Hodkinson, A, Tsimpida, D, Kontopantelis, E, Rutter, MK, Mamas, MA ORCID: https://orcid.org/0000-0001-9241-8890 and Panagioti, M (2022) Comparative Effectiveness of Statins on Non-HDL Cholesterol by Type and Intensity in People with Diabetes and at Risk of Cardiovascular Disease: Systematic Review and Network Meta-Analysis. BMJ: British Medical Journal. (In Press)

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Abstract

Objective: To compare the efficacy of different statin therapies by intensity for prevention of cardiovascular disease (CVD) in people with diabetes according to non-high-density lipoprotein cholesterol (non-HDL-C). Design: Systematic review and network meta-analysis. Data Sources: Searches in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE until December 2021. Review Methods: Randomised controlled trials comparing different type(s) and intensity of statins including placebo in adults with diabetes mellitus (type 1 or 2) were included. Main Outcome Measure: Primary outcome was non-HDL-C, calculated using total cholesterol and high-density lipoprotein cholesterol measures. Secondary outcomes include low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), 3-point major cardiovascular events (MACE) (non-fatal stroke, non-fatal myocardial infarction, and cardiovascular related death) and discontinuations due to adverse events. Data Synthesis: A Bayesian network meta-analysis of statin intensity (low, moderate, or high) using random-effects evaluated treatment effect on non-HDL-C through mean difference and 95% credible intervals. Subgroup analysis of patients at greater risk of MACE was compared with patients at low/moderate risk. The Confidence In Network Meta-Analysis (CINeMA) framework was applied to ensure the certainty of evidence. Results: Forty-two trials randomizing 20,193 adults of which 11,698 were included in the meta-analysis. Compared to placebo, the greatest reductions in non-HDL-C were observed in Rosuvastatin at high (-2.31 mmol/L, 95% credible interval: -3.39 to -1.21) and moderate intensities (-2.27 mmol/L, -3.00 to -1.49), and Simvastatin (-2.26 mmol/L, -2.99 to -1.51) and Atorvastatin (-2.20 mmol/L, -2.69 to -1.70) at high intensity. Atorvastatin and Simvastatin at any intensity and Pravastatin at low intensity were also effective at reducing non-HDL-C. In 4,670 patients at greater risk of a MACE, Atorvastatin at high intensity was best ranked (-1.98 mmol/L, -4.16 to 0.26, surface under the cumulated ranking curve: 64%) in terms of non-HDL-C. Simvastatin (-1.93, -2.63 to -1.21 mmol/L) and Rosuvastatin (-1.76, -2.37 to -1.15 mmol/L) delivered at a high intensity level were the most significant treatment options for reducing LDL-C. Atorvastatin (-2.21, -2.62 to -1.74 mmol/L), Rosuvastatin (-2.18, -3.19 to -1.20 mmol/L) and Simvastatin (-2.20, -2.96 to -1.42 mmol/L) delivered at a high intensity level were the most significant treatment options for reducing TC. There was a significant reduction in non-fatal myocardial infarction for Atorvastatin delivered at moderate intensity when compared with placebo (RR=0.57, 95% CI: 0.43 to 0.76, n=4 studies). No significant differences were found for discontinuations, non-fatal stroke and cardiovascular deaths. Conclusions: This network meta-analysis indicates that Rosuvastatin at moderate or high intensity and Simvastatin and Atorvastatin at high intensity were most effective at moderately lowering non-HDL-C in patients with diabetes. Given the potential improvement in accuracy in predicting CVD by means of the non-HDL-C target, our findings serve as a convenient guidance on which statin types and intensities are most effective by reducing non-HDL-C in patients with diabetes. Systematic Review Registration: PROSPERO CRD42021258819.

Item Type: Article
Additional Information: The final version of this article and all relevant information related to it, including copyrights, can be found on the publisher website
Subjects: R Medicine > RC Internal medicine > RC660 Diabetes
R Medicine > RC Internal medicine > RC666 Diseases of the circulatory (Cardiovascular) system
Divisions: Faculty of Medicine and Health Sciences > School of Medicine
Depositing User: Symplectic
Date Deposited: 08 Feb 2022 12:11
Last Modified: 08 Feb 2022 12:11
URI: https://eprints.keele.ac.uk/id/eprint/10574

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