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Thrombosis and Haemostasis Jan 2013Administration of a P2Y 12 -receptor antagonist in addition to aspirin is mandatory in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary... (Meta-Analysis)
Meta-Analysis Review
Impact of clopidogrel and potent P2Y 12 -inhibitors on mortality and stroke in patients with acute coronary syndrome or undergoing percutaneous coronary intervention: a systematic review and meta-analysis.
Administration of a P2Y 12 -receptor antagonist in addition to aspirin is mandatory in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI) to reduce the occurrence of thrombotic events; however, their impact on mortality and stroke is unclear. We aimed to evaluate the influence of moderate (clopidogrel) or potent (prasugrel/ticagrelor) P2Y 12 -receptor inhibition on major cardiovascular outcomes among patients with ACS or undergoing PCI. Systematic literature search was performed to find randomised, controlled clinical trials comparing the clinical impact of clopidogrel with placebo or prasugrel/ticagrelor versus clopidogrel. Outcome measures included cardiovascular death, myocardial infarction (MI), total stroke and intracranial haemorrhage (ICH). Random-effects model with Mantel-Heanszel weighting was used to pool outcomes into a meta-analysis. Four studies comparing clopidogrel with placebo and five trials comparing clopidogrel with new P2Y 12 -receptor inhibitors were identified including a total of 107,473 patients. Compared to placebo, clopidogrel reduced the risk of cardiovascular death (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.87-0.99, p=0.02), MI (OR 0.80; 95%CI 0.74-0.88, p<0.00001) and stroke (OR 0.84; 95%CI 0.72-0.97, p=0.02), without influencing risk for ICH (OR 0.96; 95%CI 0.69-1.33, p=0.79). Treatment with prasugrel/ticagrelor provided additional benefit over clopidogrel regarding cardiovascular mortality (OR 0.86; 95%CI 0.78-0.94, p=0.002) and MI (OR: 0.83; 95%CI 0.74-0.93, p<0.001), but no advantage in stroke (OR: 1.06; 95%CI 0.88-1.26, p=0.55) and in ICH (OR: 1.16; 95%CI 0.75-1.81; p=0.49) was observed. Increased potency of P2Y 12 -receptor inhibition is associated with decreased risk in cardiovascular death and MI; however, this association is not true in case of stroke, where potent P2Y 12 -receptor antagonists have no incremental benefit over clopidogrel.
Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Coronary Thrombosis; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; Stroke; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome
PubMed: 23197191
DOI: 10.1160/TH12-06-0377 -
Multiple Sclerosis (Houndmills,... May 2023Multiple sclerosis patients experience 3-6 times more seizures than the general population, but observations vary among studies. Seizure risk in disease-modifying... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis patients experience 3-6 times more seizures than the general population, but observations vary among studies. Seizure risk in disease-modifying therapy recipients remains unknown.
OBJECTIVE
The objective of this study was to compare seizure risk in multiple sclerosis patients receiving disease-modifying therapy versus placebo.
METHODS
MEDLINE(OVID), Embase, CINAHL, and ClinicalTrials.gov were searched from database inception until August 2021. Phase 2-3 randomized, placebo-controlled trials reporting efficacy and safety data for disease-modifying therapies were included. Network meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using Bayesian random effects model for individual and pooled (by drug target) therapies. Main outcome was log seizure risk ratios [95% credible intervals]. Sensitivity analysis included meta-analysis of non-zero-event studies.
RESULTS
A total of 1993 citations and 331 full-texts were screened. Fifty-six included studies (29,388 patients-disease-modifying therapy = 18,909; placebo = 10,479) reported 60 seizures (therapy = 41; placebo = 19). No individual therapy was associated with altered seizure risk ratio. Exceptions were daclizumab (-17.90 [-65.31; -0.65]) and rituximab (-24.86 [-82.71; -1.37]) trending toward lower risk ratio; cladribine (25.78 [0.94; 4.65]) and pegylated interferon-beta-1a (25.40 [0.78; 85.47]) trended toward higher risk ratio. Observations had wide credible intervals. Sensitivity analysis of 16 non-zero-event studies revealed no difference in risk ratio for pooled therapies (l0.32 [-0.94; 0.29]).
CONCLUSION
No evidence of association was found between disease-modifying therapy and seizure risk-this informs seizure management in multiple sclerosis patients.
Topics: Humans; Multiple Sclerosis; Network Meta-Analysis; Bayes Theorem; Seizures; Cladribine; Anticonvulsants
PubMed: 36802988
DOI: 10.1177/13524585231151400 -
Cell Death & Disease Apr 2024N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating... (Review)
Review
N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating variable splicing, RNA maturation, transcription, and nuclear export, and also is vital for regulating RNA translation, stability, and cytoplasmic degradation. For example, m6A methylation can regulate pre-miRNA expression by affecting both splicing and maturation. Non-coding RNA (ncRNA), which includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), does not encode proteins but has powerful impacts on transcription and translation. Conversely, ncRNAs may impact m6A methylation by affecting the expression of m6A regulators, including miRNAs targeting mRNA of m6A regulators, or lncRNAs, and circRNAs, acting as scaffolds to regulate transcription of m6A regulatory factors. Dysregulation of m6A methylation is common in urinary tumors, and the regulatory role of ncRNAs is also important for these malignancies. This article provides a systematic review of the role and mechanisms of action of m6A methylation and ncRNAs in urinary tumors.
Topics: Humans; RNA, Long Noncoding; RNA, Circular; RNA, Untranslated; Neoplasms; MicroRNAs; Adenosine
PubMed: 38632251
DOI: 10.1038/s41419-024-06664-z -
Texas Heart Institute Journal May 2023For patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), prasugrel was recommended over ticagrelor in a recent randomized controlled trial,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
For patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), prasugrel was recommended over ticagrelor in a recent randomized controlled trial, although more data are needed on the rationale. Here, the effects of P2Y12 inhibitors on ischemic and bleeding events in patients with NSTE-ACS were investigated.
METHODS
Clinical trials that enrolled patients with NSTE-ACS were included, relevant data were extracted, and a network meta-analysis was performed.
RESULTS
This study included 37,268 patients with NSTE-ACS from 11 studies. There was no significant difference between prasugrel and ticagrelor for any end point, although prasugrel had a higher likelihood of event reduction than ticagrelor for all end points except cardiovascular death. Compared with clopidogrel, prasugrel was associated with decreased risks of major adverse cardiovascular events (MACE) (hazard ratio [HR], 0.84; 95% CI, 0.71-0.99) and myocardial infarction (HR, 0.82; 95% CI, 0.68-0.99) but not an increased risk of major bleeding (HR, 1.30; 95% CI, 0.97-1.74). Similarly, compared with clopidogrel, ticagrelor was associated with a reduced risk of cardiovascular death (HR, 0.79; 95% CI, 0.66-0.94) and an increased risk of major bleeding (HR, 1.33; 95% CI, 1.00-1.77; P = .049). For the primary efficacy end point (MACE), prasugrel showed the highest likelihood of event reduction (P = .97) and was superior to ticagrelor (P = .29) and clopidogrel (P = .24).
CONCLUSION
Prasugrel and ticagrelor had comparable risks for every end point, although prasugrel had the highest probability of being the best treatment for reducing the primary efficacy end point. This study highlights the need for further studies to investigate optimal P2Y12 inhibitor selection in patients with NSTE-ACS.
Topics: Humans; Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Network Meta-Analysis; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome
PubMed: 37302149
DOI: 10.14503/THIJ-22-7916 -
Dyspnea and reversibility profile of P2Y₁₂ antagonists: systematic review of new antiplatelet drugs.American Journal of Cardiovascular... Aug 2014Dyspnea has been consecutively reported in some trials evaluating new P2Y₁₂ inhibitors. (Review)
Review
BACKGROUND
Dyspnea has been consecutively reported in some trials evaluating new P2Y₁₂ inhibitors.
OBJECTIVE
We aimed to review and quantify the global risk of dyspnea of recent P2Y₁₂ inhibitor drugs, and evaluate its association with the reversibility profile of P2Y₁₂ inhibitors.
METHODS
A database search (March 2013) retrieved randomized controlled trials (RCTs) comparing new antiplatelet drugs (ticagrelor, prasugrel, cangrelor, elinogrel) with clopidogrel. The primary outcome was the incidence of dyspnea. Placebo-controlled trials were excluded. Meta-analysis was performed and estimates were expressed as risk ratio (RR) and 95% confidence intervals (95% CIs). Dyspnea incidence was evaluated according to the reversibility profile of P2Y₁₂ antagonists.
RESULTS
We found eight RCTs including 41,289 patients. Prasugrel was not associated with an increased risk of dyspnea (RR 1.09, 95% CI 0.93-1.27), whereas ticagrelor (RR 1.95, 95% CI 1.37-2.77), cangrelor (RR 2.42, 95% CI 1.36-4.33), and elinogrel (RR 3.25, 95% CI 1.57-6.72) showed an increased risk of dyspnea. Reversible inhibitors significantly increased the risk of dyspnea compared with the irreversible inhibitor, prasugrel, through adjusted indirect comparison (RR 1.99, 95% CI 1.40-2.82).
CONCLUSIONS
The reversible P2Y₁₂ antagonists ticagrelor, cangrelor, and elinogrel have an increased incidence of dyspnea in increasing order when compared with irreversible P2Y₁₂ inhibitors such as clopidogrel or prasugrel.
Topics: Adenosine; Adenosine Monophosphate; Clopidogrel; Dyspnea; Humans; Incidence; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Quinazolinones; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Sulfonamides; Thiophenes; Ticagrelor; Ticlopidine
PubMed: 24659260
DOI: 10.1007/s40256-014-0071-6 -
The Cochrane Database of Systematic... 2001Cholestasis of pregnancy has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is unresolved, therapies have been empiric. (Review)
Review
BACKGROUND
Cholestasis of pregnancy has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is unresolved, therapies have been empiric.
OBJECTIVES
The objective of the review is to evaluate the effectiveness and safety of therapeutic interventions in women with a clinical diagnosis of cholestasis of pregnancy (CIP) SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register, the Cochrane Controlled Trials Register, MEDLINE and PREMEDLINE, EMBASE, CINAHL and Current Contents. Date of last search: March 2001.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that compared an intervention to either a placebo or alternative treatment in women with a diagnosis of intrahepatic cholestasis of pregnancy. Trials published only as abstracts were excluded.
DATA COLLECTION AND ANALYSIS
Reviewers assessed identified trials for 1) eligibility and 2) methodological quality. Attempts were made to contact authors for missing data.
MAIN RESULTS
Nine RCTs involving 227 women were included but adequate data for appropriate comparisons in pruritus, bile acids or liver enzymes were not consistently reported. S-adenosylmethionine (SAMe) versus placebo (four trials, 82 women): only one trial showed significantly greater improvements in pruritus, bile salts and liver enzymes with SAMe. Ursodeoxycholic acid (UDCA) versus placebo (three trials, 56 women): in two trials a significant difference in pruritus relief was not detected. One trial observed greater reductions in bile salts and liver enzymes with UDCA. Preterm births were fewer with UDCA in one study while two studies reported no difference in fetal distress incidence. Guar gum versus placebo (one trial, 48 patients): no differences in pruritus, bile salts, or fetal/neonatal outcomes were observed. Activated charcoal versus no treatment (one trial, 20 patients): the reduction in bile salts was greater with charcoal, but no difference in pruritus relief: relative risk (RR) 9.0 95% confidence interval (CI) 0.6 - 148 or fetal/neonatal outcomes. UDCA versus SAMe (two trials, 36 patients): pruritus relief was better with UDCA in one study and with SAMe in the other. UDCA was better in reducing bile acids but not liver enzymes in one trial. UDCA + SAMe versus placebo, UDCA or SAMe (one study, eight patients/arm): UDCA + SAMe versus placebo or UDCA resulted in greater improvements in pruritus, bile salts and selected liver function assays; UDCA + SAMe versus SAMe resulted in greater improvements in bile salts and ALP only. No treatments were found to be unsafe.
REVIEWER'S CONCLUSIONS
There is insufficient evidence to recommend guar gum, activated charcoal, SAMe and UDCA alone or in combination in treating women with CIP. Inconsistent and inadequate reporting of results precluded pooling the results of small studies.
Topics: Charcoal; Cholestasis; Female; Galactans; Humans; Mannans; Plant Gums; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; S-Adenosylmethionine; Ursodeoxycholic Acid
PubMed: 11687082
DOI: 10.1002/14651858.CD000493 -
BMC Cardiovascular Disorders Mar 2022Studies show inconsistent results regarding the impact of CYP2C19 genotype on the pharmacodynamics (PD) and clinical outcomes of ticagrelor. With the implementation of... (Meta-Analysis)
Meta-Analysis
Effect of CYP2C19 genetic polymorphism on the pharmacodynamics and clinical outcomes for patients treated with ticagrelor: a systematic review with qualitative and quantitative meta-analysis.
BACKGROUND
Studies show inconsistent results regarding the impact of CYP2C19 genotype on the pharmacodynamics (PD) and clinical outcomes of ticagrelor. With the implementation of genotype-guided individualized antiplatelet therapy, the association between CYP2C19 polymorphism and the efficacy and safety of ticagrelor for patients is still worthy of exploring and studying.
METHODS
This systematic review protocol has been registered in the PROSPERO network (No. CRD 42020158920). Electronic databases of PubMed, EmBase, and the Cochrane Library were systematically searched from inception to January 6th, 2022 to select studies investigating the impact of CYP2C19 genotype on PD and clinical outcomes of ticagrelor. The results were presented as odds ratio (OR) or weight mean difference with its 95% confidence interval (CI) by using the random-effects model. Trial sequential analysis (TSA) was used to control risk of random errors and detect the robustness of outcomes.
RESULTS
Eight studies recruited a total of 6405 patients treated with ticagrelor. Mostly trials reported no significant effect of any or no CYP2C19 loss-of-function (LOF) allele (*2 or *3) on all the endpoints. Compared with no LOF allele carriers, subgroup analysis suggested any LOF allele in Asian patients was associated with a significant decreased risk of bleeding events (OR: 0.41; 95% CI: 0.22-0.75; P = 0.004). Furthermore, any LOF allele carriers didn't yield any impact on the risk of MACEs (OR: 1.11; 95% CI: 0.76-1.64; P = 0.586), stroke (OR: 1.71; 95% CI: 0.99-2.96; P = 0.054), definite stent thrombosis (OR: 0.88; 95% CI: 0.17-4.60; P = 0.882), bleeding (OR: 0.63; 95% CI: 0.27-1.46; P = 0.281), myocardial infarction (OR: 0.81; 95% CI: 0.30-2.20; P = 0.682), and revascularization (OR: 0.81; 95% CI: 0.33-2.00; P = 0.649) in all patients. The results of TSA were indicated that more further trials would be required.
CONCLUSIONS
This qualitative and quantitative study suggested Asian patients carrying any CYP2C19 LOF allele might have a lower risk of bleeding events comparing with no LOF allele carriers when treated with ticagrelor. However, we did not prove an important role of CYP2C19 genotype on the risk of PD and clinical endpoints in the whole cohort. In future, more large-scale prospective studies and more different ethnic populations should be included.
Topics: Clopidogrel; Cytochrome P-450 CYP2C19; Genotype; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Prospective Studies; Ticagrelor; Treatment Outcome
PubMed: 35300607
DOI: 10.1186/s12872-022-02547-3 -
Journal of Cardiovascular Pharmacology Jan 2024Aim of our systematic review and meta-analysis is to compare shortened (≤3 months) dual antiplatelet therapy (DAPT) with longer DAPT in diabetic patients undergoing... (Meta-Analysis)
Meta-Analysis
Aim of our systematic review and meta-analysis is to compare shortened (≤3 months) dual antiplatelet therapy (DAPT) with longer DAPT in diabetic patients undergoing percutaneous coronary interventions.We systematically screened 3 major databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus) searching for randomized-controlled trials or subanalyses of them, which compared shortened DAPT (S-DAPT) with longer DAPT regimens of DAPT. Primary end point of systematic review and meta-analysis is the net adverse clinical events (NACE), and secondary are major adverse cardiac events (MACE), mortality, bleedings, myocardial infarction, and stent thrombosis. Subgroup analyses included studies using only ticagrelor-based regimens and 3-month duration of DAPT.A total of 8 studies and 12,665 patients were included in our analysis. Our meta-analysis met its primary end point because S-DAPT was associated significantly with a reduced risk ratio (RR) by 17% [RR: 0.83, 95% confidence intervals (CI), 0.72-0.96]. Nonsignificant difference among the rest end points was detected between the 2 groups. Subgroup analyses showed that ticagrelor-based regimens were associated with a significant reduction of mortality (RR: 0.67, 95% CI, 0.48-0.93) and 3-month DAPT reduced furtherly NACE by 27% (RR: 0.73, 95% CI, 0.60-0.89).In conclusion, our systematic review and meta-analysis showed that (i) S-DAPT was significantly associated with a lower incidence of NACE, (ii) ticagrelor-based S-DAPT was associated with decreased mortality rates, and (iii) the benefit of 3-month duration of DAPT achieved an even greater NACE reduction. Thus, S-DAPT could be considered as a safe and feasible option in diabetic patients.
Topics: Humans; Diabetes Mellitus; Drug Therapy, Combination; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome
PubMed: 37944149
DOI: 10.1097/FJC.0000000000001503 -
Artificial Organs May 2016Organ preservation solution has been designed to attenuate the detrimental effects during the ischemic period. The aim of this study was to systematically evaluate the... (Meta-Analysis)
Meta-Analysis Review
Organ preservation solution has been designed to attenuate the detrimental effects during the ischemic period. The aim of this study was to systematically evaluate the evidence comparing preservation solutions for heart preservation. Studies were searched in PubMed, Embase, the Cochrane Library, the Transplant Library, and the International Clinical Trials Registry Platform. The primary outcomes were patient survival and donor heart dysfunction. The secondary outcomes were in-hospital mortality and enzyme gene expression. The University of Wisconsin solution (UW) was associated with a significantly improved survival at 30 days and 90 days (hazard ratio = 1.16, 95% confidence interval [CI] = 1.11-1.22, P < 0.00001; risk difference [RD] = 0.03, 95% CI = 0.01-0.05, P = 0.002), compared with Celsior. Hearts preserved with UW exhibited less ischemic necrosis than those preserved with Celsior (RD = -0.07, 95% CI = -0.08 to 0.05, P < 0.00001). UW was associated with better survival compared with histidine-tryptophan-ketoglutarate solution (HTK). There was no statistical difference in donor heart dysfunction and in-hospital mortality outcomes when comparing HTK with Celsior solution. During static cold storage preservation, this study suggests that UW solution has better clinical outcomes for heart transplantation compared with the other two organ preservation solutions. Besides, the protective effect of Celsior solution is similar to HTK solution in donor heart preservation.
Topics: Adenosine; Allografts; Allopurinol; Disaccharides; Electrolytes; Glucose; Glutamates; Glutathione; Heart; Heart Transplantation; Histidine; Humans; Insulin; Mannitol; Organ Preservation; Organ Preservation Solutions; Potassium Chloride; Procaine; Raffinose
PubMed: 26526678
DOI: 10.1111/aor.12585 -
Journal of Interventional Cardiology 2022This systematic review and meta-analysis evaluates the safety and efficacy of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic review and meta-analysis evaluates the safety and efficacy of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS).
BACKGROUND
The safety and efficacy of DAPT in elderly patients with ACS is not well characterized.
METHODS
We performed a systematic literature review to identify clinical studies that reported safety and efficacy outcomes after DAPT for ACS in elderly patients. The primary outcomes of primary efficacy endpoint rates and bleeding event rates were reported as random effects risk ratio (RR) with 95% confidence interval. No prior ethical approval was required since all data are public.
RESULTS
Our search yielded 660 potential studies. We included 8 studies reporting on 29,217 patients. There was a higher risk of bleeding event rates in elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 1.17 (95% CI 1.08 to 1.27, < 0.05). There was no difference in primary efficacy endpoint rates between elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 0.85 (95% CI 0.68 to 1.07, =0.17).
CONCLUSIONS
This systematic review and meta-analysis suggests that DAPT with prasugrel or ticagrelor compared to clopidogrel is associated with a higher risk of bleeding events in elderly patients with ACS. There was no difference in the primary efficacy endpoints between the two treatment groups.
Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Assessment; Ticagrelor; Treatment Outcome
PubMed: 36176329
DOI: 10.1155/2022/3111840