-
Rheumatology (Oxford, England) Dec 2023To evaluate the evidence concerning systemic pharmacological treatments for SSc digital ulcers (DUs) to inform the development of evidence-based treatment guidelines.
OBJECTIVE
To evaluate the evidence concerning systemic pharmacological treatments for SSc digital ulcers (DUs) to inform the development of evidence-based treatment guidelines.
METHODS
A systematic literature review of seven databases was performed to identify all original research studies of adult patients with SSc DUs. Randomized controlled trials (RCTs) and prospective longitudinal observational studies (OBSs) were eligible for inclusion. Data were extracted, applying the patient, intervention, comparison, outcome framework, and risk of bias (RoB) was assessed. Due to study heterogeneity, narrative summaries were used to present data.
RESULTS
Forty-seven studies that evaluated the treatment efficacy or safety of pharmacological therapies were identified among 4250 references. Data from 18 RCTs of 1927 patients and 29 OBSs of 661 patients, at various RoB (total 2588 patients) showed that i.v. iloprost, phosphodiesterase-5 inhibitors and atorvastatin are effective for the treatment of active DUs. Bosentan reduced the rate of future DUs in two RCTs (moderate RoB) and eight OBSs at low to high RoB. Two small studies (moderate RoB) indicate that Janus kinase inhibitors may be effective for the treatment of active DUs, otherwise there are no data to support the use of immunosuppression or anti-platelet agents in the management of DUs.
CONCLUSION
There are several systemic treatments, across four medication classes, that are effective therapies for the management of SSc DUs. However, a lack of robust data means it is not possible to define the optimal treatment regimen for SSc DUs. The relatively low quality of evidence available has highlighted further areas of research need.
Topics: Adult; Humans; Skin Ulcer; Fingers; Scleroderma, Systemic; Bosentan
PubMed: 37335850
DOI: 10.1093/rheumatology/kead289 -
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 -
World Neurosurgery: X Jul 2023Despite recent encouraging pharmaceutical and technical breakthroughs in neurosurgical critical care, traumatic brain injury (TBI)-related mortality and morbidity remain... (Review)
Review
Despite recent encouraging pharmaceutical and technical breakthroughs in neurosurgical critical care, traumatic brain injury (TBI)-related mortality and morbidity remain substantial clinical issues. Medication of statins was revealed to enhance outcomes following TBI in animal research. In addition to their main role of decreasing serum cholesterol, statins decrease inflammation and enhance cerebral blood flow. However, research on the efficacy of statins in TBI is still limited. This systematic review was conducted to determine the efficacy of statins in enhancing the clinical outcomes of TBI individuals, and specifically investigate the optimal dose and form of statins. The databases of PubMed, DOAJ, EBSCO, and Cochrane were extensively researched. The date of publication within the last fifteen years was the inclusion criterion. Meta-analyses, clinical trials, and randomized controlled trials were prioritized forms of research publications. Ambiguous remarks, irrelevant correlations to the main issue, or a focus on disorders other than TBI were the exclusion criteria. Thirteen research were included in this study. Simvastatin, atorvastatin, and rosuvastatin were the main form of statins discussed in this study. Enhancement of the Glasgow Coma Scale, survival rates, hospital length of stay, and cognitive outcomes were revealed in this study. This study suggests either simvastatin 40 mg, atorvastatin 20 mg, or rosuvastatin 20 mg for 10 days as the optimal therapeutic forms and doses to be applied in the management of TBI. Pre-TBI statin use was linked to lower risk of mortality in TBI individuals compared to nonusers, whereas statin discontinuation was linked to an increase in mortality.
PubMed: 37251243
DOI: 10.1016/j.wnsx.2023.100211 -
Pharmacotherapy Apr 2022Colchicine and statins are frequently co-prescribed for prevention and treatment of cardiovascular diseases, auto-inflammatory diseases, and gout. Both are substrates... (Review)
Review
Colchicine and statins are frequently co-prescribed for prevention and treatment of cardiovascular diseases, auto-inflammatory diseases, and gout. Both are substrates and inhibitors of the cytochrome P-450 (CYP) 3A4 isozyme and P-glycoprotein so that taken together, they represent a clinically significant interaction. Data suggest the interaction may be associated with potentially life-threatening myopathies and rhabdomyolysis. The purposes of this systematic review (SR) were to gather and appraise evidence surrounding the statin-colchicine drug interaction and discuss related risk-mitigation strategies. An electronic literature search was performed. Twenty-one articles met the protocol to be included in the qualitative analysis: 18 case reports/series, 2 retrospective observational cohort studies, and 1 retrospective case-control study. Thirty-eight patients developed an adverse drug event (ADE) receiving statin-colchicine combination therapy; 25 (66%) patients developed myopathy; 10 (26%) patients developed rhabdomyolysis, and three (8%) patients developed neuromyopathy. Over 70% of patients developed ADEs on simvastatin or atorvastatin, and 80% of studies reported moderate-to-high intensity statins. Colchicine dosing varied but ranged between 0.5 to 1.5 mg daily. Sixty-two percent of patients in the case reports/series had comorbid renal disease. Seven studies (33% of all included studies) reported patients taking concomitant interacting medications at the CYP3A4 and/or P-glycoprotein efflux pump. Seventeen studies (81% of all included studies) reported ADEs leading to hospitalization. A multivariate analysis from one case-control study identified risk factors prognosticating myopathy ADEs in patients taking statin-colchicine therapy: comorbid renal disease and/or cirrhosis, colchicine doses 1.2 mg daily or greater, and concomitant interacting medications. Clinicians must be cognizant that the statin-colchicine drug interaction may lead to patient harm and thus should employ risk-mitigation strategies for statin-associated muscle symptoms. Future studies are warranted to validate clinically relevant risk factors that are strongly associated with the complications owing to the statin-colchicine drug interaction.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Case-Control Studies; Colchicine; Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Retrospective Studies; Rhabdomyolysis
PubMed: 35175631
DOI: 10.1002/phar.2674 -
Medicine Oct 2023The optimal drug for treatment with polycystic ovary syndrome (PCOS) was in debate. We did this network meta-analysis to assess the efficacy and safety of different... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The optimal drug for treatment with polycystic ovary syndrome (PCOS) was in debate. We did this network meta-analysis to assess the efficacy and safety of different drugs for reducing testosterone levels in women with PCOS.
METHODS
We searched studies from inception until January 10, 2023, through PubMed, Embase, and Cochrane Library database. All studies comparing different drugs for reducing testosterone levels in women with polycystic ovary syndrome were included in this network meta-analysis. Outcomes were total testosterone levels, free testosterone levels, and withdraw due to adverse events. We calculated the surface under the cumulative ranking curve (SUCRA) for each treatment.
RESULTS
Finally, a total of 13 studies were finally included in this network meta-analysis. In head-to-head comparison, atorvastatin (WMD -3.1, 95% CrI: -3.7 to -2.5), metformin (WMD -2.6, 95% CrI: -3.5 to -1.6), metformin + simvastatin (WMD -2.8, 95% CrI: -4.1 to -1.5), simvastatin (WMD -2.7, 95% CrI: -4.2 to -1.3), spironolactone (WMD -3.1, 95% CrI: -4.3 to -1.9), spironolactone + metformin (WMD -3.2, 95% CrI: -4.5 to -2.0) were all more effective than the placebo, and the difference was statistically significant (P < .05). The SUCRA shows that spironolactone + metformin ranked first (SUCRA, 85.0%), Atorvastatin ranked second (SUCRA, 77.7%), Spironolactone ranked third (SUCRA, 77.2%), and metformin + simvastatin ranked the fourth. The SUCRA of different drugs for free testosterone levels shows that atorvastatin ranked first (SUCRA, 75.0%), spironolactone + metformin ranked second (SUCRA, 5.3%), metformin + simvastain ranked third (SUCRA, 62.6%), and spironolactone ranked the fourth (SUCRA, 56.4%). No statistically significant differences were found between the 2 treatment groups for withdrawn due to adverse events (P > .05).
CONCLUSIONS
Considering the network meta-analysis and rankings, atorvastatin was recommended to be the optimal drug for treatment PCOS. However, the optimal dose of atorvastatin was unknown and should be verified by more randomized controlled trials.
Topics: Humans; Female; Spironolactone; Atorvastatin; Network Meta-Analysis; Polycystic Ovary Syndrome; Metformin; Simvastatin; Testosterone
PubMed: 37832133
DOI: 10.1097/MD.0000000000035152 -
Journal of Drugs in Dermatology : JDD Dec 2023Porokeratosis is a group of disorders characterized by aberrant skin keratinization secondary to genetic alterations in the mevalonate pathway, which participates in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Porokeratosis is a group of disorders characterized by aberrant skin keratinization secondary to genetic alterations in the mevalonate pathway, which participates in cholesterol synthesis. While a rare disorder, malignant transformation to squamous cell carcinoma is seen in up to 11% of cases. Recently, topical cholesterol and topical statin therapy have been suggested as a pathogenesis-directed treatment for porokeratosis.
METHODS
A PubMed/MEDLINE and Embase literature search was performed using the search terms: "porokeratosis" AND "cholesterol" OR "lovastatin" OR "simvastatin" OR "atorvastatin" OR "fluvastatin" OR "pitavastatin" OR "pravastatin" OR "rosuvastatin" OR "statin." Peer-reviewed clinical trials, case series, and case reports of all porokeratosis subtypes were included.
RESULTS
Eleven articles were included in the systematic review and 9 articles in the meta-analysis. The systematic review consisted of an aggregate of 33 patients, most of whom (n=31, 93.9%) applied the treatment twice daily for an average of 9.4 weeks (median=8 weeks), with 93.9% (n=31) experiencing improvement or resolution of porokeratosis. Sixteen patients (48.5%) used lovastatin and 16 (48.5%) used simvastatin with concurrent cholesterol therapy. Mild adverse events including erythema and contact dermatitis were experienced by 12.1% of patients. Our meta-analysis yielded a random effects model supporting a robust reduction in porokeratosis severity (OR = .076, 95% CI [0.022, 0.262]).
CONCLUSION
This underpowered meta-analysis provides limited, preliminary evidence supporting the efficacy of topical cholesterol/statin therapy. Overall, quality studies and aggregated sample size are limited; future large clinical trials are needed to further elucidate the role of topical cholesterol/statin therapy in the treatment of porokeratosis. J Drugs Dermatol. 2023;22(12):1160-1165. doi:10.36849/JDD.7775.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Porokeratosis; Lovastatin; Simvastatin; Cholesterol
PubMed: 38051843
DOI: 10.36849/JDD.7775 -
PloS One 2024Atorvastatin is widely recommended for long-term secondary prevention in STEMI patients with no contraindication. Although high-dose atorvastatin has been shown to... (Meta-Analysis)
Meta-Analysis
Atorvastatin is widely recommended for long-term secondary prevention in STEMI patients with no contraindication. Although high-dose atorvastatin has been shown to reduce important patient outcomes such as MACE, there is still doubt that high-dose atorvastatin could have the same protective effect in patients undergoing PCI in the short and long term. We searched the following electronic databases: Scopus, Web of Science, MEDLINE, EMBASE, and Cochrane Central considering studies that enrolled adult patients with a confirmed diagnosis of STEMI or NSTEMI undergoing PCI. The intervention must have been atorvastatin alone compared to a placebo, standard care, or a different atorvastatin dose. A total of (n = 11) studies were included in the quantitative analysis. Information on (N = 5,399) patients was available; 2,654 were assigned to receive high-dose atorvastatin therapy, and 2,745 comprised the control group. High-dose atorvastatin pre-loading significantly reduced MACE at one month of follow-up (RR: 0.78; 95% CI: 0.67-0.91; p = 0.014) in both STEMI and NSTEMI. All-cause mortality was reduced in patients with STEMI (RR: 0.28; 95% CI: 0.10-0.81; p = 0.029). The quality of the body of evidence was rated overall as moderate. Patients presenting with STEMI or NSTEMI benefit from high-dose atorvastatin pre-loading before PCI by reducing MACE at 30 days. The use of high-dose atorvastatin in STEMI patients reduced all-cause mortality. The beneficial effects of atorvastatin pre-loading are limited to 30 days post-PCI.
Topics: Humans; Atorvastatin; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Treatment Outcome
PubMed: 38165842
DOI: 10.1371/journal.pone.0293404 -
Clinical Endocrinology Apr 2022Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD).
OBJECTIVE
To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS.
DATA SOURCES
We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021.
STUDY SELECTION
The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).
DATA EXTRACTION
Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection.
DATA SYNTHESIS
In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I = 75%, very low-grade evidence).
CONCLUSION
There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.
Topics: Atorvastatin; C-Reactive Protein; Cholesterol, LDL; Female; Humans; Metformin; Polycystic Ovary Syndrome
PubMed: 34779013
DOI: 10.1111/cen.14636 -
Drugs in R&D Sep 2023At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis.
METHODS
The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis.
RESULTS
There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR).
CONCLUSION
A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.
Topics: Humans; Cardiomyopathy, Dilated; Carvedilol; Ivabradine; Stroke Volume; Trimetazidine; Network Meta-Analysis; Ventricular Function, Left; Verapamil; Randomized Controlled Trials as Topic
PubMed: 37556093
DOI: 10.1007/s40268-023-00435-5 -
Pharmaceuticals (Basel, Switzerland) May 2023Statins have been established in the market not only due to their ability to lower plasma cholesterol levels but also due to their pleiotropic effects. In the... (Review)
Review
AIM
Statins have been established in the market not only due to their ability to lower plasma cholesterol levels but also due to their pleiotropic effects. In the literature, there is a controversy regarding the role of statins in ophthalmology. We aimed to systematically address the possible effect of statin therapy on ocular diseases and to identify if there is a beneficial relationship.
METHODS
We searched PubMed and Cochrane Library databases up to 31 December 2022 for studies evaluating the effect of statins on ocular diseases. We included all relevant Randomized Control Trials (RCTs) that have been conducted in the adult population. PROSPERO registration number: CRD42022364328.
RESULTS
Nineteen RCTs were finally considered eligible for this systematic review, with a total of 28,940 participants. Ten studies investigated the role of simvastatin, suggesting a lack of cataractogenic effect and a possible protective role in cataract formation, retinal vascular diseases, and especially diabetic retinopathy, age-related macular disease progression, and non-infectious uveitis. Four studies investigated lovastatin, showing no cataractogenic effect. Three studies examined atorvastatin, revealing conflicting results regarding diabetic retinopathy. Two studies examined rosuvastatin, indicating a possibly harmful effect on lenses and a significant protective effect on retinal microvasculature.
CONCLUSIONS
Based on our findings, we believe that statins have no cataractogenic effect. There are indications that statins may have a protective role against cataract formation, AMD, diabetic retinopathy progression, and non-infectious uveitis. However, our results were insufficient for any robust conclusion. Future RCTs, with large sample sizes, on the current topic are therefore recommended to provide more solid evidence.
PubMed: 37242493
DOI: 10.3390/ph16050711