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British Journal of Clinical Pharmacology Aug 2022To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing... (Meta-Analysis)
Meta-Analysis Review
AIMS
To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs).
METHODS
More than 500 databases were searched between 1 November 2020 and 2 October 2021 to identify RCTs that were published after our baseline review. One reviewer extracted data with other reviewers verifying the extracted data for accuracy and completeness.
RESULTS
After screening 22 414 records, we included 24 and 21 RCTs in the qualitative and quantitative syntheses, respectively. The most investigated drug classes were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARBs) and anticoagulants, investigated by 10 and 11 studies respectively. In meta-analyses, ACEI/ARBs did not affect hospitalization length (mean difference -0.42, 95% confidence interval [CI] -1.83; 0.98 d, n = 1183), COVID-19 severity (risk ratio/RR 0.90, 95% CI 0.71; 1.15, n = 1661) or mortality (risk ratio [RR] 0.92, 95% CI 0.58; 1.47, n = 1646). Therapeutic anticoagulation also had no effect (hospitalization length mean difference -0.29, 95% CI -1.13 to 0.56 d, n = 1449; severity RR 0.86, 95% CI 0.70; 1.04, n = 2696; and, mortality RR 0.93, 95% CI 0.77; 1.13, n = 5689). Other investigated drug classes were antiplatelets (aspirin, 2 trials), antithrombotics (sulodexide, 1 trial), calcium channel blockers (amlodipine, 1 trial) and lipid-modifying drugs (atorvastatin, 1 trial).
CONCLUSION
Moderate- to high-certainty RCT evidence suggests that cardiovascular drugs such as ACEIs/ARBs are not associated with poor COVID-19 outcomes, and should therefore not be discontinued. These cardiovascular drugs should also not be initiated to treat or prevent COVID-19 unless they are needed for an underlying currently approved therapeutic indication.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Agents; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; COVID-19 Drug Treatment
PubMed: 35322889
DOI: 10.1111/bcp.15331 -
Revista Medica Del Instituto Mexicano... Oct 2023Atorvastatin has been used in the management of dyslipidemia and little is known about the efficacy and safety of high-dose atorvastatin administration for secondary... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Atorvastatin has been used in the management of dyslipidemia and little is known about the efficacy and safety of high-dose atorvastatin administration for secondary prevention of Major Cardiovascular Events (MACE).
OBJECTIVE
To evaluate the impact of high-dose atorvastatin on secondary prevention of MACE and adverse events.
MATERIAL AND METHODS
A systematic review and meta-analysis of Pubmed, Embase, Bireme and Cochrane Library Plus databases was performed, with a time scope from 1990 to July 2022. Six randomized clinical trials were included with a total of 29,333 patients who were treated with 80 mg, 10 mg or placebo doses of Atorvastatin where the main outcomes evaluated were Major Cardiovascular Events (MACE), mortality and treatment safety.
RESULTS
In the comparative study between the use of Atorvastatin 80 mg and other therapies, a relative risk (RR) of 0.8 (95%CI 0.69-0.92) was found, representing a 20% reduction in risk (RRR) and a number needed to treat (NNT) of 30-55. In the analysis of adverse effects, an RR of 2.37 (95% CI 0.86-6.53) and a number needed to harm (NNH) of 14-19 were observed. The use of 80 mg atorvastatin is associated with similar adverse events at lower doses.
CONCLUSIONS
The use of atorvastatin 80 mg is effective in the secondary prevention of Major Cardiovascular Event (MACE). The drug has adverse events that should be taken into account in secondary prevention.
Topics: Humans; Atorvastatin; Cardiovascular Diseases
PubMed: 37934798
DOI: 10.5281/zenodo.8319748 -
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 -
European Journal of Internal Medicine Apr 2017
Meta-Analysis Review
Topics: Atorvastatin; Child; Cholesterol, LDL; Drug Administration Schedule; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myalgia; Randomized Controlled Trials as Topic; Rosuvastatin Calcium
PubMed: 28063659
DOI: 10.1016/j.ejim.2016.12.014 -
Reumatologia 2022Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing... (Review)
Review
Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing autoimmune myopathy in some patients. We reviewed case reports of 80 patients from 2010 to present diagnosed with statin-induced necrotizing autoimmune myopathy (SINAM), aiming to analyze the clinical, physiological, serologic characteristics and outcomes of SINAM. The mean age of these patients was 66 ±9.4, the majority being male (61.3%). All patients reported proximal muscle weakness, and a few had myalgias, extra muscular symptoms such as dysphagia, and pulmonary complications. Most of the patients were on atorvastatin, simvastatin, or rosuvastatin. The mean creatine kinase was 10,094.2 ±7,351.7 U/l, and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme was positive for 93.8% of patients. The majority of patients were started on steroids; other treatments were also used. Prompt cessation of statins and initiation of immunosuppressants reduced morbidity and mortality.
PubMed: 35645423
DOI: 10.5114/reum.2022.114108 -
The Cochrane Database of Systematic... Dec 2012Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. It is therefore important to know the dose-related magnitude... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. It is therefore important to know the dose-related magnitude of effect of atorvastatin on blood lipids.
OBJECTIVES
To quantify the dose-related effects of atorvastatin on blood lipids and withdrawals due to adverse effects (WDAE).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 4, 2011, MEDLINE (1966 to November 2011), EMBASE (1980 to November 2011), ISI Web of Science (1899 to November 2011) and BIOSIS Previews (1969 to November 2011). No language restrictions were applied.
SELECTION CRITERIA
Randomised controlled and uncontrolled before-and-after trials evaluating the dose response of different fixed doses of atorvastatin on blood lipids over a duration of 3 to 12 weeks.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. WDAE information was collected from the placebo-controlled trials.
MAIN RESULTS
Two hundred fifty-four trials evaluated the dose-related efficacy of atorvastatin in 33,505 participants. Log dose-response data revealed linear dose-related effects on blood total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Combining all the trials using the generic inverse variance fixed-effect model for doses of 10 to 80 mg/day resulted in decreases of 36% to 53% for LDL-cholesterol. There was no significant dose-related effects of atorvastatin on blood high-density lipoprotein (HDL)-cholesterol. WDAE were not statistically different between atorvastatin and placebo for these short-term trials (risk ratio 0.99; 95% confidence interval 0.68 to 1.45).
AUTHORS' CONCLUSIONS
Blood total cholesterol, LDL-cholesterol and triglyceride lowering effect of atorvastatin was dependent on dose. Log dose-response data was linear over the commonly prescribed dose range. Manufacturer-recommended atorvastatin doses of 10 to 80 mg/day resulted in 36% to 53% decreases of LDL-cholesterol. The review did not provide a good estimate of the incidence of harms associated with atorvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 37% of the placebo-controlled trials.
Topics: Atorvastatin; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dose-Response Relationship, Drug; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipids; Pyrroles; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 23235655
DOI: 10.1002/14651858.CD008226.pub2 -
World Neurosurgery May 2024Chronic subdural hematoma (CSDH) is a common neurological condition, especially in the elderly population. Atorvastatin has shown the potential to reduce the recurrence... (Review)
Review
BACKGROUND
Chronic subdural hematoma (CSDH) is a common neurological condition, especially in the elderly population. Atorvastatin has shown the potential to reduce the recurrence of CSDH and improve overall outcomes. New studies have emerged since the last meta-analysis, increasing the sample size and the variety of outcomes analyzed.
METHODS
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for studies comparing the use of atorvastatin in CSDH patients with a control group or placebo. The primary outcome was the recurrence of CSDH. Secondary outcomes of interest were hematoma volume, composite adverse effects, mortality, and neurological function, measured by the Glasgow Outcome Scale and Barthel index for activities of daily living.
RESULTS
Seven studies, of which 2 were randomized controlled trials, were included, containing 1192 patients. Overall recurrence significantly decreased compared to the control group (risk ratio [RR] 0.46; 95% confidence interval [CI] 0.25-0.83; P=0.009). The benefits of atorvastatin were sustained in the subgroup analysis of patients who underwent initial conservative therapy (RR 0.40; 95% CI 0.22-0.70; P=0.001). However, there was no significant difference when atorvastatin was combined with surgical intervention (RR 0.53; 95% CI 0.21-1.32; P=0.17). Adverse effects were not increased by atorvastatin (RR 0.82; 95% CI 0.51-1.34; P=0.44).
CONCLUSIONS
Atorvastatin might be beneficial in reducing CSDH recurrence, especially in conservative treatment patients. Atorvastatin was not significantly associated with adverse effects. Larger, higher-quality randomized studies are needed to adequately evaluate the efficacy, safety, and optimal dose of atorvastatin in CSDH patients.
PubMed: 38759787
DOI: 10.1016/j.wneu.2024.05.069 -
The Cochrane Database of Systematic... Dec 2011Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system. Statins, prescribed as cholesterol lowering agents, have shown... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system. Statins, prescribed as cholesterol lowering agents, have shown possible effects for treating MS in experimental and preliminary clinical studies.
OBJECTIVES
To evaluate the efficacy and safety of statins administered alone or as add-on to approved treatments for MS.
SEARCH METHODS
The Trials Search Coordinator searched the Cochrane MS Group Trials Register (1 August 2011). We searched the Chinese National Knowledge Infrastructure (CNKI) (1979 to 1 August 2011), trials registers and conference proceedings. Pharmaceutical companies and authors of included studies were contacted for additional information.There were no language restrictions.
SELECTION CRITERIA
Randomised controlled trials comparing statins with placebo, or comparing statins in combination with approved treatments alone for patients with MS.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed trial quality and extracted data.
MAIN RESULTS
Four trials involving 458 participants were included. All trials compared statins (two evaluating atorvastatin and two simvastatin) plus interferon beta-1a with interferon beta-1a alone for treating MS. The methodological quality was good for three studies and poor for remaining one. None of them showed statistically significant difference between both treatment groups in reducing relapses, preventing disease progression or developing new T2 or gadolinium-enhanced lesions on MRI after 9, 12, 24 months follow up period. Statins resulted to be safe and well tolerated, no serious adverse effects were reported. Changes on quality of life after receiving statins were not reported in the trials.
AUTHORS' CONCLUSIONS
There is no convincing evidence to support the use of either atorvastatin or simvastatin as an adjunctive therapy in MS.
Topics: Atorvastatin; Disease Progression; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interferon-beta; Multiple Sclerosis; Pyrroles; Randomized Controlled Trials as Topic; Secondary Prevention; Simvastatin
PubMed: 22161428
DOI: 10.1002/14651858.CD008386.pub3 -
Cardiovascular Drugs and Therapy Aug 2017We conducted a meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs to synthesize evidence about the efficacy and safety of alternate-day vs daily dosing... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We conducted a meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs to synthesize evidence about the efficacy and safety of alternate-day vs daily dosing of statins.
METHODS
We searched selected databases through January 2, 2017 to identify relevant RCTs and quasi-RCTs. The primary outcome was change in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG), while secondary outcomes included adverse events and adherence.
RESULTS
Twelve RCTs and 1 quasi-RCT (n = 1023 patients) were included in the analysis. Pooled analysis revealed no statistically significant difference between alternate-day and daily regimens of atorvastatin and rosuvastatin in terms of change in LDL-C (mean difference [MD] 6.79 mg/dL, 95% confidence interval [CI] -1.59, 15.17, p = 0.11, and 10.51 mg/dL, 95%CI -0.23, 21.26, p = 0.06, respectively) and TG (p > 0.05). Daily regimens of atorvastatin and rosuvastatin were superior to alternate-day regimes in term of change in TC (MD 12.45 mg/L, 95%CI 8.14, 16.76, p < 0.00001, and 15.80 mg/dL, 95%CI 5.66, 25.95, p = 0.002, respectively). For all outcomes, there was no statistically significant difference between alternate-day and daily regimens for both fluvastatin and pravastatin (p > 0.05). Both regimens of statins were generally well tolerated with good adherence.
CONCLUSIONS
Alternate-day dosing of individual statins (especially atorvastatin and rosuvastatin) is as efficacious as daily dosing on LDL-C and TG.
Topics: Cholesterol; Cholesterol, LDL; Drug Administration Schedule; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Medication Adherence; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 28741244
DOI: 10.1007/s10557-017-6743-0 -
Obesity Reviews : An Official Journal... May 2024To evaluate the impact of bariatric surgery on the pharmacokinetic (PK) parameters of orally administered medications and supplements. (Review)
Review
OBJECTIVES
To evaluate the impact of bariatric surgery on the pharmacokinetic (PK) parameters of orally administered medications and supplements.
METHODS
Systematic searches of bibliographic databases were conducted to identify studies. Pooled effect estimates from different surgical procedures were calculated using a random-effects model.
RESULTS
Quantitative data were synthesized from 58 studies including a total of 1985 participants. Whilst 40 medications and 6 supplements were evaluated across these studies, heterogeneity and missing information reduced the scope of the meta-analysis to the following medications and supplements: atorvastatin, paracetamol, omeprazole, midazolam, vitamin D, calcium, zinc, and iron supplements. There were no significant differences in PK parameters post-surgery for the drugs atorvastatin and omeprazole, and supplements calcium, ferritin, and zinc supplements. Paracetamol showed reduced clearance (mean difference [MD] = -15.56 L/hr, p = 0.0002, I = 67%), increased maximal concentration (MD = 6.90 μg/ml, p = 0.006, I = 92%) and increased terminal elimination half-life (MD = 0.49 hr, p < 0.0001, I = 3%) post-surgery. The remaining 36 medications and 2 supplements were included in a systematic review. Overall, 18 of the 53 drugs and supplements showed post-operative changes in PK parameters.
CONCLUSION
This study demonstrates heterogeneity in practice and could not reach conclusive findings for most PK parameters. Prospective studies are needed to inform best practice and enhance patient healthcare and safety following bariatric surgery.
PubMed: 38710656
DOI: 10.1111/obr.13759