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The Cochrane Database of Systematic... Jun 2020Pitavastatin is the newest statin on the market, and the dose-related magnitude of effect of pitavastatin on blood lipids is not known. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pitavastatin is the newest statin on the market, and the dose-related magnitude of effect of pitavastatin on blood lipids is not known.
OBJECTIVES
Primary objective To quantify the effects of various doses of pitavastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in participants with and without cardiovascular disease. To compare the effect of pitavastatin on surrogate markers with other statins. Secondary objectives To quantify the effect of various doses of pitavastatin on withdrawals due to adverse effects. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for trials up to March 2019: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2019), MEDLINE (from 1946), Embase (from 1974), the World Health Organization 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 We also contacted authors of relevant papers regarding further published and unpublished work.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
RCT and controlled before-and-after studies evaluating the dose response of different fixed doses of pitavastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered data from RCT and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data, respectively. Withdrawals due to adverse effects (WDAE) information was collected from the RCTs. We assessed all included trials using the Cochrane 'Risk of bias' tool under the categories of allocation (selection bias), blinding (performance bias and detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other potential sources of bias.
MAIN RESULTS
Forty-seven studies (five RCTs and 42 before-and-after studies) evaluated the dose-related efficacy of pitavastatin in 5436 participants. The participants were of any age with and without cardiovascular disease, and pitavastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 1 mg to 16 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol and triglycerides. There was no dose-related effect of pitavastatin on blood HDL cholesterol, which was increased by 4% on average by pitavastatin. Pitavastatin 1 mg/day to 16 mg/day reduced LDL cholesterol by 33.3% to 54.7%, total cholesterol by 23.3% to 39.0% and triglycerides by 13.0% to 28.1%. For every two-fold dose increase, there was a 5.35% (95% CI 3.32 to 7.38) decrease in blood LDL cholesterol, a 3.93% (95% CI 2.35 to 5.50) decrease in blood total cholesterol and a 3.76% (95% CI 1.03 to 6.48) decrease in blood triglycerides. The certainty of evidence for these effects was judged to be high. When compared to other statins for its effect to reduce LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. For the placebo group, there were no participants who withdrew due to an adverse effect per 109 subjects and for all doses of pitavastatin, there were three participants who withdrew due to an adverse effect per 262 subjects.
AUTHORS' CONCLUSIONS
Pitavastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. There were not enough data to determine risk of withdrawal due to adverse effects due to pitavastatin.
Topics: Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Controlled Before-After Studies; Drug Administration Schedule; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Pyridines; Quinolines; Randomized Controlled Trials as Topic; Rosuvastatin Calcium; Sex Factors; Triglycerides
PubMed: 32557581
DOI: 10.1002/14651858.CD012735.pub2 -
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 -
Turk Kardiyoloji Dernegi Arsivi : Turk... Mar 2020The aim of this study was to examine and present the effect of statin treatment on the low-density lipoprotein (LDL) cholesterol level of patients in Turkey by...
OBJECTIVE
The aim of this study was to examine and present the effect of statin treatment on the low-density lipoprotein (LDL) cholesterol level of patients in Turkey by evaluating the data of studies conducted in the country.
METHODS
Manuscripts published between January 1, 2008 and December 31, 2017 with terms 'LDL' and 'TURK' in the title or abstract and reporting LDL cholesterol data of patients treated with statins were evaluated for inclusion in the study. From the initial search result a total of 1795 papers, 39 manuscripts with 63 study arms were selected for analysis and the data of 3486 patients were included. Descriptive analysis was used to assess the data. Weighted averages of the data were also calculated.
RESULTS
The female/male ratio was 42/58. The mean age was 52.9±10.1 years. The proportion of patients with the recommended LDL cholesterol level of <70 mg/dL after treatment with statins was 15.3%;. In all, 10.2% of the patients who were prescribed a low-dose statin and 28.0% of those who were prescribed a high-dose statin had an LDL cholesterol of <70 mg/dL after treatment. Among patients who were being treated with statins for ≤2 months, 25.7% achieved an LDL cholesterol level of <70 mg/dL. Among those who were being treated with statins for 2-4 months and >4 months the proportion was 11.4% and 9.7%, respectively. The percentage of patients at the target level was 21.8%, 21.7%, 17.9%;, 8.6%, and 0.8% among those using atorvastatin, simvastatin, rosuvastatin, fluvastatin, and pravastatin, respectively.
CONCLUSION
In Turkey, only 15% of the patients who had received statin therapy had a LDL cholesterol level of <70 mg/dL. Revision of the current treatment should be considered to reach the target levels recommended in the guidelines, especially for patients with high cardiovascular risk.
Topics: Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Turkey
PubMed: 32147651
DOI: 10.5543/tkda.2019.45156 -
Annals of Translational Medicine Dec 2019Pulmonary hypertension (PH) is a multi-causal disease and no satisfactory therapeutic strategies for it. Statins have been suggested as potential drugs in PH, whose...
BACKGROUND
Pulmonary hypertension (PH) is a multi-causal disease and no satisfactory therapeutic strategies for it. Statins have been suggested as potential drugs in PH, whose effects in different clinic types of PH have not been conclusive. In this study, we included randomized controlled clinical trials (RCTs) evaluating the efficacy and safety of statins therapy in PH.
METHODS
We searched databases including Medline, Embase, Cochrane, PubMed and Web of science, with time up to January 1, 2019. With 95% confidence interval (CI), weighted mean difference (WMD) or standardized mean difference (SMD) was pooled and calculated in a random or fixed effect model according to I2 statistic.
RESULTS
A total of nine RCTs with 657 patients were included. Four types of statins (atorvastatin, pravastatin, rosuvastatin and simvastatin) were used at different doses (10-80 mg daily) for up to 6 months. In the pooled-data analysis, compared with placebo, there were significant improvements in pulmonary arterial pressure (PAP), in addition to low-density lipoprotein (LDL) in patients treated with statins, but not in 6-minute walking distance (6MWD), cardiac index (CDI). No more adverse events and all-cause mortality were revealed. Subgroup analysis indicated that statins could decrease PAP in the subtype of PH due to chronic obstructive pulmonary disease (COPD), but not pulmonary arterial hypertension (PAH).
CONCLUSIONS
This study indicates that statins can efficiently and safely reduce PAP in PH, especially in the subtype due to COPD. Further RCTs are needed to focus on the efficacy and safety of statin therapy in different subtypes of PH.
PubMed: 32042802
DOI: 10.21037/atm.2019.11.19 -
The Cochrane Database of Systematic... Jan 2020Cerivastatin was the most potent statin until it was withdrawn from the market due to a number of fatalities due to rhabdomyolysis, however, the dose-related magnitude... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cerivastatin was the most potent statin until it was withdrawn from the market due to a number of fatalities due to rhabdomyolysis, however, the dose-related magnitude of effect of cerivastatin on blood lipids is not known.
OBJECTIVES
Primary objective To quantify the effects of various doses of cerivastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in children and adults with and without cardiovascular disease. The aim of this review is to examine the pharmacology of cerivastatin by characterizing the dose-related effect and variability of the effect of cerivastatin on surrogate markers. Secondary objectives To quantify the effect of various doses of cerivastatin compared to placebo on withdrawals due to adverse effects. To compare the relative potency of cerivastatin with respect to fluvastatin, atorvastatin and rosuvastatin for LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for RCTs up to March 2019: CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov.We also searched the European Patent Office, FDA.gov, and ProQuest Dissertations & Theses, and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
SELECTION CRITERIA
RCTs and controlled before-and-after studies evaluating the dose response of different fixed doses of cerivastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility criteria for trials to be included and extracted data. We entered data from RCTs and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data respectively. We collected information on withdrawals due to adverse effects from the RCTs. We assessed all trials using the 'Risk of bias' tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.
MAIN RESULTS
Fifty trials (19 RCTs and 31 before-and-after studies) evaluated the dose-related efficacy of cerivastatin in 12,877 participants who had their LDL cholesterol measured. The participants were of any age with and without cardiovascular disease and the trials studied cerivastatin effects within a treatment period of three to 12 weeks. Cerivastatin 0.025 mg/day to 0.8 mg/day caused LDL cholesterol decreases of 11.0% to 40.8%, total cholesterol decreases of 8.0% to 28.8% and triglyceride decreases of 9.0% to 21.4%. We judged the certainty of evidence for these effects to be high. Log dose-response data over doses of 2.5 mg to 80 mg revealed strong linear dose-related effects on LDL cholesterol, total cholesterol and triglycerides. When compared to fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250-fold more potent than fluvastatin, 20-fold more potent than atorvastatin and 5.5-fold more potent than rosuvastatin at reducing LDL cholesterol; 233-fold more potent than fluvastatin, 18-fold more potent than atorvastatin and six-fold more potent than rosuvastatin at reducing total cholesterol; and 125-fold more potent than fluvastatin, 11-fold more potent than atorvastatin and 13-fold more potent than rosuvastatin at reducing triglycerides. There was no dose-related effect of cerivastatin on HDL cholesterol, but overall cerivastatin increased HDL cholesterol by 5%. There was a high risk of bias for the outcome withdrawals due to adverse effects, but a low risk of bias for the lipid measurements. Withdrawals due to adverse effects were not different between cerivastatin and placebo in 11 of 19 of these short-term trials (risk ratio 1.09, 95% confidence interval 0.68 to 1.74).
AUTHORS' CONCLUSIONS
The LDL cholesterol, total cholesterol, and triglyceride lowering effect of cerivastatin was linearly dependent on dose. Cerivastatin log dose-response data were linear over the commonly prescribed dose range. Based on an informal comparison with fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250-fold more potent than fluvastatin, 20-fold more potent than atorvastatin and 5.5-fold more potent than rosuvastatin in reducing LDL cholesterol, and 233-fold greater potency than fluvastatin, 18-fold greater potency than atorvastatin and six-fold greater potency than rosuvastatin at reducing total cholesterol. This review did not provide a good estimate of the incidence of harms associated with cerivastatin because of the short duration of the trials and the lack of reporting of adverse effects in 42% of the RCTs.
Topics: Cholesterol, HDL; Cholesterol, LDL; Dose-Response Relationship, Drug; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipids; Pyridines; Randomized Controlled Trials as Topic; Treatment Outcome; Triglycerides
PubMed: 31981471
DOI: 10.1002/14651858.CD012501.pub2 -
Journal of Cardiovascular Pharmacology Mar 2020This meta-analysis demonstrated the effect of intensive versus standard statins on the risk of stroke in patients with coronary artery syndromes (CAS). PubMed, Embase,... (Meta-Analysis)
Meta-Analysis
Effect of Intensive and Standard Lipid-Lowering Therapy on the Progression of Stroke in Patients With Coronary Artery Syndromes: A Meta-Analysis of Randomized Controlled Trials.
This meta-analysis demonstrated the effect of intensive versus standard statins on the risk of stroke in patients with coronary artery syndromes (CAS). PubMed, Embase, the Cochrane library, and clinicaltrials.gov were searched, and the retrieved studies were undertaken for randomized controlled trials (RCTs) throughout September 2018. Studies that were designed as RCTs and recruited at least 1000 CAS patients followed up greater than 1 year were eligible for this study. The summary relative risk with the 95% confidence interval was used as an effect estimate and calculated using the random-effects model. Five RCTs comprising a total of 39,612 coronary syndrome patients with reported 1236 stroke events were included in this meta-analysis. The summary result indicated a 14% reduction in the risk of stroke in CAS patients receiving intensive statin therapy as compared to standard statin therapy. The significant differences mainly occurred in mean age ≥60 years (P = 0.007), percentage of males ≥80% (P = 0.011), percentage diabetes mellitus ≥ 15% (P = 0.018), percentage hypertension ≥50% (P = 0.030), percentage of current smokers <30% (P = 0.011), percentage of prior myocardial infarction ≥50% (P = 0.011), percentage of peripheral arterial disease ≥10% (P = 0.030), patients with stable CAS (P = 0.011), patients using atorvastatin (P = 0.015), follow-up duration ≥3 years (P = 0.011), and study with moderate quality (P = 0.013). Intensive statin therapy should be considered for CAS patients at high risk of stroke events. Further large-scale RCT should be conducted to verify the results of stratified analysis in this study.
Topics: Acute Coronary Syndrome; Biomarkers; Coronary Artery Disease; Down-Regulation; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Stroke; Treatment Outcome
PubMed: 31876797
DOI: 10.1097/FJC.0000000000000784 -
Scientific Reports Nov 2019Previous studies showed that statins reduce the progression of kidney function decline and proteinuria, but whether specific types of statins are more beneficial than... (Meta-Analysis)
Meta-Analysis
Previous studies showed that statins reduce the progression of kidney function decline and proteinuria, but whether specific types of statins are more beneficial than others remains unclear. We performed a network meta-analysis of randomized controlled trials (RCT) to investigate which statin most effectively reduces kidney function decline and proteinuria. We searched MEDLINE, Embase, Web of Science, and the Cochrane database until July 13, 2018, and included 43 RCTs (>110,000 patients). We performed a pairwise random-effects meta-analysis and a network meta-analysis according to a frequentist approach. We assessed network inconsistency, publication bias, and estimated for each statin the probability of being the best treatment. Considerable heterogeneity was present among the included studies. In pairwise meta-analyses, 1-year use of statins versus control reduced kidney function decline by 0.61 (95%-CI: 0.27; 0.95) mL/min/1.73 m and proteinuria with a standardized mean difference of -0.58 (95%-CI:-0.88; -0.29). The network meta-analysis for the separate endpoints showed broad confidence intervals due to the small number available RCTs for each individual comparison. In conclusion, 1-year statin use versus control attenuated the progression of kidney function decline and proteinuria. Due to the imprecision of individual comparisons, results were inconclusive as to which statin performs best with regard to renal outcome.
Topics: Atorvastatin; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney; Kidney Diseases; Lovastatin; Network Meta-Analysis; Pravastatin; Proteinuria; Rosuvastatin Calcium; Simvastatin; Treatment Outcome
PubMed: 31719617
DOI: 10.1038/s41598-019-53064-x -
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 -
European Cardiology Jul 2019Acute coronary syndrome (ACS) is characterised by increased effector cells and decreased regulatory T-cells (Tregs). Statins have been shown to be clinically beneficial... (Review)
Review
The Effect of Statins on the Functionality of CD4+CD25+FOXP3+ Regulatory T-cells in Acute Coronary Syndrome: A Systematic Review and Meta-analysis of Randomised Controlled Trials in Asian Populations.
Acute coronary syndrome (ACS) is characterised by increased effector cells and decreased regulatory T-cells (Tregs). Statins have been shown to be clinically beneficial in ACS patients. This effect could be mediated via the induction of Tregs in ACS patients. The aim of this systemic review and meta-analysis was to evaluate whether statin therapy enhances the frequency of Tregs determined by CD4+CD25+FOXP3+ in this subset of patients. A comprehensive search of PubMed and Embase was performed. Studies were restricted to randomised controlled trials that quantified CD4+CD25+FOXP3+ cell frequency by flow cytometric analysis before and after statin treatment in adults diagnosed with ACS. A minimum of at least two of the conventional markers to identify Tregs was compulsory. Four randomised controlled trials studies (439 participants) were included, all with low-to-moderate risk of bias. Pooled data showed a significant increase in Treg frequency after statin therapy in ACS patients. A further meta-regression and subgroup analysis also showed a negative dose-related effect, and a statin type-related effect (rosuvastatin versus atorvastatin), respectively. The results confirmed that statins positively alter the frequency of Tregs, which may indicate a potential mechanism of their therapeutic effect. However, there was a risk of information bias due to the markers used to identify Tregs, which was not fully explored, therefore, further randomised controlled trials should utilise markers of Tregs, such as the FOXP3 locus (Treg-specific demethylated region), for identification.
PubMed: 31360235
DOI: 10.15420/ecr.2019.9.2 -
BMJ Open Jul 2019Statins may improve outcomes in patients with cirrhosis. We performed a systematic review and meta-analysis to evaluate the effect of statins on patients with cirrhosis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Statins may improve outcomes in patients with cirrhosis. We performed a systematic review and meta-analysis to evaluate the effect of statins on patients with cirrhosis and related complications, especially portal hypertension and variceal haemorrhage.
METHODS
Studies were searched in the PubMed, Embase and Cochrane library databases up to February 2019. The outcomes of interest were associations between statin use and improvement in portal hypertension (reduction >20% of baseline or <12 mm Hg) and the risk of variceal haemorrhage. The relative risk (RR) with a 95% CI was pooled and calculated using a random effects model. Subgroup analyses were performed based on the characteristics of the studies.
RESULTS
Eight studies (seven randomised controlled trials (RCTs) and one observational study) with 3195 patients were included. The pooled RR for reduction in portal hypertension was 1.91 (95% CI, 1.04 to 3.52; I=63%) in six RCTs. On subgroup analysis of studies that used statin for 1 month, the RR was 2.01 (95% CI, 1.31 to 3.10; I=0%); the pooled RR for studies that used statins for 3 months was 3.76 (95% CI, 0.36 to 39.77; I=75%); the pooled RR for studies that used non-selective beta-blockers in the control group was 1.42 (95% CI, 0.82 to 2.45; I=64%); the pooled RR for studies that used a drug that was not reported in the control group was 4.21 (95% CI, 1.52 to 11.70; I=0%); the pooled RR for studies that used simvastatin was 2.20 (95% CI, 0.92 to 5.29; I=69%); RR for study using atorvastatin was 1.82 (95% CI, 1.00 to 3.30). For the risk of a variceal haemorrhage, the RR based on an observational study was 0.47 (95% CI, 0.23 to 0.94); in two RCTs, the pooled RR was 0.88 (95% CI, 0.52 to 1.50; I=0%). Overall, the summed RR was 0.64 (95% CI, 0.42 to 0.99; I=6%).
CONCLUSION
Statins may improve hypertension and decrease the risk of variceal haemorrhage according to our assessment. However, further and larger RCTs are needed to confirm this conclusion.
Topics: Esophageal and Gastric Varices; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension, Portal; Liver Cirrhosis
PubMed: 31315875
DOI: 10.1136/bmjopen-2019-030038