-
Current Medical Research and Opinion May 2022Network meta-analysis was used to derive estimates of the relative efficacy of inclisiran, evolocumab, alirocumab, bempedoic acid, and ezetimibe in patients with... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Network meta-analysis was used to derive estimates of the relative efficacy of inclisiran, evolocumab, alirocumab, bempedoic acid, and ezetimibe in patients with hypercholesterolemia and/or at increased cardiovascular risk due to elevated low-density lipoprotein cholesterol taking maximum tolerated dose statins.
METHODS
Clinical trials published through February 2021 comparing percent change from baseline in low-density lipoprotein cholesterol were identified a systematic review. Bayesian network meta-analyses were performed for patients with atherosclerotic cardiovascular disease and/or high cardiovascular risk on maximally tolerated statins in the base case, which included 23 trials.
RESULTS
Results from the base-case analyses demonstrated that inclisiran, evolocumab, and alirocumab provide superior efficacy over placebo, bempedoic acid, and ezetimibe in terms of reduction in low-density lipoprotein cholesterol. Inclisiran was also comparable to alirocumab (mean difference: 0.78% [95% CrI: -8.35, 9.88]) and evolocumab (8.16%, [95% CrI: -1.82, 18.49]). Findings of a scenario which also included trials conducted in patients with heterozygous familial hypercholesterolemia were consistent with the base case. There was evidence of statistical heterogeneity across the included trials, roughly equivalent to variation of 5-10% change in low-density lipoprotein cholesterol, suggesting that any differences between treatments that were greater than 5-10% are generalizable.
CONCLUSIONS
This study provides insight regarding the comparative efficacy of drugs for which no head-to-head trials exist and suggests that inclisiran, alirocumab, and evolocumab are expected to provide similar clinically meaningful improvements in low-density lipoprotein cholesterol in patients with hypercholesterolemia on maximally tolerated statins who are at increased cardiovascular risk.
Topics: Anticholesteremic Agents; Bayes Theorem; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Ezetimibe; Heart Disease Risk Factors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Network Meta-Analysis; Risk Factors; Treatment Outcome
PubMed: 35262430
DOI: 10.1080/03007995.2022.2049164 -
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 -
JAMA Nov 2016Cardiovascular disease (CVD), the leading cause of mortality and morbidity in the United States, may be potentially preventable with statin therapy. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Cardiovascular disease (CVD), the leading cause of mortality and morbidity in the United States, may be potentially preventable with statin therapy.
OBJECTIVE
To systematically review benefits and harms of statins for prevention of CVD to inform the US Preventive Services Task Force.
DATA SOURCES
Ovid MEDLINE (from 1946), Cochrane Central Register of Controlled Trials (from 1991), and Cochrane Database of Systematic Reviews (from 2005) to June 2016.
STUDY SELECTION
Randomized clinical trials of statins vs placebo, fixed-dose vs titrated statins, and higher- vs lower-intensity statins in adults without prior cardiovascular events.
DATA EXTRACTION AND SYNTHESIS
One investigator abstracted data, a second checked data for accuracy, and 2 investigators independently assessed study quality using predefined criteria. Data were pooled using random-effects meta-analysis.
MAIN OUTCOMES AND MEASURES
All-cause mortality, CVD-related morbidity or mortality, and harms.
RESULTS
Nineteen trials (n = 71 344 participants [range, 95-17 802]; mean age, 51-66 years) compared statins vs placebo or no statin. Statin therapy was associated with decreased risk of all-cause mortality (risk ratio [RR], 0.86 [95% CI, 0.80 to 0.93]; I2 = 0%; absolute risk difference [ARD], -0.40% [95% CI, -0.64% to -0.17%]), cardiovascular mortality (RR, 0.69 [95% CI, 0.54 to 0.88]; I2 = 54%; ARD, -0.43% [95% CI, -0.75% to -0.11%]), stroke (RR, 0.71 [95% CI, 0.62 to 0.82]; I2 = 0; ARD, -0.38% [95% CI, -0.53% to -0.23%]), myocardial infarction (RR, 0.64 [95% CI, 0.57 to 0.71]; I2 = 0%; ARD, -0.81% [95% CI, -1.19 to -0.43%]), and composite cardiovascular outcomes (RR, 0.70 [95% CI, 0.63 to 0.78]; I2 = 36%; ARD, -1.39% [95% CI, -1.79 to -0.99%]). Relative benefits appeared consistent in demographic and clinical subgroups, including populations without marked hyperlipidemia (total cholesterol level <200 mg/dL); absolute benefits were higher in subgroups at higher baseline risk. Statins were not associated with increased risk of serious adverse events (RR, 0.99 [95% CI, 0.94 to 1.04]), myalgias (RR, 0.96 [95% CI, 0.79 to 1.16]), or liver-related harms (RR, 1.10 [95% CI, 0.90 to 1.35]). In pooled analysis, statins were not associated with increased risk of diabetes (RR, 1.05 [95% CI, 0.91 to 1.20]), although statistical heterogeneity was present (I2 = 52%), and 1 trial found high-intensity statins associated with increased risk (RR, 1.25 [95% CI, 1.05 to 1.49]). No trial directly compared titrated vs fixed-dose statins, and there were no clear differences based on statin intensity.
CONCLUSIONS AND RELEVANCE
In adults at increased CVD risk but without prior CVD events, statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and CVD events, with greater absolute benefits in patients at greater baseline risk.
Topics: Aged; Cardiovascular Diseases; Cause of Death; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Reduction Behavior
PubMed: 27838722
DOI: 10.1001/jama.2015.15629 -
Journal of Clinical Lipidology 2017Evidence about the optimal time of day at which to administer statins is lacking. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Evidence about the optimal time of day at which to administer statins is lacking.
OBJECTIVE
The objective of this study is to synthesize evidence about effects of morning vs evening statin administration on lipid profile.
METHODS
We searched PubMed, SCOPUS, Web of Science, and Embase databases (from inception up to July 24, 2016) to identify the relevant studies. Mean differences (MDs) between the change scores in lipid parameters were pooled using a fixed-effect model.
RESULTS
Eleven articles with 1034 participants were eligible for the analysis. The pooled analysis comparing effects of morning vs evening administration of statins on plasma total cholesterol (TC; P = .10), high-density lipoprotein cholesterol (P = .90), and triglycerides (P = .45) was not statistically significant. Low-density lipoprotein cholesterol (LDL-C) lowering was statistically greater in the evening-dose group (MD: 3.24 mg/dL, 95% CI: 1.23-5.25, P = .002). Subgroup analysis according to statin half-lives showed that evening dose of statins was significantly superior to morning dose for lowering LDL-C in case of both short and long half-life statins (MD: 9.68 mg/dL, 95% CI: 3.32-16.03, P = .003 and MD: 2.53 mg/dL, 95% CI: 0.41-4.64, P = .02, respectively) and also for TC reduction in case of short half-life statins only (P = .0005).
CONCLUSIONS
LDL-C and TC lowering was significantly greater in the evening dose than in the morning dose in case of short-acting statins. Besides slight but significant effect on LDL-C, the efficacy of long-acting statins was equivalent for both regimens. Therefore, long-acting statins should be given at a time that will best aid compliance. Short-acting statins should be given in the evening.
Topics: Drug Administration Schedule; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids
PubMed: 28826569
DOI: 10.1016/j.jacl.2017.06.001 -
PloS One 2023Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear.
OBJECTIVE
The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials.
METHODS
Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic.
RESULTS
In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p<0.01) and Alirocumab reduced LDL-c by -46.35% (95% CI: -51.75, -41.13, p<0.01). Inclisiran 284mg reduced LDL-c by -54.83% (95% CI: -59.04, -50.62, p = 0.05) and Inclisiran 300mg reduced LDL-c by -43.11% (95% CI: -52.42, -33.80, p = 0.01). After a median of 8 months (IQR 6-15), Evolocumab reduced the risk of myocardial infarction (MI), OR 0.72 (95% CI: 0.64, 0.81, p<0.01), coronary revascularization, 0.77 (95% CI: 0.70, 0.84, p<0.01), stroke, 0.79 (95% CI: 0.66, 0.94, p = 0.01) and overall MACE 0.85 (95% CI: 0.80, 0.89, p<0.01). Alirocumab reduced MI, 0.57 (0.38, 0.86, p = 0.01), cardiovascular mortality 0.35 (95% CI: 0.16, 0.77, p = 0.01), all-cause mortality 0.60 (95% CI: 0.43, 0.84, p<0.01), and overall MACE 0.35 (0.16, 0.77, p = 0.01).
CONCLUSION
PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.
Topics: Humans; PCSK9 Inhibitors; Cholesterol, LDL; Myocardial Infarction; Proprotein Convertase 9; Atherosclerosis; Heart Disease Risk Factors; RNA, Small Interfering; Anticholesteremic Agents; Cardiovascular Diseases; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 38055686
DOI: 10.1371/journal.pone.0295359 -
Circulation Research Feb 2019Loss-of-function variants in PCSK9 (proprotein convertase subtilisin-kexin type 9) are associated with lower lifetime risk of atherosclerotic cardiovascular disease)...
Loss-of-function variants in PCSK9 (proprotein convertase subtilisin-kexin type 9) are associated with lower lifetime risk of atherosclerotic cardiovascular disease) events. Confirmation of these genetic observations in large, prospective clinical trials in participants with atherosclerotic cardiovascular disease has provided guidance on risk stratification and enhanced our knowledge on hitherto unresolved and contentious issues concerning the efficacy and safety of markedly lowering LDL-C (low-density lipoprotein cholesterol). PCSK9 has a broad repertoire of molecular effects. Furthermore, clinical trials with PCSK9 inhibitors demonstrate that reductions in atherosclerotic cardiovascular disease events are more effective in patients with recent myocardial infarction, multiple myocardial infarctions, multivessel coronary artery disease, and lower extremity arterial disease. The potent LDL-C lowering efficacy of PCSK9 inhibitors provides the opportunity for more aggressive LDL-lowering strategies in high-risk patients with atherosclerotic cardiovascular disease and supports the notion that there is no lower limit for LDL-C. Aggressive LDL-C lowering with fully human PCSK9 monoclonal antibodies has been associated by a safety profile superior to that of other classes of LDL-lowering agents. These clinical trials provide evidence that LDL lowering with PCSK9 inhibitors is an effective therapy for lowering cardiovascular events in high-risk patients with LDL-C levels ≥70 mg/dL on maximally tolerated oral therapies, including statins and ezetimibe.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Atherosclerosis; Cardiovascular Diseases; Cholesterol, LDL; Clinical Trials as Topic; Diabetes Mellitus, Type 2; HIV Infections; Humans; Hyperlipoproteinemia Type II; Lipoproteins; Mutation; PCSK9 Inhibitors; Proprotein Convertase 9; Renal Insufficiency, Chronic
PubMed: 30702994
DOI: 10.1161/CIRCRESAHA.118.313238 -
The Cochrane Database of Systematic... Oct 2020Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important cause of mortality and morbidity. Therefore, additional LDL-C reduction may be warranted, especially for people who are unresponsive to, or unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9 inhibitors) reduce LDL-C and CVD risk.
OBJECTIVES
Primary To quantify the effects of PCSK9 inhibitors on CVD, all-cause mortality, myocardial infarction, and stroke, compared to placebo or active treatment(s) for primary and secondary prevention. Secondary To quantify the safety of PCSK9 inhibitors, with specific focus on the incidence of influenza, hypertension, type 2 diabetes, and cancer, compared to placebo or active treatment(s) for primary and secondary prevention.
SEARCH METHODS
We identified studies by systematically searching CENTRAL, MEDLINE, Embase, and Web of Science in December 2019. We also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform in August 2020 and screened the reference lists of included studies. This is an update of the review first published in 2017.
SELECTION CRITERIA
All parallel-group and factorial randomised controlled trials (RCTs) with a follow-up of at least 24 weeks were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed and extracted data. Where data were available, we calculated pooled effect estimates. We used GRADE to assess certainty of evidence and in 'Summary of findings' tables.
MAIN RESULTS
We included 24 studies with data on 60,997 participants. Eighteen trials randomised participants to alirocumab and six to evolocumab. All participants received background lipid-lowering treatment or lifestyle counselling. Six alirocumab studies used an active treatment comparison group (the remaining used placebo), compared to three evolocumab active comparison trials. Alirocumab compared with placebo decreased the risk of CVD events, with an absolute risk difference (RD) of -2% (odds ratio (OR) 0.87, 95% confidence interval (CI) 0.80 to 0.94; 10 studies, 23,868 participants; high-certainty evidence), decreased the risk of mortality (RD -1%; OR 0.83, 95% CI 0.72 to 0.96; 12 studies, 24,797 participants; high-certainty evidence), and MI (RD -2%; OR 0.86, 95% CI 0.79 to 0.94; 9 studies, 23,352 participants; high-certainty evidence) and for any stroke (RD 0%; OR 0.73, 95% CI 0.58 to 0.91; 8 studies, 22,835 participants; high-certainty evidence). Compared to active treatment the alirocumab effects, for CVD, the RD was 1% (OR 1.37, 95% CI 0.65 to 2.87; 3 studies, 1379 participants; low-certainty evidence); for mortality, RD was -1% (OR 0.51, 95% CI 0.18 to 1.40; 5 studies, 1333 participants; low-certainty evidence); for MI, RD was 1% (OR 1.45, 95% CI 0.64 to 3.28, 5 studies, 1734 participants; low-certainty evidence); and for any stroke, RD was less than 1% (OR 0.85, 95% CI 0.13 to 5.61; 5 studies, 1734 participants; low-certainty evidence). Compared to placebo the evolocumab, for CVD, the RD was -2% (OR 0.84, 95% CI 0.78 to 0.91; 3 studies, 29,432 participants; high-certainty evidence); for mortality, RD was less than 1% (OR 1.04, 95% CI 0.91 to 1.19; 3 studies, 29,432 participants; high-certainty evidence); for MI, RD was -1% (OR 0.72, 95% CI 0.64 to 0.82; 3 studies, 29,432 participants; high-certainty evidence); and for any stroke RD was less than -1% (OR 0.79, 95% CI 0.65 to 0.94; 2 studies, 28,531 participants; high-certainty evidence). Compared to active treatment, the evolocumab effects, for any CVD event RD was less than -1% (OR 0.66, 95% CI 0.14 to 3.04; 1 study, 218 participants; very low-certainty evidence); for all-cause mortality, the RD was less than 1% (OR 0.43, 95% CI 0.14 to 1.30; 3 studies, 5223 participants; very low-certainty evidence); and for MI, RD was less than 1% (OR 0.66, 95% CI 0.23 to 1.85; 3 studies, 5003 participants; very low-certainty evidence). There were insufficient data on any stroke. AUTHORS' CONCLUSIONS: The evidence for the clinical endpoint effects of evolocumab and alirocumab were graded as high. There is a strong evidence base to prescribe PCSK9 monoclonal antibodies to people who might not be eligible for other lipid-lowering drugs, or to people who cannot meet their lipid goals on more traditional therapies, which was the main patient population of the available trials. The evidence base of PCSK9 inhibitors compared with active treatment is much weaker (low very- to low-certainty evidence) and it is unclear whether evolocumab or alirocumab might be effectively used as replacement therapies. Related, most of the available studies preferentially enrolled people with either established CVD or at a high risk already, and evidence in low- to medium-risk settings is minimal. Finally, there is very limited evidence on any potential safety issues of both evolocumab and alirocumab. While the current evidence synthesis does not reveal any adverse signals, neither does it provide evidence against such signals. This suggests careful consideration of alternative lipid lowering treatments before prescribing PCSK9 inhibitors.
Topics: Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Cardiovascular Diseases; Cause of Death; Cholesterol, LDL; Cholinergic Antagonists; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Middle Aged; Myocardial Infarction; PCSK9 Inhibitors; Primary Prevention; Proprotein Convertase 9; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke; Time Factors
PubMed: 33078867
DOI: 10.1002/14651858.CD011748.pub3 -
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... 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 -
BMJ Clinical Evidence Jan 2011Up to 20% of adults aged over 55 years have detectable peripheral arterial disease of the legs, but this may cause symptoms of intermittent claudication in only a small... (Review)
Review
INTRODUCTION
Up to 20% of adults aged over 55 years have detectable peripheral arterial disease of the legs, but this may cause symptoms of intermittent claudication in only a small proportion of affected people. The main risk factors are smoking and diabetes mellitus, but other risk factors for cardiovascular disease are also associated with peripheral arterial disease.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for people with chronic peripheral arterial disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010. Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review. We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 70 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antiplatelet agents, bypass surgery, cilostazol, exercise, pentoxifylline, percutaneous transluminal angioplasty (PTA), prostaglandins, smoking cessation, and statins.
Topics: Administration, Oral; Angioplasty; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intermittent Claudication; Peripheral Arterial Disease; Platelet Aggregation Inhibitors
PubMed: 21477401
DOI: No ID Found