Influence of body size on platelet response to ticagrelor and prasugrel in patients with acute coronary syndromes.
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SUBMITTER: Ndrepepa G
PROVIDER: S-EPMC9242954 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
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Influence of body size on platelet response to ticagrelor and prasugrel in patients with acute coronary syndromes.
Ndrepepa Gjin G Holdenrieder Stefan S Bernlochner Isabell I Kastrati Adnan A
Clinical research in cardiology : official journal of the German Cardiac Society 20211201 7
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Project description:Background The relative efficacy and safety of ticagrelor and prasugrel based dual antiplatelet therapy strategies according to the platelet count (PC) in patients with acute coronary syndromes (ACS) have not been defined.Methods This is a posthoc analysis of the ISAR-REACT 5 trial, in which patients presenting with ACS were randomized to treatment with ticagrelor versus prasugrel. Patients were divided into quartiles according to PC. The primary endpoint was incidence of death, myocardial infarction, or stroke, and the safety endpoint was incidence of BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 12 months.Results A total of 3,943 patients with known PC (997 patients in quartile 1 (Q1), 1,003 in quartile 2 (Q2) [205 ± 10.3 × 109/L], 961 patients in quartile 3 (Q3) [241 ± 11.7 × 109/L], and 982 patients in quartile 4 (Q4) [317 ± 68.6 × 109/L]). There was no significant interaction between treatment arm (ticagrelor vs. prasugrel) and PC group with respect to primary endpoint (Q1: 8.8 vs. 6.3%, hazard ratio [HR] =1.41, 95% confidence interval [CI]: 0.89-2.23; p = 0.148; Q2: 9.9 vs. 5.8%, HR = 1.68, 95% CI: 1.06-2.66; p = 0.027; Q3: 7.8 vs. 5.5%, HR = 1.43, 95% CI: 0.87-2.37; p = 0.159; Q4: 10.1 vs. 10.1%, HR = 1.05, 95% CI: 0.71-1.57; p = 0.799; p for interaction [p int] = 0.482) and with respect to bleeding endpoint (Q1: 5.8 vs. 4.2%, HR = 1.41, 95% CI: 0.76-2.63; p = 0.279; Q2: 6.4 vs. 3.7%, HR = 1.62, 95% CI: 0.85-2.06; p = 0.140; Q3: 4.4 vs. 3.0%, HR = 1.53, 95% CI: 0.73-3.18; p = 0.258; Q4: 5.6 vs. 8.5%, HR = 0.67, 95% CI: 0.40-1.14; p = 0.138, p int = 0.102).Conclusions In this analysis, incidences of ischemic and bleeding events at 12 months are comparable across quartiles of platelet count.
| S-EPMC10060058 | biostudies-literature
Project description:BackgroundPotent P2Y12 inhibitors such as ticagrelor and prasugrel are superior to clopidogrel in acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). Whether this benefit extends to a patient population with chronic coronary syndromes (CCS) is unclear.AimsWe sought to compare the safety and efficacy of prasugrel and ticagrelor versus clopidogrel in patients undergoing PCI for CCS.MethodsConsecutive patients undergoing PCI for CCS at a tertiary centre between 2014 and 2019 who were discharged on prasugrel or ticagrelor were compared with those on clopidogrel. The primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularisation at 1 year.ResultsOverall, 11,508 patients were included in the study (ticagrelor/prasugrel n=2,860 [24.9%], clopidogrel n=8,648 [75.1%]) with an increasing frequency of potent P2Y12 inhibitor use over the study period (ptrend<0.001). Clopidogrel was used more frequently in patients with multimorbid risk factors, whereas anatomical or procedural complexity was associated with ticagrelor/prasugrel use (left main PCI, bifurcation PCI, number of lesions, rotational atherectomy). No difference in the incidence of death or MI was noted across the groups (ticagrelor/prasugrel vs clopidogrel: 2.7% vs 3.1%, adjusted hazard ratio [adjHR] 0.86, 95% confidence interval [CI]: 0.62-1.17; p=0.33) or secondary outcomes including bleeding (adjHR 0.75, 95% CI: 0.46-1.21; p=0.23) on propensity score stratification analysis. Additionally, no difference in the primary outcome was observed across subgroups, including those undergoing complex PCI.ConclusionsTicagrelor and prasugrel are increasingly used in patients with CCS undergoing PCI with similar 1-year efficacy and safety when compared to clopidogrel. Whether use of these agents can be beneficial in patients undergoing PCI for CCS with a high thrombotic and low bleeding risk warrants further study.
| S-EPMC10018287 | biostudies-literature
Project description:BackgroundThis meta-analysis mainly aimed to compare the impact of prasugrel and ticagrelor on platelet reactivity (PR) in patients with acute coronary syndrome (ACS).MethodsWe searched four electronic databases to identify randomized controlled trials and cohort studies comparing the impact of prasugrel and ticagrelor on PR in patients with ACS. We performed group analyses according to three detection methods, drug dose [loading dose (LD) and maintenance dose (MTD)] and LD effect time, and assessed the robustness of the results through sensitivity analysis.ResultsTwenty-five studies with 5,098 patients were eligible. After LD, the incidence of high on-treatment platelet reactivity (HTPR) of ticagrelor was significantly lower than that of prasugrel within 6-18 h based on vasodilator-stimulated phosphoprotein (VASP) test [RR = 0.25 (0.07, 0.85), P = 0.03], there was no significant difference between ticagrelor and prasugrel in the following results: platelets inhibitory effect within 24-48 h based on VerifyNow P2Y12 (VN) assay (P = 0.11) and VASP test (P = 0.20), and the incidence of HTPR within 2-6 h based on VN assay (P = 0.57) and within 24-48 h based on VN assay (P = 0.46) and VASP test (P = 0.72), the incidence of low on-treatment platelet reactivity (LTPR) within 6-18 h based on VASP test (P = 0.46) and 48 h based on VN assay (P = 0.97) and VASP test (P = 0.73). After MTD, the platelet inhibitory effect of ticagrelor was stronger than that of prasugrel based on VN assay [WMD = -41.64 (-47.16, -36.11), P < 0.00001]and VASP test [WMD = -9.10 (-13.88, -4.32), P = 0.0002], the incidence of HTPR of ticagrelor was significantly lower than that of prasugrel based on VN assay [RR = 0.05 (0.02, 0.16), P < 0.00001], the incidence of LTPR of ticagrelor was significantly higher than prasugrel based on VN assay [RR = 6.54 (4.21, 10.14), P < 0.00001] and VASP test [RR = 2.65 (1.78, 3.96), P < 0.00001], the results of Multiple Electrode Aggregometry (MEA) test was inconsistent with the other two detection methods in platelet inhibitory effect and the incidence of HTPR and LTPR. There was no significant difference between ticagrelor and prasugrel in the following clinical outcomes: all-cause death (P = 0.86), cardiovascular death (P = 0.49), myocardial infarction (P = 0.67), stroke (P = 0.51), target vessel revascularization (P = 0.51), stent thrombosis (P = 0.90), TIMI major bleeding (P = 0.86) and bleeding BARC type ≥ 2 (P = 0.77). The risk of bleeding BARC type 1 of ticagrelor was significantly higher than prasugrel [RR = 1.44 (1.03, 2.02), P = 0.03].ConclusionsCompared with prasugrel, ticagrelor might have a stronger platelet inhibition effect, with a lower incidence of HTPR and a higher incidence of LTPR and bleeding BARC type 1, while there might be no significant difference in the risk of thrombosis/ischemic, bleeding BARC Type ≥ 2 and TIMI major bleeding. A higher incidence of LTPR might indicate a higher risk of bleeding BARC type 1. The results of VN assay were consistent with that of VASP test, and not with the MEA test.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304205, identifier: CRD42022304205.
| S-EPMC9226562 | biostudies-literature
Project description:ImportanceIn patients with acute coronary syndrome (ACS) undergoing invasive treatment, ticagrelor and prasugrel are guideline-recommended P2Y12 receptor inhibitors. The ISAR-REACT5 randomized clinical trial demonstrated superiority for prasugrel, although concerns were raised about the generalizability of some underpowered subgroup analyses.ObjectivesTo emulate a randomized clinical trial evaluating the safety and effectiveness of ticagrelor vs prasugrel under the conditions of routine care in individuals with ACS planned to undergo an invasive treatment strategy.Design, setting, and participantsThis new-user cohort study included secondary data from a German statutory health insurance claims database between January 2012 and December 2021, using 1:1 propensity score nearest-neighbor matching to emulate ISAR-REACT5. Individuals with ACS receiving either ticagrelor or prasugrel treatment after hospital discharge were followed up for 1 year. Eligibility criteria closely emulated those of ISAR-REACT5 and included age of 18 years or older and cardiovascular risk factors. Data were analyzed from May 2023 to May 2024.ExposureOutpatient prescription of ticagrelor or prasugrel.Main outcomes and measuresThe primary end point was the composite of all-cause mortality, myocardial infarction (MI), or stroke within 1 year of outpatient treatment initiation. Secondary end points included individual components of the primary end point and stent thrombosis. The safety end point was major bleeding. A Cox proportional hazards regression model was fitted to the overall cohort.ResultsOf 17 642 propensity score-matched individuals (mean [SD] age, 63.1 [10.9] years; 73.9% male), 8821 received ticagrelor and 8821 received prasugrel. Agreement was met in 11 of 12 predefined agreement metrics when comparing the results with ISAR-REACT5. The primary composite end point of all-cause mortality, MI, or stroke occurred in 815 individuals (9.2%) receiving ticagrelor and 663 (7.5%) receiving prasugrel (hazard ratio [HR], 1.24; 95% CI, 1.12-1.37). Myocardial infarction (HR, 1.20; 95% CI, 1.06-1.36) and stroke (HR, 1.33; 95% CI, 1.02-1.74) each occurred significantly more often in the ticagrelor group. Analysis of all-cause mortality (HR, 1.27; 95% CI, 0.99-1.64), stent thrombosis (HR, 1.11; 95% CI, 0.89-1.30), and major bleeding (HR, 1.12; 95% CI, 0.96-1.32) revealed no significant differences between treatment groups. Subgroup analysis showed that prasugrel was associated with the primary composite end point in fewer individuals with ST-segment elevation MI (338 of 4941 [6.8%] vs 451 of 4852 [9.3%]).Conclusions and relevanceThis cohort study found that prasugrel was associated with lower rates of all-cause mortality, MI, or stroke compared with ticagrelor in individuals with ACS undergoing an invasive treatment strategy in routine care, particularly in individuals with ST-segment elevation MI. The findings suggest that carefully designed database studies can complement and extend findings from randomized clinical trials, informing guidelines and clinical decision-making.
| S-EPMC11612834 | biostudies-literature
Project description:High platelet reactivity (HPR) is a risk factor for stent thrombosis, a potentially lethal complication of percutaneous coronary intervention. HPR is also associated with increased risk of myocardial infarction and death in invasively-treated patients with acute coronary syndrome (ACS). HPR occurs even in ACS patients treated with ticagrelor, a state-of-the-art antiplatelet agent, especially during the first hours of treatment. Patient-level pharmacodynamic data obtained from 102 ACS subjects enrolled in two prospective, pharmacodynamic trials were analysed in order to identify clinical features related with increased odds of on-ticagrelor HPR during the first two hours after ticagrelor loading dose in ACS patients. Presence of ST-segment elevation myocardial infarction (versus non-ST-segment elevation ACS) and morphine co-administration were the strongest predictors of HPR at 1 and 2 hours after ticagrelor loading dose according to linear regression analyses, multiple backward stepwise logistic regression analyses and generalized estimating equation model. By pinpointing simple to recognize clinical features, the results of this study facilitate identification of ACS patients who have the highest odds of HPR during the initial phase of treatment with ticagrelor, and who could potentially benefit from alternative treatment strategies.
| S-EPMC6408477 | 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:BackgroundPrasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited.ObjectivesTo determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS).PatientsPatients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. "poor responders" were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors.ResultsAt 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively.ConclusionsRoutine platelet function testing identifies patients with high residual platelet reactivity ("poor responders") on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit.Trial registrationClinicalTrials.gov NCT01339026.
| S-EPMC4552627 | biostudies-literature
Project description:Cross-trial comparisons are typically inappropriate as there are often numerous differences in study designs, populations, end points, and loading doses of the study drugs. These differences are clearly reflected in the most recent updates to the European Society of Cardiology (ESC) non-ST elevation acute coronary syndrome (NSTE-ACS) and ST elevation myocardial infarction (STEMI) guidelines, which include recommendations for the use of the antiplatelet agents ticagrelor, prasugrel, and clopidogrel, based in part on results from the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel-Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38, TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY-ACS) and PLATelet inhibition and patient Outcomes (PLATO) trials. Here, we describe each of these trials in detail and explain the differences between them that make direct comparisons difficult. In conclusion, this information, along with the current guidelines and recommendations, will assist clinicians in deciding the most appropriate treatment pathway for their patients with NSTE-ACS and STEMI.
| S-EPMC5102280 | biostudies-literature
Project description:Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.
| S-EPMC6078957 | biostudies-literature
Project description:BackgroundPrasugrel and ticagrelor have demonstrated higher efficacy than clopidogrel in their main clinical trials for patients with acute coronary syndrome (ACS). However, the long-term prognosis and different clinical characteristics related to the type of antiplatelet prescription in current clinical practice ACS patients have not been analysed in depth. The objective of this study was to analyse the clinical profile of ACS and the efficacy and safety of novel oral P2Y12 inhibitors in current clinical practice patients discharged afterACS.MethodsWe collected data from the ACHILLES registry, and an observational, prospective and multicentre registry of patients discharged after ACS. We analysed baseline characteristics, clinical profile and therapy during ACS admission and compared with the different treatments at discharge. After 1 year of follow-up, ischaemic and major bleeding events were analysed. Multivariate Cox regression analysis and Kaplan Meier curves were also plotted.ResultsOf 1717 consecutive patients, 1294 (75.4%) were discharged with a P2Y12 inhibitor without oral anticoagulation. Novel oral P2Y12 inhibitors were indicated in 47%. Patients treated with clopidogrel were elderly (69.1 ± 13.4 vs 60.4 ± 11.5 years; P < .001) and had a higher prevalence of cardiovascular risk factors. GRACE and CRUSADE scores were higher in the clopidogrel than in novel oral P2Y12 inhibitors group (P < .001). After 1 year of follow-up, 64(5.0%/year) patients had a new myocardial infarction, 127(10.0%/year) had a major adverse cardiovascular event (MACE) and 78(6.1%/year) died. Patients treated with clopidogrel had a significantly higher annual rate of cardiovascular mortality, MACE and all-cause mortality (allP < .001) without differences in major bleeding (P = .587) compared with novel oral P2Y12 inhibitors. After multivariate adjustment for the main clinical variables related to adverse prognosis in ACS patients, the discharge with novel oral P2Y12 inhibitors therapy was independently associated with lower risk of all-cause mortality (HR0.49, 95% CI [0.24-0.98], P = .044) and lower risk of MACE (HR0.64, 95% CI [0.41-0.98], P = .044).ConclusionsIn this prospective, observational and current clinical practice ACS registry, the use of novel oral P2Y12 inhibitors was associated with a reduction in adverse events compared with clopidogrel in patients with ACS. Novel oral P2Y12 inhibitors prescription at discharge was independently associated with lower all-cause mortality and MACE without differences in bleeding events. However, clopidogrel remained the most common P2Y12 inhibitor employed for ACS, especially in older and high-risk patients.
| S-EPMC7256120 | biostudies-literature