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Molecules (Basel, Switzerland) Apr 2023This review article describes studies published over the past five years on the combination of polyphenols, which are the most studied in the field of anticancer effects... (Review)
Review
This review article describes studies published over the past five years on the combination of polyphenols, which are the most studied in the field of anticancer effects (curcumin, quercetin, resveratrol, epigallocatechin gallate, and apigenin) and chemotherapeutics such as cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, etc. According to WHO data, research has been limited to five cancers with the highest morbidity rate (lung, colorectal, liver, gastric, and breast cancer). A systematic review of articles published in the past five years (from January 2018 to January 2023) was carried out with the help of all Web of Science databases and the available base of clinical studies. Based on the preclinical studies presented in this review, polyphenols can enhance drug efficacy and reduce chemoresistance through different molecular mechanisms. Considering the large number of studies, curcumin could be a molecule in future chemotherapy cocktails. One of the main problems in clinical research is related to the limited bioavailability of most polyphenols. The design of a new co-delivery system for drugs and polyphenols is essential for future clinical research. Some polyphenols work in synergy with chemotherapeutic drugs, but some polyphenols can act antagonistically, so caution is always required.
Topics: Polyphenols; Curcumin; Resveratrol; Antioxidants; Drug Therapy, Combination
PubMed: 37175156
DOI: 10.3390/molecules28093746 -
Cardiology 2023The treatment strategy for dual antiplatelet therapy (DAPT) with ticagrelor has been controversial in East Asian patients with acute coronary syndrome (ACS) undergoing... (Comparative Study)
Comparative Study Meta-Analysis
Safety and Efficacy of Ticagrelor versus Clopidogrel in East Asian Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention Treated with Dual Antiplatelet Therapy: A Meta-Analysis of Randomized Controlled Trials.
INTRODUCTION
The treatment strategy for dual antiplatelet therapy (DAPT) with ticagrelor has been controversial in East Asian patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Our meta-analysis aimed to demonstrate whether intensified antithrombotic regimens with ticagrelor plus aspirin have more beneficial effects and fewer adverse events compared to those of clopidogrel plus aspirin in East Asian patients with ACS undergoing PCI.
METHODS
We searched PubMed, Embase, Web of Science, ScienceDirect, Clinical Trials, Cochrane Library, and Chinese Clinical Trial Registry for randomized controlled trials (RCTs) comparing the efficacy of DAPT with ticagrelor or clopidogrel plus aspirin for secondary prevention of ACS in East Asian patients undergoing PCI. Risk ratios (RRs) and 95% confidence intervals (CIs) were used as the metrics of choice for assessing treatment effects. The primary endpoint was bleeding events, and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs, including cardiovascular death, nonfatal myocardial infarction [MI], and stroke), all-cause death, and definite/probable/possible stent thrombosis. The I2 index was used to assess heterogeneity.
RESULTS
Six RCTs involving a total of 2,725 patients met the inclusion criteria. The incidence of all bleeding events with ticagrelor was higher than that with clopidogrel (RR, 1.65; 95% CI, 1.31-2.07), but the incidence of MACCE was not significantly different between the two groups (RR, 1.08; 95% CI, 0.54-2.16). All-cause death (RR, 1.10; 95% CI, 0.67-1.79), cardiovascular death (RR, 1.42; 95% CI, 0.68-2.98), nonfatal MI (RR, 0.92; 95% CI, 0.48-1.78), stroke (RR, 1.00; 95% CI, 0.40-2.50), and stent thrombosis (RR, 0.76; 95% CI, 0.19-2.98) were not statistically different between the two groups.
CONCLUSION
Ticagrelor increased the risk of bleeding and did not increase treatment efficacy compared to that of clopidogrel in the East Asian population who have ACS treated with PCI.
Topics: Humans; Acute Coronary Syndrome; Aspirin; Clopidogrel; East Asian People; Hemorrhage; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Ticagrelor; Treatment Outcome
PubMed: 37094558
DOI: 10.1159/000530602 -
Frontiers in Cardiovascular Medicine 2023Antithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and... (Review)
Review
BACKGROUD
Antithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and efficacy remains undefined. Our objective was to evaluate the effectiveness and safety of antithrombotic options and identify the optimal treatment option for patients with CCS.
METHODS
We used the MEDLINE, CENTRAL and Embase databases to search for randomized controlled trials with follow-up periods longer than 12 months that compared aspirin (ASA) monotherapy with other antithrombotic therapies in patients with CCS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Extracted data [hazard ratios (HR)] were pooled using Bayesian fixed-effect models, allowing the estimation of credible intervals (CrI) and posterior probabilities of benefit, harm, and practical equivalence. Confidence in the results was assessed with the Confidence In Network Meta-Analysis (CINeMA) tool. The primary efficacy and safety outcomes were major adverse cardiovascular events (MACE) and primary bleeding, respectively. Secondary outcomes were acute myocardial infarction, ischemic stroke, all-cause, and cardiovascular-specific mortality.
RESULTS
Five trials with a total of 80,605 patients were included. Mean patient age ranged from 61 to 69 years, while 20.3% to 31.4% were women. The reference treatment was ASA monotherapy. ASA + prasugrel 10 mg and clopidogrel 75 mg monotherapy presented the greatest benefit for MACE [HR 0.52 (95% CrI, 0.39-0.71); and 0.68 (95% CrI, 0.54-0.88)]. There was a probability of 98.8% that ASA + ticagrelor was practically equivalent to ASA monotherapy. Regarding the primary bleeding outcome, clopidogrel 75 mg monotherapy performed best [HR 0.64 (0.42, 0.99)]. There was a probability of 97.4% that ASA + Prasugrel 10 mg increases bleeding (HR > 1.0). Secondary outcome results followed a similar treatment ranking pattern as in primary outcomes. Overall, CINeMA confidence ratings were judged as either low or very low.
CONCLUSIONS
These results revealed that clopidogrel monotherapy might provide the best risk-benefit balance in treating CCS. However, low CINeMA confidence ratings may preclude more forceful conclusions. Our analysis suggests that current guidelines recommending ASA as first-line therapy for CCS management need to be revised to include additional pharmacological options.
PubMed: 37089879
DOI: 10.3389/fcvm.2023.1040936 -
European Neurology 2023Currently, it is still controversial to treat stroke with ticagrelor alone. The purpose of our study was to systematically review and analyze the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Currently, it is still controversial to treat stroke with ticagrelor alone. The purpose of our study was to systematically review and analyze the efficacy and safety of ticagrelor on cerebrovascular outcomes in patients with vascular risk factors.
METHODS
The PubMed, Cochrane Library, and Embase databases were systematically searched using the keywords stroke, ticagrelor, clopidogrel, and aspirin to identify randomized controlled trials (RCTs). Primary outcomes included reported stroke, ischemic stroke, and complex events; the secondary outcome was hemorrhagic stroke. The safety outcomes included major bleeding events, major or minor bleeding, and intracranial bleeding. The pooled odds ratio (OR), hazard ratios (HRs), and 95% confidence interval (CI) were calculated. We used I2 statistics to assess statistical heterogeneity.
RESULTS
This meta-analysis included 15 RCTs involving 63,865 patients. Compared to the control group, ticagrelor reduced the risk of stroke (OR: 0.90; 95% CI: 0.81-0.99, p = 0.03; I2 = 3%), ischemic stroke (OR: 0.81; 95% CI: 0.74-0.90, p < 0.0001; I2 = 0%). Ticagrelor was not associated with an increased risk of all-cause mortality (OR: 0.94; 95% CI: 0.84-1.06, p = 0.31; I2 = 62%), major bleeding (OR: 1.06; 95% CI: 0.97-1.15, p = 0.20; I2 = 17%), hemorrhagic strokes (OR: 1.22, 95% CI: 0.76-1.96, p = 0.41; I2 = 0%), and intracranial hemorrhage (OR: 1.06; 95% CI: 0.78-1.43, p = 0.71; I2 = 12%). There was an increased risk of major or minor bleeding with ticagrelor compared to the control group (OR: 1.40; 95% CI: 1.19-1.66, p < 0.0001; I2 = 56%). Additional analyses demonstrated that ticagrelor reduced the risk of incident recurrent stroke (HR: 0.83; 95% CI: 0.75-0.93, p = 0.0009; I2 = 0%), recurrent ischemic stroke (HR: 0.79; 95% CI: 0.71-0.89, p < 0.0001; I2 = 0%) among patients with a history of acute ischemic stroke (AIS) or transient ischemic attack (TIA). There were no significant differences in safety outcomes.
CONCLUSION
Ticagrelor is slightly better than clopidogrel and aspirin in preventing stroke, especially ischemic stroke, with significant safety risks. For patients with a history of AIS/TIA, the use of ticagrelor was superior to the use of clopidogrel or aspirin in reducing the risk of subsequent stroke. We believe that ticagrelor is a potential alternative to aspirin or clopidogrel in some cases, especially for patients with CYP2C19 deficiency.
Topics: Humans; Aspirin; Clopidogrel; Ticagrelor; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Drug Therapy, Combination; Stroke; Hemorrhage; Intracranial Hemorrhages; Ischemic Stroke; Treatment Outcome
PubMed: 37068471
DOI: 10.1159/000530504 -
Frontiers in Immunology 2023To evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA).
METHODS
CNKI, Pubmed, Cochrane library, Embase were searched to collect randomized controlled trials (RCTs) of dietary polyphenols in the treatment of RA. The databases were searched from the time of their establishment to November 8nd, 2022. After 2 reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies, Meta-analysis was performed using RevMan5.4 software.
RESULTS
A total of 49 records (47 RCTs) were finally included, involving 3852 participants and 15 types of dietary polyphenols (Cinnamon extract, Cranberry extract, Crocus sativus L. extract, Curcumin, Garlic extract, Ginger extract, Hesperidin, Olive oil, Pomegranate extract, Puerarin, Quercetin, Resveratrol, Sesamin, Tea polyphenols, Total glucosides of paeony). Pomegranate extract, Resveratrol, Garlic extract, Puerarin, Hesperidin, Ginger extract, Cinnamon extract, Sesamin only involve in 1 RCT. Cranberry extract, Crocus sativus L. extract, Olive oil, Quercetin, Tea polyphenols involve in 2 RCTs. Total glucosides of paeony and Curcumin involve in more than 3 RCTs. These RCTs showed that these dietary polyphenols could improve disease activity score for 28 joints (DAS28), inflammation levels or oxidative stress levels in RA. The addition of dietary polyphenols did not increase adverse events.
CONCLUSION
Dietary polyphenols may improve DAS28, reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and improve oxidative stress, etc. However, more RCTs are needed to verify or modify the efficacy and safety of dietary polyphenols.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022315645.
Topics: Humans; Resveratrol; Curcumin; Hesperidin; Olive Oil; Quercetin; Randomized Controlled Trials as Topic; Arthritis, Rheumatoid; Glucosides; Tea
PubMed: 37033930
DOI: 10.3389/fimmu.2023.1024120 -
Chinese Medical Journal Apr 2023Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents.
METHODS
We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study.
RESULTS
Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44-0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43-0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43-0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13-1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo.
CONCLUSIONS
Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence.
REGISTRATION
PROSPERO, No. CRD42022296376.
Topics: Humans; Cyclooxygenase 2 Inhibitors; Calcium; Network Meta-Analysis; Vitamins; Colorectal Neoplasms; Chemoprevention; Aspirin; Adenoma; Vitamin D
PubMed: 37027286
DOI: 10.1097/CM9.0000000000002514 -
Acta Medica Indonesiana Jan 2023Arteriovenous fistula (FAV) is the most widely used vascular access for end-stage renal disease (ESRD) patients undergoing routine hemodialysis in Indonesia. However,...
BACKGROUND
Arteriovenous fistula (FAV) is the most widely used vascular access for end-stage renal disease (ESRD) patients undergoing routine hemodialysis in Indonesia. However, FAV can become dysfunctional before it is used for the initiation of hemodialysis, a condition known as primary failure. Clopidogrel is an anti-platelet aggregation that has been reported to reduce the incidence of primary failure in FAV compared to other anti-platelet aggregation agents. Through this systematic review, we aimed to assess the role of clopidogrel to the incidence of primary FAV failure and the risk of bleeding in ESRD patients.
METHODS
A literature search was carried out to obtain randomized Control Trial studies conducted since 1987 from Medline / Pubmed, EbscoHost, Embase, Proquest, Scopus, and Cochrane Central without language restrictions. Risk of bias assessment was performed with the Cochrane Risk of Bias 2 application.
RESULTS
All of the three studies involved indicated the benefit of clopidogrel for the prevention of AVF primary failure. However, all of the studies have substantial differences. Abacilar's study included only participants with diabetes mellitus. This study also administered a combination of clopidogrel 75 mg and prostacyclin 200 mg/day, while Dember's study gave an initial dose of clopidogrel 300 mg followed by daily dose 75 mg and Ghorbani's study only gave clopidogrel 75 mg/day. Ghorbani and Abacilar started the intervention 7-10 days before AVF creation, while Dember started 1 day after VAF creation. Dember gave treatment for 6 weeks with an assessment of primary failure at the end of week 6, Ghorbani's treatment lasted for 6 weeks with an assessment at week 8, while Abacilar gave treatment for one year with an assessment at weeks 4 after AVF creation. In addition, the prevalence of bleeding did not differ between the treatment and control groups.
CONCLUSION
Clopidogrel can reduce the incidence of primary FAV failure without significant increase of bleeding events.
Topics: Humans; Clopidogrel; Arteriovenous Shunt, Surgical; Kidney Failure, Chronic; Renal Dialysis; Hemorrhage; Arteriovenous Fistula; Randomized Controlled Trials as Topic
PubMed: 36999257
DOI: No ID Found -
Kidney360 May 2023Postprocedural bleeding is the main complication of percutaneous kidney biopsy (PKB). Therefore, aspirin is routinely withheld in patients undergoing PKB to reduce the... (Meta-Analysis)
Meta-Analysis
Postprocedural bleeding is the main complication of percutaneous kidney biopsy (PKB). Therefore, aspirin is routinely withheld in patients undergoing PKB to reduce the bleeding risk. The authors aimed to examine the association between aspirin use and bleeding during PKB. This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The article search was performed on MEDLINE and Scopus using queries specific to each database. Article inclusion was limited to primary studies. The meta-analysis compared the risk of major bleeding events between the aspirin-exposed versus nonexposed group. Pooled effect estimate was examined using random effects presented as odds ratio with 95% confidence intervals. Heterogeneity was assessed through Cochrane I 2 test statistics. Sensitivity and subgroup analyses were also performed according to kidney type. Ten studies were included in the review and four studies were included in the meta-analysis, reviewing a total of 34,067 PKBs. Definitions for significant aspirin exposure were inconsistent between studies, limiting comparisons. Studies with broader definitions for aspirin exposure mostly showed no correlation between aspirin use and postbiopsy bleeding. Studies with strict definitions for aspirin exposure found an increased risk of hemorrhagic events in the aspirin-exposed group. No significant differences were found between the aspirin-exposed and comparison groups regarding major bleeding events (odds ratio 1.72; 95% confidence interval 0.50 to 5.89, I 2 =84%). High-quality evidence on the effect of aspirin on the bleeding risk is limited. Our meta-analysis did not show a significantly increased risk of major bleeding complications in aspirin-exposed patients. Further studies are needed to define a more comprehensive approach for clinical practice.
Topics: Humans; Aspirin; Hemorrhage; Kidney; Biopsy
PubMed: 36951435
DOI: 10.34067/KID.0000000000000091 -
British Journal of Anaesthesia Jan 2023Intrapulmonary shunt is a major determinant of oxygenation in thoracic surgery under one-lung ventilation. We reviewed the effects of available treatments on shunt,... (Meta-Analysis)
Meta-Analysis
Impact of pharmacological interventions on intrapulmonary shunt during one-lung ventilation in adult thoracic surgery: a systematic review and component network meta-analysis.
BACKGROUND
Intrapulmonary shunt is a major determinant of oxygenation in thoracic surgery under one-lung ventilation. We reviewed the effects of available treatments on shunt, Pao/FiO and haemodynamics through systematic review and network meta-analysis.
METHODS
Online databases were searched for RCTs comparing pharmacological interventions and intrapulmonary shunt in thoracic surgery under one-lung ventilation up to March 30, 2022. Random-effects (component) network meta-analysis compared 24 treatments and 19 treatment components. The Confidence in Network Meta-Analysis (CINeMA) framework assessed evidence certainty. The primary outcome was intrapulmonary shunt fraction during one-lung ventilation.
RESULTS
A total of 55 RCTs were eligible for systematic review (2788 participants). The addition of NO (mean difference [MD]=-15%; 95% confidence interval [CI], -25 to -5; P=0.003) or almitrine (MD=-13%; 95% CI, -20 to -6; P<0.001) to propofol anaesthesia were efficient at decreasing shunt. Combined epidural anaesthesia (MD=3%; 95% CI, 1-5; P=0.005), sevoflurane (MD=5%; 95% CI, 2-8; P<0.001), isoflurane (MD=6%; 95% CI, 4-9; P<0.001), and desflurane (MD=9%; 95% CI, 4-14; P=0.001) increased shunt vs propofol. Almitrine (MD=147 mm Hg; 95% CI, 58-236; P=0.001), dopexamine (MD=88 mm Hg; 95% CI, 4-171; P=0.039), and iloprost (MD=81 mm Hg; 95% CI, 4-158; P=0.038) improved Pao/FiO. Certainty of evidence ranged from very low to moderate.
CONCLUSIONS
Adding NO or almitrine to propofol anaesthesia reduced intrapulmonary shunt during one-lung ventilation. Halogenated anaesthetics increased shunt in comparison with propofol. The effects of NO, iloprost, and dexmedetomidine should be investigated in future research. NO results constitute a research hypothesis currently not backed by any direct evidence. The clinical availability of almitrine is limited.
SYSTEMATIC REVIEW PROTOCOL
PROSPERO CRD42022310313.
Topics: Adult; Humans; Almitrine; Iloprost; Network Meta-Analysis; One-Lung Ventilation; Propofol; Thoracic Surgery
PubMed: 36939497
DOI: 10.1016/j.bja.2022.08.039 -
Frontiers in Endocrinology 2023Clopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. Discontinuing clopidogrel and substituting it with ticagrelor has been revealed as an effective treatment in previous studies. Since hypoglycemia serves as a risk factor for cardiovascular and cerebrovascular events, we aimed to determine the association between hypoglycemia/IAS and clopidogrel and to investigate whether clopidogrel is a modifiable and causal risk factor of hypoglycemia/IAS.
METHODS
MEDLINE, Embase, Cochrane databases, and clinical trial registries were searched for randomized controlled trials (RCTs) of clopidogrel from inception to 28 February 2022. RCTs comparing clopidogrel with placebo or other antiplatelet drugs were eligible if meeting the inclusion criteria: 1) clopidogrel was administrated 75 mg qd orally as a long-term antiplatelet prescription at least for months, and 2) hypoglycemia-inducible drugs were not used in the control arm. One investigator abstracted articles and performed a quality assessment. Uncertainties were resolved by discussions with two investigators independently. Odds ratio (OR) and risk difference (RD) were calculated and performed with subgroup analyses. The pre-specified protocol was registered in PROSPERO (CRD42022299622).
RESULTS
Six trials with 61,399 participants in total fulfilled the criteria and were included in the meta-analysis. Clopidogrel might not be associated with higher hypoglycemia odds (OR 0.95, 95% CI 0.65 to 1.40). However, Asian participants (p = 0.0437) seemed more likely to develop clopidogrel-associated hypoglycemia. Clopidogrel-associated hypoglycemia occurred at the highest rate of 0.03% (RD -0.00023, 95% CI -0.00077 to 0.00031), and this increased to 0.91% (RD 0.00210, 95% CI -0.00494 to 0.00914) in an aging population and to 0.18% (RD 0.00040, 95% CI -0.00096 to 0.00177) when Asian ratio of the population was elevated.
CONCLUSIONS
We raise the concern that clopidogrel might be a modifiable and causal risk factor of hypoglycemia. The Asian population might be more vulnerable and need additional care.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022299622.
Topics: Humans; Aged; Clopidogrel; Aspirin; Ticlopidine; Platelet Aggregation Inhibitors; Hypoglycemia
PubMed: 36926026
DOI: 10.3389/fendo.2023.1091933