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Basic & Clinical Pharmacology &... Apr 2020The high prevalence of statin and clarithromycin utilization creates potential for overlapping use. The objectives of this MiniReview were to investigate the evidence... (Comparative Study)
Comparative Study
The high prevalence of statin and clarithromycin utilization creates potential for overlapping use. The objectives of this MiniReview were to investigate the evidence base for drug-drug interactions between clarithromycin and currently marketed statins and to present management strategies for these drug combinations. We conducted a systematic literature review following PRISMA guidelines with English language studies retrieved from PubMed and EMBASE (from inception through March 2019). We included 29 articles (16 case reports, 5 observational, 5 clinical pharmacokinetic and 3 in vitro studies). Based on mechanistic/clinical studies involving clarithromycin or the related macrolide erythromycin (both strong inhibitors of CYP3A4 and of hepatic statin uptake transporters OATP1B1 and OATP1B3), clarithromycin is expected to substantially increase systemic exposure to simvastatin and lovastatin (>5-fold increase in area under the plasma concentration-time curve (AUC)), moderately increase AUCs of atorvastatin and pitavastatin (2- to 4-fold AUC increase) and slightly increase pravastatin exposure (≈2-fold AUC increase) while having little effect on fluvastatin or rosuvastatin. The 16 cases of statin-clarithromycin adverse drug reactions (rhabdomyolysis (n = 14) or less severe clinical myopathy) involved a CYP3A4-metabolized statin (simvastatin, lovastatin or atorvastatin). In line, a cohort study found concurrent use of clarithromycin and CYP3A4-metabolized statins to be associated with a doubled risk of hospitalization with rhabdomyolysis or other statin-related adverse events as compared with azithromycin-statin co-administration. If clarithromycin is necessary, we recommend (a) avoiding co-administration with simvastatin, lovastatin or atorvastatin; (b) withholding or dose-reducing pitavastatin; (c) continuing pravastatin therapy with caution, limiting pravastatin dose to 40 mg daily; and (d) continuing fluvastatin or rosuvastatin with caution.
Topics: Area Under Curve; Clarithromycin; Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rhabdomyolysis
PubMed: 31628882
DOI: 10.1111/bcpt.13343 -
Frontiers in Cardiovascular Medicine 2022The objective of this study was to measure the efficacy of various types and dosages of statins on C-reactive protein (CRP) levels in patients with dyslipidemia or...
The effect of various types and doses of statins on C-reactive protein levels in patients with dyslipidemia or coronary heart disease: A systematic review and network meta-analysis.
OBJECTIVE
The objective of this study was to measure the efficacy of various types and dosages of statins on C-reactive protein (CRP) levels in patients with dyslipidemia or coronary heart disease.
METHODS
Randomized controlled trials were searched from PubMed, Embase, Cochrane Library, OpenGray, and ClinicalTrials.gov. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for data extraction and synthesis. The pairwise meta-analysis compared statins and controls using a random-effects model, and a network meta-analysis compared the types and dosages of statins using the Bayesian random-effects model. The PROSPERO registration number is CRD42021242067.
RESULTS
The study included 37 randomized controlled trials with 17,410 participants and 20 interventions. According to the pairwise meta-analysis, statins significantly decreased CRP levels compared to controls (weighted mean difference [WMD] = -0.97, 95% confidence interval [CI] [-1.31, -0.64], < 0.0001). In the network meta-analysis, simvastatin 40 mg/day appeared to be the best strategy for lowering CRP (Rank = 0.18, WMD = -4.07, 95% CI = [-6.52, -1.77]). The same was true for the high-sensitivity CRP, non-acute coronary syndrome (ACS), <12 months duration, and clear measurement subgroups. In the CRP subgroup (rank = 0.79, WMD = -1.23, 95% CI = [-2.48, -0.08]) and ≥12-month duration subgroup (Rank = 0.40, WMD = -2.13, 95% CI = [-4.24, -0.13]), atorvastatin 80 mg/day was most likely to be the best. There were no significant differences in the dyslipidemia and ACS subgroups ( > 0.05). Node-splitting analysis showed no significant inconsistency ( > 0.05), except for the coronary heart disease subgroup.
CONCLUSION
Statins reduced serum CRP levels in patients with dyslipidemia or coronary heart disease. Simvastatin 40 mg/day might be the most effective therapy, and atorvastatin 80 mg/day showed the best long-term effect. This study provides a reference for choosing statin therapy based on LDL-C and CRP levels.
PubMed: 35966518
DOI: 10.3389/fcvm.2022.936817 -
Frontiers in Clinical Diabetes and... 2022Hyperglycemia is associated with a higher cardiovascular risk, as evidenced by increased carotid-intima media thickness (CIMT) in youth with diabetes. We conducted a...
INTRODUCTION
Hyperglycemia is associated with a higher cardiovascular risk, as evidenced by increased carotid-intima media thickness (CIMT) in youth with diabetes. We conducted a systematic review and meta-analysis to assess the effect of pharmacological or non-pharmacological interventions on CIMT in children and adolescents with prediabetes or diabetes.
METHODS
We conducted systematic searches of MEDLINE, EMBASE, and CENTRAL, together with supplementary searches in trial registers and other sources for studies completed up to September 2019. Interventional studies assessing ultrasound CIMT in children and adolescents with prediabetes or diabetes were considered for inclusion. Where appropriate, data were pooled across studies using random-effect meta-analysis. Quality was assessed using The Cochrane Collaboration's risk-of-bias tool and a CIMT reliability tool.
RESULTS
Six studies involving 644 children with type 1 diabetes mellitus were included. No study involved children with prediabetes or type 2 diabetes. Three randomized controlled trials (RCTs) evaluated the effects of metformin, quinapril, and atorvastatin. Three non-randomized studies, with a before-and-after design, evaluated the effects of physical exercise and continuous subcutaneous insulin infusion (CSII). The mean CIMT at baseline ranged from 0.40 to 0.51 mm. The pooled difference in CIMT was -0.01 mm (95% CI: -0.04 to 0.01) for metformin compared to placebo (2 studies; 135 participants; I: 0%). The difference in CIMT was -0.01 mm (95% CI: -0.03 to 0.01) for quinapril compared to placebo (1 study; 406 participants). The mean change from baseline in CIMT was -0.03 mm (95% CI: -0.14 to 0.08) after physical exercise (1 study; 7 participants). Inconsistent results were reported for CSII or for atorvastatin. CIMT measurement was rated at a higher quality on all reliability domains in 3 (50%) studies. The confidence in results is limited by the low number of RCTs and their small sample sizes, as well as the high risk of bias in before-and-after studies.
CONCLUSIONS
Some pharmacological interventions may decrease CIMT in children with type 1 diabetes. However, there is great uncertainty with respect to their effects and no strong conclusions can be drawn. Further evidence from larger RCTs is required.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42017075169.
PubMed: 36992735
DOI: 10.3389/fcdhc.2022.882504 -
Endocrine Jan 2024Thyroid eye disease (TED) is the foremost extrathyroidal manifestation of Graves' disease (GD). Currently, available treatments do not entirely prevent the long-term... (Review)
Review
PURPOSE
Thyroid eye disease (TED) is the foremost extrathyroidal manifestation of Graves' disease (GD). Currently, available treatments do not entirely prevent the long-term consequences of TED and have distinct disadvantages. Therefore, this systematic review explored available evidence regarding the efficacy of statins in preventing and treating TED.
METHODS
Relevant studies investigating statin usage in patients with GD or TED were identified by searching Medline (Pubmed and Ovid), Scopus, Web of Science, ProQuest, and Cochrane Library databases (from the database inception to September 2023). The review was done according to the PRISMA statement. Web searching was done independently by two investigators. Two researchers independently extracted the data, and any disagreement was adjudicated by consensus. Based on the study design, the studies' quality appraisal was done using the Newcastle-Ottawa Scale (NOS) and Version 2 of the Cochrane risk-of-bias tool (RoB2).
RESULTS
The literature search identified 145 publications, of which four met the inclusion criteria (Three retrospective cohort studies and one randomized clinical trial) and were reviewed in full text. The two retrospective cohort studies demonstrated the beneficial effects of statins on TED in newly diagnosed GD Stein et al. showed that statins, regardless of the type, prevent or delay TED (HR: 0.74 (0.65-0.84)), especially in men or treatment duration of more than one year. Nilsson et al. fascinatingly revealed that at least 60 days of statin usage in the preceding year could decrease the risk of TED development by around 40%. One RCT showed a higher treatment response for active moderate-to-severe TED in patients with hypercholesterolemia who took atorvastatin 20 mg in addition to ivGC for 24 weeks without any increase in serious side effects. The retrospective study revealed that the need for reconstructive surgery was reduced in patients with severe TED who received statin therapy.
CONCLUSION
Statin therapy could be a potential adjunctive modality for preventing and treating TED.
TRIAL REGISTRATION
PROSPERO registration number: CRD42022315522.
PubMed: 38194219
DOI: 10.1007/s12020-023-03680-5 -
Frontiers in Aging Neuroscience 2021Several pharmacological treatments have been used to treat patients with chronic subdural hematoma (CSDH), although little is known about the comparative effectiveness...
Several pharmacological treatments have been used to treat patients with chronic subdural hematoma (CSDH), although little is known about the comparative effectiveness of different classes of medication. We performed a Bayesian network meta-analysis to compare and rank the efficacy and safety of five drug regimens to determine the best treatment for this group of patients. We systematically searched PubMed, Medline, clinicaltrials.gov, the Cochrane database, and Embase to identify relevant randomized clinical trials (RCTs) comparing drug treatments in adult patients with CSDH. A network meta-analysis was conducted using a Bayesian framework. Random- and fixed-effects models were used to pool the network results, and the preferred model was selected by comparing the deviance information criteria (DIC). Efficacy outcomes included recurrence requiring surgery, changes in hematoma volume, and a good recovery. The safety outcomes were treatment-related adverse events and all-cause mortality. In this Bayesian network meta-analysis, available data were obtained from 12 eligible trials, including 2,098 patients and 5 techniques. Compared to placebo, atorvastatin (RR: 0.45, 95% CrI: 0.24-0.81) and dexamethasone (RR: 0.38, 95% CrI: 0.22-0.63) were similarly effective in reducing recurrence requiring surgery by 55% and 62%, respectively. Dexamethasone (RR: 0.46, 95% CrI: 0.23-0.91) was more effective in reducing recurrence requiring surgery than goreisan. Additionally, atorvastatin reduced the hematoma volume to a greater extent than placebo (MD: -7.44, 95% CrI: -9.49 to -5.43) or goreisan (MD: -14.09, 95% CrI: -23.35 to -4.82). Moreover, tranexamic acid (MD: -12.07, 95% CrI: -21.68 to -2.29) reduced the hematoma volume to a greater extent than goreisan. No significant differences were detected between drugs and placebo with regard to a good recovery. In terms of safety, dexamethasone (RR: 1.96, 95% CrI: 1.20-3.28) increased the risk of mortality compared to placebo. These findings suggest that dexamethasone is the best treatment to reduce recurrence and atorvastatin is the best treatment to reduce hematoma volume in patients with CSDH. However, clinicians should pay close attention to the elevated risk of all-cause mortality and potential adverse events caused by dexamethasone. Future well-designed RCTs with more participants are needed to verify these findings. http://osf.io/u9hqp.
PubMed: 34276343
DOI: 10.3389/fnagi.2021.684501 -
The Pharmacogenomics Journal Jun 2021This meta-analysis was conducted to determine the genotypic effects of rs4149056 and rs2306283 polymorphism in SLCO1B1 gene on myopathy in patients with statin. Studies... (Meta-Analysis)
Meta-Analysis
This meta-analysis was conducted to determine the genotypic effects of rs4149056 and rs2306283 polymorphism in SLCO1B1 gene on myopathy in patients with statin. Studies were searched using multiple databases and selected following inclusion criteria. Two reviewers independently performed data extraction and assessments for risk of bias. Fixed-or-random-effect was applied to pool allele frequency/effects. Mixed-effect logit model was used to pool genotypic effects using individual patient data. Heterogeneity and publication bias were explored. Fourteen studies were pooled for rs4149056; the minor C allele frequency were 15% in Caucasians and 14% in Asians. Six studies were pooled for rs2306283; the minor G allele frequency was 34% in Caucasian and 75% in Asians. Genotypic effects of rs4149056 polymorphism in Caucasians indicated that statin users who carried CC and TC genotypes had a significantly higher risk of myopathy than those who carried TT genotype, with a pooled odds ratio (OR) of 2.9 (95% confidence interval, 1.59, 5.34) and 1.6 (1.20, 2.16), respectively. For subgroup analysis, CC and TC genotypes also suggested a higher risk of myopathy in simvastatin users [OR = 2.8 (1.17, 6.77) and OR = 1.8 (1.15, 2.77), respectively] and in atorvastatin users [OR = 4.0 (1.23, 12.63) and OR = 2.0 (1.11, 3.52), respectively] than those who carried TT genotype. There was no significant association between rs2306283 polymorphism and myopathy in Caucasians and Asians. There was no evidence of publication bias for both polymorphisms.
Topics: Animals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver-Specific Organic Anion Transporter 1; Muscular Diseases
PubMed: 33608664
DOI: 10.1038/s41397-021-00208-w -
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 -
European Review For Medical and... Sep 2021The aim of this systematic review is to assess the efficacy of locally delivered statins used in adjunct to scaling and root planing (SRP), compared with SRP alone. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this systematic review is to assess the efficacy of locally delivered statins used in adjunct to scaling and root planing (SRP), compared with SRP alone.
MATERIALS AND METHODS
An electronic and hand search was carried out up to April 2020. Only randomized controlled trials (RCTs) were included. Clinical attachment level gain (CALgain) and probing depth reduction (PDred), modified sulcular bleeding index reduction (mSBIred), and intrabony defect reduction (IBDred) were the investigated outcomes. Meta-analysis was performed, and the power of the meta-analytic findings was determined by trial sequential analysis (TSA). Studies were also sub-grouped based on the type of statin used. Statistical heterogeneity and publication bias were assessed.
RESULTS
Twenty RCTs were included (1212 patients, 1289 defects). An overall statistically significant effect size in favor of statins for CALgain and PDred was found. As opposed to atorvastatin and rosuvastatin, simvastatin did not reach statistical significance for these outcomes, as shown by the sub-group analysis.
CONCLUSIONS
Within the limits of the available studies, the local administration of statins (in particular, atorvastatin and rosuvastatin) in adjunct to SRP may result in additional significant improvement in terms of CALgain and PDred compared with SRP alone. The high heterogeneity of data and the high risk of bias found, however, impose caution. No approved preparations, moreover, exist, and further well-designed RCTs from independent research centers are needed to confirm the beneficial effects of the different statins and their mutual differences in the non-surgical periodontal treatment.
Topics: Chronic Periodontitis; Combined Modality Therapy; Dental Scaling; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Root Planing; Treatment Outcome
PubMed: 34604965
DOI: 10.26355/eurrev_202109_26792 -
The Journal of Pharmacy and Pharmacology Apr 2023Peripheral neuropathy (PN), as an adverse reaction attributed to statin drugs, as well as the beneficial neuroprotective properties of statins, have been widely reported...
OBJECTIVES
Peripheral neuropathy (PN), as an adverse reaction attributed to statin drugs, as well as the beneficial neuroprotective properties of statins, have been widely reported and discussed in the literature. The aim of this study was to systematically review original publications that investigated the association of statin use and PN in diabetic and non-diabetic models, whether determined as a result of laboratory experimentation, or in a clinical setting.
KEY FINDINGS
A comprehensive search of the databases Google Scholar, PubMed/MEDLINE and Scopus was conducted. Sixty-six articles, which evaluated the link between statins and PN in either a clinical or in-vivo/in-vitro condition were included. Statin treatment in neuropathy-induced animal models demonstrates favourable neurological effects in both the morphological and functional aspects of neurons. However, an extended duration of statin treatment is minimally associated with the development of non-diabetic idiopathic neuropathy. Importantly, statins have the potential to regress diabetic PN through anti-inflammatory, anti-oxidant and immunomodulatory properties.
SUMMARY
When interpreting the results from studies that deal with the relationship between statins and PN, it is important to determine the mechanism(s) underlying the development of any potential neuropathies (in the presence or absence of diabetes), the type of model used (human or animal) and the duration of statin treatment.
Topics: Animals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Diabetic Neuropathies; Diabetes Mellitus
PubMed: 36843566
DOI: 10.1093/jpp/rgac104 -
Central European Journal of Urology 2021The clinical effect of pharmacotherapy on prostate morphometric parameters is largely unknown. The sole exception is 5α-reductase inhibitors (5-ARI) that reduce...
The effect of pharmacotherapy on prostate volume, prostate perfusion and prostate-specific antigen (prostate morphometric parameters) in patients with lower urinary tract symptoms and benign prostatic obstruction. A systematic review and meta-analysis.
INTRODUCTION
The clinical effect of pharmacotherapy on prostate morphometric parameters is largely unknown. The sole exception is 5α-reductase inhibitors (5-ARI) that reduce prostate volume and prostate-specific antigen (PSA). This review assesses the effect of pharmacotherapy on prostate parameters effect on prostate parameters, namely total prostate volume (TPV), transitional zone volume (TZV), PSA and prostate perfusion.
MATERIAL AND METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) reporting on morphometric parameters' changes after pharmacotherapy, as primary or secondary outcomes. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RCTs' quality was assessed by the Cochrane tool and the criteria of the Agency for Healthcare Research and Quality. The effect magnitude was expressed as standard mean difference (SMD). The study protocol was published on PROSPERO (CRD42020170172).
RESULTS
Sixty-seven RCTs were included in the review and 18 in the meta-analysis. The changes after alpha-blockers are comparable to placebo. Long-term studies reporting significant changes from baseline, result from physiologic growth. Finasteride and dutasteride demonstrated large effect sizes in TPV reduction ([SMD]: -1.15 (95% CI: -1.26 to -1.04, p <0.001, and [SMD]:-0.66 (95% CI: -0.83 to -0.49, p <0.001, respectively), and similar PSA reductions. Dutasteride's effect appears earlier (1 vs 3 month), the changes reach a maximum at month 12 and are sustained thereafter. Phosphodiesterase-5 (PDE-5) inhibitors have no effect on morphometric parameters. Phytotherapy's effect on TPV is non-significant [SMD]: 0.12 (95% CI: -0.03 to 0.27, p = 0.13). Atorvastatin reduces TPV as compared to placebo (-11.7% vs +2.5%, p <0.01). Co-administration of testosterone with dutasteride spares the prostate from the androgenic stimulation as both TPV and PSA are reduced significantly.
CONCLUSIONS
The 5-ARIs show large effect size in reducing TPV and PSA. Tamsulosin improves perfusion but no other effect is evident. PDE-5 inhibitors and phytotherapy do not affect morphometric parameters. Atorvastatin reduces TPV and PSA as opposed to testosterone supplementation.
PubMed: 34729231
DOI: 10.5173/ceju.2021.132.R1