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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 -
Clinical Therapeutics Aug 2013The aim of this study was to investigate the effectiveness and safety of aggressive statin versus moderate statin therapy on patients with saphenous vein grafts (SVGs)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aim of this study was to investigate the effectiveness and safety of aggressive statin versus moderate statin therapy on patients with saphenous vein grafts (SVGs) in randomized, controlled trials (RCTs).
METHODS
We searched MEDLINE (1980-June 2012), the Cochrane Controlled Trials Register, EMBASE, Science Citation Index, and PubMed (to June 2012), and found 10 relevant RCTs, including 7 substudy analyses from a Post-CABG trial, and 1 pooled analysis of the PROVE-IT TIMI 22 trial (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators) and A to Z trial. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes; phase Z of the A to Z trial.
RESULTS
A total of 6645 of participants, ages ranging from 21 to 75 years old, were treated with coronary artery bypass graft (CABG) and were followed for 2 to 5 years. Eight studies showed that aggressive statin therapy had lower LDL-C levels and a decrease of 39% in graft atherosclerotic progression, 12% in new occlusions, and 19% in new lesions more than moderate statin therapy. Three reports indicated that aggressive statin therapy lowered the risk of repeated myocardial infarction more than moderate statin therapy for coronary revascularization (95% CI, 0.66-0.95; risk ratio [RR] = 0.80; and 95% CI, 0.66-0.85; RR = 0.75) and lowered the risk of cardiac death as well (95% CI, 0.64-1.08; RR = 0.83). Aggressive statin therapy had safety similar to that of moderate statin therapy except for a slight increase in myopathic events and aminotransferase levels. Seventy percent to 90% of patients took statin treatment as prescribed in long-term.
CONCLUSIONS
Compared with moderate statin therapy, long-term aggressive statin lowered the LDL-C level significantly, further decreased the atherosclerotic progression of SVG, reduced the risks of repeated myocardial infarction and coronary revascularization after CABG, and revealed similar patient compliance and statin-related adverse effects but slightly increased myopathy events and aminotransferase levels.
Topics: Adult; Aged; Atorvastatin; Cholesterol, LDL; Coronary Artery Bypass; Coronary Artery Disease; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Myocardial Infarction; Pravastatin; Pyrroles; Randomized Controlled Trials as Topic; Registries; Saphenous Vein; Simvastatin; Treatment Outcome; Young Adult
PubMed: 23932462
DOI: 10.1016/j.clinthera.2013.06.006 -
The Cochrane Database of Systematic... Jul 2014Familial hypercholesterolemia is one of the most common inherited metabolic diseases; the average worldwide prevalence of heterozygous familial hypercholesterolemia is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Familial hypercholesterolemia is one of the most common inherited metabolic diseases; the average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500. Diagnosis of familial hypercholesterolemia in children is based on highly elevated low-density lipoprotein (LDL) cholesterol level 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 hypolipidemic measures, started in childhood, are needed to reduce the risk of cardiovascular disease. In children with familial hypercholesterolemia, diet is as yet the cornerstone of treatment. Anion exchange resins, such as cholestyramine and colestipol, have also been found to be effective, but are poorly tolerated. Since the 1990s statin studies have been carried out among children with familial hypercholesterolemia (aged 7 to 17 years). Statins greatly reduced their serum LDL cholesterol levels. Even though statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established.
OBJECTIVES
To assess the effectiveness and safety of statins in children with 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: 14 October 2013.
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 21 potentially eligible studies, of which we included eight randomized placebo-controlled studies (1074 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 LDL cholesterol concentration at all time points. Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point. The risks of myopathy and clinical adverse events were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery, and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness.
AUTHORS' CONCLUSIONS
Statin treatment is an efficient lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety is unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians or physicians into adulthood. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.
Topics: Adolescent; Child; Child, Preschool; Cholesterol, LDL; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Male; Randomized Controlled Trials as Topic
PubMed: 25054950
DOI: 10.1002/14651858.CD006401.pub3 -
JACC. Cardiovascular Imaging Feb 2015Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular... (Review)
Review
Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50% to 65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively-defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve or myocardial perfusion reserve <2.5 by positron emission tomography, cardiac magnetic resonance imaging, dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 papers met the strict inclusion criteria. The papers were heterogeneous, using different treatments, endpoints, and definitions of CMD. The small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded published data. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD.
Topics: Coronary Angiography; Coronary Circulation; Diagnosis, Differential; Humans; Magnetic Resonance Imaging, Cine; Microcirculation; Microvascular Angina; Myocardial Revascularization; Positron-Emission Tomography; Practice Guidelines as Topic; Regional Blood Flow
PubMed: 25677893
DOI: 10.1016/j.jcmg.2014.12.008 -
Pharmacological Research Mar 2021Recent studies have suggested that statins may be associated with a lower risk of recurrent venous thromboembolism (VTE). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent studies have suggested that statins may be associated with a lower risk of recurrent venous thromboembolism (VTE).
METHODS
We systematically searched PubMed, Web of Science and Cochrane Library from inception until May 2020 to identify any eligible studies that reported the association between statin use and the risk of recurrent VTE, and conducted a comprehensive systematic review and meta-analysis (PROSPERO registration number: CRD42020190169) on this matter.
RESULTS
A total of 14 observational studies were included for qualitative review and 12 of them qualified for meta-analyses. The main meta-analysis found that statin use was associated with a lower risk of disease recurrence among patients with VTE (pooled adjusted HR: 0.76, 95% CI: 0.69-0.83), which was robust in sensitivity analyses and free of significant publication bias. Additionally, such association was present when restricting to periods after anticoagulation withdrawal (pooled adjusted HR: 0.78, 95% CI: 0.70-0.88) and when separately analyzing recurrent deep vein thrombosis (pooled adjusted HR: 0.71, 95% CI: 0.62-0.81) and recurrent pulmonary embolism (pooled adjusted HR: 0.80, 95% CI: 0.66-0.97; P = 0.027). Furthermore, statin use in patients with VTE was also found to be associated with a lower risk of all-cause mortality (adjusted HR: 0.65, 95% CI: 0.56-0.77), and possibly an even lower risk of bleeding (adjusted HR: 0.88, 95% CI: 0.73-1.07), albeit not statistically significant.
CONCLUSION
Statins have the potential to reduce recurrent events among patient with VTE. Randomized clinical trials to better explore the effect of statins in secondary prevention of VTE are warranted.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pulmonary Embolism; Recurrence; Risk Factors; Venous Thromboembolism; Venous Thrombosis
PubMed: 33412275
DOI: 10.1016/j.phrs.2020.105413 -
European Journal of Neurology Jun 2020Prevention of ischaemic stroke and cardiovascular events is an established benefit of statin therapy, but the effects of statin treatment on the accrual of magnetic... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Prevention of ischaemic stroke and cardiovascular events is an established benefit of statin therapy, but the effects of statin treatment on the accrual of magnetic resonance imaging (MRI) markers of ischaemic cerebral injury remain unknown. A systematic review was performed to identify all studies that randomized patients with cardiovascular risk factors to statin treatment and assessed the effect of statin treatment on covert infarcts (asymptomatic, evident only on neuroimaging) and white matter hyperintensity (WMH) accrual on MRI.
METHODS
A systematic review in MEDLINE and Scopus from inception to 23 October 2019 was performed. A random-effects model was used to calculate the pooled estimates of the crude risk ratios and standardized mean differences.
RESULTS
Data from three randomized controlled trials (1430 participants) were included evaluating the effect of rosuvastatin (10 mg/day) in 668 hypertensive patients older than 60 years of age over 5 years, pravastatin (40 mg/day) in 554 elderly people more than 70 years of age over 3 years and simvastatin (20 mg/day) in 208 patients with asymptomatic middle cerebral artery stenosis over 2 years. Patients randomized to statin treatment had decreased accrual of new covert infarcts (risk ratio 0.63, 95% confidence interval 0.46-0.88) during a mean follow-up of 2-6 years. Only one study reported WMH decreased volume change in patients randomized to statin treatment compared to patients randomized to non-statin treatment (standardized mean difference -1.17; 95% confidence interval -1.33, -1.00).
CONCLUSION
Our findings suggest that, in addition to stroke prevention, statin treatment can reduce the accrual of covert MRI markers of ischaemic cerebral injury.
Topics: Aged; Brain Ischemia; Cerebral Infarction; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Stroke
PubMed: 32133735
DOI: 10.1111/ene.14196 -
The American Journal of Cardiology Jun 2015HIV-infected patients have a greater prevalence of dyslipidemia, earlier incidence and progression of atherosclerosis, and a nearly twofold increased risk for myocardial... (Review)
Review
HIV-infected patients have a greater prevalence of dyslipidemia, earlier incidence and progression of atherosclerosis, and a nearly twofold increased risk for myocardial infarction compared with those not infected with HIV. Pre-existing cardiovascular risk factors, viral replication, and antiviral treatments all contribute to this accelerated and increased risk for cardiovascular disease in HIV-infected subjects. Given this risk and the proven benefit of statins reducing cardiovascular events across numerous patient groups, statin therapy might be particularly beneficial for patients with HIV. However, safety concerns and a dearth of quality trial data evaluating clinical outcomes in HIV-infected patients on simultaneous antiretroviral therapy (ART) and statin therapy have likely limited statin use in HIV-infected patients chronically taking ART. We performed a systematic review evaluating 18 clinical trials of statins in HIV-infected subjects receiving ART. Simvastatin is contraindicated in the setting of protease inhibitor use because of toxic drug-drug interactions when the 2 drugs are taken concomitantly. Meanwhile, atorvastatin appears to be relatively safe at submaximal doses if monitored. Pravastatin, rosuvastatin, and pitavastatin appear to have the most benign safety profiles among statins when co-administered with ART and may not require dose adjustment. In conclusion, clinicians should be mindful of the elevated risk for atherosclerotic cardiovascular disease in HIV-infected patients when assessing the need for lifestyle interventions and statin therapy.
Topics: Anti-HIV Agents; Cardiovascular Diseases; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 25907504
DOI: 10.1016/j.amjcard.2015.03.025 -
Pharmacological Research Sep 2015Statin therapy may lower plasma coenzyme Q10 (CoQ10) concentrations, but the evidence as to the significance of this effect is unclear. We assessed the impact of statin... (Meta-Analysis)
Meta-Analysis
Statin therapy may lower plasma coenzyme Q10 (CoQ10) concentrations, but the evidence as to the significance of this effect is unclear. We assessed the impact of statin therapy on plasma CoQ10 concentrations through the meta-analysis of available RCTs. The literature search included selected databases up to April 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The data from 8 placebo-controlled treatment arms suggested a significant reduction in plasma CoQ10 concentrations following treatment with statins (WMD: -0.44 μmol/L, 95%CI: -0.52, -0.37, p<0.001). The pooled effect size was robust and remained significant in the leave-one-out sensitivity analysis. Subgroup analysis suggested that the impact of statins on plasma CoQ10 concentrations is significant for all 4 types of statins studied i.e. atorvastatin (WMD: -0.41 μmol/L, 95%CI: -0.53, -0.29, p<0.001), simvastatin (WMD: -0.47 μmol/L, 95% CI: -0.61, -0.33, p<0.001), rosuvastatin (WMD: -0.49 μmol/L, 95%CI: -0.67, -0.31, p<0.001) and pravastatin (WMD: -0.43 μmol/L, 95%CI: -0.69, -0.16, p=0.001). Likewise, there was no differential effect of lipophilic (WMD: -0.43 μmol/L, 95%CI: -0.53, -0.34, p<0.001) and hydrophilic statins (WMD: -0.47 μmol/L, 95%CI: -0.62, -0.32, p<0.001). With respect to treatment duration, a significant effect was observed in both subsets of trials lasting <12 weeks (WMD: -0.51 μmol/L, 95%CI: -0.64, -0.39, p<0.001) and ≥12 weeks (WMD: -0.40 μmol/L, 95%CI: -0.50, -0.30, p<0.001). The meta-analysis showed a significant reduction in plasma CoQ10 concentrations following treatment with statins. Further well-designed trials are required to confirm our findings and elucidate their clinical relevance.
Topics: Adult; Aged; Case-Control Studies; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Placebo Effect; Randomized Controlled Trials as Topic; Ubiquinone
PubMed: 26192349
DOI: 10.1016/j.phrs.2015.07.008 -
European Journal of Preventive... Aug 2013The extent to which individual statins vary in terms of clinical outcomes across all populations, in addition to secondary and primary prevention has not been studied... (Meta-Analysis)
Meta-Analysis Review
Comparative benefits of statins in the primary and secondary prevention of major coronary events and all-cause mortality: a network meta-analysis of placebo-controlled and active-comparator trials.
BACKGROUND
The extent to which individual statins vary in terms of clinical outcomes across all populations, in addition to secondary and primary prevention has not been studied extensively in meta-analyses.
METHODS
We systematically studied 199,721 participants in 92 placebo-controlled and active-comparator trials comparing atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin in participants with, or at risk of developing, cardiovascular disease. We performed pairwise and network meta-analyses for major coronary events and all-cause mortality outcomes, taking into account the dose differences across trials. Systematic review registration: PROSPERO 2011:CRD42011001470.
RESULTS
There were only a few trials that evaluated fluvastatin. Most frequent comparisons occurred between pravastatin and placebo, atorvastatin and placebo, and rosuvastatin and atorvastatin. No trial directly compared all six statins to each other. Across all populations, statins were significantly more effective than control in reducing all-cause mortality (OR 0.87, 95% credible interval 0.82-0.92) and major coronary events (OR 0.69, 95% CI 0.64-0.75). In terms of reducing major coronary events, atorvastatin (OR 0.66, 95% CI 0.48-0.94) and fluvastatin (OR 0.59, 95% CI 0.36-0.95) were significantly more effective than rosuvastatin at comparable doses. In participants with cardiovascular disease, statins significantly reduced deaths (OR 0.82, 95% CI 0.75-0.90) and major coronary events (OR 0.69, 95% CI 0.62-0.77). Atorvastatin was significantly more effective than pravastatin (OR 0.65, 95% CI 0.43-0.99) and simvastatin (OR 0.68, 95% CI 0.38-0.98) for secondary prevention of major coronary events. In primary prevention, statins significantly reduced deaths (OR 0.91, 95% CI 0.83-0.99) and major coronary events (OR 0.69, 95% CI 0.61-0.79) with no differences among individual statins. Across all populations, atorvastatin (80%), fluvastatin (79%), and simvastatin (62%) had the highest overall probability of being the best treatment in terms of both outcomes. Higher doses of atorvastatin and fluvastatin had the highest number of significant differences in preventing major coronary events compared with other statins. No significant heterogeneity or inconsistency was detected.
CONCLUSIONS
Statins significantly reduce the incidence of all-cause mortality and major coronary events as compared to control in both secondary and primary prevention. This analysis provides evidence for potential differences between individual statins, which are not fully explained by their low-density lipoprotein cholesterol-reducing effects. The observed differences between statins should be investigated in future prospective studies.
Topics: Controlled Clinical Trials as Topic; Coronary Disease; Dyslipidemias; Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Odds Ratio; Primary Prevention; Randomized Controlled Trials as Topic; Risk Factors; Secondary Prevention; Treatment Outcome
PubMed: 23447425
DOI: 10.1177/2047487313480435 -
Thrombosis and Haemostasis Mar 2016Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are associated with high risk of coronary artery disease. The effect of statin therapy on vWF:Ag levels... (Meta-Analysis)
Meta-Analysis Review
Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are associated with high risk of coronary artery disease. The effect of statin therapy on vWF:Ag levels remains uncertain. Therefore the aim of this meta-analysis was to evaluate the effect of statin therapy on vWF:Ag Levels. A systematic multiple-database search was carried out to identify randomized controlled trials (RCTs) that investigated the effect of statins on plasma vWF:Ag levels. Random-effect meta-analysis of 21 treatment arms revealed a significant decrease in plasma vWF:Ag levels following statin therapy (SMD: -0.54, 95 %CI: -0.87, -0.21, p=0.001). In subgroup analyses, the greatest effect was observed with simvastatin (SMD: -1.54, 95 %CI: -2.92, -0.17, p=0.028) and pravastatin (SMD: -0.61, 95 %CI: -1.18, -0.04, p=0.035), but not with fluvastatin (SMD: -0.34, 95 %CI: -0.69, 0.02, p=0.065), atorvastatin (SMD: -0.23, 95 %CI: -0.57, 0.11, p=0.179) and rosuvastatin (SMD: -0.20, 95 % CI: -0.71, 0.30, p=0.431). The lowering effect of statins on plasma vWF:Ag levels was greater in the subset of studies lasting ≥ 12 weeks (SMD: -0.70, 95 %CI: -1.19, -0.22, p=0.005) compared with that of studies lasting < 12 weeks (SMD: -0.34, 95 %CI: -0.67, 0.003, p=0.052). Finally, low-intensity statin therapy was not associated with a significant reduction in vWF:Ag levels (SMD: -0.28, 95 %CI: -0.82, 0.27, p=0.320), but a significant effect was observed in high-intensity statin trials (SMD: -0.66, 95 %CI: -1.07, -0.24, p=0.002). This meta-analysis of available RCTs demonstrates a significant reduction in plasma vWF:Ag levels following statin therapy.
Topics: Adult; Aged; Antigens; Atherosclerosis; Atorvastatin; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Middle Aged; Pravastatin; Randomized Controlled Trials as Topic; Regression Analysis; Risk Assessment; Rosuvastatin Calcium; Simvastatin; Thrombosis; Young Adult; von Willebrand Factor
PubMed: 26632869
DOI: 10.1160/TH15-08-0620