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The American Journal of Cardiology Feb 2024In patients with stable atherosclerotic cardiovascular disease, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) have shown a 50% to 60% reduction in... (Meta-Analysis)
Meta-Analysis
In patients with stable atherosclerotic cardiovascular disease, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) have shown a 50% to 60% reduction in low-density lipoprotein cholesterol (LDL-C) from baseline when added to high-intensity statin therapy. However, less is known about the impact of PCSK9is in the setting of an acute coronary syndrome (ACS). Therefore, we performed a systematic review and meta-analysis comparing PCSK9is with placebo in the setting of ACS added to guideline-directed high-intensity or maximally tolerated statin therapy. We included randomized controlled trials with initiation of a PCSK9i or placebo within 1 week of presentation or percutaneous coronary intervention for ACS. PubMed, EMBASE, and Cochrane Central were searched. This study followed the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations. A total of 6 randomized controlled trials were included, with a total of 996 patients, of whom 503 (50.5%) received PCSK9is. The mean follow-up ranged from 4 to 52 weeks. The LDL-C (mean difference [MD] -44.0 mg/100 ml, CI -54.3 to -33.8, p <0.001) and lipoprotein (a) levels (MD -24.0 nmol/L, confidence interval [CI] -43.0 to -4.9, p = 0.01) were significantly lower at follow-up with PCSK9is. Similarly, the total cholesterol (MD -49.2 mg/100 ml, CI -59.0 to -39.3), triglycerides (MD -19.0 mg/100 ml, CI -29.9 to -8.2), and apolipoprotein B (MD -33.3 mg/100 ml, CI -44.4 to -22.1) were significantly reduced with PCSK9is. In conclusion, in patients with ACS, early initiation of PCSK9i added to statin significantly reduces LDL-C and lipoprotein (a) levels compared with placebo. Whether the differences in these atherogenic lipoproteins translate into a reduction in clinical end points is yet to be determined.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Proprotein Convertase 9; PCSK9 Inhibitors; Acute Coronary Syndrome; Atherosclerosis; Lipoprotein(a); Anticholesteremic Agents
PubMed: 37875235
DOI: 10.1016/j.amjcard.2023.10.043 -
Carcinogenesis Feb 2024Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have... (Meta-Analysis)
Meta-Analysis
Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians' Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69-0.93), with little heterogeneity between studies (I2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy.
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; Androgens; Follow-Up Studies; Cohort Studies; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Prospective Studies; Genotype; Organic Anion Transporters; Solute Carrier Organic Anion Transporter Family Member 1B3
PubMed: 37856781
DOI: 10.1093/carcin/bgad075 -
European Journal of Preventive... Feb 2024The effect of fibrate treatment on cardiovascular risk is inconsistent. This meta-analysis aimed to assess the effect of fibrates on major adverse cardiovascular outcome... (Meta-Analysis)
Meta-Analysis
AIMS
The effect of fibrate treatment on cardiovascular risk is inconsistent. This meta-analysis aimed to assess the effect of fibrates on major adverse cardiovascular outcome (MACE) reduction.
METHODS AND RESULTS
PubMed, Embase, and Cochrane library databases were searched up to February 2023 for randomized controlled trials comparing fibrate therapy against placebo and reporting cardiovascular outcomes and lipid profile changes. The primary outcome was the clinical outcomes of each trial that most closely corresponding to MACE, a composite of cardiovascular death, acute myocardial infarction, stroke, and coronary revascularization. A pre-specified meta-regression analysis to examine the relationship between the changes in lipid levels after fibrate treatment and the risk of MACE was also performed. Twelve trials were selected for final analysis, with 25 781 patients and 2741 MACEs in the fibrate group and 27 450 patients and 3754 MACEs in the control group. Overall, fibrate therapy was associated with decreased risk of MACE [RR 0.87, 95% confidence interval (CI) 0.81-0.94] with moderate heterogeneity (I2 = 47%). In meta-regression analysis, each 1 mmol/L reduction in low-density lipoprotein cholesterol (LDL-C) after fibrate treatment reduced MACE (RR 0.71, 95% CI 0.49-0.94, P = 0.01), while triglyceride level changes did not show a significant association (RR per 1mmol/L reduction 0.96, 95% CI 0.53-1.40, P = 0.86). A sensitivity analysis with the composite outcome of cardiovascular death or acute myocardial infarction produced similar results.
CONCLUSION
Treatment with fibrates was associated with decreased risk of MACE. The reduction in MACE risk with fibrate therapy appears to be attributable to LDL-C reduction rather than a decrease in triglyceride levels.
Topics: Humans; Cholesterol, LDL; Fibric Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular Diseases; Risk Factors; Myocardial Infarction; Triglycerides; Heart Disease Risk Factors
PubMed: 37855457
DOI: 10.1093/eurjpc/zwad331 -
Frontiers in Immunology 2023Cancer is a major global health concern, and immune checkpoint inhibitors (ICIs) offer a promising treatment option for cancer patients. However, the efficacy of ICIs...
INTRODUCTION
Cancer is a major global health concern, and immune checkpoint inhibitors (ICIs) offer a promising treatment option for cancer patients. However, the efficacy of ICIs can be influenced by various factors, including the use of concomitant medications.
METHODS
We searched databases (PubMed, Embase, Cochrane Library, Web of Science) for systematic reviews and meta-analyses for systematic reviews and meta-analyses on the impact of concomitant medications on ICIs efficacy, published from inception to January 1, 2023. We evaluated the methodological quality of the included meta-analyses, and re-synthesized data using a random-effects model and evidence stratification.
RESULTS
We included 23 publications, comprising 11 concomitant medications and 112 associations. Class II-IV evidence suggested that antibiotics have a negative impact on ICIs efficacy. However, ICIs efficacy against melanoma, hepatocellular carcinoma, and esophageal squamous cell carcinoma was not affected, this effect was related to the exposure window (class IV). Class III evidence suggested that proton pump inhibitors have a negative impact on ICIs efficacy; nevertheless, the efficacy against melanoma and renal cell carcinoma was not affected, and the effect was related to exposure before the initiation of ICIs therapy (class II). Although class II/III evidence suggested that steroids have a negative impact, this effect was not observed when used for non-cancer indications and immune-related adverse events (class IV). Class IV evidence suggested that opioids reduce ICIs efficacy, whereas statins and probiotics may improve ICIs efficacy. ICIs efficacy was not affected by histamine 2 receptor antagonists, aspirin, metformin, β-blockers, and nonsteroidal anti-inflammatory agents.
CONCLUSION
Current evidence suggests that the use of antibiotics, PPIs, steroids, and opioids has a negative impact on the efficacy of ICIs. However, this effect may vary depending on the type of tumor, the timing of exposure, and the intended application. Weak evidence suggests that statins and probiotics may enhance the efficacy of ICIs. Aspirin, metformin, β-blockers, and NSAIDs do not appear to affect the efficacy of ICIs. However, caution is advised in interpreting these results due to methodological limitations.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO,identifier, CRD42022328681.
Topics: Humans; Analgesics, Opioid; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Esophageal Neoplasms; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immune Checkpoint Inhibitors; Kidney Neoplasms; Liver Neoplasms; Melanoma; Metformin; Steroids; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 37841249
DOI: 10.3389/fimmu.2023.1218386 -
Canadian Family Physician Medecin de... Oct 2023To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe,...
OBJECTIVE
To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe, fibrates, niacin, omega-3 supplements, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, and statins.
DATA SOURCES
MEDLINE, the Cochrane Database of Systematic Reviews, and a grey literature search.
STUDY SELECTION
Systematic reviews of randomized controlled trials published between January 2017 and March 2022 looking at statins, ezetimibe, PCSK9 inhibitors, fibrates, BAS, niacin, and omega-3 supplements for preventing cardiovascular outcomes were selected. Outcomes of interest included major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, and adverse events.
SYNTHESIS
A total of 76 systematic reviews were included. Four randomized controlled trials were also included for BAS because no efficacy systematic review was identified. Statins significantly reduced MACE (6 systematic reviews; median risk ratio [RR]=0.74; interquartile range [IQR]=0.71 to 0.76), cardiovascular mortality (7 systematic reviews; median RR=0.85, IQR=0.83 to 0.86), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.88 to 0.92). Major adverse cardiovascular events were also significantly reduced by ezetimibe (3 systematic reviews; median RR=0.93, IQR=0.93 to 0.94), PCSK9 inhibitors (14 systematic reviews; median RR=0.84, IQR=0.83 to 0.87), and fibrates (2 systematic reviews; mean RR=0.86), but these interventions had no effect on cardiovascular or all-cause mortality. Fibrates had no effect on any cardiovascular outcomes when added to a statin. Omega-3 combination supplements had no effect on MACE or all-cause mortality but significantly reduced cardiovascular mortality (5 systematic reviews; median RR=0.93, IQR=0.93 to 0.94). Eicosapentaenoic acid ethyl ester alone significantly reduced MACE (1 systematic review, RR=0.78) and cardiovascular mortality (2 systematic reviews; RRs of 0.82 and 0.82). In primary cardiovascular prevention, only statins showed consistent benefits on MACE (6 systematic reviews; median RR=0.75, IQR=0.73 to 0.78), cardiovascularall-cause mortality (7 systematic reviews, median RR=0.83, IQR=0.81 to 0.90), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.87 to 0.91).
CONCLUSION
Statins have the most consistent evidence for the prevention of cardiovascular complications with a relative risk reduction of about 25% for MACE and 10% to 15% for mortality. The addition of ezetimibe, a PCSK9 inhibitor, or eicosapentaenoic acid ethyl ester to a statin provides additional MACE risk reduction but has no effect on all-cause mortality.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proprotein Convertase 9; Cardiovascular Diseases; PCSK9 Inhibitors; Niacin; Systematic Reviews as Topic; Ezetimibe; Lipids; Fibric Acids; Primary Health Care; Anticholesteremic Agents
PubMed: 37833094
DOI: 10.46747/cfp.6910701 -
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 -
Current Reviews in Clinical and... 2024This research aimed to examine the relationship between the intake of statins and the risk of post-stroke pneumonia in a systematic review and meta-analysis study. (Meta-Analysis)
Meta-Analysis
AIM
This research aimed to examine the relationship between the intake of statins and the risk of post-stroke pneumonia in a systematic review and meta-analysis study.
METHODS
An extensive search of published articles on March 2, 2023, was done in several databases, like Web of Science (ISI), PubMed, Cochrane Library, Embase, Scopus, and Google Scholar. The Newcastle Ottawa Scale (NOS) checklist was employed to evaluate the quality of observational studies. Statistical tests (Chi-square test and I) and graphical techniques (Forest plot) were used to determine whether heterogeneity existed in the meta-analysis studies. Funnel plots and Begg and Egger's tests were used to assess the publication bias.
RESULTS
Seven studies (5 cohort and 2 case-control studies) were retrieved to examine the association between statins and post-stroke pneumonia. The sample size of the studies compiled in the meta- analysis was obtained to be 68,966 participants. Meta-analysis demonstrated that the overall odds of post-stroke pneumonia in the statin group was equal to 0.87 (95% CI: 0.67 - 1.13; p-value 0.458). Subgroup analysis indicated that the odds of post-stroke pneumonia in the statin group was equal to 0.93 (95% CI: 0.73-1.18; p-value = 0.558) in the cohort studies, and equal to 0.92 (95% CI: 0.37-2.26; p-value = 0.857) in the case-control studies. The examination of the association between the intake of statins and post-stroke pneumonia showed no evidence of publication bias (Begg's test, p-value = 0.368; Eggers test, p-value = 0.282).
CONCLUSION
In this study, no relationship has been observed between receiving statins and the risk of post-stroke pneumonia.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pneumonia; Stroke; Risk Factors
PubMed: 37817662
DOI: 10.2174/0127724328258172230926070748 -
BMC Oral Health Oct 2023Statins are a category of medications widely used to reduce plasma LDL-cholesterol levels, that also possess antibacterial, anti-inflammatory, and immunomodulatory...
OBJECTIVES
Statins are a category of medications widely used to reduce plasma LDL-cholesterol levels, that also possess antibacterial, anti-inflammatory, and immunomodulatory action. The aim of this systematic review was to explore the effects of systemic statins therapy on the development and treatment of apical periodontitis (AP) on humans and animals.
MATERIAL AND METHODS
Three electronic databases (PubMed, Web of Science, and Scopus) and grey literature were searched from their inception until February, 20 2023 (PROSPERO CRD42021246231). For the quality assessment and risk of bias, different guidelines were used according to the typology of the studies considered (Animal Research Reporting of In Vivo Experiments, Newcastle-Ottawa Quality Assessment Form for Cohort Studies, Systematic Review Centre for Laboratory animal Experimentation Risk of Bias tool and Tool to assess risk of bias in cohort studies of CLARITY Group).
RESULTS
Seven hundred eleven records were screened, and six articles were included for this qualitative review. The eligible studies showed a moderate overall quality and risk of bias. Human patients in treatment with statins exhibited a higher healing rate of AP following root canal treatment. In experimental animal models, statins had a beneficial effect on the development of AP.
CONCLUSIONS
Despite the limited number of studies and considering that most of them are on animals, our findings suggest that systemically administered statins make a positive contribution to prevent the development and help healing of AP.
CLINICAL RELEVANCE
There is an increased evidence that a pharmacologic adjunct to endodontic treatment may be considered to enhance healing of AP. Among other medications, statins seem to have a positive impact on the disease.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Periapical Periodontitis; Root Canal Therapy; Anti-Bacterial Agents; Wound Healing
PubMed: 37805447
DOI: 10.1186/s12903-023-03472-3 -
Current Atherosclerosis Reports Nov 2023This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population,... (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs).
RECENT FINDINGS
A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04). Meta-regression and subgroup analyses did not show any significant differences in pooled estimates across covariates. The effect of statins on CAC differs across study designs. OSs demonstrate associations between statin use and higher CAC scores and presence while being prone to confounding by indication. Effects from RCTs do not reach statistical significance and vary depending on the quantification method, hampering drawing conclusions. Further investigations are required to address the limitations inherent in each approach.
Topics: Humans; Coronary Artery Disease; Coronary Vessels; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Risk Factors; Vascular Calcification; Observational Studies as Topic
PubMed: 37796384
DOI: 10.1007/s11883-023-01151-w -
Archivio Italiano Di Urologia,... Oct 2023Renal cell carcinoma (RCC) is regarded as one of the most common malignant tumors. Various concomitant medications in RCC patients undergoing surgery are investigated to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Renal cell carcinoma (RCC) is regarded as one of the most common malignant tumors. Various concomitant medications in RCC patients undergoing surgery are investigated to explore the potential for improving survival and preventing disease recurrence, including statin. It has been observed that these drugs induce apoptosis, thereby inhibiting tumor growth and angiogenesis. We aimed to perform a systematic review and meta-analysis to enhance the level of evidence for statin in RCC.
METHODS
A systematic literature search was conducted in several online databases, including PubMed, Scopus, and Sciencedirect, using terms relevant to the use of statins in RCC patients undergoing nephrectomy for publications published up to July 2023, according to a registered review procedure (CRD42023452318). The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias of the included study. Review Manager 5.4 was used for all analyses.
RESULTS
Seven articles was eligible for our study. The analysis revealed that patients receiving statin had a better overall survival compared to patients who does not receive statin (HR 0.71, 95% CI 0.51-0.97, p = 0.03, I2 = 76%). However, there was insignificant difference in terms of CSS, DFS, and PFS between RCC patients receiving statin and without statin.
CONCLUSIONS
Statin has substantial benefits for improving OS. Even though the outcomes for CSS, DFS, and PFS were insignificant, the potential role of statins as a supplementary therapy in surgically treated RCC still requires further investigation.
Topics: Humans; Carcinoma, Renal Cell; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Neoplasms; Neoplasm Recurrence, Local; Nephrectomy
PubMed: 37791546
DOI: 10.4081/aiua.2023.11672