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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 -
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 -
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 -
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 -
Arquivos de Neuro-psiquiatria Jan 2023Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent...
BACKGROUND
Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent of platelet aggregation and vasoconstriction, and it is used to prevent CVD. Nevertheless, patients may have treatment failure due to genetic variants that modify the metabolism of the drug causing aspirin resistance (AR).
OBJECTIVES
To realize a systematic literature review to determine the impact of genetic variants on AR.
METHODS
Articles published in the MEDLINE/PubMed, Cochrane, Scopus, LILACS, and SCIELO databases were systematically screened. A total of 290 articles were identified and 269 articles were excluded because they did not comply with the previously established inclusion criteria. A total of 20 case-control studies and 1 cohort was included.
RESULTS
The genetic variants rs1126643 (), rs3842787 (), rs20417 (), and rs5918 () were the most studied. As for relevance, of the 64 genetic variants evaluated by the articles, 14 had statistical significance ( < 0.05; 95% confidence interval [CI]) in at least one article. Among them, the following have had unanimous results: rs1371097 (), rs1045642 (), rs1051931 and rs7756935 (), rs2071746 (), rs1131882 and rs4523 (), rs434473 (), rs9315042 (), and rs662 (), while these differ in real interference in AR: rs5918 (), rs2243093 (), rs1330344 (), and rs20417 (). As study limitations, we highlight the nonuniform methodologies of the analyzed articles and population differences.
CONCLUSION
It is noteworthy that pharmacogenetics is an expanding area. Therefore, further studies are needed to better understand the association between genetic variants and AR.
Topics: Humans; Aspirin; Cardiovascular Diseases; Cyclooxygenase 2; Pharmacogenetics; Platelet Aggregation Inhibitors; Drug Resistance
PubMed: 36918009
DOI: 10.1055/s-0042-1758445 -
Frontiers in Pharmacology 2023Transjugular intrahepatic portosystemic shunt (TIPS) is an effective way to improve portal hypertension, however, the role of anticoagulation or antiplatelet therapy...
Transjugular intrahepatic portosystemic shunt (TIPS) is an effective way to improve portal hypertension, however, the role of anticoagulation or antiplatelet therapy following TIPS remains controversial. We conducted this study to evaluate the efficacy and safety of anticoagulation or antiplatelet therapy following TIPS. A literature search was conducted on anticoagulation or antiplatelet therapy after TIPS using Pubmed, Web of Science, EMBASE, and Cochrane. The retrieval period was from the earliest accessible date in the database to 31 October 2022. We collected information on the incidence of stent dysfunction, bleeding, hepatic encephalopathy, the new occurrence of portal vein thrombosis, and the survival rate. Stata was analyzed in RevMan. 1. Four studies received anticoagulation or antiplatelet therapy after TIPS without control groups. According to the single-group rate meta-analysis, stent dysfunction occurred at 27% [95% CI (0.19, 0.38)], bleeding occurred at 21% [95% CI (0.14, 0.29)], new portal vein thrombosis occurred at 17% [(95%CI(0.04.0.71)], hepatic encephalopathy occurred at 47% [95%CI (0.34, 0.63)], and death occurred at 31% [95% CI (0.22, 0.42)]. 2. Eight studies, including 1025 patients, compared anticoagulation and antiplatelet therapy after TIPS to TIPS alone. In terms of stent dysfunction, bleeding, and hepatic encephalopathy, there were no significant differences between the two groups. The use of anticoagulation or antiplatelet therapy may result in a significant decrease in the incidence of new portal vein thrombosis and mortality over 1 year. Anticoagulant or antiplatelet therapy may not improve the patency rate of TIPS, but may effectively prevent new portal vein thrombosis after TIPS. Following TIPS, the use of anticoagulants or antiplatelet drugs does not lead to an increase in bleeding or death.
PubMed: 36891262
DOI: 10.3389/fphar.2023.1116177 -
CMAJ Open 2023Dual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting; however, optimal duration remains uncertain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting; however, optimal duration remains uncertain in some situations. We assessed the benefits and harms of extending DAPT beyond 1 year after PCI in clinically important patient subgroups.
METHODS
We conducted a systematic review and meta-analysis. We searched electronic databases (Embase, MEDLINE, PubMed, Cochrane Library) and grey literature (from inception to Nov. 5, 2021) and included randomized controlled trials (RCTs) of extended DAPT (> 12 mo) compared with DAPT for 6-12 months following PCI with stenting. The primary outcome was death (all cause, cardiovascular, noncardiovascular); secondary outcomes included major adverse cardiovascular and cerebrovascular events, myocardial infarction (MI), stroke, stent thrombosis and bleeding. Subgroups were based on prespecified patient characteristics (prior MI, acute coronary syndrome [ACS], diabetes mellitus, age, smoking status). Data were analyzed by random-effects pairwise meta-analysis.
RESULTS
We identified 9 RCTs that provided subgroup data. We found that extended DAPT reduced the risk of MI and stent thrombosis but increased the risk of bleeding, compared with standard DAPT, with no difference in the risk of all-cause death (relative risk [RR] 1.07, 95% confidence interval [CI] 0.80-1.42) or cardiovascular death (RR 0.98, 95% CI 0.74-1.30). We found that patients with a prior MI, with ACS at presentation, without diabetes or aged younger than 75 years may derive the most benefit from extended DAPT. Among patients who received extended DAPT, the risk of all-cause death was significantly increased among those with no prior MI (RR 1.64, 95% CI 1.08-2.24), whereas there was no significant difference in the risk of all-cause death between standard and extended DAPT for patients with ACS (RR 1.20, 95% CI 0.51-2.83), with diabetes (RR 1.27, 95% CI 0.86-1.89), aged older than 75 years (RR 1.32, 95% CI 0.39-4.54) or who smoked (RR 0.90, 95% CI 0.42-1.92). Similar results were found for cardiovascular death, where data were available.
INTERPRETATION
Patients with a previous MI with ACS at presentation, without diabetes, or aged younger than 75 years may derive the most benefit from extended DAPT. These findings support the need for careful selection of patients who may benefit most from extended DAPT.
STUDY REGISTRATION
PROSPERO no. CRD42018082587.
Topics: Humans; Aged; Platelet Aggregation Inhibitors; Myocardial Infarction; Acute Coronary Syndrome; Hemorrhage; Thrombosis; Percutaneous Coronary Intervention
PubMed: 36750248
DOI: 10.9778/cmajo.20210119 -
Hellenic Journal of Cardiology : HJC =... 2023Optimal duration of dual antiplatelet therapy (DAPT) in patients undergoing complex percutaneous coronary intervention (PCI) remains under investigation. Our aim is to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Optimal duration of dual antiplatelet therapy (DAPT) in patients undergoing complex percutaneous coronary intervention (PCI) remains under investigation. Our aim is to compare shortened (≤3 months) DAPT with longer DAPT in patients undergoing complex PCIs.
METHODS
Three major databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus) were screened. The primary endpoint was major bleedings as they are defined by the Bleeding Academic Research Consortium (BARC) 3-5. The secondary endpoints were major adverse cardiovascular events, all-cause and cardiovascular mortality, myocardial infarction, stroke, and stent thrombosis.
RESULTS
Five studies were included in our analysis, with a total of 9,115 patients. Our meta-analysis met its primary endpoint, as abbreviated DAPT significantly reduced major bleedings by 43% (95% confidence intervals: 0.35-0.93). Ischemic events and mortality were not affected by the shortening of DAPT.
CONCLUSION
Shortened DAPT significantly reduced the odds of major bleedings in patients undergoing complex PCI without increasing the ischemic events or mortality. Thus, it could be considered a safe and feasible option in such patients.
Topics: Humans; Platelet Aggregation Inhibitors; Percutaneous Coronary Intervention; Myocardial Infarction; Dual Anti-Platelet Therapy; Hemorrhage; Drug Therapy, Combination; Treatment Outcome
PubMed: 36736730
DOI: 10.1016/j.hjc.2023.01.005