Alexander Hodkinson
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
Hodkinson, Alexander; Tsimpida, Dialechti; Kontopantelis, Evangelos; Rutter, Martin K; Mamas, Mamas; Panagioti, Maria
Authors
Dialechti Tsimpida
Evangelos Kontopantelis
Martin K Rutter
Mamas Mamas m.mamas@keele.ac.uk
Maria Panagioti
Abstract
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.
Journal Article Type | Article |
---|---|
Acceptance Date | Feb 3, 2022 |
Online Publication Date | Mar 24, 2022 |
Publication Date | Mar 24, 2022 |
Journal | BMJ: British Medical Journal |
Print ISSN | 0959-8138 |
Publisher | BMJ Publishing Group |
Peer Reviewed | Peer Reviewed |
Volume | 376 |
Article Number | e067731 |
DOI | https://doi.org/10.1136/bmj-2021-067731 |
Publisher URL | https://www.bmj.com/content/376/bmj-2021-067731 |
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