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Mayo Clinic Proceedings. Innovations,... Jun 2019To assess the effect of statins compared with placebo on the risk of developing hypertransaminasemia.
OBJECTIVE
To assess the effect of statins compared with placebo on the risk of developing hypertransaminasemia.
PATIENTS AND METHODS
We performed a systematic review of electronic databases and included articles published between January 1, 1965, and April 10, 2017. Randomized clinical trials (RCTs) comparing statins vs placebo were included. Odds ratios (ORs) were pooled in random-effect meta-analyses according to established methods recommended by the Cochrane Collaboration.
RESULTS
Seventy-three eligible RCTs, comprising 123,051 patients, were identified. Statins associated with a significantly risk of hypertransaminasemia (OR 1.45; 95% confidence interval [CI], 1.24-1.69; <.001). Atorvastatin showed the highest odds (OR 2.66; 95% CI, 1.74-4.06; <.001) followed by rosuvastatin (OR 1.35; 95% CI, 1.06-1.70; =.01) and lovastatin (OR 1.53; 95% CI, 1.03-2.28; =.04). Pravastatin, fluvastatin, and simvastatin yielded no statistically different odds compared with placebo.
CONCLUSIONS
A dose-dependent risk of developing hypertransaminasemia occurs in patients taking atorvastatin, rosuvastatin, and lovastatin.
PubMed: 31193835
DOI: 10.1016/j.mayocpiqo.2019.01.003 -
Health Technology Assessment... Apr 2007To evaluate the clinical effectiveness and cost-effectiveness of statins for the primary and secondary prevention of cardiovascular events in adults with, or at risk of,... (Review)
Review
OBJECTIVES
To evaluate the clinical effectiveness and cost-effectiveness of statins for the primary and secondary prevention of cardiovascular events in adults with, or at risk of, coronary heart disease (CHD).
DATA SOURCES
Electronic databases were searched between November 2003 and April 2004.
REVIEW METHODS
A review was undertaken to identify and evaluate all literature relating to the clinical and cost effectiveness of statins in the primary and secondary prevention of CHD and cardiovascular disease (CVD) in the UK. A Markov model was developed to explore the costs and health outcomes associated with a lifetime of statin treatment using a UK NHS perspective.
RESULTS
Thirty-one randomised studies were identified that compared a statin with placebo or with another statin, and reported clinical outcomes. Meta-analysis of the available data from the placebo-controlled studies indicates that, in patients with, or at risk of, CVD, statin therapy is associated with a reduced relative risk of all cause mortality, cardiovascular mortality, CHD mortality and fatal myocardial infarction (MI), but not of fatal stroke. It is also associated with a reduced relative risk of morbidity [non-fatal stroke, non-fatal MI, transient ischaemic attack (TIA), unstable angina] and of coronary revascularisation. It is hardly possible, on the evidence available from the placebo-controlled trials, to differentiate between the clinical efficacy of atorvastatin, fluvastatin, pravastatin and simvastatin. However, there is some evidence from direct comparisons between statins to suggest that atorvastatin may be more effective than pravastatin in patients with symptomatic CHD. There is limited evidence for the effectiveness of statins in different subgroups. Statins are generally considered to be well tolerated and to have a good safety profile. This view is generally supported both by the evidence of the trials included in this review and by postmarketing surveillance data. Increases in creatine kinase and myopathy have been reported, but rhabdomyolysis and hepatotoxicity are rare. However, some patients may receive lipid-lowering therapy for as long as 50 years, and long-term safety over such a timespan remains unknown. In secondary prevention of CHD, the incremental cost-effectiveness ratios (ICERs) increase with age varying between pound 10,000 and pound 17,000 per quality adjusted life year (QALY) for ages 45 and 85 respectively. Sensitivity analyses show these results are robust. In primary prevention of CHD there is substantial variation in ICERs by age and risk. The average ICERs weighted by risk range from pound 20,000 to pound 27,500 for men and from pound 21,000 to pound 57,000 for women. The results are sensitive to the cost of statins, discount rates and the modelling time frame. In the CVD analyses, which take into account the benefits of statins on reductions in stroke and TIA events, the average ICER weighted by risk level remains below pound 20,000 at CHD risk levels down to 0.5%. Limitations of the analyses include the requirement to extrapolate well beyond the timeframe of the trial period, and to extrapolate effectiveness results from higher risk primary prevention populations to the treatment of populations at much lower risk. Consequently, the results for the lower age bands and lower risks are subject to greater uncertainty and need to be treated with caution.
CONCLUSIONS
There is evidence to suggest that statin therapy is associated with a statistically significant reduction in the risk of primary and secondary cardiovascular events. As the confidence intervals for each outcome in each prevention category overlap, it is not possible to differentiate, in terms of relative risk, between the effectiveness of statins in primary and secondary prevention. However, the absolute risk of CHD death/non-fatal MI is higher, and the number needed to treat to avoid such an event is consequently lower, in secondary than in primary prevention. The generalisability of these results is limited by the exclusion, in some studies, of patients who were hypersensitive to, intolerant of, or known to be unresponsive to, statins, or who were not adequately compliant with study medication during a placebo run-in phase. Consequently, the treatment effect may be reduced when statins are used in an unselected population. The results of the economic modelling show that statin therapy in secondary prevention is likely to be considered cost-effective. In primary prevention, the cost-effectiveness ratios are dependent on the level of CHD risk and age, but the results for the CVD analyses offer support for the more aggressive treatment recommendation issued by recent guidelines in UK. Evidence on clinical endpoints for rosuvastatin is awaited from on-going trials. The potential targeting of statins at low-risk populations is however associated with major uncertainties, particularly the likely uptake and long-term compliance to lifelong medication by asymptomatic younger patients. The targeting, assessment and monitoring of low-risk patients in primary care would be a major resource implication for the NHS. These areas require further research.
Topics: Bayes Theorem; Coronary Disease; Cost-Benefit Analysis; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Meta-Analysis as Topic; Quality of Life
PubMed: 17408535
DOI: 10.3310/hta11140 -
Andrology Sep 2021Statins constitute the mainstay of treatment in patients with hypercholesterolemia. However, their effect on semen parameters is unknown.
BACKGROUND
Statins constitute the mainstay of treatment in patients with hypercholesterolemia. However, their effect on semen parameters is unknown.
OBJECTIVE
This study aimed to systematically review the best available evidence regarding the effect of statins on ejaculate volume and sperm concentration, motility, morphology, or vitality.
MATERIALS/METHODS
A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases up to January 10, 2021. Either randomized-controlled trials or prospective cohorts, conducted in males with hypercholesterolemia, were included.
RESULTS
Four studies, published between 1992 and 2014, were eligible. The number of participants ranged from 8 to 120 (n = 161). Study duration ranged from 14 to 48 weeks. The type and dose of statin used were pravastatin 20-80 mg/day and simvastatin 20-40 mg/day. With regard to ejaculate volume (n = 3) and sperm concentration (n = 4), no effect was shown with either pravastatin or simvastatin. Regarding sperm motility, either an increase (n = 2; pravastatin, simvastatin), decrease (n = 1; pravastatin), or no effect (n = 1; pravastatin, simvastatin) was found. With respect to sperm morphology, either a decrease (n = 2; pravastatin, simvastatin) or no effect (n = 2; pravastatin, simvastatin) was shown. Concerning sperm vitality, a single study showed a decrease with simvastatin. Because of the high heterogeneity of the populations studied and the limited number of studies, a meta-analysis was not performed.
CONCLUSION
This is the first systematic review on the effect of statins on semen parameters. As there is no evidence for such a detrimental effect, no specific approach has to be suggested regarding the preservation of reproductive function in men with hypercholesterolemia.
Topics: Adult; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Pravastatin; Prospective Studies; Randomized Controlled Trials as Topic; Semen; Simvastatin; Sperm Motility
PubMed: 33998174
DOI: 10.1111/andr.13039 -
Clinical Cardiology Oct 2009Recent studies have demonstrated that statins may possess antiarrhythmic properties in addition to their lipid-lowering effects. (Review)
Review
BACKGROUND
Recent studies have demonstrated that statins may possess antiarrhythmic properties in addition to their lipid-lowering effects.
METHODS
Studies which reported the association of statins with the incidence of atrial arrhythmias were identified through a systematic review of published literature.
RESULTS
One randomized, placebo-controlled trial of 200 patients undergoing cardiac surgery showed that atorvastatin decreased the incidence of postoperative atrial fibrillation by 61%. Observational studies in patients with stable coronary disease, left ventricular dysfunction, or those undergoing cardiac or noncardiac surgery show that statin therapy is associated with an approximately 50% lower rate of atrial fibrillation. Two small randomized trials reported conflicting results: one showing that atorvastatin reduced the recurrence of AF after electrical cardioversion and the other finding that pravastatin did not.
CONCLUSIONS
Published data suggests that statins may possess antiarrhythmic properties that reduce the propensity for atrial fibrillation. Most of this data is observational; more randomized, placebo-controlled trials are needed.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Risk Factors; Secondary Prevention; Treatment Outcome
PubMed: 19911349
DOI: 10.1002/clc.20669 -
Frontiers in Pharmacology 2022Different treatment protocols have been employed to manage heparin/low-dose aspirin refractory or high-risk pregnancies in antiphospholipid antibody syndrome (APS)...
Different treatment protocols have been employed to manage heparin/low-dose aspirin refractory or high-risk pregnancies in antiphospholipid antibody syndrome (APS) pregnancies. A systematic review of the literature on additional treatments used in refractory and/or high-risk APS pregnancies was conducted. Records from February 2006 to October 2021 were retrieved from PubMed, Web of Science, Cochrane, and the www.clinicaltrials.gov platform. Twenty-one studies met our eligibility criteria. Live birth rate is this study's primary endpoint, while pregnancy complications and adverse events are secondary endpoints. A total of 434 pregnancies, 162 (37.3%) refractory and 272 (62.7%) high-risk/refractory pregnancies, were included. Both IVIG <2 gr/kg/monthly/HCQ/LDS and PEX/IA ± LDS led to 100% viable infants in refractory APS. Furthermore, HCQ 200-400 mg showed a higher live birth rate than HCQ + LDS (88.6% . 82.7%). Following treatment protocol with HCQ 200-400 mg and IVIG <2 gr/kg/monthly/HCQ/LDS, pregnancy complications rates of 16.7 and 83.3% were registered, respectively. Pravastatin 20 mg, IA weekly + IVIG 2 gr/monthly, and PEX weekly + IVIg 2 gr/kg/monthly showed higher live birth rates in high-risk APS pregnancies of 100, 100 and 92%, respectively, whereas the lower severe pregnancy complications were reported in pregnancies treated with PEX weekly + IVIg 2 gr/kg/monthly (11.1%). One (0.6%) case of dermatitis during treatment with HCQ was observed. The results of this study showed that HCQ 200-400 mg and PEX weekly + IVIG 2 gr/kg/monthly achieved a higher live birth rate in refractory APS and high-risk/refractory APS, respectively. The results presented provide clinicians with up-to-date knowledge in the management of APS pregnancies according to risk stratification.
PubMed: 35662738
DOI: 10.3389/fphar.2022.849692 -
Drug Design, Development and Therapy 2019Pravastatin has been suggested to increase circulating adiponectin in humans. However, results of randomized controlled trials (RCTs) are inconsistent. We aimed to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Pravastatin has been suggested to increase circulating adiponectin in humans. However, results of randomized controlled trials (RCTs) are inconsistent. We aimed to systematically evaluate the influence of pravastatin on circulating adiponectin in humans by performing a meta-analysis of RCTs.
MATERIALS AND METHODS
Studies were identified via systematic searching of PubMed, Embase, and Cochrane's Library databases. A random effect model was used to pool the results. Meta-regression and subgroup analyses were applied to explore the source of heterogeneity.
RESULTS
Eight RCTs with nine comparisons of 595 participants were included. Pravastatin treatment was associated with a significant increased level of circulating adiponectin as compared with controls (weighted mean difference [WMD] =0.63 µg/mL; 95% CI, 0.17-1.09 µg/mL; =0.007) with moderate heterogeneity (I2=28%). These results were confirmed by meta-analysis of double-blinded placebo-controlled RCTs (WMD =0.82 µg/mL; =0.01). Meta-regression analyses indicated that proportions of males in each study were positively correlated with the effect of pravastatin on adiponectin (coefficient: 0.015, =0.03). Subgroup analyses confirmed that pravastatin significantly increased adiponectin in studies of males (WMD =1.41 µg/mL; =0.008), but not in those of females (WMD =-0.04 µg/mL; =0.94).
CONCLUSION
Pravastatin treatment is associated with increased circulating adiponectin. Gender difference may exist regarding the effect of pravastatin treatment on adiponectin.
Topics: Adiponectin; Cardiovascular Diseases; Humans; Pravastatin; Randomized Controlled Trials as Topic
PubMed: 31190742
DOI: 10.2147/DDDT.S186992 -
Nutrients Jul 2020Statins and omega-3 supplementation have been recommended for cardiovascular disease prevention, but comparative effects have not been investigated. This study aimed to... (Comparative Study)
Comparative Study Meta-Analysis
Comparative Effect of Statins and Omega-3 Supplementation on Cardiovascular Events: Meta-Analysis and Network Meta-Analysis of 63 Randomized Controlled Trials Including 264,516 Participants.
Statins and omega-3 supplementation have been recommended for cardiovascular disease prevention, but comparative effects have not been investigated. This study aimed to summarize current evidence of the effect of statins and omega-3 supplementation on cardiovascular events. A meta-analysis and a network meta-analysis of 63 randomized controlled trials were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs) for the effects of specific statins and omega-3 supplementation compared with controls. Overall, the statin group showed significant risk reductions in total cardiovascular disease, coronary heart disease, myocardial infarction, and stroke; however, omega-3 supplementation significantly decreased the risks of coronary heart disease and myocardial infarction only, in the comparison with the control group. In comparison with omega-3 supplementation, pravastatin significantly reduced the risks of total cardiovascular disease (RR = 0.81, 95% CI = 0.72-0.91), coronary heart disease (RR = 0.75, 95% CI = 0.60-0.94), and myocardial infarction (RR = 0.71, 95% CI = 0.55-0.94). Risks of total cardiovascular disease, coronary heart disease, myocardial infarction, and stroke in the atorvastatin group were statistically lower than those in the omega-3 group, with RRs (95% CIs) of 0.80 (0.73-0.88), 0.64 (0.50-0.82), 0.75 (0.60-0.93), and 0.81 (0.66-0.99), respectively. The findings of this study suggest that pravastatin and atorvastatin may be more beneficial than omega-3 supplementation in reducing the risk of total cardiovascular disease, coronary heart disease, and myocardial infarction.
Topics: Aged; Atorvastatin; Cardiovascular Diseases; Coronary Disease; Dietary Supplements; Fatty Acids, Omega-3; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Myocardial Infarction; Network Meta-Analysis; Pravastatin; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome
PubMed: 32722395
DOI: 10.3390/nu12082218 -
Hellenic Journal of Cardiology : HJC =... 2019Observational studies have suggested that statins might reduce postoperative atrial fibrillation (AF) in patients undergoing cardiac surgery. However, a number of...
BACKGROUND
Observational studies have suggested that statins might reduce postoperative atrial fibrillation (AF) in patients undergoing cardiac surgery. However, a number of retrospective studies have shown equivocal results. We aimed to evaluate whether different statins can reduce the risk for AF at different doses.
METHODS
We searched PubMed, EMBASE, and the Cochrane Database for all published randomized controlled trials (RCTs) that examined the effects of statin therapy on AF up to June 2016. A random-effects model was used when there was substantial heterogeneity.
RESULTS
Eighteen published studies that included 4003 statin-naive patients (2009 receiving satins and 1994 receiving regime) with sinus rhythm before cardiac surgeries were identified for inclusion in the analysis. Thirteen studies investigated the prevention of AF by atorvastatin, two studies investigated the prevention of AF by rosuvastatin, two studies investigated the prevention of AF by simvastatin, and one study investigated the prevention of AF by pravastatin. The remaining two studies compared the effects of different doses of atorvastatin on the prevention of AF in patients undergoing coronary artery bypass grafting (CABG). Overall, statin therapy was associated with a significant decrease in the risk for AF (relative risk [RR]: 0.57, 95% confidence interval [CI]: 0.45-0.73, P = 0.000). However, subgroup analyses showed that only atorvastatin reduced the risk for new-onset AF in patients after cardiac surgery (RR: 0.53, 95% CI: 0.41-0.69, P = 0.000). Patients undergoing CABG possibly received more benefits from statin therapy (RR: 0.52, 95% CI: 0.39-0.68).Statin therapy in a moderate dose may be optimal (RR: 0.42, 95% CI: 0.28-0.64).
CONCLUSIONS
This meta-analysis suggests that statin therapy has an overall protective effect against postoperative AF, among which atorvastatin in a moderate dose was significantly associated with a decreased risk for new-onset AF in patients after CABG. Moreover, simvastatin may also exert a significant protective effect against the AF recurrences in patients undergoing cardiac surgeries; hence, further prospective studies are warranted.
Topics: Atorvastatin; Atrial Fibrillation; Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Postoperative Complications; Prognosis
PubMed: 29307691
DOI: 10.1016/j.hjc.2017.12.012 -
Journal of Atherosclerosis and... 2013To evaluate the effect of statin therapy on the decrease of common carotid artery intima-media thickness (CCA-IMT) compared to placebo or usual care. (Meta-Analysis)
Meta-Analysis
Effect of statin therapy on the progression of common carotid artery intima-media thickness: an updated systematic review and meta-analysis of randomized controlled trials.
AIM
To evaluate the effect of statin therapy on the decrease of common carotid artery intima-media thickness (CCA-IMT) compared to placebo or usual care.
METHODS
A systematic search of electronic databases (MEDLINE, EMBASE, and Cochrane Center Register) up to December 2011 was performed. Two reviewers independently determined the eligibility of randomized controlled trials (RCTs) comparing statin therapy with a placebo or usual care with a minimum follow-up of 6 months.
RESULTS
Twenty-one RCTs involving 6317 individuals were included in this review. The pooled weighted mean difference (WMD) between statin therapy and placebo or usual care on CCA-IMT was -0.029 mm (95%CI: -0.045, -0.013). Subgroup analyses showed significant effects of lovastatin (WMD: -0.077; 95%CI: -0.082, -0.073) and simvastatin (WMD: -0.069; 95%CI: -0.094, -0.045), followed by pravastatin and rosuvastatin, but no significant benefits of atorvastatin, fluvastatin, or cerivastatin. A greater decrease in mean CCA-IMT was observed in the setting of secondary prevention versus primary prevention (WMD: -0.045 vs. -0.004), in younger patients versus older patients (WMD: -0.057 vs. -0.041), and in studies where the patient proportion was males ≥ females (-0.044 vs. -0.008). Meta-regression analysis showed a significant association between changes in mean CCA-IMT with decreasing triglyceride levels. A similar, but not statistically significant trend was also found between CCA-IMT decrease and the decrease in LDL-C levels or increase in HDL-C levels.
CONCLUSION
Statin therapy is associated with a favorable decrease in CCA-IMT, an effect that seems to be mainly driven by the CCA-IMT at baseline and the extent of lipid decrease, specifically triglycerides.
Topics: Carotid Arteries; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Placebos; Randomized Controlled Trials as Topic; Tunica Intima
PubMed: 23095240
DOI: 10.5551/jat.14001