Walking the Line with Ticagrelor: Meta-Analysis Comparing the Safety and Efficacy of Ticagrelor Monotherapy after a Short Course of Ticagrelor-Based Dual Antiplatelet Therapy versus Standard Therapy in Complex Percutaneous Coronary Intervention.
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SUBMITTER: Condello F
PROVIDER: S-EPMC8658113 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention-to-treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention-to-treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per-protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time-varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all-cause mortality or nonfatal Q-wave myocardial infarction at 2 years. At 2-year follow-up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per-protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75-1.03; P=0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79-1.26; P=0.99). The per-protocol and intention-to-treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1-year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.
| S-EPMC9238541 | biostudies-literature
Project description:The use of antiplatelet agents, specifically the thienopyridines, has become a standard of care in the approach to the patient presenting with an acute coronary syndrome. These drugs irreversibly inhibit the platelet by permanently binding to the surface P2Y12 receptor and blocking the downstream fibrinogen cross-linking between platelets, which leads to aggregation and thrombus. However, currently available therapeutic choices are limited by potential interaction with other medications, slow hepatic conversion to active metabolite, genetic resistance, and narrow therapeutic safety margin. In order to overcome these disadvantages, there has been an interest in developing alternatives to thienopyridines. Recent investigations have included ticagrelor, a reversible inhibitor of the P2Y12 platelet receptor, which appears to have overcome several drawbacks of the current thienopyridines. Its unique pharmacokinetic and pharmacodynamic profiles result in an inhibition of platelet aggregation that is rapid, high, consistent, and less susceptible to interpatient variability than currently available P2Y12 inhibitors. In addition, ticagrelor offers a potential mortality advantage not apparent with current agents. Although questions regarding the nature, magnitude, and clinical significance of several observed adverse effects (dyspnea and ventricular pauses) remain unanswered, it appears that ticagrelor may represent a significant advancement over currently available oral antiplatelet agents.
| S-EPMC3262315 | biostudies-other
Project description:BACKGROUND:The efficacy of antiplatelet therapies following percutaneous coronary intervention (PCI) may be affected by body mass index (BMI). METHODS AND RESULTS:This is a prespecified subgroup analysis of the GLOBAL LEADERS trial, a prospective, multicenter, open-label, randomized controlled trial in an all-comer population undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with a reference regimen (12-month aspirin monotherapy following 12-month DAPT). A total of 15,968 patients were stratified by baseline BMI with prespecified threshold of 27 kg/m2. Of those, 6973 (43.7%) patients with a BMI?<?27 kg/m2 had a higher risk of all-cause mortality at 2 years than those with BMI???27 kg/m2 (adjusted HR 1.24, 95% CI 1.02-1.49). At 2 years, the rates of the primary endpoint (all-cause mortality or new Q-wave myocardial infarction) were similar between treatment strategies in either BMI group (pinteraction?=?0.51). In acute coronary syndrome, however, the experimental strategy was associated with significant reduction of the primary endpoint compared to the reference strategy in patients with BMI?<?27 kg/m2 (HR 0.69, 95% CI 0.51-0.94), but not in the ones with BMI???27 kg/m2 (pinteraction?=?0.047). In chronic coronary syndrome, there was no between-group difference in the efficacy and safety of the two antiplatelet strategies. CONCLUSIONS:Overall, BMI did not influence the treatment effect seen with ticagrelor monotherapy; however, a beneficial effect of ticagrelor monotherapy was seen in ACS patients with BMI?<?27 kg/m2. TRIAL REGISTRATION:The trial has been registered with ClinicalTrials.gov, Number NCT01813435.
| S-EPMC7449952 | biostudies-literature
Project description:Dual antiplatelet therapy (DAPT) and subsequent P2Y12 inhibitor monotherapy, particularly ticagrelor, is an emerging treatment strategy in patients undergoing percutaneous coronary intervention (PCI). This meta-analysis was designed to investigate whether short-term DAPT followed by ticagrelor monotherapy is associated with a favorable outcome as compared with standard DAPT (1-3 months of DAPT was termed "short-term" DAPT, 6-12 months DAPT was termed "standard" DAPT). The primary outcome was the composite of major adverse cardiovascular events (MACE) comprising myocardial infarction, stroke, and cardiovascular death. Secondary outcomes included all-cause mortality and net adverse clinical events (NACE; myocardial infarction, stroke, all-cause death, stent thrombosis, and major bleeding). The primary safety outcome was major bleeding. Three studies comprising 26,143 patients were included. The risk of MACE was similar between the two treatment groups (risk ratio (RR) 0.86, 95% confidence interval (CI), 0.72-1.02, P = 0.08, I2 = 22%). Short-term DAPT followed by ticagrelor monotherapy resulted in a 20% relative risk reduction of all-cause mortality (RR 0.80, 95% CI, 0.65-0.98, P = 0.03, I2 = 0%) and an 18% relative risk reduction of NACE (RR 0.82, 95% CI, 0.71-0.94, P = 0.005, I2 = 33%) as compared with standard DAPT. Short-term DAPT followed by ticagrelor monotherapy significantly decreased the risk of major bleeding (RR 0.67, 95% CI, 0.49-0.92, P = 0.01, I2 = 65%). In patients with acute coronary syndrome, short-term DAPT followed by ticagrelor monotherapy resulted in an unchanged ischemic risk but a significantly lower bleeding risk compared with standard DAPT. Short-term DAPT followed by ticagrelor monotherapy compared with standard DAPT resulted in a favorable safety and efficacy profile. Direct comparisons of aspirin vs. ticagrelor monotherapy following PCI are needed.
| S-EPMC8359988 | biostudies-literature
Project description:BackgroundThere are no data on comparison between clopidogrel monotherapy and prolonged dual antiplatelet therapy (DAPT) in patients at high-risk undergoing percutaneous coronary intervention (PCI).MethodsOf 2,082 consecutive patients undergoing PCI using second-generation drug-eluting stent (DES), we studied 637 patients at high-risk either angiographically or clinically who received clopidogrel longer than 24 months and were event-free at 12 months after index PCI. Patients were divided into 2 groups: the clopidogrel monotherapy group and the prolonged DAPT group. The primary outcome was a composite of all-cause death, non-fatal myocardial infarction (MI), definite or probable stent thrombosis, or stroke between 12 months and 36 months after the index PCI.ResultsIn propensity score-matched population (246 pairs), the cumulative rate of primary outcome was 4.5% in the clopidogrel monotherapy group and 4.9% in the prolonged DAPT group (hazard ratio, 1.21; 95% confidence interval, 0.54-2.75; P = 0.643). There was no significant difference in all-cause death, MI, stent thrombosis, stroke between the clopidogrel monotherapy group and the prolonged DAPT group.ConclusionCompared with prolonged DAPT, clopidogrel monotherapy showed similar long-term outcomes in patients at high-risk after second-generation DES implantation.
| S-EPMC8076847 | biostudies-literature
Project description:Background: Warfarin, along with aspirin and clopidogrel, has long been recommended for patients with atrial fibrillation (AF) who are undergoing percutaneous coronary intervention with a drug-eluting stent (PCI-DES). However, this triple therapy has been known to increase the risk of bleeding complications. Meanwhile, there is no evidence from prospective trials on the use of ticagrelor in a dual therapy. We here aimed to compare the antiplatelet drug ticagrelor as a dual antithrombotic agent to aspirin and clopidogrel in bleeding events. Methods: In this multicenter, active-controlled, open-label, randomized trial, patients with AF taking warfarin who had undergone PCI-DES were randomly assigned to the ticagrelor therapy group (Dual group) or the clopidogrel plus aspirin therapy group (Triple group). The primary and secondary endpoints were overall bleeding events and major bleeding events, respectively, according to the Thrombolysis in Myocardial Infarction (TIMI) criteria at 6 months. Cardiovascular events [re-PCI, surgical bypass, myocardial infarction (MI), heart failure, rehospitalization due to angina pectoris, stent thrombosis and death due to cardiovascular causes] at 6 months were also recorded. Results: A total of 296 patients from 12 medical centers in China were randomized after PCI-DES to either the Dual therapy group (n = 148) or the Triple group (n = 146) for 6 months. The overall incidence of bleeding events at 6 months was 36.49% in the Dual therapy group and 35.62% in the Triple group [hazard ratio, 0.930; 95% confidence interval (CI), 0.635 to 1.361; P = 0.7088]. The incidence of the secondary endpoint over 6 months was 4.73% in the Dual therapy group and 1.37% in the Triple group (hazard ratio, 0.273; 95% CI, 0.057 to 1.315; P = 0.1056). Cardiovascular event occurrence was also comparable in both groups at 6 months (18.24 vs. 16.44%; hazard ratio, 0.845; 95% CI, 0.488 to 1.465; P = 0.5484). Conclusions: The incidence of total bleeding events in AF patients treated with ticagrelor was comparable to that in patients treated with clopidogrel plus aspirin at 6 month; Meanwhile, the incidence of cardiovascular events were also comparable between the groups. Clinical Trial Registration: MANJUSRI, ClinicalTrials.gov# NCT02206815, 2014, August 1st
| S-EPMC8545975 | biostudies-literature
Project description:ImportanceData on P2Y12 inhibitor monotherapy after short-duration dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention are limited.ObjectiveTo determine whether P2Y12 inhibitor monotherapy after 3 months of DAPT is noninferior to 12 months of DAPT in patients undergoing PCI.Design, setting, and participantsThe SMART-CHOICE trial was an open-label, noninferiority, randomized study that was conducted in 33 hospitals in Korea and included 2993 patients undergoing PCI with drug-eluting stents. Enrollment began March 18, 2014, and follow-up was completed July 19, 2018.InterventionsPatients were randomly assigned to receive aspirin plus a P2Y12 inhibitor for 3 months and thereafter P2Y12 inhibitor alone (n = 1495) or DAPT for 12 months (n = 1498).Main outcomes and measuresThe primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 12 months after the index procedure. Secondary end points included the components of the primary end point and bleeding defined as Bleeding Academic Research Consortium type 2 to 5. The noninferiority margin was 1.8%.ResultsAmong 2993 patients who were randomized (mean age, 64 years; 795 women [26.6%]), 2912 (97.3%) completed the trial. Adherence to the study protocol was 79.3% of the P2Y12 inhibitor monotherapy group and 95.2% of the DAPT group. At 12 months, major adverse cardiac and cerebrovascular events occurred in 42 patients in the P2Y12 inhibitor monotherapy group and in 36 patients in the DAPT group (2.9% vs 2.5%; difference, 0.4% [1-sided 95% CI, -∞% to 1.3%]; P = .007 for noninferiority). There were no significant differences in all-cause death (21 [1.4%] vs 18 [1.2%]; hazard ratio [HR], 1.18; 95% CI, 0.63-2.21; P = .61), myocardial infarction (11 [0.8%] vs 17 [1.2%]; HR, 0.66; 95% CI, 0.31-1.40; P = .28), or stroke (11 [0.8%] vs 5 [0.3%]; HR, 2.23; 95% CI, 0.78-6.43; P = .14) between the 2 groups. The rate of bleeding was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (2.0% vs 3.4%; HR, 0.58; 95% CI, 0.36-0.92; P = .02).Conclusions and relevanceAmong patients undergoing percutaneous coronary intervention, P2Y12 inhibitor monotherapy after 3 months of DAPT compared with prolonged DAPT resulted in noninferior rates of major adverse cardiac and cerebrovascular events. Because of limitations in the study population and adherence, further research is needed in other populations.Trial registrationClinicalTrials.gov Identifier: NCT02079194.
| S-EPMC6593635 | biostudies-literature
Project description:The risk for gastrointestinal bleeding from dual antiplatelet therapy (DAPT) with new antiplatelets (prasugrel/ticagrelor) compared to clopidogrel is unclear. AIM:To determine the risk and type of major (gastrointestinal bleeding requiring hospitalization) and minor (anemia and iron deficiency) gastrointestinal events with different types of DAPT. METHODS:Retrospective observational cohort study of patients who started DAPT after percutaneous coronary intervention. Follow-up was censored after 12 months of DAPT, when a major gastrointestinal event occurred, or when DAPT was discontinued. RESULTS:Among 1,327 patients (54.03% were treated with clopidogrel-based DAPT, 38.13% with ticagrelor-based DAPT, and 7.84% with prasugrel-based DAPT), 29.5% had at least one gastrointestinal event. Patients taking clopidogrel-DAPT were older, with more comorbidities, and higher gastrointestinal risk compared to those taking other DAPT regimens. Adjusted hazard ratios (HRs) showed no between-group differences in the risk for major (clopidogrel vs. new antiplatelets: HR 0.996; 95% confidence interval 0.497-1.996) and minor (HR 0.920; 0.712-1.189) gastrointestinal events. Most patients received proton pump inhibitors while on DAPT (93.3%) and after withdrawal (83.2%). CONCLUSION:Prasugrel- or ticagrelor-based DAPT was not associated with increased gastrointestinal bleeding risk when compared to clopidogrel-DAPT. New antiplatelets do not necessarily need to be restricted to patients with low gastrointestinal risk.
| S-EPMC7290690 | biostudies-literature
Project description:ObjectivesTo describe and evaluate outcomes in STEMI patients sustained on clopidogrel compared to those switched to ticagrelor following fibrinolysis.BackgroundWorld-wide, many STEMI patients cannot achieve timely PCI and therefore require fibrinolysis. Although comparable 30-day and 1-year safety was shown with clopidogrel or ticagrelor in the TREAT study, there is paucity of long-term outcomes in pharmacoinvasive treated STEMI.MethodsWe conducted an observational cohort study evaluating consecutive pharmacoinvasive STEMI patients treated in a network, comparing those switched to ticagrelor to those sustained on clopidogrel. The primary efficacy composite was one-year all-cause death, recurrent myocardial infarction, and stroke with major bleeding and intracranial hemorrhage (ICH) as the safety outcomes. Multivariable Cox regression model was used to examine the association between P2Y12 inhibitor and outcomes with inverse probability weighting.ResultsOf 1426 pharmacoinvasive STEMI patients, 28% (n = 396) were converted to ticagrelor at a mean of 9.9 h after fibrinolysis with comparable GRACE Risk Scores (median; 158 vs 157, p0.352). The primary composite occurred in 3.5% of ticagrelor and 7.0% of clopidogrel treated patients (p0.014). Following adjustment, ticagrelor was associated with a 54% lower composite outcome (adjusted HR 0.46, 95% confidence interval 0.26-0.84). Major bleeding 6.3% vs 6.1% (NS) and ICH 0.0% vs 0.2% (NS) were similar.ConclusionsIn a prospective STEMI cohort, switching to ticagrelor compared with sustaining clopidogrel following fibrinolysis pharmacoinvasive reperfusion reduced recurrent ischemic events at 1-year with no differences in major bleeding or ICH. Aligned with randomized data, these findings provide support to switch pharmaco-invasively treated STEMI patients.
| S-EPMC8571547 | biostudies-literature
Project description:OBJECTIVE:To evaluate the clinical utility of individualising dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in an all-comers population, including ST-elevation myocardial infarction (STEMI) patients. SETTING:Tertiary care single centre registry. PARTICIPANTS:1008 consecutive PCI patients with stent implantation, without exclusion criteria. INTERVENTION:Peri-interventional individualisation of DAPT, guided by multiple electrode aggregometry (MEA), to overcome high on-treatment platelet reactivity (HPR) to ADP-induced (?50 U) and arachidonic acid (AA)-induced aggregation (>35 U). OUTCOME MEASURES:The primary efficacy end point was definite stent thrombosis (ST) at 30 days. The primary safety end point was thrombolysis in myocardial infarction (TIMI) major and minor bleeding. Secondary end points were probable ST, myocardial infarction, cardiovascular death and the combined end point: major cardiac adverse event (MACE). RESULTS:53% of patients presented with acute coronary syndrome (9% STEMI, 44% non-ST-elevation). HPR to ADP after 600 mg clopidogrel loading occurred in 30% of patients (73±19 U vs 28±11 U; p<0.001) and was treated by prasugrel or ticagrelor (73%), or clopidogrel (27%) reloading (22±12 U; p<0.001). HPR to ADP after prasugrel loading occurred in 2% of patients (82±26 U vs 19±10 U; p<0.001) and was treated with ticagrelor (34±15 U; p=0.02). HPR to AA occurred in 9% of patients with a significant higher proportion in patients with HPR to ADP (22% vs 4%, p<0.001) and was treated with aspirin reloading. Definite ST occurred in 0.09% of patients (n=1); probable ST, myocardial infarction, cardiovascular death and MACE occurred in 0.19% (n=2), 0.09% (n=1) and 1.8% (n=18) of patients. TIMI major and minor bleeding did not differ between patients without HPR and individualised patients (2.6% for both). CONCLUSIONS:Individualisation of DAPT with MEA minimises early thrombotic events in an all-comers PCI population to an unreported degree without increasing bleeding. A randomised multicentre trial utilising MEA seems warranted. TRIAL REGISTRATION NUMBER:http://www.clinicaltrials.gov; NCT01515345.
| S-EPMC4216867 | biostudies-literature