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BMJ (Clinical Research Ed.) Mar 2022To compare the efficacy of different statin treatments by intensity on levels of non-high density lipoprotein cholesterol (non-HDL-C) for the prevention of... (Meta-Analysis)
Meta-Analysis
Comparative effectiveness of statins on non-high density lipoprotein cholesterol in people with diabetes and at risk of cardiovascular disease: systematic review and network meta-analysis.
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.
Topics: Adult; Bayes Theorem; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Network Meta-Analysis
PubMed: 35331984
DOI: 10.1136/bmj-2021-067731 -
Cardiovascular Therapeutics 2020The drug efficacy may differ among different statins, and evidence from head-to-head comparisons is sparse and inconsistent. The study is aimed at comparing the... (Meta-Analysis)
Meta-Analysis
Comparative Lipid-Lowering/Increasing Efficacy of 7 Statins in Patients with Dyslipidemia, Cardiovascular Diseases, or Diabetes Mellitus: Systematic Review and Network Meta-Analyses of 50 Randomized Controlled Trials.
OBJECTIVE
The drug efficacy may differ among different statins, and evidence from head-to-head comparisons is sparse and inconsistent. The study is aimed at comparing the lipid-lowering/increasing effects of 7 different statins in patients with dyslipidemia, cardiovascular diseases, or diabetes mellitus by conducting systematic review and network meta-analyses (NMA) of the lipid changes after certain statins' use.
METHODS
In this study, we searched four electronic databases for randomized controlled trials (RCTs) published through February 25, 2020, comparing the lipid-lowering efficacy of no less than two of the included statins (or statin vs. placebo). Three reviewers independently extracted data in duplicate. Firstly, mixed treatment overall comparison analyses, in the form of frequentist NMAs, were conducted using STATA 15.0 software. Then, subgroup analyses were conducted according to different baseline diseases. At last, sensitivity analyses were conducted according to age and follow-up duration. The trial was registered with PROSPERO (number CRD42018108799).
RESULTS
As a result, seven statin monotherapy treatments in 50 studies (51956 participants) were used for the analyses. The statins included simvastatin (SIM), fluvastatin (FLU), atorvastatin (ATO), rosuvastatin (ROS), lovastatin (LOV), pravastatin (PRA), and pitavastatin (PIT). In terms of LDL-C lowering, rosuvastatin ranked 1 with a surface under cumulated ranking (SUCRA) value of 93.1%. The comparative treatment efficacy for LDL-C lowering was ROS>ATO>PIT>SIM>PRA>FLU>LOV>PLA. All of the other ranking and NMA results were reported in SUCRA plots and league tables.
CONCLUSIONS
According to the NMAs, it can be concluded that rosuvastatin ranked 1 in LDL-C, ApoB-lowering efficacy and ApoA1-increasing efficacy. Lovastatin ranked 1 in TC- and TG-lowering efficacy, and fluvastatin ranked 1 in HDL-C-increasing efficacy. The results should be interpreted with caution due to some limitations in our review. However, they can provide references and evidence-based foundation for drug selection in both statin monotherapies and statin combination therapies.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus; Down-Regulation; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Middle Aged; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult
PubMed: 32411300
DOI: 10.1155/2020/3987065 -
Frontiers in Medicine 2022To review of the efficacy and safety of pravastatin use for prophylaxis and treatment of preeclampsia.
OBJECTIVE
To review of the efficacy and safety of pravastatin use for prophylaxis and treatment of preeclampsia.
DESIGN
Systematic review and meta-analysis of clinical studies evaluating pravastatin for treatment and/or prophylaxis of preeclampsia.
DATA COLLECTION
Two independent reviewers systematically searched data from PubMed, Scopus, Web of Science, Cochrane, Embase, and clinicaltrials.gov databases, for studies evaluating pravastatin for prevention of pre-eclampsia.
RESULTS
Fourteen studies were identified, including 1,570 pregnant women who received either pravastatin or placebo, published between 2003 and 2022. From these studies, 5 studies were identified for inclusion in the meta-analysis to evaluate the role of pravastatin use prior to 20 weeks of gestation, to prevent pre-eclampsia, Pravastatin treatment reduced the incidence of preeclampsia by 61% and premature birth by 45%. Among the newborns, there was a 45% reduction in intrauterine growth retardation (IUGR) in the treated group, as well as a 77% reduction in those receiving neonatal intensive care unit (NICU) admissions.
CONCLUSION
Prophylactic treatment with pravastatin appears to reduce risk of developing pre-eclampsia as well as potentially lowering risk of IUGR, preterm birth, and NICU admission in neonates.
PubMed: 36714131
DOI: 10.3389/fmed.2022.1076372 -
Pravastatin and placental insufficiency associated disorders: A systematic review and meta-analysis.Frontiers in Pharmacology 2022Uteroplacental insufficiency associated disorders, such as preeclampsia, fetal growth restriction and obstetrical antiphospholipid syndrome, share pathophysiology and...
Uteroplacental insufficiency associated disorders, such as preeclampsia, fetal growth restriction and obstetrical antiphospholipid syndrome, share pathophysiology and risk factors with cardiovascular diseases treated with statins. To evaluate pregnancy outcomes among women with uteroplacental insufficiency disorders who were treated with statins. Electronic databases were searched from inception to January 2022 Cohort studies and randomized controlled trials. Pooled odds ratios were calculated using a random-effects model; meta-regression was utilized when applicable. The analysis included ten studies describing 1,391 women with uteroplacental insufficiency disorders: 703 treated with pravastatin and 688 not treated with statins. Women treated with pravastatin demonstrated significant prolongation of pregnancy (mean difference 0.44 weeks, 95%CI:0.01-0.87, = 0.04, I = 96%) and less neonatal intensive care unit admissions (OR = 0.42, 95%CI: 0.23-0.75, = 0.004, I = 25%). In subgroup analysis, prolongation of pregnancy from study entry to delivery was statistically significant in cohort studies (mean difference 8.93 weeks, 95%CI:4.22-13.95, = 0.00) but not in randomized control studies. Trends were observed toward a decrease in preeclampsia diagnoses (OR = 0.54, 95%CI:0.27-1.09, = 0.09, I = 44%), perinatal death (OR = 0.32, 95%CI:0.09-1.13, = 0.08, I = 54%) and an increase in birth weight (mean difference = 102 g, 95%CI: -14-212, = 0.08, I = 96%). A meta-regression analysis demonstrated an association between earlier gestational age at initiation of treatment and a lower risk of preeclampsia development (R = 1). Pravastatin treatment prolonged pregnancy duration and improved associated obstetrical outcomes in pregnancies complicated with uteroplacental insufficiency disorders in cohort studies. https://www.crd.york.ac.uk/prospero/ identifier CRD42020165804 17/2/2020.
PubMed: 36438820
DOI: 10.3389/fphar.2022.1021548 -
TouchREVIEWS in Endocrinology Nov 2022Statin use has been linked with new-onset diabetes mellitus (NODM). In the present systematic review, we aimed to determine the incidence of NODM with statin use by... (Review)
Review
Statin use has been linked with new-onset diabetes mellitus (NODM). In the present systematic review, we aimed to determine the incidence of NODM with statin use by assessing and summarizing the data generated by different systematic reviews and metaanalyses published on this topic. We conducted a systematic review of systematic reviews and meta-analyses using a pre-defined study protocol. Two authors independently performed a literature search using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies reporting data on statin use and NODM incidence and screened and extracted data for the outcomes of interest. The Assessing the Methodological Auality of Systematic Reviews 2 (AMSTAR 2) checklist was used to evaluate the quality of the included systematic reviews and meta-analyses. The initial search yielded 621 potential records, and 16 relevant systematic reviews and meta-analyses were included in the present systematic review. The included studies showed an increase in the risk of NODM with statin use. In particular, rosuvastatin and atorvastatin were associated with NODM in many systematic reviews or meta-analyses; however, pravastatin and pitavastatin were found to be associated with lower or no risk. We observed a positive trend of development of NODM with statin use became more evident with advancing years as more number of studies were added. Intensive doses of statins and use in older subjects were found to be important risk factors for NODM. Finally, the quality assessment revealed that the included systematic reviews and metaanalyses were of critically low or low quality. We concluded that statin use carries a risk of causing NODM. Statins should not be discouraged in anticipation of NODM. However, glycaemic monitoring should be encouraged with the on-going statin therapy. Furthermore, clinical studies addressing the use of statins and the incidence of NODM as their primary objective should be planned.
PubMed: 36694884
DOI: 10.17925/EE.2022.18.2.96 -
The Cochrane Database of Systematic... Nov 2019Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review.
OBJECTIVES
To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia.
SEARCH METHODS
Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline. Date of most recent search: 04 November 2019.
SELECTION CRITERIA
Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion and extracted data.
MAIN RESULTS
We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (high-quality evidence). There may be little or no difference in liver function (serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations) between treated and placebo groups at any time point (low-quality evidence). There may be little or no difference in myopathy (as measured in change in creatinine levels) (low-quality evidence) or clinical adverse events (moderate-quality evidence) with statins compared to placebo. One study on simvastatin showed that this may slightly improve flow-mediated dilatation of the brachial artery (low-quality evidence), and on pravastatin for two years may have induced a regression in carotid intima media thickness (low-quality evidence). No studies reported rhabdomyolysis (degeneration of skeletal muscle tissue) or death due to rhabdomyolysis, quality of life or compliance to study medication.
AUTHORS' CONCLUSIONS
Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. Few or no safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.
Topics: Adolescent; Adult; Child; Cholesterol, LDL; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Male; Randomized Controlled Trials as Topic; Young Adult
PubMed: 31696945
DOI: 10.1002/14651858.CD006401.pub5 -
Basic & Clinical Pharmacology &... Apr 2020The high prevalence of statin and clarithromycin utilization creates potential for overlapping use. The objectives of this MiniReview were to investigate the evidence... (Comparative Study)
Comparative Study
The high prevalence of statin and clarithromycin utilization creates potential for overlapping use. The objectives of this MiniReview were to investigate the evidence base for drug-drug interactions between clarithromycin and currently marketed statins and to present management strategies for these drug combinations. We conducted a systematic literature review following PRISMA guidelines with English language studies retrieved from PubMed and EMBASE (from inception through March 2019). We included 29 articles (16 case reports, 5 observational, 5 clinical pharmacokinetic and 3 in vitro studies). Based on mechanistic/clinical studies involving clarithromycin or the related macrolide erythromycin (both strong inhibitors of CYP3A4 and of hepatic statin uptake transporters OATP1B1 and OATP1B3), clarithromycin is expected to substantially increase systemic exposure to simvastatin and lovastatin (>5-fold increase in area under the plasma concentration-time curve (AUC)), moderately increase AUCs of atorvastatin and pitavastatin (2- to 4-fold AUC increase) and slightly increase pravastatin exposure (≈2-fold AUC increase) while having little effect on fluvastatin or rosuvastatin. The 16 cases of statin-clarithromycin adverse drug reactions (rhabdomyolysis (n = 14) or less severe clinical myopathy) involved a CYP3A4-metabolized statin (simvastatin, lovastatin or atorvastatin). In line, a cohort study found concurrent use of clarithromycin and CYP3A4-metabolized statins to be associated with a doubled risk of hospitalization with rhabdomyolysis or other statin-related adverse events as compared with azithromycin-statin co-administration. If clarithromycin is necessary, we recommend (a) avoiding co-administration with simvastatin, lovastatin or atorvastatin; (b) withholding or dose-reducing pitavastatin; (c) continuing pravastatin therapy with caution, limiting pravastatin dose to 40 mg daily; and (d) continuing fluvastatin or rosuvastatin with caution.
Topics: Area Under Curve; Clarithromycin; Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rhabdomyolysis
PubMed: 31628882
DOI: 10.1111/bcpt.13343 -
PloS One 2022Disturbed cognitive function is associated with several causes of mortality; however, the association between cognitive function and the risk of cancer death has not... (Meta-Analysis)
Meta-Analysis
Association of cognitive function with increased risk of cancer death and all-cause mortality: Longitudinal analysis, systematic review, and meta-analysis of prospective observational studies.
BACKGROUND
Disturbed cognitive function is associated with several causes of mortality; however, the association between cognitive function and the risk of cancer death has not been extensively investigated yet. We aimed to evaluate the association of cognitive function with the risk of cancer death and all-cause mortality in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) and Leiden 85-plus Study. Additionally, a systematic review and meta-analysis of longitudinal studies were conducted to evaluate the association of cognitive function and risk of cancer death.
METHODS
Risk of cancer death and all-cause mortality were reported using hazard ratios (HRs) with 95% confidence interval (CI) in tertiles of cognitive function of PROSPER and Leiden85-Plus Study. Additionally, PubMed, Embase, Web of Science, Cochrane, PsycINFO, Academic Search Premier, CINHAL, and Emcare were searched up to November 1st, 2020 to perform a systematic review and meta-analysis. The relative risks (RRs) with 95%CI of cancer death per each standard deviation lower performance in cognitive measurements were calculated.
RESULTS
Participants of PROSPER had 1.65-fold (95%CI 1.11-2.47) greater risk of cancer death (P for trend = 0.016) and 1.85-fold (95%CI 1.46-2.34) higher risk of all-cause mortality (P for trend<0.001), in multivariable models. Results of the Leiden-85 Plus Study showed that subjects with MMSE score below 24 had a lower chance of cancer death (HR 0.79, 95%CI 0.36-1.70, P for trend = 0.820) but had 2.18-fold (95%CI 1.57-3.02) higher risk of all-cause mortality compared to the reference group (P for trend<0.001). Besides, the results of systematic review and meta-analysis showed that per each standard deviation lower performance in cognitive function, individuals were at a 10% higher chance of cancer death (RR 1.10, 95%CI 1.00-1.20, P-value = 0.044).
CONCLUSIONS
Lower cognitive function performance is associated with a marginally increased risk of cancer death, in line with a significantly greater risk of all-cause mortality.
Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Cognition; Cognitive Dysfunction; Female; Humans; Male; Neoplasms; Pravastatin; Prospective Studies
PubMed: 34995287
DOI: 10.1371/journal.pone.0261826 -
Cancer Causes & Control : CCC Oct 2020The link between lipid-stabilizing medications and epithelial ovarian carcinogenesis is incompletely understood. Statins may reduce ovarian cancer risk, but results are... (Meta-Analysis)
Meta-Analysis
PURPOSE
The link between lipid-stabilizing medications and epithelial ovarian carcinogenesis is incompletely understood. Statins may reduce ovarian cancer risk, but results are inconclusive.
METHODS
We conducted a systematic review and meta-analysis of studies reporting associations between statin use and ovarian cancer risk in PubMed. Summary risk ratios (RRs) and confidence intervals (CIs) were calculated. Subgroup analyses by cancer histotype, statin class (lipo- or hydrophilic) and duration of statin use were conducted. Use of individual statins in populations was assessed to determine population-specific differences in statin types.
RESULTS
Nine studies with 435,237 total women were included (1 randomized controlled trial (RCT); 4 prospective; 4 case-control). Statin use was associated with a reduced risk of ovarian cancer (RR 0.87, 95% CI 0.74-1.03) and risk was significantly reduced in populations with low pravastatin use (RR 0.83, 95% CI 0.70-0.99). Risk estimates varied by statin class (3 studies; lipophilic: RR 0.88, 95% CI 0.69-1.12; hydrophilic: RR 1.06, 95% CI 0.72-1.57) and cancer histotype (3 studies; serous: RR 0.95, 95% CI 0.69-1.30; clear cell: RR 1.17, 95% CI 0.74-1.86). Long-term use was associated with a reduced risk of ovarian cancer (RR 0.77, 95% CI 0.54-1.10) that further reduced when pravastatin use was low (RR 0.68, 95% CI 0.46-1.01). Between-study heterogeneity was high overall and in subgroups (I > 60%).
CONCLUSION
Statins may be associated with a reduced risk of ovarian cancer, but the effect likely differs by individual statin, duration of use and cancer histotype. Additional well-powered studies are needed to elucidate important subgroup effects.
Topics: Case-Control Studies; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ovarian Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Risk
PubMed: 32685996
DOI: 10.1007/s10552-020-01327-8 -
BMC Gastroenterology Mar 2021There is increased interest in the therapeutic use of statins in cirrhosis, but preferred statin and safety outcomes are still not well known. In this systematic review...
BACKGROUND/AIMS
There is increased interest in the therapeutic use of statins in cirrhosis, but preferred statin and safety outcomes are still not well known. In this systematic review we aimed to address pharmacokinetics (PK), safety, and effects on cardiovascular (CV) outcomes of statins in cirrhosis.
METHODS
Our systematic search in several electronic databases and repositories of two regulatory bodies up to 2020-06-11 yielded 22 articles and 2 drug monographs with relevant data.
RESULTS
Rosuvastatin and pitavastatin showed minimal PK changes in Child-Pugh A cirrhosis. Only rosuvastatin was assessed in a repeated dosing PK study. Atorvastatin showed pronounced PK changes in cirrhosis. No PK data was found for simvastatin, the most commonly used statin in cirrhosis trials. There was insufficient data to assess CV effects of statins in cirrhosis. Clinical trials in cirrhosis were limited to simvastatin, atorvastatin, and pravastatin. In patients taking simvastatin 40 mg, pooled frequency of rhabdomyolysis was 2%, an incidence 40-fold higher than that reported in non-cirrhosis patients, while this was no rhabdomyolysis observed in patients on simvastatin 20 mg, atorvastatin 20 mg, or pravastatin 40 mg. Drug-induced liver injury was of difficult interpretation due to co-existence of muscle damage. No overt liver failure was reported.
CONCLUSIONS
Simvastatin 40 mg should be avoided in decompensated cirrhosis. Safety data on simvastatin 20 mg or other statins are based on small study sample size. This rarity of evidence combined with lack of data in dose adjustment methods in cirrhosis is a barrier for using statins for CV indications or for investigational use for liver indications.
Topics: Atorvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver Cirrhosis; Pravastatin; Simvastatin
PubMed: 33726685
DOI: 10.1186/s12876-021-01704-w