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Cardiology 2022There have been inconsistent data on the direct comparison of prasugrel and ticagrelor. This meta-analysis was conducted to summarize the current available evidence. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
There have been inconsistent data on the direct comparison of prasugrel and ticagrelor. This meta-analysis was conducted to summarize the current available evidence.
METHODS
We performed a meta-analysis (PROSPERO-registered CRD42020166810) of randomized trials up to February 2020 that compared prasugrel and ticagrelor in acute coronary syndrome with respect to the composite endpoint of myocardial infarction (MI), stroke, or cardiovascular death and secondary endpoints including MI, stroke, cardiovascular death, major bleeding (Bleeding Academic Research Consortium (BARC) type 2 or above), stent thrombosis, all-cause death, and other safety outcomes.
RESULTS
Of the 11 eligible RCTs with 6,098 patients randomized to prasugrel (n = 3,050) or ticagrelor (n = 3,048), 180 and 207 had the composite endpoint events in the prasugrel arm and the ticagrelor arm, respectively, over a weighted mean follow-up period of 11 ± 2 months. Compared with prasugrel, the ticagrelor group had similar risk in the primary composite endpoint (risk ratio [RR] = 1.17; 95% CI = 0.96-1.42; p = 0.12, I2 = 0%). Compared to prasugrel, there was no significant difference associated with the ticagrelor groups with respect to stroke (RR = 1.05; 95% CI = 0.66-1.67; p = 0.84, I2 = 0%), cardiovascular death (RR = 1.01; 95% CI = 0.75-1.36; p = 0.95, I2 = 0%), BARC type 2 or above bleeding (RR = 1.16; 95% CI = 0.89-1.52; p = 0.26, I2 = 0%), stent thrombosis (RR = 1.58; 95% CI = 0.90-2.76; p = 0.11, I2 = 0%), and all-cause death (RR = 1.10; 95% CI = 0.86-1.43; p = 0.45, I2 = 0%) except MI (RR = 1.38; 95% CI = 1.05-1.81; p = 0.02, I2 = 0%) Conclusion: Compared with prasugrel, ticagrelor did not reduce the primary composite endpoint of MI, stroke, and cardiovascular death at a weighted mean follow-up of 11 months. There was no significant difference between the secondary outcomes except MI.
Topics: Acute Coronary Syndrome; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome
PubMed: 34743081
DOI: 10.1159/000520673 -
Epigenetics Aug 2021N6-methyladenosine (m6A), the most prevalent RNA internal modification, is present in most eukaryotic species and prokaryotes. Studies have highlighted an intricate...
N6-methyladenosine (m6A), the most prevalent RNA internal modification, is present in most eukaryotic species and prokaryotes. Studies have highlighted an intricate network architecture by which m6A epitranscriptome impacts on immune response and function. However, it was only until recently that the mechanisms underlying the involvement of m6A modification in immune system were uncovered. Here, we systematically review the m6A involvement in the regulation of innate and adaptive immune cells. Further, the interplay between m6A modification and anti-inflammatory, anti-viral and anti-tumour immunity is also comprehensively summarized. Finally, we focus on the future prospects of m6A modification in immune modulation. A better understanding of the crosstalk between m6A modification and immune system is of great significance to reveal new pathogenic pathways and to develop promising therapeutic targets of diseases.
Topics: Adenosine; DNA Methylation; Immune System; Logic
PubMed: 33070685
DOI: 10.1080/15592294.2020.1827722 -
PloS One 2023The function of coronary microcirculation is an important factor in predicting the prognosis of patients with acute coronary syndrome (ACS) who receive percutaneous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The function of coronary microcirculation is an important factor in predicting the prognosis of patients with acute coronary syndrome (ACS) who receive percutaneous coronary intervention (PCI) therapy. Ticagrelor, a type of oral P2Y12 inhibitor, is widely prescribed to ACS patients and can improve prognosis compared to clopidogrel. However, the efficacy of ticagrelor on coronary microcirculation, compared to clopidogrel, remains unclear. The objective of this meta-analysis was to determine the efficacy of ticagrelor on coronary microcirculation.
METHODS
The PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were comprehensively searched to identify studies until November 2022. Data was pooled using the fixed effects model or random effects model based on the level of heterogeneity. Sensitivity analyses were performed to measure the effects of potential confounders.
RESULTS
After screening, 16 trials with a total of 3676 participants were ultimately included in the analysis. The meta-analysis revealed that compared to clopidogrel, patients receiving ticagrelor exhibited a more significant reduction in the IMR (WMD: -6.23, 95% CI: -8.41 to -4.04), a reduction in the cTFC (WMD: -1.88; 95% CI: -3.32 to -0.45), and greater increases in CFR (WMD: 0.38; 95% CI: 0.18 to 0.57), MBG (RR 1.29, 95% CI 1.12 to 1.48), and TIMI (RR 1.03, 95% CI 1.00 to 1.06).
CONCLUSION
Our findings suggest that, compared to clopidogrel, ticagrelor has a significant effect in reducing coronary microcirculatory resistance, enhancing coronary blood flow reserve, and improving myocardial perfusion.
Topics: Humans; Acute Coronary Syndrome; Clopidogrel; Ticagrelor; Microcirculation; Percutaneous Coronary Intervention
PubMed: 37643179
DOI: 10.1371/journal.pone.0289243 -
Medicine Nov 2023To ascertain the efficacy and safety of cladribine, cytarabine, and filgrastim-based regimen in relapsed or refractory (R/R) AML patients. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To ascertain the efficacy and safety of cladribine, cytarabine, and filgrastim-based regimen in relapsed or refractory (R/R) AML patients.
METHODS
Clinical studies were searched in PubMed, Cochrane Library, Embase data. We selected available factors including complete remission (CR), overall response rate (ORR), overall survival (OS) to evaluate the efficacy, and early death (ED), and adverse events to evaluate safety.
RESULTS
15 records with 812 R/R AML patients were finally included and analyzed using the R software. Subgroups analysis was also conducted. The pooled CR rate for CLAG regimen, CLAG-M regimen, and CLAG combined with any other drugs regimen is 56% (95% CI: 46-66), 46% (95% CI: 34-56), 44% (95% CI: 26-64), respectively. The relapsed and refractory groups showed a CR rate of 68% (95% CI: 53-80), and 51% (95% CI: 45-58) with CLAG related regimens. As risk grade decreases, the pooled CR rate increases. Regarding the safety for CLAG-related protocols, systematic review was conducted.
CONCLUSION
The CLAG-related regimen is an effective and safe therapy for R/R AML patients, CLAG seems to have more superiority than CLAG combined therapy, though further studies including cladribine combination treatment protocols, are still needed to confirm our results further.
Topics: Humans; Filgrastim; Cladribine; Leukemia, Myeloid, Acute; Remission Induction; Cytarabine; Antineoplastic Combined Chemotherapy Protocols; Granulocyte Colony-Stimulating Factor
PubMed: 37933074
DOI: 10.1097/MD.0000000000034949 -
Neurologia I Neurochirurgia Polska 2022This study was performed to compare probabilities of SDI on the Expanded Disability Status Scale (EDSS) in patients with relapsing-remitting multiple sclerosis (RRMS),... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This study was performed to compare probabilities of SDI on the Expanded Disability Status Scale (EDSS) in patients with relapsing-remitting multiple sclerosis (RRMS), treated with cladribine tablets (CT) or fingolimod (FTY), natalizumab (NAT), alemtuzumab (ALE) and ocrelizumab (OCR).
CLINICAL RATIONALE FOR THE STUDY
Progression of neurological disability as measured by the EDSS has been a common endpoint in multiple sclerosis (MS) trials. Novel therapies can not only slow this process, but in some patients even reverse it. This effect can be measured by the sustained disability improvement (SDI) - an endpoint that seems to continuously gain importance in clinical practice. Despite that, SDI has rarely been explored as an outcome in MS clinical studies, mostly as post-hoc analyses from randomised trials or as retrospective analyses based on patient registry records.
MATERIAL AND METHODS
A systematic review was conducted in Medline, Embase and Cochrane to identify clinical trials (RCT or non-RCT) evaluating 6-month SDI. An indirect comparison via network meta-analysis (NMA) was performed. Bayesian inference with Markov chains Monte Carlo methods were applied.
RESULTS
Eight trials presenting SDI results and applicable for NMA were included: six non-RCTs, with control groups selected by propensity score matching, and two RCTs. NMA results revealed that probability of achieving 6-month SDI with CT was significantly higher compared to all other high efficacy disease-modifying drugs with available data - HR (95% Crl - Bayesian Credibility Interval) vs. FTY: 4.98 (2.11-11.79); vs. NAT: 3.12 (1.31-7.27); vs. ALE: 9.29 (3.40-25.21). The main results were confirmed in the sensitivity analyses.
CONCLUSIONS
Of all considered therapies, treatment with cladribine tablets was associated with a higher probability of sustained disability improvement in RRMS patients. As this conclusion is based on available clinical data of limited quality, future studies, as well as real-world data, would be valuable to provide further evidence regarding the comparative effectiveness of RRMS therapies.
Topics: Humans; Cladribine; Multiple Sclerosis; Immunosuppressive Agents; Network Meta-Analysis; Retrospective Studies; Bayes Theorem; Multiple Sclerosis, Relapsing-Remitting; Tablets
PubMed: 36421066
DOI: 10.5603/PJNNS.a2022.0068 -
British Journal of Clinical Pharmacology Aug 2020We performed a systematic review and meta-analysis to compare the efficacy and safety of ticagrelor and prasugrel with those of clopidogrel in CYP2C19... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of clopidogrel versus prasugrel and ticagrelor for coronary artery disease treatment in patients with CYP2C19 LoF alleles: a systemic review and meta-analysis.
AIM
We performed a systematic review and meta-analysis to compare the efficacy and safety of ticagrelor and prasugrel with those of clopidogrel in CYP2C19 reduced-metabolizers.
METHODS
PubMed, Cochrane and Web of Science were systematically searched for randomized controlled trials or cohort studies up to January 2020. The primary endpoint was major adverse cardiovascular events (MACE), including cardiovascular (CV) death, all-cause death, myocardial infarction (MI), stent thrombosis and stroke. The secondary endpoint was bleeding. Pooled effects were measured by relative risk (RR) with 95% confidence intervals (CIs). Publication bias was evaluated with Egger's regression test and adjusted by trim and fill method.
RESULTS
Twelve studies comprising 5829 CV patients with CYP2C19 loss-of-function alleles were included. Patients who received ticagrelor or prasugrel showed a lower risk of MACE than those who received clopidogrel (RR 0.524; 95% CI: 0.375, 0.731). The former also had lower risks of CV death (RR 0.409; 95% CI: 0.177, 0.946), all-cause death (RR 0.441; 95% CI: 0.263, 0.739), MI (RR 0.554; 95% CI: 0.414, 0.741) and stent thrombosis (RR 0.587; 95% CI: 0.348, 0.988) than the latter patient group. The risk of stroke was not significantly different between patients receiving the alternatives and those receiving clopidogrel (RR 0.605; 95% CI: 0.257, 1.425). Major and minor bleeding risk was not significantly different between patients treated with alternatives and clopidogrel (RR 1.019; 95% CI: 0.827, 1.260 and RR 1.235; 95% CI: 0.581, 2.628, respectively).
CONCLUSION
CYP2C19 reduced-metabolizers can expect better clinical outcome on using prasugrel or ticagrelor rather than clopidogrel.
Topics: Acute Coronary Syndrome; Alleles; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome
PubMed: 32320492
DOI: 10.1111/bcp.14317 -
PloS One 2021Patients with minor ischemic stroke or transient ischemic attack represent a high-risk population for recurrent stroke. No direct comparison exists comparing dual... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Patients with minor ischemic stroke or transient ischemic attack represent a high-risk population for recurrent stroke. No direct comparison exists comparing dual antiplatelet therapy regimens-namely, Ticagrelor and Aspirin versus Clopidogrel and Aspirin. This systematic review and network meta-analysis (NMA) will examine the efficacy of these two different antiplatelet regimens in preventing recurrent stroke and mortality up to 30 days.
METHODS AND ANALYSIS
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched with the assistance of a medical information specialist. Two independent reviewers will screen studies for inclusion; eligible studies will include randomized controlled trials that enrolled adults presenting with acute minor ischemic stroke or transient ischemic attack and compared one or more of the interventions against each other and/or a control. The primary outcomes will be recurrent ischemic stroke up to 30 days from symptom onset. Secondary outcomes will include safety outcomes (I.e. major bleeding and mortality), functional disability, and outcomes up to 90 days from symptom onset. A Bayesian approach to NMA will be implemented using the BUGSnet function in R Software. Between group comparisons for time-to-event (TTE) and dichotomous outcomes will be presented in terms of hazard ratios and odds ratios with 95% credible intervals, respectively. Secondary effect measures of treatment ranking will also be estimated.
ETHICS AND DISSEMINATION
No formal research ethics approval are necessary. We will disseminate our findings through scientific conference presentations, peer-reviewed publications, and social media/the press. The findings from this review will aid clinicians in decision-making on the choice of antithrombotic therapy in a high-risk stroke population and could be important in the development of future treatment trials and guidelines. Registration ID with Open Science Framework: 10.17605/OSF.IO/XDJYZ.
Topics: Aspirin; Bayes Theorem; Brain Ischemia; Clopidogrel; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Network Meta-Analysis; Platelet Aggregation Inhibitors; Ticagrelor
PubMed: 33909676
DOI: 10.1371/journal.pone.0250553 -
Medicine May 2021We aimed to systematically evaluate the efficacy and safety ticagrelor monotherapy following percutaneous coronary intervention. (Meta-Analysis)
Meta-Analysis
BACKGROUND
We aimed to systematically evaluate the efficacy and safety ticagrelor monotherapy following percutaneous coronary intervention.
METHODS
Online databases were searched for relevant studies (published between the years 2015 and 2020) comparing 1-month Dual antiplatelet therapy (DAPT) followed by 23-month ticagrelor monotherapy with 12-month DAPT followed by 12-month aspirin monotherapy following percutaneous coronary intervention. Primary outcomes assessed efficacy whereas secondary outcomes assessed safety. Odds ratios (OR) with 95% confidence intervals (CIs) based on a random effect model were calculated and the analysis was carried out by the RevMan 5.3 software.
RESULTS
Only 6 studies were selected for this meta-analytical research. The meta-analysis results: MI(OR:0.96, 95% CI:0.86-1.06, P = .40), stroke (OR:1.04, 95% CI: 0.87-1.25, P = .68), stent thrombosis (OR: 0.91,95% CI:0.76-1.10,P = .32),New-Q Wave (OR:0.85,95% CI: 0.72-1.00, P = .05), all cause death (OR:0.91, 95% CI: 0.87-0.96, P < .0001), death from cardiovascular (OR: 0.76, 95% CI: 0.58-0.99, P = .04), revascularization (OR: 0.93, 95% CI: 0.87-0.99, P = .03). Ticagrelor monotherapy was associated with a significantly lower rate of myocardial Infarction (MI), stroke, stent thrombosis, all cause death, death from cardiovascular and revascularization (OR:0.91,95% CI:0.87-0.96, P < .0001) when compared to DAPT. Besides, DAPT was associated with a significantly higher rate of BARC3 or 5 bleeding (OR:0.85, 95% CI: 0.68-1.06; P = .16) when compared to ticagrelor. When bleeding was further subdivided, minor or major bleeding was also significantly higher with DAPT (OR: 0.72, 95% CI: 0.41-1.27; P = .26). GUSTO moderate or severe bleeding was also significantly higher with DAPT (OR: 0.77, 95% CI: 0.39-1.52; P = .45).
CONCLUSION
Ticagrelor monotherapy after short-term dual-antiplatelet therapy (DAPT) can optimize ischemic and bleeding risks. And, it can reduce the occurrence of events outcome (MI, revascularization, stroke, stent thrombosis).
Topics: Drug Administration Schedule; Dual Anti-Platelet Therapy; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor
PubMed: 34011127
DOI: 10.1097/MD.0000000000026070 -
British Journal of Haematology Jun 2020Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete...
Long-term efficacy and safety of 2CdA (cladribine) in extra-pulmonary adult-onset Langerhans cell histiocytosis: analysis of 23 cases from the French Histiocytosis Group and systematic literature review.
Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete picture of the efficacy and safety of 2CdA (2-chlorodeoxyadenosine, cladribine) is lacking. We report a retrospective multicentre study of 23 adult LCH (a-LCH) patients who received single-agent 2CdA and a systematic literature review. All had previously received systemic therapy (vinblastine, n = 19). Response to 2CdA was evaluable in 22 cases. Overall response rate (ORR) was 91%. Complete response (CR) occurred in 11 cases (50%). Nine patients (39%) developed grade 3-4 neutropenia and/or severe infection. A literature review yielded 48 additional cases. A pooled analysis confirmed our findings (ORR: 88%, CR: 49%). CRs were rare with cumulative dose <50 mg/m . Disease progression rates were 20% and 30% at two and five years, respectively. Partial response (PR) to 2CdA was predictive of disease progression. Among eight re-treated patients, five went into CR, two in PR, and one died. Single-agent 2CdA is effective in reactivated a-LCH, including at intermediate doses. Toxicity, significant but acceptable, warrants infectious prophylaxis. Complete responders may enter prolonged remission. Further studies are needed to determine 2CdA sequencing with other agents (vinblastine, cytarabine).
Topics: Adult; Age of Onset; Aged, 80 and over; Antimetabolites; Cladribine; Dose-Response Relationship, Drug; Female; France; Histiocytosis, Langerhans-Cell; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Proportional Hazards Models; Remission Induction; Retrospective Studies; Sepsis; Virus Diseases
PubMed: 32191819
DOI: 10.1111/bjh.16449 -
Clinical Cardiology Apr 2021Clopidogrel, prasugrel and ticagrelor, acting on platelet P2Y12 receptor, are commonly used for prevention of stent thrombosis (ST) among patients who underwent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clopidogrel, prasugrel and ticagrelor, acting on platelet P2Y12 receptor, are commonly used for prevention of stent thrombosis (ST) among patients who underwent percutaneous coronary intervention (PCI). This study aimed to compare the effects of these drugs by a systematic review and network meta-analysis.
HYPOTHESIS
Efficacies of clopidogrel, prasugrel and ticagrelor on preventing ST are not the same.
METHODS
PubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) that investigated the effect of clopidogrel, prasugrel, or ticagrelor on prevention of ST in patients who underwent PCI. The efficacies between groups were compared by a Bayesian network meta-analysis, by which the pooled odds ratios (ORs) and 95% confidence intervals (CIs) was calculated.
RESULTS
Fourteen studies and 46 983 participants were included in this study. The pooled results illustrated that clopidogrel, prasugrel and ticagrelor were effective on prevention of ST. Patients treated with prasugrel (OR = 0.30, 95% CI = 0.052 ~ 0.73, P < 0.05) and ticagrelor (OR = 0.25, 95% CI = 0.035 ~ 0.65, P < 0.05) had lower incidence of ST compared to those treated with clopidogrel. Patients treated with ticagrelor showed similar frequency with those in prasugrel group (OR = 0.86, 95% CI = 0.22 ~ 2.3, P > 0.05). No significant heterogeneity was observed across included studies.
CONCLUSIONS
Our findings suggest that prasugrel and ticagrelor are more effective than clopidogrel on prevention of ST among patients underwent PCI. Simultaneously, there is no significant difference in the prevention of ST between prasugrel and ticagrelor.
Topics: Clopidogrel; Humans; Network Meta-Analysis; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Stents; Thrombosis; Ticagrelor
PubMed: 33704801
DOI: 10.1002/clc.23536