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Journal of Comparative Effectiveness... Mar 2023To summarize the evidence in terms of efficacy and safety of head-to-head studies of high-intensity statins regardless of the underlying population. A systematic... (Meta-Analysis)
Meta-Analysis Review
To summarize the evidence in terms of efficacy and safety of head-to-head studies of high-intensity statins regardless of the underlying population. A systematic review and meta-analysis was conducted to summarize the effect sizes in randomized controlled trials and cohort studies that compared high-intensity statins. Based on 44 articles, similar effectiveness was observed across the statins in reducing LDL levels from baseline. All statins were observed to have similar adverse drug reactions (ADRs), although higher dosages were associated with more ADRs. Based on a pooled quantitative analysis of atorvastatin 80 mg versus rosuvastatin 40 mg, rosuvastatin was statistically more effective in reducing LDL. This review further confirms that high-intensity statins reduce LDL by ≥50%, favoring rosuvastatin over atorvastatin. Additional data are needed to confirm the clinical significance on cardiovascular outcomes using real-world studies.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Atorvastatin; Cohort Studies
PubMed: 36847307
DOI: 10.57264/cer-2022-0163 -
BMJ (Clinical Research Ed.) Mar 2022To compare the efficacy of different statin treatments by intensity on levels of non-high density lipoprotein cholesterol (non-HDL-C) for the prevention of... (Meta-Analysis)
Meta-Analysis
Comparative effectiveness of statins on non-high density lipoprotein cholesterol in people with diabetes and at risk of cardiovascular disease: systematic review and network meta-analysis.
OBJECTIVE
To compare the efficacy of different statin treatments by intensity on levels of non-high density lipoprotein cholesterol (non-HDL-C) for the prevention of cardiovascular disease in people with diabetes.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Medline, Cochrane Central Register of Controlled Trials, and Embase from inception to 1 December 2021.
REVIEW METHODS
Randomised controlled trials comparing different types and intensities of statins, including placebo, in adults with type 1 or type 2 diabetes mellitus were included. The primary outcome was changes in levels of non-HDL-C, calculated from measures of total cholesterol and HDL-C. Secondary outcomes were changes in levels of low density lipoprotein cholesterol (LDL-C) and total cholesterol, three point major cardiovascular events (non-fatal stroke, non-fatal myocardial infarction, and death related to cardiovascular disease), and discontinuations because of adverse events. A bayesian network meta-analysis of statin intensity (low, moderate, or high) with random effects evaluated the treatment effect on non-HDL-C by mean differences and 95% credible intervals. Subgroup analysis of patients at greater risk of major cardiovascular events was compared with patients at low or moderate risk. The confidence in network meta-analysis (CINeMA) framework was applied to determine the certainty of evidence.
RESULTS
In 42 randomised controlled trials involving 20 193 adults, 11 698 were included in the meta-analysis. Compared with placebo, the greatest reductions in levels of non-HDL-C were seen with rosuvastatin at high (-2.31 mmol/L, 95% credible interval -3.39 to -1.21) and moderate (-2.27, -3.00 to -1.49) intensities, and simvastatin (-2.26, -2.99 to -1.51) and atorvastatin (-2.20, -2.69 to -1.70) at high intensity. Atorvastatin and simvastatin at any intensity and pravastatin at low intensity were also effective in reducing levels of non-HDL-C. In 4670 patients at greater risk of a major cardiovascular events, atorvastatin at high intensity showed the largest reduction in levels of non-HDL-C (-1.98, -4.16 to 0.26, surface under the cumulative ranking curve 64%). Simvastatin (-1.93, -2.63 to -1.21) and rosuvastatin (-1.76, -2.37 to -1.15) at high intensity were the most effective treatment options for reducing LDL-C. Significant reductions in non-fatal myocardial infarction were found for atorvastatin at moderate intensity compared with placebo (relative risk=0.57, confidence interval 0.43 to 0.76, n=4 studies). No significant differences were found for discontinuations, non-fatal stroke, and cardiovascular deaths.
CONCLUSIONS
This network meta-analysis indicated that rosuvastatin, at moderate and high intensity doses, and simvastatin and atorvastatin, at high intensity doses, were most effective at moderately reducing levels of non-HDL-C in patients with diabetes. Given the potential improvement in accuracy in predicting cardiovascular disease when reduction in levels of non-HDL-C is used as the primary target, these findings provide guidance on which statin types and intensities are most effective by reducing non-HDL-C in patients with diabetes.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021258819.
Topics: Adult; Bayes Theorem; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Network Meta-Analysis
PubMed: 35331984
DOI: 10.1136/bmj-2021-067731 -
BMJ (Clinical Research Ed.) Jul 2021To assess the associations between statins and adverse events in primary prevention of cardiovascular disease and to examine how the associations vary by type and dosage... (Meta-Analysis)
Meta-Analysis
Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses.
OBJECTIVE
To assess the associations between statins and adverse events in primary prevention of cardiovascular disease and to examine how the associations vary by type and dosage of statins.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Studies were identified from previous systematic reviews and searched in Medline, Embase, and the Cochrane Central Register of Controlled Trials, up to August 2020.
REVIEW METHODS
Randomised controlled trials in adults without a history of cardiovascular disease that compared statins with non-statin controls or compared different types or dosages of statins were included.
MAIN OUTCOME MEASURES
Primary outcomes were common adverse events: self-reported muscle symptoms, clinically confirmed muscle disorders, liver dysfunction, renal insufficiency, diabetes, and eye conditions. Secondary outcomes included myocardial infarction, stroke, and death from cardiovascular disease as measures of efficacy.
DATA SYNTHESIS
A pairwise meta-analysis was conducted to calculate odds ratios and 95% confidence intervals for each outcome between statins and non-statin controls, and the absolute risk difference in the number of events per 10 000 patients treated for a year was estimated. A network meta-analysis was performed to compare the adverse effects of different types of statins. An E model based meta-analysis was used to examine the dose-response relationships of the adverse effects of each statin.
RESULTS
62 trials were included, with 120 456 participants followed up for an average of 3.9 years. Statins were associated with an increased risk of self-reported muscle symptoms (21 trials, odds ratio 1.06 (95% confidence interval 1.01 to 1.13); absolute risk difference 15 (95% confidence interval 1 to 29)), liver dysfunction (21 trials, odds ratio 1.33 (1.12 to 1.58); absolute risk difference 8 (3 to 14)), renal insufficiency (eight trials, odds ratio 1.14 (1.01 to 1.28); absolute risk difference 12 (1 to 24)), and eye conditions (six trials, odds ratio 1.23 (1.04 to 1.47); absolute risk difference 14 (2 to 29)) but were not associated with clinically confirmed muscle disorders or diabetes. The increased risks did not outweigh the reduction in the risk of major cardiovascular events. Atorvastatin, lovastatin, and rosuvastatin were individually associated with some adverse events, but few significant differences were found between types of statins. An E dose-response relationship was identified for the effect of atorvastatin on liver dysfunction, but the dose-response relationships for the other statins and adverse effects were inconclusive.
CONCLUSIONS
For primary prevention of cardiovascular disease, the risk of adverse events attributable to statins was low and did not outweigh their efficacy in preventing cardiovascular disease, suggesting that the benefit-to-harm balance of statins is generally favourable. Evidence to support tailoring the type or dosage of statins to account for safety concerns before starting treatment was limited.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020169955.
Topics: Aged; Cardiovascular Diseases; Comorbidity; Dose-Response Relationship, Drug; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Primary Prevention; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 34261627
DOI: 10.1136/bmj.n1537 -
BMC Medicine Mar 2019Statins may prevent recurrent ischemic events after ischemic stroke. Determining which statin to use remains controversial. We aimed to summarize the evidence for the...
BACKGROUND
Statins may prevent recurrent ischemic events after ischemic stroke. Determining which statin to use remains controversial. We aimed to summarize the evidence for the use of statins in secondary prevention for patients with ischemic stroke by comparing benefits and harms of various statins.
METHODS
We searched for randomized controlled trials (RCTs) assessing statins in patients with ischemic stroke or transient ischemic attack (TIA) in MEDLINE, EMBASE, and CENTRAL up to July 2017. Two authors extracted data and appraised risks of bias. We performed pairwise meta-analyses and trial sequential analyses (TSA) to compare statins versus placebo/no statin, and network meta-analyses using frequentist random-effects models to compare statins through indirect evidence. We used GRADE to rate the overall certainty of evidence. Primary outcomes were all-cause mortality and all strokes. Secondary outcomes were different types of strokes, cardiovascular events, and adverse events.
RESULTS
We identified nine trials (10,741 patients). No head-to-head RCTs were found. The median follow-up period was 2.5 years. Statins did not seem to modify all stroke and all-cause mortality outcomes; they were associated with a decreased risk of ischemic stroke (odds ratio, OR, 0.81 [95% CI, 0.70 to 0.93]; absolute risk difference, ARD, - 1.6% [95% CI, - 2.6 to - 0.6%]), ischemic stroke or TIA (OR, 0.75 [95% CI, 0.64 to 0.87]; ARD, - 4.2% [95% CI, - 6.2 to - 2.1%]), and cardiovascular event (OR, 0.75 [95% CI, 0.69 to 0.83]; ARD, - 5.4% [95% CI, - 6.8 to - 3.6%]), and did not seem to modify rhabdomyolysis, myalgia, or rise in creatine kinase. In the comparison of different statins, moderate- to high-quality evidence indicated that differences between pharmaceutical products seemed modest, with high doses (e.g., atorvastatin 80 mg/day and simvastatin 40 mg/day) associated with the greatest benefits. TSA excluded random error as a cause of the findings for ischemic stroke and cardiovascular event outcomes. Evidence for increased risk of hemorrhagic stroke was sensitive to the exclusion of the SPARCL trial.
CONCLUSIONS
Evidence strongly suggests that statins are associated with a reduction in the absolute risk of ischemic strokes and cardiovascular events. Differences in effects among statins were modest, signaling potential therapeutic equivalence.
TRIAL REGISTRATION
PROSPERO CRD42018079112.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ischemic Attack, Transient; Network Meta-Analysis; Secondary Prevention; Stroke
PubMed: 30914063
DOI: 10.1186/s12916-019-1298-5 -
American Heart Journal Apr 2019The current guidelines of statins for primary cardiovascular disease (CVD) prevention were based on results from systematic reviews and meta-analyses that suffer from... (Comparative Study)
Comparative Study Meta-Analysis
Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants.
UNLABELLED
The current guidelines of statins for primary cardiovascular disease (CVD) prevention were based on results from systematic reviews and meta-analyses that suffer from limitations.
METHODS
We searched in PubMed for existing systematic reviews and individual open-label or double-blinded randomized controlled trials that compared a statin with a placebo or another, which were published in English until January 01, 2018. We performed a random-effect pairwise meta-analysis of all statins as a class and network meta-analysis for the specific statins on different benefit and harm outcomes.
RESULTS
In the pairwise meta-analyses, statins as a class showed statistically significant risk reductions on non-fatal MI (risk ratio [RR] 0.62, 95% CI 0.53-0.72), CVD mortality (RR 0.80, 0.71-0.91), all-cause mortality (RR 0.89, 0.85-0.93), non-fatal stroke (RR 0.83, 0.75-0.92), unstable angina (RR 0.75, 0.63-0.91), and composite major cardiovascular events (RR 0.74, 0.67-0.81). Statins increased statistically significantly relative and absolute risks of myopathy (RR 1.08, 1.01-1.15; Risk difference [RD] 13, 2-24 per 10,000 person-years); renal dysfunction (RR 1.12, 1.00-1.26; RD 16, 0-36 per 10,000 person-years); and hepatic dysfunction (RR 1.16, 1.02-1.31; RD 8, 1-16 per 10,000 person-years). The drug-level network meta-analyses showed that atorvastatin and rosuvastatin were most effective in reducing CVD events while atorvastatin appeared to have the best safety profile.
CONCLUSIONS
All statins showed statistically significant risk reduction of CVD and all-cause mortality in primary prevention populations while increasing the risk for some harm risks. However, the benefit-harm profile differed by statin type. A quantitative assessment of the benefit-harm balance is thus needed since meta-analyses alone are insufficient to inform whether statins provide net benefit.
Topics: Atorvastatin; Cardiovascular Diseases; Cause of Death; Chemical and Drug Induced Liver Injury; Double-Blind Method; Fluvastatin; Headache; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Lovastatin; Middle Aged; Muscular Diseases; Nausea; Neoplasms; Network Meta-Analysis; Placebos; Pravastatin; Randomized Controlled Trials as Topic; Risk Assessment; Rosuvastatin Calcium; Simvastatin; Withholding Treatment
PubMed: 30716508
DOI: 10.1016/j.ahj.2018.12.007 -
Herz Sep 2020The VOYAGER meta-analysis reported on the low-density lipoprotein cholesterol (LDL-C)-lowering effect of commonly used statins in Caucasian subjects. As there is limited... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The VOYAGER meta-analysis reported on the low-density lipoprotein cholesterol (LDL-C)-lowering effect of commonly used statins in Caucasian subjects. As there is limited literature available on the efficacy of statins in Asian populations, the current meta-analysis compared the effects of rosuvastatin and atorvastatin on LDL-C levels in an East Asian population.
METHODS
The MEDLINE, PubMed, Embase, Cochrane Library, and Web of Science databases were searched for randomized controlled trials comparing lipid-lowering effects of rosuvastatin and atorvastatin in an East Asian population. Data on the study design, participant characteristics, and outcomes were extracted. Odds ratios (OR), weighted mean differences (WMD), or standardized mean differences were calculated using the random-effects model.
RESULTS
The meta-analysis comprised 16 randomized controlled trials with 5930 participants. Compared with atorvastatin, patients treated with rosuvastatin had a significant reduction in LDL-C: WMD = -7.15 mg/dl (95% confidence intervals [CI]: -10.71--3.60) mg/dl, p < 0.0001. Meta-regression analyses revealed no significant association between the superior benefits of rosuvastatin and other variables including age, sex, baseline LDL-C level, and follow-up duration. Additionally, the rosuvastatin group of patients, who were treated with half the dose of atorvastatin, achieved a significantly greater reduction in LDL-C levels (WMD = -3.57; 95% CI: -5.40--1.74 mg/dl, p < 0.001). Both rosuvastatin and atorvastatin were well tolerated, with similar incidences of adverse events.
CONCLUSION
Similar to the VOYAGER meta-analysis, which reported a greater efficacy of rosuvastatin in comparison with atorvastatin and simvastatin in Caucasian patients, we found that the efficacy of rosuvastatin was superior to atorvastatin in East Asian patients with hypercholesterolemia.
Topics: Atorvastatin; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Rosuvastatin Calcium; Treatment Outcome
PubMed: 30483816
DOI: 10.1007/s00059-018-4767-2 -
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 -
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 -
The Cochrane Database of Systematic... Jul 2020Asthma is a common chronic respiratory disease. People with asthma have inflammation of their airways that causes recurrent episodes of wheezing, breathlessness and...
BACKGROUND
Asthma is a common chronic respiratory disease. People with asthma have inflammation of their airways that causes recurrent episodes of wheezing, breathlessness and chest tightness, with or without a cough. Statins possess multiple therapeutic effects, including lowering lipid levels in the blood. Statins are reported to have a potential role as an adjunct treatment in asthma. However, comprehensive evidence of the benefits and harms of using statins is required to facilitate decision making.
OBJECTIVES
To assess the benefits and harms of statins as an adjunct therapy for asthma in adults and children.
SEARCH METHODS
We searched for studies in the Cochrane Airways Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid SP and Embase Ovid SP, from their inception dates We handsearched the proceedings of major respiratory conferences. We also searched clinical trials registries for completed, ongoing and unpublished studies, and scanned the reference lists of included studies and relevant reviews to identify additional studies. The search is current to 7 February 2020.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with a parallel-group design that assessed statins for at least 12 weeks' duration. We considered all participants with a clinical diagnosis of asthma to be eligible, regardless of age, sex, disease severity and previous or current treatment. We planned to include studies reported as full text, those published as abstract only, and unpublished data.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened and selected the studies, extracted outcome data and intervention characteristics from included studies, and assessed risk of bias according to standard Cochrane methodological procedures. We resolved any disagreement through discussion.
MAIN RESULTS
We found only one trial involving a total of 60 people living with asthma. The trial compared the effect of atorvastatin with a placebo (dummy treatment containing lactose) in treating people with chronic asthma. The trial did not report data for the primary outcomes or adverse events. There was uncertainty about the relative effect on forced expiratory volume in one second (FEV) and peak expiratory flow (PEF) in the atorvastatin group compared with the placebo group. The study did not report serious adverse effects for the interventions. The included study had internal discrepancies in its reported data.
AUTHORS' CONCLUSIONS
The evidence was of very low certainty, so we are unable to draw conclusions about the effectiveness and safety of statins to treat asthma. High-quality RCTs are needed to assess the effect of statins on people with asthma. Well-designed multicentre trials with larger samples and longer duration of treatment are required, which assess outcomes such as adverse events, hospital utilisation and costs, to provide better quality evidence. Future studies that include subgroups of obese people with asthma are also required.
Topics: Anti-Asthmatic Agents; Asthma; Atorvastatin; Forced Expiratory Volume; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Peak Expiratory Flow Rate
PubMed: 32668027
DOI: 10.1002/14651858.CD013268.pub2 -
The Cochrane Database of Systematic... Mar 2018Fluvastatin is thought to be the least potent statin on the market, however, the dose-related magnitude of effect of fluvastatin on blood lipids is not known. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fluvastatin is thought to be the least potent statin on the market, however, the dose-related magnitude of effect of fluvastatin on blood lipids is not known.
OBJECTIVES
Primary objectiveTo quantify the effects of various doses of fluvastatin on blood total cholesterol, low-density lipoprotein (LDL cholesterol), high-density lipoprotein (HDL cholesterol), and triglycerides in participants with and without evidence of cardiovascular disease.Secondary objectivesTo quantify the variability of the effect of various doses of fluvastatin.To quantify withdrawals due to adverse effects (WDAEs) in randomised placebo-controlled trials.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to February 2017: the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 1), MEDLINE (1946 to February Week 2 2017), MEDLINE In-Process, MEDLINE Epub Ahead of Print, Embase (1974 to February Week 2 2017), the World Health Organization International Clinical Trials Registry Platform, CDSR, DARE, Epistemonikos and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. No language restrictions were applied.
SELECTION CRITERIA
Randomised placebo-controlled and uncontrolled before and after trials evaluating the dose response of different fixed doses of fluvastatin 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 data from placebo-controlled and uncontrolled before and after trials into Review Manager 5 as continuous and generic inverse variance data, respectively. WDAEs information was collected from the placebo-controlled trials. 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
One-hundred and forty-five trials (36 placebo controlled and 109 before and after) evaluated the dose-related efficacy of fluvastatin in 18,846 participants. The participants were of any age with and without evidence of cardiovascular disease, and fluvastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 2.5 mg to 80 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 fluvastatin on blood HDL cholesterol. Fluvastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 15% to 33%, total cholesterol by 11% to 25% and triglycerides by 3% to 17.5%. For every two-fold dose increase there was a 6.0% (95% CI 5.4 to 6.6) decrease in blood LDL cholesterol, a 4.2% (95% CI 3.7 to 4.8) decrease in blood total cholesterol and a 4.2% (95% CI 2.0 to 6.3) decrease in blood triglycerides. The quality of evidence for these effects was judged to be high. When compared to atorvastatin and rosuvastatin, fluvastatin was about 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin at reducing LDL cholesterol. Very low quality of evidence showed no difference in WDAEs between fluvastatin and placebo in 16 of 36 of these short-term trials (risk ratio 1.52 (95% CI 0.94 to 2.45).
AUTHORS' CONCLUSIONS
Fluvastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, fluvastatin is 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin. This review did not provide a good estimate of the incidence of harms associated with fluvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 56% of the placebo-controlled trials.
Topics: Cholesterol; Cholesterol, LDL; Controlled Before-After Studies; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 29508377
DOI: 10.1002/14651858.CD012282.pub2