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The Cochrane Database of Systematic... Sep 2023A detailed summary and meta-analysis of the dose-related effect of pravastatin on lipids is not available. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A detailed summary and meta-analysis of the dose-related effect of pravastatin on lipids is not available.
OBJECTIVES
Primary objective To assess the pharmacology of pravastatin by characterizing the dose-related effect and variability of the effect of pravastatin on the surrogate marker: low-density lipoprotein (LDL cholesterol). The effect of pravastatin on morbidity and mortality is not the objective of this systematic review. Secondary objectives • To assess the dose-related effect and variability of effect of pravastatin on the following surrogate markers: total cholesterol; high-density lipoprotein (HDL cholesterol); and triglycerides. • To assess the effect of pravastatin on withdrawals due to adverse effects.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to September 2021: CENTRAL (2021, Issue 8), Ovid MEDLINE, Ovid Embase, Bireme LILACS, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
SELECTION CRITERIA
Randomized placebo-controlled trials evaluating the dose response of different fixed doses of pravastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without evidence of cardiovascular disease.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered lipid data from placebo-controlled trials into Review Manager 5 as continuous data and withdrawal due to adverse effects (WDAEs) data as dichotomous data. We searched for WDAEs information from all trials. We assessed all trials using Cochrane's risk of bias tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.
MAIN RESULTS
Sixty-four RCTs evaluated the dose-related efficacy of pravastatin in 9771 participants. The participants were of any age, with and without evidence of cardiovascular disease, and pravastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over the doses of 5 mg to 160 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol, and a weak linear dose-related effect on blood triglycerides. There was no dose-related effect of pravastatin on blood HDL cholesterol. Pravastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 21.7% to 31.9%, total cholesterol by 16.1% to 23.3%,and triglycerides by 5.8% to 20.0%. The certainty of evidence for these effects was judged to be moderate to high. For every two-fold dose increase there was a 3.4% (95% confidence interval (CI) 2.2 to 4.6) decrease in blood LDL cholesterol. This represented a dose-response slope that was less than the other studied statins: atorvastatin, rosuvastatin, fluvastatin, pitavastatin and cerivastatin. From other systematic reviews we conducted on statins for its effect to reduce LDL cholesterol, pravastatin is similar to fluvastatin, but has a decreased effect compared to atorvastatin, rosuvastatin, pitavastatin and cerivastatin. The effect of pravastatin compared to placebo on WADES has a risk ratio (RR) of 0.81 (95% CI 0.63 to 1.03). The certainty of evidence was judged to be very low.
AUTHORS' CONCLUSIONS
Pravastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. This review did not provide a good estimate of the incidence of harms associated with pravastatin because of the lack of reporting of adverse effects in 48.4% of the randomized placebo-controlled trials.
Topics: Humans; Infant, Newborn; Infant; Pravastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Fluvastatin; Rosuvastatin Calcium; Drug-Related Side Effects and Adverse Reactions
PubMed: 37721222
DOI: 10.1002/14651858.CD013673.pub2 -
Clinical and Translational Science Nov 2023Ziritaxestat, an autotaxin inhibitor, was under development for the treatment of idiopathic pulmonary fibrosis. It is a substrate of cytochrome P450 3A4 (CYP3A4) and...
Ziritaxestat, an autotaxin inhibitor, was under development for the treatment of idiopathic pulmonary fibrosis. It is a substrate of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein and a weak inhibitor of the CYP3A4 and OATP1B1 pathways. We developed a physiologically based pharmacokinetic (PBPK) network interaction model for ziritaxestat that incorporated its metabolic and transporter pathways, enabling prediction of its potential as a victim or perpetrator of drug-drug interactions (DDIs). Concurrently, we evaluated CYP3A4 autoinhibition, including time-dependent inhibition. In vitro information and clinical data from healthy volunteer studies were used for model building and validation. DDIs with rifampin, itraconazole, voriconazole, pravastatin, and rosuvastatin were predicted, followed by validation against a test dataset. DDIs of ziritaxestat as a victim or perpetrator were simulated using the final model. Predicted-to-observed DDI ratios for the maximum plasma concentration (C ) and the area under the plasma concentration-time curve (AUC) were within a two-fold ratio for both the metabolic and transporter-mediated simulated DDIs. The predicted impact of autoinhibition/autoinduction or time-dependent inhibition of CYP3A4 was a 12% decrease in exposure. Model-based predictions for ziritaxestat as a victim of DDIs with a moderate CYP3A4 inhibitor (fluconazole) suggested a 2.6-fold increase in the AUC of ziritaxestat, while multiple doses of a strong inhibitor (voriconazole) would increase the AUC by 15-fold. Efavirenz would yield a three-fold decrease in the AUC of ziritaxestat. As a perpetrator, ziritaxestat was predicted to increase the AUC of the CYP3A4 index substrate midazolam by 2.7-fold. An overarching PBPK model was developed that could predict DDI liability of ziritaxestat for both CYP3A4 and the transporter pathways.
Topics: Humans; Cytochrome P-450 CYP3A; Voriconazole; Models, Biological; Area Under Curve; Drug Interactions
PubMed: 37667518
DOI: 10.1111/cts.13622 -
Frontiers in Pharmacology 2023Preterm birth rates and maternal and neonatal mortality remain concerning global health issues, necessitating improved strategies for testing therapeutic compounds...
Preterm birth rates and maternal and neonatal mortality remain concerning global health issues, necessitating improved strategies for testing therapeutic compounds during pregnancy. Current 2D or 3D cell models and animal models often fail to provide data that can effectively translate into clinical trials, leading to pregnant women being excluded from drug development considerations and clinical studies. To address this limitation, we explored the utility of in silico simulation modeling and microfluidic-based organ-on-a-chip platforms to assess potential interventional agents. We developed a multi-organ feto-maternal interface on-chip (FMi-PLA-OOC) utilizing microfluidic channels to maintain intercellular interactions among seven different cell types (fetal membrane-decidua-placenta). This platform enabled the investigation of drug pharmacokinetics in vitro. Pravastatin, a model drug known for its efficacy in reducing oxidative stress and inflammation during pregnancy and currently in clinical trials, was used to test its transfer rate across both feto-maternal interfaces. The data obtained from FMi-PLA-OOC were compared with existing data from in vivo animal models and ex vivo placenta perfusion models. Additionally, we employed mechanistically based simulation software (Gastroplus®) to predict pravastatin pharmacokinetics in pregnant subjects based on validated nonpregnant drug data. Pravastatin transfer across the FMi-PLA-OOC and predicted pharmacokinetics in the in silico models were found to be similar, approximately 18%. In contrast, animal models showed supraphysiologic drug accumulation in the amniotic fluid, reaching approximately 33%. The results from this study suggest that the FMi-PLA-OOC and in silico models can serve as alternative methods for studying drug pharmacokinetics during pregnancy, providing valuable insights into drug transport and metabolism across the placenta and fetal membranes. These advanced platforms offer promising opportunities for safe, reliable, and faster testing of therapeutic compounds, potentially reducing the number of pregnant women referred to as "therapeutic orphans" due to the lack of consideration in drug development and clinical trials. By bridging the gap between preclinical studies and clinical trials, these approaches hold great promise in improving maternal and neonatal health outcomes.
PubMed: 37663251
DOI: 10.3389/fphar.2023.1241815 -
Current Medicinal Chemistry Aug 2023The literature suggests that statins may increase superoxide dismutase (SOD) levels by different mechanisms. These effects may contribute to the antioxidant and...
BACKGROUND AND OBJECTIVE
The literature suggests that statins may increase superoxide dismutase (SOD) levels by different mechanisms. These effects may contribute to the antioxidant and anti-inflammatory effects of statins, which are thought to be beneficial in preventing cardiovascular events. However, there are also conflicting results concerning the effect of statins on SOD levels. The goal of this systematic review was to evaluate the effect of statin therapy on SOD activity.
METHODS
This systematic review was performed based on the PRISMA statement. The terms ("statin" or "HMG-CoA reductase inhibitor" OR "lipid-lowering agents" OR "Atorvastatin" OR "Simvastatin" OR "Pravastatin" OR "Fluvastatin" OR "Lovastatin") AND ("superoxide dismutase" OR "SOD" OR "anti-oxidative" OR "oxidative stress") were searched in database systems Google Scholar, PubMed/MEDLINE, and Scopus from inception to April 2022.
RESULTS
A total of 14 controlled clinical trials - 10 randomized and 4 non-randomized - were found to be eligible. Four studies measured SOD levels in plasma, six in serum, two in red blood cells, one in venous blood, and one on both red blood cells and venous blood matrices. Seven clinical trials used atorvastatin, six used simvastatin, and four used rosuvastatin. Six studies reported an increase in SOD activity, seven found no significant changes, and one showed a reduced SOD activity.
CONCLUSION
Our systematic review suggests that treatment with statins has a positive effect on SOD activity. However, evidence from further randomized controlled trials is required to confirm the potential antioxidant effect of statin therapy.
PubMed: 37653630
DOI: 10.2174/0929867331666230831145809 -
Journal of Pharmaceutical Health Care... Aug 2023Difficulty in taking solid medicines is a common issue particularly for the elderly because of a decline in swallowing function, also known as dysphagia. For patients...
BACKGROUND
Difficulty in taking solid medicines is a common issue particularly for the elderly because of a decline in swallowing function, also known as dysphagia. For patients with such a dysfunction, a simple suspension method, in which solid medicines are disintegrated and suspended using warm water, has been developed and widely used in Japanese clinical settings. However, there is little information on drug stability in the simple co-suspension of multiple formulations especially including acidic or alkaline ones. In this study, the chemical stability of typical cholesterol-lowering drugs was investigated in a simple co-suspension with alkaline magnesium oxide (MgO) which is frequently used as a laxative or antacid in Japan.
METHODS
A cholesterol-lowering drug (one tablet) was soaked with or without MgO in warm water (55°C), and the vessel was left at room temperature for 10 min or 5 h. The suspensions prepared were then analyzed by high-performance liquid chromatography. Degradation products were analyzed by nuclear magnetic resonance spectroscopy and mass spectrometry for the structural elucidation.
RESULTS
In the simple co-suspension with MgO, no significant degradation was observed for atorvastatin or pravastatin, while a significant decrease of the recovery from the co-suspension was observed for rosuvastatin after 5 h. On the other hand, simvastatin and ezetimibe co-suspended with MgO were partially degraded to simvastatin acid and a pyran compound, respectively.
CONCLUSIONS
A simple co-suspension with MgO is feasible for atorvastatin, pravastatin, and rosuvastatin, although the rosuvastatin tablet should not be left soaking for a long time. Further it is inadvisable to suspend simvastatin or ezetimibe together with MgO because of their partial degradation.
PubMed: 37644559
DOI: 10.1186/s40780-023-00301-1 -
Therapie 2024Immune-mediated necrotizing myopathy (IMNM) is a form of statin myopathy characterized by the presence of antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A...
INTRODUCTION
Immune-mediated necrotizing myopathy (IMNM) is a form of statin myopathy characterized by the presence of antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti HMGCR).
OBJECTIVES
The aim of this study was to investigate the relationship between the different statins and the risk of IMNM.
METHODS
A two-time approach was used. First, we performed a descriptive analysis of the French national pharmacovigilance database (FNPV) for the period from 1985 to december2020. To identify relevant cases, we used Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PTs) related to IMNM. We performed a quantitative and qualitative review of individual case safety reports (ICSRs) recorded in the french vigilance spontaneous reporting system. In a second time, we performed a comparative analysis with the World Health Organization global individual case safety reports database (Vigibase). The association between IMNM and statins exposure was assessed by calculating the reporting odds ratio (ROR) and its 95% confidence interval.
RESULTS
After analysis, a total of 25 ICSRs were related to IMNM in the FNPV. The suspected statins were atorvastatin (n=21), simvastatin (n=2), pravastatin (n=1) and rosuvastatin (n=1). In Vigibase, 567 notifications were identified. A significant ROR value was found for atorvastatin, pitavastatin, simvastatin, pravastatin and rosuvastatin.
CONCLUSION
Atorvastatin presents the highest risk of IMNM. Our data suggest that the occurrence of IMNM is a class effect.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Pharmacovigilance; Male; Female; Middle Aged; Aged; France; Hydroxymethylglutaryl CoA Reductases; Adult; Adverse Drug Reaction Reporting Systems; Necrosis; Databases, Factual; Atorvastatin; Aged, 80 and over
PubMed: 37625939
DOI: 10.1016/j.therap.2023.07.005 -
Expert Opinion on Drug Safety Mar 2024Statins, previously rated as pregnancy category X agents, were contraindicated during pregnancy due to the teratogenic effects observed in animal studies. However, it is...
BACKGROUND
Statins, previously rated as pregnancy category X agents, were contraindicated during pregnancy due to the teratogenic effects observed in animal studies. However, it is still controversial whether statins have detrimental impact on pregnant women or not, and some studies even suggest a potential benefit of statin use against pregnancy complications. The aim of this study was to explore whether maternal exposure to statins is associated with increased rates of pregnancy-related adverse events (AEs), including abortion, abortion spontaneous, preterm birth, low birth weight, stillbirth/fetal death, and fetal complications.
RESEARCH DESIGN AND METHODS
Data from 1 January 2004 to 30 June 2022 were extracted through the U.S. FDA Adverse Event Reporting System (FAERS) database, to conduct disproportionality analysis and Bayesian analysis by reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) algorithms. To identify the potential risks of pregnancy-related AEs, each statin was compared to all the other drugs, all the other statins, and the reference drugs (fenofibrate and evolocumab).
RESULTS
A total of 477 cases involving pregnancy-related AEs associated with stains were submitted to the FAERS database by healthcare professionals. No obvious disproportionate association of abortion, abortion spontaneous, or stillbirth/fetal death was identified for all statins during gestation. In comparison with all the other drugs, lovastatin showed an increased risk of fetal complications (ROR = 2.45, 95% CI, 1.22-4.95; IC = 0.63), and pravastatin demonstrated increased risks of preterm birth (ROR = 4.89, 95% CI, 3.65-6.54; IC = 1.69) and low birth weight (ROR = 9.60, 95% CI, 5.56-16.56; IC = 1.88). Similar results were found when compared lovastatin or pravastatin with fenofibrate. Furthermore, statins were associated with higher proportion of fetal complications and preterm birth when comparing with evolocumab.
CONCLUSIONS
Statins did not increase the risk of pregnancy-related AEs, including abortion, abortion spontaneous, or stillbirth/fetal death. However, we did find significant disproportionality signals for preterm birth and low birth weight associated with pravastatin, and lovastatin was related to a higher proportion of fetal complications. The results in this study may provide evidence on the safety of statins during pregnancy, which need to be verified in further investigations.
Topics: Humans; Infant, Newborn; Female; Pregnancy; United States; Pharmacovigilance; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pravastatin; Premature Birth; Stillbirth; Bayes Theorem; Fenofibrate; Lovastatin; Adverse Drug Reaction Reporting Systems; United States Food and Drug Administration
PubMed: 37612600
DOI: 10.1080/14740338.2023.2251888 -
The Cochrane Database of Systematic... Aug 2023Carotid artery stenosis is narrowing of the carotid arteries. Asymptomatic carotid stenosis is when this narrowing occurs in people without a history or symptoms of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Carotid artery stenosis is narrowing of the carotid arteries. Asymptomatic carotid stenosis is when this narrowing occurs in people without a history or symptoms of this disease. It is caused by atherosclerosis; that is, the build-up of fats, cholesterol, and other substances in and on the artery walls. Atherosclerosis is more likely to occur in people with several risk factors, such as diabetes, hypertension, hyperlipidaemia, and smoking. As this damage can develop without symptoms, the first symptom can be a fatal or disabling stroke, known as ischaemic stroke. Carotid stenosis leading to ischaemic stroke is most common in men older than 70 years. Ischaemic stroke is a worldwide public health problem.
OBJECTIVES
To assess the effects of pharmacological interventions for the treatment of asymptomatic carotid stenosis in preventing neurological impairment, ipsilateral major or disabling stroke, death, major bleeding, and other outcomes.
SEARCH METHODS
We searched the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, two other databases, and three trials registers from their inception to 9 August 2022. We also checked the reference lists of any relevant systematic reviews identified and contacted specialists in the field for additional references to trials.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs), irrespective of publication status and language, comparing a pharmacological intervention to placebo, no treatment, or another pharmacological intervention for asymptomatic carotid stenosis.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. Two review authors independently extracted the data and assessed the risk of bias of the trials. A third author resolved disagreements when necessary. We assessed the evidence certainty for key outcomes using GRADE.
MAIN RESULTS
We included 34 RCTs with 11,571 participants. Data for meta-analysis were available from only 22 studies with 6887 participants. The mean follow-up period was 2.5 years. None of the 34 included studies assessed neurological impairment and quality of life. Antiplatelet agent (acetylsalicylic acid) versus placebo Acetylsalicylic acid (1 study, 372 participants) may result in little to no difference in ipsilateral major or disabling stroke (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.47 to 2.47), stroke-related mortality (RR 1.40, 95% CI 0.54 to 3.59), progression of carotid stenosis (RR 1.16, 95% CI 0.79 to 1.71), and adverse events (RR 0.81, 95% CI 0.41 to 1.59), compared to placebo (all low-certainty evidence). The effect of acetylsalicylic acid on major bleeding is very uncertain (RR 0.98, 95% CI 0.06 to 15.53; very low-certainty evidence). The study did not measure neurological impairment or quality of life. Antihypertensive agents (metoprolol and chlorthalidone) versus placebo The antihypertensive agent, metoprolol, may result in no difference in ipsilateral major or disabling stroke (RR 0.14, 95% CI 0.02 to1.16; 1 study, 793 participants) and stroke-related mortality (RR 0.57, 95% CI 0.17 to 1.94; 1 study, 793 participants) compared to placebo (both low-certainty evidence). However, chlorthalidone may slow the progression of carotid stenosis (RR 0.45, 95% CI 0.23 to 0.91; 1 study, 129 participants; low-certainty evidence) compared to placebo. Neither study measured neurological impairment, major bleeding, adverse events, or quality of life. Anticoagulant agent (warfarin) versus placebo The evidence is very uncertain about the effects of warfarin (1 study, 919 participants) on major bleeding (RR 1.19, 95% CI 0.97 to 1.46; very low-certainty evidence), but it may reduce adverse events (RR 0.89, 95% CI 0.81 to 0.99; low-certainty evidence) compared to placebo. The study did not measure neurological impairment, ipsilateral major or disabling stroke, stroke-related mortality, progression of carotid stenosis, or quality of life. Lipid-lowering agents (atorvastatin, fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin) versus placebo or no treatment Lipid-lowering agents may result in little to no difference in ipsilateral major or disabling stroke (atorvastatin, lovastatin, pravastatin, and rosuvastatin; RR 0.36, 95% CI 0.09 to 1.53; 5 studies, 2235 participants) stroke-related mortality (lovastatin and pravastatin; RR 0.25, 95% CI 0.03 to 2.29; 2 studies, 1366 participants), and adverse events (fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin; RR 0.76, 95% CI 0.53 to1.10; 7 studies, 3726 participants) compared to placebo or no treatment (all low-certainty evidence). The studies did not measure neurological impairment, major bleeding, progression of carotid stenosis, or quality of life.
AUTHORS' CONCLUSIONS
Although there is no high-certainty evidence to support pharmacological intervention, this does not mean that pharmacological treatments are ineffective in preventing ischaemic cerebral events, morbidity, and mortality. High-quality RCTs are needed to better inform the best medical treatment that may reduce the burden of carotid stenosis. In the interim, clinicians will have to use other sources of information.
Topics: Humans; Warfarin; Carotid Stenosis; Metoprolol; Atorvastatin; Chlorthalidone; Fluvastatin; Pravastatin; Probucol; Rosuvastatin Calcium; Stroke; Hemorrhage; Aspirin; Ischemic Stroke; Atherosclerosis
PubMed: 37565307
DOI: 10.1002/14651858.CD013573.pub2 -
BJOG : An International Journal of... Nov 2023Although historically pre-eclampsia, preterm birth, abruption, fetal growth restriction and stillbirth have been viewed as clinically distinct entities, a growing body... (Review)
Review
Although historically pre-eclampsia, preterm birth, abruption, fetal growth restriction and stillbirth have been viewed as clinically distinct entities, a growing body of literature has demonstrated that the placenta and its development is the root cause of many cases of these conditions. This has led to the term 'the great obstetrical syndromes' being coined to reflect this common origin. Although these conditions mostly manifest in the second half of pregnancy, a failure to complete deep placentation (the transition from histiotrophic placentation to haemochorial placenta at 10-18 weeks of gestation via a second wave of extravillous trophoblast invasion), is understood to be key to the pathogenesis of the great obstetrical syndromes. While the reasons that the placenta fails to achieve deep placentation remain active areas of investigation, maternal inflammation and thrombosis have been clearly implicated. From a clinical standpoint these mechanisms provide a biological explanation of how low-dose aspirin, which affects the COX-1 receptor (thrombosis) and the COX-2 receptor (inflammation), prevents not just pre-eclampsia but all the components of the great obstetrical syndromes if initiated early in pregnancy. The optimal dose of low-dose aspirin that is maximally effective in pregnancy remains a question open for further research. Additionally, other candidate medications have been identified that may also prevent pre-eclampsia, and further study of them may offer therapeutic options beyond low-dose aspirin. Interestingly, three of the eight identified compounds (hydroxychloroquine, metformin and pravastatin) are known to decrease inflammation.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Pre-Eclampsia; Premature Birth; Placenta; Aspirin; Inflammation; Thrombosis
PubMed: 37530495
DOI: 10.1111/1471-0528.17613 -
Balkan Medical Journal Sep 2023Anticoagulants are the mainstay of treatment for venous thromboembolism (VTE). Studies have shown conflicting results regarding statins ability to reduce the incidence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anticoagulants are the mainstay of treatment for venous thromboembolism (VTE). Studies have shown conflicting results regarding statins ability to reduce the incidence of VTE.
AIMS
To perform a network meta-analysis to determine which lipid-lowering agent was more efficacious in and had more evidence regarding reducing the VTE risk.
STUDY DESIGN
Network meta-analysis of the randomized controlled trials (RCTs).
METHODS
RCTs that assessed the effectiveness and safety of statins or fibrates and compared them to a placebo or another statin were eligible for the study. The outcomes examined in the study were deep vein thrombosis, pulmonary embolism, and/or VTE. We conducted a comprehensive search of the Medline database from 1966 to February 2017, using specific search terms related to VTE and statins. Additionally, we screened, and cross-checked relevant systematic reviews and meta-analyses. We performed a network meta-analysis to compare the different lipid-lowering agents to each other and the placebo and their effectiveness.
RESULTS
Twenty-seven RCTs were included in the network meta-analysis (n = 137,940). Pairwise meta-analysis revealed a statistically significant lower incidence of VTE with statins than with placebos (0.79% vs 0.99%, respectively; risk ratios: 0.87, 0.77-0.98; = 0.022). Rosuvastatin had the most favorable effect in reducing VTE risk than the other statins, fenofibrate, and placebo. Fenofibrate was ranked the worst drug choice, because it increased risk of VTE when compared with the other statins. Rosuvastatin was the best choice for reducing the VTE risk when compared with the placebo (OR: 0.56, 0.42-0.75), atorvastatin (OR: 0.64, 0.44-0.95), pravastatin (OR: 0.50, 0.34-0.74), simvastatin (OR: 0.60, 0.42-0.86) and fenofibrate (OR: 0.37, 0.25-0.56). Compared with a placebo, rosuvastatin reduced the VTE risk by around 45% and fenofibrate increased the risk by 65%.
CONCLUSION
Rosuvastatin is significantly reduces the risk of VTE when compared with a placebo, other statin subtypes, and fibrate. Furthermore, fenofibrate increased the VTE risk when compared with a placebo and statins.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Venous Thromboembolism; Rosuvastatin Calcium; Fenofibrate; Network Meta-Analysis; Atorvastatin
PubMed: 37519020
DOI: 10.4274/balkanmedj.galenos.2023.2023-5-26