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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 -
JPMA. the Journal of the Pakistan... Jul 2019To review evidence-based data with respect to safety and efficacy of alternate-day statin therapy in dyslipidaemia compared to the standard daily dose.
OBJECTIVE
To review evidence-based data with respect to safety and efficacy of alternate-day statin therapy in dyslipidaemia compared to the standard daily dose.
METHODS
The literature review was conducted at Aga Khan University Hospital, Karachi from July, 2016 to August, 2017. Electronic database search was carried out to compile available literature using PubMed, Excerpta Medica database and Google Scholar. The most relevant evidence-based research articles published over 10 years were selected. The latest search was dated August 03, 2017.
RESULTS
A total of 2,074 articles were initially located. Alternate day statin regimen was reported in 53% of articles. Adverse effects on muscle and tendon were reported in 69% of articles. After scrutiny, 19(0.9%) studies covering alternate-day statin-mediated muscle and tendon disorders and 9(0.4%) studies encompassing the potential pathophysiological mechanisms of statin-associated muscle and tendon injury were selected. Except pravastatin and lovastatin, alternate-day statin therapy was almost as effective in lowering total cholesterol, low-density lipoprotein cholesterol and triglycerides as the daily dosing with low incidence of muscle toxicity and tends in opathy.
CONCLUSIONS
Alternate-day statin regimen was found to be very well tolerated and might be an effective and safe remedy in clinical practice.
Topics: Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscle Cramp; Muscular Diseases; Myalgia; Tendinopathy
PubMed: 31308572
DOI: No ID Found -
European Journal of Clinical... Dec 2020A growing body of preclinical and observational research suggests that statins have potential as a therapeutic strategy in patients with cancer. This systematic review...
PURPOSE
A growing body of preclinical and observational research suggests that statins have potential as a therapeutic strategy in patients with cancer. This systematic review of randomised controlled trials (RCTs) in patients with solid tumours aimed to determine the efficacy of statin therapy on mortality outcomes, their safety profile and the risk of bias of included studies.
METHODS
Full-text articles comparing statin therapy versus control in solid tumours and reporting mortality outcomes were identified from Medline and Embase from conception to February 2020. A systematic review with qualitative (primarily) and quantitative synthesis was conducted. This systematic review was prospectively registered (Prospero registration CRD42018116364).
RESULTS
Eleven trials of 2165 patients were included. Primary tumour sites investigated included lung, colorectal, gastro-oesophageal, pancreatic and liver. Most trials recruited patients with advanced malignancy and used sub-maximal statin doses for relatively short durations. Aside from one trial which demonstrated benefit with allocation to pravastatin 40 mg in hepatocellular carcinoma, the remaining ten trials did not demonstrate efficacy with statins. The pooled hazard ratio for all-cause mortality with allocation to pravastatin in patients with hepatocellular carcinoma in two trials was 0.69 (95% confidence interval CI 0.30-1.61). Study estimates were imprecise. There were no clinically important differences in statin-related adverse events between groups. Overall, included trials were deemed low risk of bias.
CONCLUSION
The trial evidence is not sufficiently robust to confirm or refute the efficacy and safety of statins in patients with solid malignant tumours. Study and patient characteristics may explain this uncertainty. The potential role of high-dose statins in adjuvant settings deserves further research.
Topics: Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Neoplasms; Pravastatin; Progression-Free Survival; Randomized Controlled Trials as Topic; Time Factors
PubMed: 32719919
DOI: 10.1007/s00228-020-02967-0 -
Drug Design, Development and Therapy 2019Pravastatin has been suggested to increase circulating adiponectin in humans. However, results of randomized controlled trials (RCTs) are inconsistent. We aimed to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Pravastatin has been suggested to increase circulating adiponectin in humans. However, results of randomized controlled trials (RCTs) are inconsistent. We aimed to systematically evaluate the influence of pravastatin on circulating adiponectin in humans by performing a meta-analysis of RCTs.
MATERIALS AND METHODS
Studies were identified via systematic searching of PubMed, Embase, and Cochrane's Library databases. A random effect model was used to pool the results. Meta-regression and subgroup analyses were applied to explore the source of heterogeneity.
RESULTS
Eight RCTs with nine comparisons of 595 participants were included. Pravastatin treatment was associated with a significant increased level of circulating adiponectin as compared with controls (weighted mean difference [WMD] =0.63 µg/mL; 95% CI, 0.17-1.09 µg/mL; =0.007) with moderate heterogeneity (I2=28%). These results were confirmed by meta-analysis of double-blinded placebo-controlled RCTs (WMD =0.82 µg/mL; =0.01). Meta-regression analyses indicated that proportions of males in each study were positively correlated with the effect of pravastatin on adiponectin (coefficient: 0.015, =0.03). Subgroup analyses confirmed that pravastatin significantly increased adiponectin in studies of males (WMD =1.41 µg/mL; =0.008), but not in those of females (WMD =-0.04 µg/mL; =0.94).
CONCLUSION
Pravastatin treatment is associated with increased circulating adiponectin. Gender difference may exist regarding the effect of pravastatin treatment on adiponectin.
Topics: Adiponectin; Cardiovascular Diseases; Humans; Pravastatin; Randomized Controlled Trials as Topic
PubMed: 31190742
DOI: 10.2147/DDDT.S186992 -
Nutrients Jul 2020Statins and omega-3 supplementation have been recommended for cardiovascular disease prevention, but comparative effects have not been investigated. This study aimed to... (Comparative Study)
Comparative Study Meta-Analysis
Comparative Effect of Statins and Omega-3 Supplementation on Cardiovascular Events: Meta-Analysis and Network Meta-Analysis of 63 Randomized Controlled Trials Including 264,516 Participants.
Statins and omega-3 supplementation have been recommended for cardiovascular disease prevention, but comparative effects have not been investigated. This study aimed to summarize current evidence of the effect of statins and omega-3 supplementation on cardiovascular events. A meta-analysis and a network meta-analysis of 63 randomized controlled trials were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs) for the effects of specific statins and omega-3 supplementation compared with controls. Overall, the statin group showed significant risk reductions in total cardiovascular disease, coronary heart disease, myocardial infarction, and stroke; however, omega-3 supplementation significantly decreased the risks of coronary heart disease and myocardial infarction only, in the comparison with the control group. In comparison with omega-3 supplementation, pravastatin significantly reduced the risks of total cardiovascular disease (RR = 0.81, 95% CI = 0.72-0.91), coronary heart disease (RR = 0.75, 95% CI = 0.60-0.94), and myocardial infarction (RR = 0.71, 95% CI = 0.55-0.94). Risks of total cardiovascular disease, coronary heart disease, myocardial infarction, and stroke in the atorvastatin group were statistically lower than those in the omega-3 group, with RRs (95% CIs) of 0.80 (0.73-0.88), 0.64 (0.50-0.82), 0.75 (0.60-0.93), and 0.81 (0.66-0.99), respectively. The findings of this study suggest that pravastatin and atorvastatin may be more beneficial than omega-3 supplementation in reducing the risk of total cardiovascular disease, coronary heart disease, and myocardial infarction.
Topics: Aged; Atorvastatin; Cardiovascular Diseases; Coronary Disease; Dietary Supplements; Fatty Acids, Omega-3; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Myocardial Infarction; Network Meta-Analysis; Pravastatin; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome
PubMed: 32722395
DOI: 10.3390/nu12082218 -
Current Medicinal Chemistry 2024Elevated concentrations of serum uric acid (SUA) are associated with several conditions, including cardiovascular disease. The present study aimed to estimate the impact... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Elevated concentrations of serum uric acid (SUA) are associated with several conditions, including cardiovascular disease. The present study aimed to estimate the impact of statin therapy on SUA levels through a systematic review and meta-analysis of clinical trials.
METHODS
PubMed, Embase, Web of Science, and Scopus were searched on January 14, 2022, to identify eligible clinical trials. The intervention group received statins as monotherapy or in combination with other drugs, and the control group received non-statins or placebo. Studies reporting SUA levels before and after treatment were selected for further analysis. Finally, the data were pooled, and the mean changes in SUA, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides were reported.
RESULTS
Out of 1269 identified studies, 23 were included in the review. A total of 3928 participants received statin therapy, and 1294 were included in control groups. We found a significant reduction in SUA levels following statin therapy (mean difference (MD) = -26.67 μmol/L with 95% confidence interval (CI) [-44.75, -8.60] (P =0.004)). Atorvastatin (MD = -37.93 μmol/L [-67.71, -8.15]; P < 0.0001), pravastatin (MD = -12.64 μmol/L [-18.64, -6.65]; P < 0.0001), and simvastatin (MD = -5.95 μmol/L [-6.14, -5.80]; P < 0.0001), but not rosuvastatin, were significantly associated with a reduction in SUA levels. An analysis comparing different types of statins showed that pravastatin 20-40 mg/day could significantly reduce SUA when compared to simvastatin 10-20 mg/day (-21.86 μmol/L [-36.33,-7.39]; P =0.003).
CONCLUSION
Statins were significantly associated with a decrease in SUA levels, particularly atorvastatin, which was found to be most effective in lowering SUA. Atorvastatin may be the most appropriate cholesterol-lowering agent for patients with or at risk of hyperuricemia.
Topics: Uric Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
PubMed: 36748810
DOI: 10.2174/0929867330666230207124516 -
Atherosclerosis Nov 2016Our study aims to evaluate the efficacy and safety of long-term treatment of statins for coronary heart disease (CHD). (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Our study aims to evaluate the efficacy and safety of long-term treatment of statins for coronary heart disease (CHD).
METHODS
Efficacy outcomes included changes in blood lipids, risk of CHD mortality and all-cause mortality. Safety outcomes were evaluated by the risk of adverse events (AE). Bayesian network meta-analysis was used to compare the direct and indirect effects between different statins.
RESULTS
The systematic review showed that levels of blood lipids decreased during statin treatment. High dose of atorvastatin was the most obvious treatment for the reduction of blood lipids. Network meta-analysis showed that statins were significantly more effective than the control in reducing the risk of CHD mortality (Odds Ratio (OR) 0.69, 95% CI 0.61-0.77) and all-cause mortality (OR 0.84, 95% CI 0.80-0.87). In terms of reducing the risk of CHD morality, fluvastatin (77.3%), atorvastatin (72.3%) and lovastatin (68.4%) had higher cumulative probability than other statins, which were more effective treatments for the reduction of CHD morality. In terms of reducing all-cause mortality, atorvastatin (78.6%), fluvastatin (77.1%) and pitavastatin (74.1%) had higher cumulative probability than other statins, which were more effective treatment for reducing the all-cause mortality. Compared with placebo, statins increased the incidence risk of muscle disease (OR 1.05, 95% CI 1.00-1.10) and kidney disease (OR 1.11, 95% CI 1.05-1.72).
CONCLUSIONS
Statins significantly reduced levels of blood lipids, with a high dose of atorvastatin being the most effective in blood-lipid level modification. Statins reduced the risk of CHD mortality and all-cause mortality, with atorvastatin and fluvastatin being the most effective in reducing the risk of CHD mortality and all-cause mortality. Statins increased the risk of muscle disease and kidney damage.
Topics: Anticholesteremic Agents; Atorvastatin; Bayes Theorem; Coronary Disease; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Kidney Diseases; Lipids; Lovastatin; Muscles; Network Meta-Analysis; Patient Safety; Pravastatin; Quinolines; Randomized Controlled Trials as Topic; Simvastatin; Treatment Outcome
PubMed: 27764723
DOI: 10.1016/j.atherosclerosis.2016.10.025 -
Hellenic Journal of Cardiology : HJC =... 2019Observational studies have suggested that statins might reduce postoperative atrial fibrillation (AF) in patients undergoing cardiac surgery. However, a number of...
BACKGROUND
Observational studies have suggested that statins might reduce postoperative atrial fibrillation (AF) in patients undergoing cardiac surgery. However, a number of retrospective studies have shown equivocal results. We aimed to evaluate whether different statins can reduce the risk for AF at different doses.
METHODS
We searched PubMed, EMBASE, and the Cochrane Database for all published randomized controlled trials (RCTs) that examined the effects of statin therapy on AF up to June 2016. A random-effects model was used when there was substantial heterogeneity.
RESULTS
Eighteen published studies that included 4003 statin-naive patients (2009 receiving satins and 1994 receiving regime) with sinus rhythm before cardiac surgeries were identified for inclusion in the analysis. Thirteen studies investigated the prevention of AF by atorvastatin, two studies investigated the prevention of AF by rosuvastatin, two studies investigated the prevention of AF by simvastatin, and one study investigated the prevention of AF by pravastatin. The remaining two studies compared the effects of different doses of atorvastatin on the prevention of AF in patients undergoing coronary artery bypass grafting (CABG). Overall, statin therapy was associated with a significant decrease in the risk for AF (relative risk [RR]: 0.57, 95% confidence interval [CI]: 0.45-0.73, P = 0.000). However, subgroup analyses showed that only atorvastatin reduced the risk for new-onset AF in patients after cardiac surgery (RR: 0.53, 95% CI: 0.41-0.69, P = 0.000). Patients undergoing CABG possibly received more benefits from statin therapy (RR: 0.52, 95% CI: 0.39-0.68).Statin therapy in a moderate dose may be optimal (RR: 0.42, 95% CI: 0.28-0.64).
CONCLUSIONS
This meta-analysis suggests that statin therapy has an overall protective effect against postoperative AF, among which atorvastatin in a moderate dose was significantly associated with a decreased risk for new-onset AF in patients after CABG. Moreover, simvastatin may also exert a significant protective effect against the AF recurrences in patients undergoing cardiac surgeries; hence, further prospective studies are warranted.
Topics: Atorvastatin; Atrial Fibrillation; Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Postoperative Complications; Prognosis
PubMed: 29307691
DOI: 10.1016/j.hjc.2017.12.012 -
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