PMID- 38379445 OWN - NLM STAT- MEDLINE DCOM- 20240409 LR - 20240426 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 5 DP - 2024 May TI - 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. PG - 1877-1887 LID - 10.1111/dom.15503 [doi] 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. CI - (c) 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Wan, Eric Yuk Fai AU - Wan EYF AUID- ORCID: 0000-0002-6275-1147 AD - Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. AD - Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Sha Tin, Hong Kong Special Administrative Region, China. FAU - Xu, Wanchun AU - Xu W AD - Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. FAU - Mok, Anna Hoi Ying AU - Mok AHY AD - Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. FAU - Chin, Weng Yee AU - Chin WY AD - Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. FAU - Yu, Esther Yee Tak AU - Yu EYT AD - Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. FAU - Chui, Celine Sze Ling AU - Chui CSL AD - Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Sha Tin, Hong Kong Special Administrative Region, China. AD - School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. AD - School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. FAU - Chan, Esther Wai Yin AU - Chan EWY AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. AD - Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Sha Tin, Hong Kong Special Administrative Region, China. FAU - Wong, Ian Chi Kei AU - Wong ICK AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. AD - Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Sha Tin, Hong Kong Special Administrative Region, China. AD - Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom. FAU - Lam, Cindy Lo Kuen AU - Lam CLK AD - Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. FAU - Danaei, Goodarz AU - Danaei G AD - Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, Massachusetts, USA. AD - Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts, USA. LA - eng GR - 05190107/Health and Medical Research Fund, Health Bureau/ GR - Health and Medical Research Fund Research Fellowship Scheme/ PT - Journal Article DEP - 20240221 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Cholesterol, LDL) SB - IM MH - Humans MH - *Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Cholesterol, LDL MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Myocardial Infarction OTO - NOTNLM OT - cardiovascular disease OT - hyperlipidaemia OT - statin OT - type 2 diabetes mellitus EDAT- 2024/02/21 11:15 MHDA- 2024/04/09 06:45 CRDT- 2024/02/21 03:23 PHST- 2024/01/27 00:00 [revised] PHST- 2023/11/23 00:00 [received] PHST- 2024/02/05 00:00 [accepted] PHST- 2024/04/09 06:45 [medline] PHST- 2024/02/21 11:15 [pubmed] PHST- 2024/02/21 03:23 [entrez] AID - 10.1111/dom.15503 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 May;26(5):1877-1887. doi: 10.1111/dom.15503. Epub 2024 Feb 21.