarction, heart failure), all-cause mortality and major adverse events (myopathies and liver dysfunction) of statin therapy. Results: The estimated hazard ratios (95% confidence intervals) of CVD incidence for statin initiation were 0.78 (0.72, 0.84) in patients with baseline LDL-C of 1.8-2.5 mmol/L (i.e., 70-99 mg/dL) and 0.90 (0.88, 0.92) in patients with baseline LDL-C ≥2.6 mmol/L (i.e., ≥100 mg/dL) in intention-to-treat analysis, which was 0.59 (0.51, 0.68) and 0.77 (0.74, 0.81) in per-protocol analysis, respectively. No significant increased risks were observed for the major adverse events. The absolute 10-year risk difference of overall CVD in per-protocol analysis was −7.1% (−10.7%, −3.6%) and −3.9% (−5.1%, −2.7%) in patients with baseline LDL-C 1.8-2.5 and ≥2.6 mmol/L, respectively. The effectiveness and safety were consistently observed in patients aged >75 years initiating statin at both LDL-C thresholds. Conclusions: Compared with the threshold of 2.6 mmol/L, initiating statin in patients with a lower baseline LDL-C level at 1.8-2.5 mmol/L can further reduce the risks of CVD and all-cause mortality without significantly increasing the risk of major adverse events in patients with T2DM, including patients aged >75 years.

Original language	English
Pages (from-to)	1877-1887
Number of pages	11
Journal	Diabetes, Obesity and Metabolism
Volume	26
Issue number	5
Early online date	21 Feb 2024
DOIs	https://doi.org/10.1111/dom.15503
Publication status	Published - May 2024

Bibliographical note

Copyright © 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Data Access Statement

The data underlying this article were provided by the Hospital Authority of Hong Kong. The data can be accessed upon request to the Hospital Authority of Hong Kong.

Funding

This study is supported by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China (project no. 05190107) and Health and Medical Research Fund Research Fellowship Scheme.

Keywords

cardiovascular disease
hyperlipidaemia
statin
type 2 diabetes mellitus

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10.1111/dom.15503Licence: CC BY-NC-ND 4.0

Diabetes Obesity Metabolism - 2024 - Wan - Evaluating different low‐density lipoprotein cholesterol thresholds to initiate
Copyright © 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Final published version, 1.09 MBLicence: CC BY-NC-ND 4.0

Cite this

Wan, E. Y. F., Xu, W., Mok, A. H. Y., Chin, W. Y., Yu, E. Y. T., Chui, C. S. L., Chan, E. W. Y., Wong, I. C. K., Lam, C. L. K., & Danaei, G. (2024). Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study. Diabetes, Obesity and Metabolism, 26(5), 1877-1887. https://doi.org/10.1111/dom.15503

@article{c7f36220457e41e7be60f463a6c76f36,

title = "Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study",

abstract = "Aim: The present study aimed to evaluate the effect of statin therapy for primary prevention of cardiovascular diseases (CVDs) when initiating therapy at different baseline low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of trials on patients with T2DM with elevated LDL-C levels in every calendar month from January 2008 to December 2014. Pooled logistic regression was applied to obtain the hazard ratios for the major CVDs (stroke, myocardial infarction, heart failure), all-cause mortality and major adverse events (myopathies and liver dysfunction) of statin therapy. Results: The estimated hazard ratios (95% confidence intervals) of CVD incidence for statin initiation were 0.78 (0.72, 0.84) in patients with baseline LDL-C of 1.8-2.5 mmol/L (i.e., 70-99 mg/dL) and 0.90 (0.88, 0.92) in patients with baseline LDL-C ≥2.6 mmol/L (i.e., ≥100 mg/dL) in intention-to-treat analysis, which was 0.59 (0.51, 0.68) and 0.77 (0.74, 0.81) in per-protocol analysis, respectively. No significant increased risks were observed for the major adverse events. The absolute 10-year risk difference of overall CVD in per-protocol analysis was −7.1% (−10.7%, −3.6%) and −3.9% (−5.1%, −2.7%) in patients with baseline LDL-C 1.8-2.5 and ≥2.6 mmol/L, respectively. The effectiveness and safety were consistently observed in patients aged >75 years initiating statin at both LDL-C thresholds. Conclusions: Compared with the threshold of 2.6 mmol/L, initiating statin in patients with a lower baseline LDL-C level at 1.8-2.5 mmol/L can further reduce the risks of CVD and all-cause mortality without significantly increasing the risk of major adverse events in patients with T2DM, including patients aged >75 years.",

keywords = "cardiovascular disease, hyperlipidaemia, statin, type 2 diabetes mellitus",

author = "Wan, {Eric Yuk Fai} and Wanchun Xu and Mok, {Anna Hoi Ying} and Chin, {Weng Yee} and Yu, {Esther Yee Tak} and Chui, {Celine Sze Ling} and Chan, {Esther Wai Yin} and Wong, {Ian Chi Kei} and Lam, {Cindy Lo Kuen} and Goodarz Danaei",

note = "Copyright {\textcopyright} 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. ",

year = "2024",

month = may,

doi = "10.1111/dom.15503",

language = "English",

volume = "26",

pages = "1877--1887",

journal = "Diabetes, Obesity and Metabolism",

issn = "1462-8902",

publisher = "Wiley-Blackwell",

number = "5",

}

Wan, EYF, Xu, W, Mok, AHY, Chin, WY, Yu, EYT, Chui, CSL, Chan, EWY, Wong, ICK, Lam, CLK & Danaei, G 2024, 'Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study', Diabetes, Obesity and Metabolism, vol. 26, no. 5, pp. 1877-1887. https://doi.org/10.1111/dom.15503

Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study. / Wan, Eric Yuk Fai; Xu, Wanchun; Mok, Anna Hoi Ying et al.
In: Diabetes, Obesity and Metabolism, Vol. 26, No. 5, 05.2024, p. 1877-1887.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study

AU - Wan, Eric Yuk Fai

AU - Xu, Wanchun

AU - Mok, Anna Hoi Ying

AU - Chin, Weng Yee

AU - Yu, Esther Yee Tak

AU - Chui, Celine Sze Ling

AU - Chan, Esther Wai Yin

AU - Wong, Ian Chi Kei

AU - Lam, Cindy Lo Kuen

AU - Danaei, Goodarz

N1 - Copyright © 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

PY - 2024/5

Y1 - 2024/5

N2 - Aim: The present study aimed to evaluate the effect of statin therapy for primary prevention of cardiovascular diseases (CVDs) when initiating therapy at different baseline low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of trials on patients with T2DM with elevated LDL-C levels in every calendar month from January 2008 to December 2014. Pooled logistic regression was applied to obtain the hazard ratios for the major CVDs (stroke, myocardial infarction, heart failure), all-cause mortality and major adverse events (myopathies and liver dysfunction) of statin therapy. Results: The estimated hazard ratios (95% confidence intervals) of CVD incidence for statin initiation were 0.78 (0.72, 0.84) in patients with baseline LDL-C of 1.8-2.5 mmol/L (i.e., 70-99 mg/dL) and 0.90 (0.88, 0.92) in patients with baseline LDL-C ≥2.6 mmol/L (i.e., ≥100 mg/dL) in intention-to-treat analysis, which was 0.59 (0.51, 0.68) and 0.77 (0.74, 0.81) in per-protocol analysis, respectively. No significant increased risks were observed for the major adverse events. The absolute 10-year risk difference of overall CVD in per-protocol analysis was −7.1% (−10.7%, −3.6%) and −3.9% (−5.1%, −2.7%) in patients with baseline LDL-C 1.8-2.5 and ≥2.6 mmol/L, respectively. The effectiveness and safety were consistently observed in patients aged >75 years initiating statin at both LDL-C thresholds. Conclusions: Compared with the threshold of 2.6 mmol/L, initiating statin in patients with a lower baseline LDL-C level at 1.8-2.5 mmol/L can further reduce the risks of CVD and all-cause mortality without significantly increasing the risk of major adverse events in patients with T2DM, including patients aged >75 years.

AB - Aim: The present study aimed to evaluate the effect of statin therapy for primary prevention of cardiovascular diseases (CVDs) when initiating therapy at different baseline low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of trials on patients with T2DM with elevated LDL-C levels in every calendar month from January 2008 to December 2014. Pooled logistic regression was applied to obtain the hazard ratios for the major CVDs (stroke, myocardial infarction, heart failure), all-cause mortality and major adverse events (myopathies and liver dysfunction) of statin therapy. Results: The estimated hazard ratios (95% confidence intervals) of CVD incidence for statin initiation were 0.78 (0.72, 0.84) in patients with baseline LDL-C of 1.8-2.5 mmol/L (i.e., 70-99 mg/dL) and 0.90 (0.88, 0.92) in patients with baseline LDL-C ≥2.6 mmol/L (i.e., ≥100 mg/dL) in intention-to-treat analysis, which was 0.59 (0.51, 0.68) and 0.77 (0.74, 0.81) in per-protocol analysis, respectively. No significant increased risks were observed for the major adverse events. The absolute 10-year risk difference of overall CVD in per-protocol analysis was −7.1% (−10.7%, −3.6%) and −3.9% (−5.1%, −2.7%) in patients with baseline LDL-C 1.8-2.5 and ≥2.6 mmol/L, respectively. The effectiveness and safety were consistently observed in patients aged >75 years initiating statin at both LDL-C thresholds. Conclusions: Compared with the threshold of 2.6 mmol/L, initiating statin in patients with a lower baseline LDL-C level at 1.8-2.5 mmol/L can further reduce the risks of CVD and all-cause mortality without significantly increasing the risk of major adverse events in patients with T2DM, including patients aged >75 years.

KW - cardiovascular disease

KW - hyperlipidaemia

KW - statin

KW - type 2 diabetes mellitus

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ER -

Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study

Abstract

Bibliographical note

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Funding

Keywords

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