Improving statins effectiveness by targeting baseline LDL cholesterol in type 2 diabetes mellitus, a systematic review and meta-analysis

Abstract

Abstract Background Although the guidelines recommend statins to prevent cardiovascular events in patients with type 2 diabetes (T2D), it remains controversial whether their cardiovascular effectiveness depends on baseline LDL-Cholesterol (LDL-C) levels at the start of statin use. Purpose To determine whether the association of statin use in T2D patients with major adverse cardiovascular events (MACE) and all-cause mortality differ according to baseline LDL-C categories. Methods This study was registered in the PROSPERO database (CRD42022374004); and was performed according to the PRISMA statement. Through January 2022, Medline, Embase, and Web of science were systematically searched from inception. Observational studies in patients with T2D comparing statin users vs non-users, with reports of the baseline LDL-C levels, were included. Random-effects meta-analysis and meta-regression were performed to study if the association between statin use and the risk of all-cause mortality and MACE (a composite of myocardial infarction, hospitalization due to heart failure, stroke, and revascularization events) modified by baseline LDL-C levels. We categorized studies according to their baseline LDL-C levels into 1) <100 mg/dl (2.59 mmol/l), 2) 100-130 mg/dl (2.59-3.37 mmol/l) and 3) ≥130 mg/dl (3.37 mmol/l) categories. Results A total of 11 cohort studies (n= 408,937 individuals) fulfilled our criteria. The follow-up duration ranged from 1.7 to 8 years. The overall combined estimate showed that statin therapy was associated with a significantly lower risk of MACE (Hazard Ratio (HR): 0.67 [95% CI 0.57 to 0.79]) and all-cause mortality (HR: 0.60 [95% CI 0.46 to 0.79]), but varied, albeit not statistically significant, by baseline LDL-C levels. Studies with baseline LDL-C levels of 130 mg/dl or higher had the greatest reduction of MACE (HR: 0.58 [95% CI 0.37 to 0.90]) and all-cause mortality risk (HR: 0.51 [95% CI [ 0.29, 0.90]). The HRs of MACE in studies with LDL-C levels of 100-130 mg/dl and <100 mg/dl categories were respectively (0.66 [95% CI 0.53 to 0.82]) and (0.83 [95% CI [0.68, 1.00]); and that of all-cause mortality were respectively (0.62 [95% CI 0.38 to 1.01]) and (0.67 [95% CI [0.44, 1.02]). Statin use was associated with reductions in HRs of MACE (0.99 [95%CI, 0.98 to 1.00]; P = 0.11) and all-cause mortality (0.99 [95% CI 0.98 to 1.01]; P = 0.8) per each mg/dl increase in baseline LDL-C level in meta-regression analyses. Conclusion The results of this study suggest that the greatest cardiovascular protective effects of statin therapy in patients with T2D are attributable to patients with baseline LDL-C levels of 130 mg/dl or higher in real-life settings of observational studies.