-
Cardiovascular Drugs and Therapy Jun 2024The benefits of statins for ischemic cardio-cerebrovascular diseases are well known. However, concerns around muscle adverse events still exist. We therefore aimed to... (Meta-Analysis)
Meta-Analysis Comparative Study
PURPOSE
The benefits of statins for ischemic cardio-cerebrovascular diseases are well known. However, concerns around muscle adverse events still exist. We therefore aimed to compare the muscle safety of individual statins in adults.
METHODS
PubMed, Embase, Cochrane Central Register of Controlled Trials and Web of Science were searched to include double-blind randomized controlled trials (RCTs) comparing one statin with another or with control treatment. Pairwise meta-analyses and network meta-analyses were undertaken with Stata 14.0 software. Relative risk (RR) with 95% confidence intervals (CIs) was adopted for each outcome.
RESULTS
A total of 83 RCTs were included. In the pairwise meta-analysis, statins were significantly associated with only a slight increase in muscle symptoms compared with control (RR=1.05; 95% CI=1.01-1.09). In the drug-level network meta-analyses, no statistically significant difference was found between individual statins in the incidence of muscle symptoms, myalgia, myopathy, rhabdomyolysis, creatine kinase (CK) >10 times the upper limit of normal (ULN) or discontinuation due to muscle adverse events. In the dose-level network meta-analyses, there were no statistically significant dose-dependent effects on any outcomes except that moderate-intensity statins had a higher incidence of muscle symptoms than control (RR=1.13; 95% CI=1.01-1.27). Moderate simvastatin (RR=6.57; 95% CI=1.26-34.41) and moderate pravastatin (RR=5.96; 95% CI=1.00-35.44) had a statistically significantly higher incidence of CK >10×ULN compared with moderate atorvastatin. Lipophilic statins and statins metabolized by liver cytochrome P450 3A4 were not associated with an increased risk of muscle adverse events.
CONCLUSION
Statins may be generally safe on muscle. Moderate atorvastatin may be superior to equivalent simvastatin and pravastatin in muscle tolerability.
Topics: Hydroxymethylglutaryl-CoA Reductase Inhibitors; Humans; Randomized Controlled Trials as Topic; Muscular Diseases; Network Meta-Analysis; Double-Blind Method; Atorvastatin; Muscle, Skeletal; Myalgia; Rhabdomyolysis
PubMed: 36447018
DOI: 10.1007/s10557-022-07405-0 -
Pravastatin and placental insufficiency associated disorders: A systematic review and meta-analysis.Frontiers in Pharmacology 2022Uteroplacental insufficiency associated disorders, such as preeclampsia, fetal growth restriction and obstetrical antiphospholipid syndrome, share pathophysiology and...
Uteroplacental insufficiency associated disorders, such as preeclampsia, fetal growth restriction and obstetrical antiphospholipid syndrome, share pathophysiology and risk factors with cardiovascular diseases treated with statins. To evaluate pregnancy outcomes among women with uteroplacental insufficiency disorders who were treated with statins. Electronic databases were searched from inception to January 2022 Cohort studies and randomized controlled trials. Pooled odds ratios were calculated using a random-effects model; meta-regression was utilized when applicable. The analysis included ten studies describing 1,391 women with uteroplacental insufficiency disorders: 703 treated with pravastatin and 688 not treated with statins. Women treated with pravastatin demonstrated significant prolongation of pregnancy (mean difference 0.44 weeks, 95%CI:0.01-0.87, = 0.04, I = 96%) and less neonatal intensive care unit admissions (OR = 0.42, 95%CI: 0.23-0.75, = 0.004, I = 25%). In subgroup analysis, prolongation of pregnancy from study entry to delivery was statistically significant in cohort studies (mean difference 8.93 weeks, 95%CI:4.22-13.95, = 0.00) but not in randomized control studies. Trends were observed toward a decrease in preeclampsia diagnoses (OR = 0.54, 95%CI:0.27-1.09, = 0.09, I = 44%), perinatal death (OR = 0.32, 95%CI:0.09-1.13, = 0.08, I = 54%) and an increase in birth weight (mean difference = 102 g, 95%CI: -14-212, = 0.08, I = 96%). A meta-regression analysis demonstrated an association between earlier gestational age at initiation of treatment and a lower risk of preeclampsia development (R = 1). Pravastatin treatment prolonged pregnancy duration and improved associated obstetrical outcomes in pregnancies complicated with uteroplacental insufficiency disorders in cohort studies. https://www.crd.york.ac.uk/prospero/ identifier CRD42020165804 17/2/2020.
PubMed: 36438820
DOI: 10.3389/fphar.2022.1021548 -
Frontiers in Cardiovascular Medicine 2022To explore the associations between different types and doses of statins and adverse events in secondary prevention of cardiovascular disease.
Associations between statins and adverse events in secondary prevention of cardiovascular disease: Pairwise, network, and dose-response meta-analyses of 47 randomized controlled trials.
OBJECTIVES
To explore the associations between different types and doses of statins and adverse events in secondary prevention of cardiovascular disease.
METHODS
We searched PubMed, Embase, and Cochrane databases for randomized controlled trials that compared statins with non-statin controls or different types or doses of statins. The primary outcomes included muscle condition, transaminase elevations, renal insufficiency, gastrointestinal discomfort, cancer, new onset or exacerbation of diabetes, cognitive impairment, and eye condition. We also analyzed myocardial infarction (MI), stroke, death from cardiovascular diseases (CVD), and all-cause death as the secondary outcomes to compare the potential harms with the benefits of statins. We conducted pairwise meta-analyses to calculate the odds ratio (OR) and 95% confidence intervals (CIs) for each outcome. Network meta-analyses were performed to compare the adverse effects of different statins. An Emax model was used to examine the dose-response relationships of the adverse effects of each statin.
RESULTS
Forty-seven trials involving 107,752 participants were enrolled and followed up for 4.05 years. Compared with non-statin control, statins were associated with an increased risk of transaminase elevations [OR 1.62 (95% CI 1.20 to 2.18)]. Statins decreased the risk of MI [OR 0.66 (95% CI 0.61 to 0.71), < 0.001], stroke [OR 0.78 (95% CI 0.72 to 0.84), < 0.001], death from CVD [OR 0.77 (95% CI 0.72 to 0.83), < 0.001] and all-cause death [OR 0.83 (95% CI 0.79 to 0.88), < 0.001]. Atorvastatin showed a higher risk of transaminase elevations than non-statin control [OR 4.0 (95% CI 2.2 to 7.6)], pravastatin [OR 3.49 (95% CI 1.77 to 6.92)] and simvastatin [OR 2.77 (95% CI 1.31 to 5.09)], respectively. Compared with atorvastatin, simvastatin was associated with a lower risk of muscle problems [OR 0.70 (95% CI 0.55 to 0.90)], while rosuvastatin showed a higher risk [OR 1.75 (95% CI 1.17 to 2.61)]. An Emax dose-response relationship was identified for the effect of atorvastatin on transaminase elevations.
CONCLUSION
Statins were associated with increased risks of transaminases elevations in secondary prevention. Our study provides the ranking probabilities of statins that can help clinicians make optimal decisions when there is not enough literature to refer to.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021285161].
PubMed: 36093163
DOI: 10.3389/fcvm.2022.929020 -
Frontiers in Pharmacology 2022Different treatment protocols have been employed to manage heparin/low-dose aspirin refractory or high-risk pregnancies in antiphospholipid antibody syndrome (APS)...
Different treatment protocols have been employed to manage heparin/low-dose aspirin refractory or high-risk pregnancies in antiphospholipid antibody syndrome (APS) pregnancies. A systematic review of the literature on additional treatments used in refractory and/or high-risk APS pregnancies was conducted. Records from February 2006 to October 2021 were retrieved from PubMed, Web of Science, Cochrane, and the www.clinicaltrials.gov platform. Twenty-one studies met our eligibility criteria. Live birth rate is this study's primary endpoint, while pregnancy complications and adverse events are secondary endpoints. A total of 434 pregnancies, 162 (37.3%) refractory and 272 (62.7%) high-risk/refractory pregnancies, were included. Both IVIG <2 gr/kg/monthly/HCQ/LDS and PEX/IA ± LDS led to 100% viable infants in refractory APS. Furthermore, HCQ 200-400 mg showed a higher live birth rate than HCQ + LDS (88.6% . 82.7%). Following treatment protocol with HCQ 200-400 mg and IVIG <2 gr/kg/monthly/HCQ/LDS, pregnancy complications rates of 16.7 and 83.3% were registered, respectively. Pravastatin 20 mg, IA weekly + IVIG 2 gr/monthly, and PEX weekly + IVIg 2 gr/kg/monthly showed higher live birth rates in high-risk APS pregnancies of 100, 100 and 92%, respectively, whereas the lower severe pregnancy complications were reported in pregnancies treated with PEX weekly + IVIg 2 gr/kg/monthly (11.1%). One (0.6%) case of dermatitis during treatment with HCQ was observed. The results of this study showed that HCQ 200-400 mg and PEX weekly + IVIG 2 gr/kg/monthly achieved a higher live birth rate in refractory APS and high-risk/refractory APS, respectively. The results presented provide clinicians with up-to-date knowledge in the management of APS pregnancies according to risk stratification.
PubMed: 35662738
DOI: 10.3389/fphar.2022.849692 -
Current Reviews in Clinical and... 2023A subpopulation of statin users such as subjects with chronic kidney disease (CKD), Human Immune virus (HIV), acute coronary syndrome (ACS), revascularization, metabolic...
BACKGROUND
A subpopulation of statin users such as subjects with chronic kidney disease (CKD), Human Immune virus (HIV), acute coronary syndrome (ACS), revascularization, metabolic syndrome, and/or diabetes may particularly benefit from pitavastatin pharmacotherapy.
AIM
The current systematic review aimed systematically to evaluate the effect of pitavastatin on primary cardiac events in subjects receiving pitavastatin in comparison to the other four statin members.
METHODS
We conducted a systematic review on phases III and IV of randomized controlled trials (RCT-s, 11 trials) for subjects with primary cardiac events who received pitavastatin. Subjects diagnosed with any type of dyslipidemia (population 4804) and received pitavastatin (interventions) versus comparator (comparison) with the primary efficacy endpoint of minimization of LDL-C and non- HDL-C, had an increase in HDL-C and/or reduction in major adverse cardiac events (MACE, cardiovascular death, myocardial infarction (fatal/nonfatal), and stroke (fatal/nonfatal) and/or their composite (outcomes). The secondary safety endpoint was the development of any adverse effects.
RESULTS
In the included trials (11), participants (4804) were randomized for pitavastatin or its comparators such as atorvastatin, pravastatin, rosuvastatin, simvastatin and followed up for 12 to 52 weeks. In terms of the primary outcome (reduction in LDL-C), pitavastatin 4 mg was superior to pravastatin 40 mg in three trials, while the 2 mg pitavastatin was comparable to atorvastatin 10 mg in four trials and simvastatin 20 and 40 mg in two 2 trials. However, rosuvastatin 2.5 mg was superior to pitavastatin 2 mg in two trials. Pitavastatin increased HDL-C and reduced non-HDL-C in eleven trials. Regarding the safety profile, pitavastatin has proved to be tolerated and safe.
CONCLUSION
The FDA-approved indications for pitavastatin included primary dyslipidemia and mixed dyslipidemia as a supplementary therapy to dietary changes to lower total cholesterol, LDL-C, apolipoprotein B (Apo B), triglycerides (TG), and enhance HDL-C. Pitavastatin might be suitable for subjects with diabetes, ACS (reduced revascularization), metabolic syndrome, CKD, HIV, and subjects with low levels of HDL-C. We highly recommend rational individualization for the selection of statin.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium; Pravastatin; Cholesterol, LDL; Metabolic Syndrome; Cholesterol, HDL; Randomized Controlled Trials as Topic; Simvastatin; Dyslipidemias; Cardiovascular Diseases; HIV Infections
PubMed: 35642121
DOI: 10.2174/2772432817666220531115314 -
Critical Care (London, England) May 2022Survival has been considered the cornerstone for clinical outcome evaluation in critically ill patients admitted to intensive care unit (ICU). There is evidence that ICU... (Review)
Review
Survival has been considered the cornerstone for clinical outcome evaluation in critically ill patients admitted to intensive care unit (ICU). There is evidence that ICU survivors commonly show impairments in long-term outcomes such as quality of life (QoL) considering them as the most relevant ones. In the last years, the concept of patient-important outcomes has been introduced and increasingly reported in peer-reviewed publications. In the present systematic review, we evaluated how many randomized controlled trials (RCTs) were conducted on critically ill patients and reporting a benefit on survival reported also data on QoL. All RCTs investigating nonsurgical interventions that significantly reduced mortality in critically ill patients were searched on MEDLINE/PubMed, Scopus and Embase from inception until August 2021. In a second stage, for all the included studies, the outcome QoL was investigated. The primary outcome was to evaluate how many RCTs analyzing interventions reducing mortality reported also data on QoL. The secondary endpoint was to investigate if QoL resulted improved, worsened or not modified. Data on QoL were reported as evaluated outcome in 7 of the 239 studies (2.9%). The tools to evaluate QoL and QoL time points were heterogeneous. Four interventions showed a significant impact on QoL: Two interventions improved survival and QoL (pravastatin in subarachnoid hemorrhage, dexmedetomidine in elderly patients after noncardiac surgery), while two interventions reduced mortality but negatively influenced QoL (caloric restriction in patients with refeeding syndrome and systematic ICU admission in elderly patients). In conclusion, only a minority of RCTs in which an intervention demonstrated to affect mortality in critically ill patients reported also data on QoL. Future research in critical care should include patient-important outcomes like QoL besides mortality. Data on this topic should be collected in conformity with PROs statement and core outcome sets to guarantee quality and comparability of results.
Topics: Aged; Critical Care; Critical Illness; Hospitalization; Humans; Intensive Care Units; Quality of Life
PubMed: 35524315
DOI: 10.1186/s13054-022-03993-3 -
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 -
PloS One 2022Disturbed cognitive function is associated with several causes of mortality; however, the association between cognitive function and the risk of cancer death has not... (Meta-Analysis)
Meta-Analysis
Association of cognitive function with increased risk of cancer death and all-cause mortality: Longitudinal analysis, systematic review, and meta-analysis of prospective observational studies.
BACKGROUND
Disturbed cognitive function is associated with several causes of mortality; however, the association between cognitive function and the risk of cancer death has not been extensively investigated yet. We aimed to evaluate the association of cognitive function with the risk of cancer death and all-cause mortality in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) and Leiden 85-plus Study. Additionally, a systematic review and meta-analysis of longitudinal studies were conducted to evaluate the association of cognitive function and risk of cancer death.
METHODS
Risk of cancer death and all-cause mortality were reported using hazard ratios (HRs) with 95% confidence interval (CI) in tertiles of cognitive function of PROSPER and Leiden85-Plus Study. Additionally, PubMed, Embase, Web of Science, Cochrane, PsycINFO, Academic Search Premier, CINHAL, and Emcare were searched up to November 1st, 2020 to perform a systematic review and meta-analysis. The relative risks (RRs) with 95%CI of cancer death per each standard deviation lower performance in cognitive measurements were calculated.
RESULTS
Participants of PROSPER had 1.65-fold (95%CI 1.11-2.47) greater risk of cancer death (P for trend = 0.016) and 1.85-fold (95%CI 1.46-2.34) higher risk of all-cause mortality (P for trend<0.001), in multivariable models. Results of the Leiden-85 Plus Study showed that subjects with MMSE score below 24 had a lower chance of cancer death (HR 0.79, 95%CI 0.36-1.70, P for trend = 0.820) but had 2.18-fold (95%CI 1.57-3.02) higher risk of all-cause mortality compared to the reference group (P for trend<0.001). Besides, the results of systematic review and meta-analysis showed that per each standard deviation lower performance in cognitive function, individuals were at a 10% higher chance of cancer death (RR 1.10, 95%CI 1.00-1.20, P-value = 0.044).
CONCLUSIONS
Lower cognitive function performance is associated with a marginally increased risk of cancer death, in line with a significantly greater risk of all-cause mortality.
Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Cognition; Cognitive Dysfunction; Female; Humans; Male; Neoplasms; Pravastatin; Prospective Studies
PubMed: 34995287
DOI: 10.1371/journal.pone.0261826 -
Cureus Sep 20213-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors are commonly used drugs in the management of elevated lipid levels and cardiovascular disease. In... (Review)
Review
3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors are commonly used drugs in the management of elevated lipid levels and cardiovascular disease. In cardiovascular diseases, among other common chronic conditions, inflammatory biomarkers are used to monitor disease progression and the risk of recurrent adverse events. We explored whether or not there was a positive effect on these biomarkers using HMG-CoA reductase inhibitors. The systematic review was conducted by gathering relevant papers mainly from three databases, identified through a generated Medical Subject Headings (MeSH) strategy. Identification of papers was subsequently followed by applying a selected inclusion and exclusion criteria to narrow the papers chosen for review. Post the application of stipulated criteria, 12 papers remained. They were subsequently assessed for risk of bias using a Cochrane risk analysis tool, identifying most as having some concerns of bias or low risk of bias. We found that HMG-CoA reductase inhibitors exhibit both a lipid-lowering effect addition to an anti-inflammatory effect.
PubMed: 34722051
DOI: 10.7759/cureus.18273 -
Andrology Sep 2021Statins constitute the mainstay of treatment in patients with hypercholesterolemia. However, their effect on semen parameters is unknown.
BACKGROUND
Statins constitute the mainstay of treatment in patients with hypercholesterolemia. However, their effect on semen parameters is unknown.
OBJECTIVE
This study aimed to systematically review the best available evidence regarding the effect of statins on ejaculate volume and sperm concentration, motility, morphology, or vitality.
MATERIALS/METHODS
A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases up to January 10, 2021. Either randomized-controlled trials or prospective cohorts, conducted in males with hypercholesterolemia, were included.
RESULTS
Four studies, published between 1992 and 2014, were eligible. The number of participants ranged from 8 to 120 (n = 161). Study duration ranged from 14 to 48 weeks. The type and dose of statin used were pravastatin 20-80 mg/day and simvastatin 20-40 mg/day. With regard to ejaculate volume (n = 3) and sperm concentration (n = 4), no effect was shown with either pravastatin or simvastatin. Regarding sperm motility, either an increase (n = 2; pravastatin, simvastatin), decrease (n = 1; pravastatin), or no effect (n = 1; pravastatin, simvastatin) was found. With respect to sperm morphology, either a decrease (n = 2; pravastatin, simvastatin) or no effect (n = 2; pravastatin, simvastatin) was shown. Concerning sperm vitality, a single study showed a decrease with simvastatin. Because of the high heterogeneity of the populations studied and the limited number of studies, a meta-analysis was not performed.
CONCLUSION
This is the first systematic review on the effect of statins on semen parameters. As there is no evidence for such a detrimental effect, no specific approach has to be suggested regarding the preservation of reproductive function in men with hypercholesterolemia.
Topics: Adult; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Pravastatin; Prospective Studies; Randomized Controlled Trials as Topic; Semen; Simvastatin; Sperm Motility
PubMed: 33998174
DOI: 10.1111/andr.13039