Associations between statins and adverse events in secondary prevention of cardiovascular disease: Pairwise, network, and dose-response meta-analyses of 47 randomized controlled trials

Abstract

ObjectivesTo explore the associations between different types and doses of statins and adverse events in secondary prevention of cardiovascular disease.MethodsWe searched PubMed, Embase, and Cochrane databases for randomized controlled trials that compared statins with non-statin controls or different types or doses of statins. The primary outcomes included muscle condition, transaminase elevations, renal insufficiency, gastrointestinal discomfort, cancer, new onset or exacerbation of diabetes, cognitive impairment, and eye condition. We also analyzed myocardial infarction (MI), stroke, death from cardiovascular diseases (CVD), and all-cause death as the secondary outcomes to compare the potential harms with the benefits of statins. We conducted pairwise meta-analyses to calculate the odds ratio (OR) and 95% confidence intervals (CIs) for each outcome. Network meta-analyses were performed to compare the adverse effects of different statins. An Emax model was used to examine the dose-response relationships of the adverse effects of each statin.ResultsForty-seven trials involving 107,752 participants were enrolled and followed up for 4.05 years. Compared with non-statin control, statins were associated with an increased risk of transaminase elevations [OR 1.62 (95% CI 1.20 to 2.18)]. Statins decreased the risk of MI [OR 0.66 (95% CI 0.61 to 0.71), P < 0.001], stroke [OR 0.78 (95% CI 0.72 to 0.84), P < 0.001], death from CVD [OR 0.77 (95% CI 0.72 to 0.83), P < 0.001] and all-cause death [OR 0.83 (95% CI 0.79 to 0.88), P < 0.001]. Atorvastatin showed a higher risk of transaminase elevations than non-statin control [OR 4.0 (95% CI 2.2 to 7.6)], pravastatin [OR 3.49 (95% CI 1.77 to 6.92)] and simvastatin [OR 2.77 (95% CI 1.31 to 5.09)], respectively. Compared with atorvastatin, simvastatin was associated with a lower risk of muscle problems [OR 0.70 (95% CI 0.55 to 0.90)], while rosuvastatin showed a higher risk [OR 1.75 (95% CI 1.17 to 2.61)]. An Emax dose-response relationship was identified for the effect of atorvastatin on transaminase elevations.ConclusionStatins were associated with increased risks of transaminases elevations in secondary prevention. Our study provides the ranking probabilities of statins that can help clinicians make optimal decisions when there is not enough literature to refer to.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021285161].

Sex differences in cardiologic medication provision for adults with coronary heart disease: an analysis of health claims data from 2018 to 2020 in Saxony-Anhalt, Germany

“…The role of physicians in primary care seems especially important considering the increase in CHD patients without statin prescription 6 months after hospital discharge in Germany and the overall low proportion of CHD patients receiving high-intensity statin therapy compared to those in other Western countries [ 37 ]. The efficacy and effectiveness of statins for the secondary prevention of cardiovascular diseases are well established for myocardial infarction, death from CVD, and overall death in both sexes [ 38 ]. Furthermore, evidence suggests that even older patients with polypharmacy do not benefit from the discontinuation of statins [ 39 ].…”

Statin-Associated Liver Dysfunction and Muscle Injury: epidemiology, Mechanisms, and Management Strategies

“…The meta-analyses of 47 randomized controlled trials showed that simvastatin was associated with a lower risk of muscle problems (OR = 0.70, 95% CI: 0.55–0.90), while rosuvastatin showed a higher risk (OR = 1.75, 95% CI: 1.17–2.61) when compared with atorvastatin. 5 However, simvastatin was associated with the highest incidence of rhabdomyolysis, followed by atorvastatin, rosuvastatin, fluvastatin, pitavastatin, pravastatin, and lovastatin. 32 …”

“…21 A meta-analyse indicated that atorvastatin showed a higher risk of transaminase elevations than non-statin control (OR = 4.0, 95% CI: 2.2–7.6), pravastatin (OR = 3.49, 95% CI: 1.77–6.92) and simvastatin (OR = 2.77, 95% CI: 1.31–5.09), respectively. 5 Besides, an Emax dose–response relationship was identified for the effect of atorvastatin on transaminase elevations. 5 Hepatocellular, cholestasis, and autoimmune hepatitis may infrequently appear months to years after the initiation of statins.…”

“… 5 Besides, an Emax dose–response relationship was identified for the effect of atorvastatin on transaminase elevations. 5 Hepatocellular, cholestasis, and autoimmune hepatitis may infrequently appear months to years after the initiation of statins. 22 …”

“…Recent pairwise, network, and dose-response meta-analyses of 47 randomized controlled trials showed that statins decreased the risk of myocardial infarction (OR = 0.66, 95% CI: 0.61–0.71, P < 0.001), stroke (OR = 0.78, 95% CI: 0.72–0.84, P < 0.001), death from cardiovascular diseases (OR = 0.77, 95% CI: 0.72–0.83, P < 0.001) and all-cause death (OR = 0.83, 95% CI: 0.79–0.88, P < 0.001). 5 Statin combined with other lipid-lowering drug therapy could also significantly improve the anatomical and physiological function of the coronary arteries and down-regulate the re-hospitalization rate due to unstable angina in ST elevation myocardial infarction patients with non-infarct-related artery. 6 A retrospective study found that statins reduced the intubation, ICU admission, and mortality in COVID-19 patients.…”