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, 376.

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Objective: To compare the efficacy of different statin treatments by intensity on levels of non-high density lipoprotein cholesterol (non-HDL-C) for the prevention of cardiovascular disease in people with diabetes.

Design: Systematic review and network meta-analysis.

Data sources: Medline, Cochrane Central Register of Controlled Trials, and Embase from inception to 1 December 2021.

Review methods: Randomised controlled trials comparing different types and intensities of statins, including placebo, in adults with type 1 or type 2 diabetes mellitus were included. The primary outcome was changes in levels of non-HDL-C, calculated from measures of total cholesterol and HDL-C. Secondary outcomes were changes in levels of low density lipoprotein cholesterol (LDL-C) and total cholesterol, three point major cardiovascular events (non-fatal stroke, non-fatal myocardial infarction, and death related to cardiovascular disease), and discontinuations because of adverse events. A bayesian network meta-analysis of statin intensity (low, moderate, or high) with random effects evaluated the treatment effect on non-HDL-C by mean differences and 95% credible intervals. Subgroup analysis of patients at greater risk of major cardiovascular events was compared with patients at low or moderate risk. The confidence in network meta-analysis (CINeMA) framework was applied to determine the certainty of evidence.

Results: In 42 randomised controlled trials involving 20 193 adults, 11 698 were included in the meta-analysis. Compared with placebo, the greatest reductions in levels of non-HDL-C were seen with rosuvastatin at high (−2.31 mmol/L, 95% credible interval −3.39 to −1.21) and moderate (−2.27, −3.00 to −1.49) intensities, and simvastatin (−2.26, −2.99 to −1.51) and atorvastatin (−2.20, −2.69 to −1.70) at high intensity. Atorvastatin and simvastatin at any intensity and pravastatin at low intensity were also effective in reducing levels of non-HDL-C. In 4670 patients at greater risk of a major cardiovascular events, atorvastatin at high intensity showed the largest reduction in levels of non-HDL-C (−1.98, −4.16 to 0.26, surface under the cumulative ranking curve 64%). Simvastatin (−1.93, −2.63 to −1.21) and rosuvastatin (−1.76, −2.37 to −1.15) at high intensity were the most effective treatment options for reducing LDL-C. Significant reductions in non-fatal myocardial infarction were found for atorvastatin at moderate intensity compared with placebo (relative risk=0.57, confidence interval 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 indicated that rosuvastatin, at moderate and high intensity doses, and simvastatin and atorvastatin, at high intensity doses, were most effective at moderately reducing levels of non-HDL-C in patients with diabetes. Given the potential improvement in accuracy in predicting cardiovascular disease when reduction in levels of non-HDL-C is used as the primary target, these findings provide 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: 09 Jun 2022 14:22
URI: https://eprints.keele.ac.uk/id/eprint/10574

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