Design and Rationale for comParison Between ticagreLor and clopidogrEl on mIcrocirculation in Patients with Acute cOronary Syndrome Undergoing Percutaneous Coronary Intervention (PLEIO) Trial.
Ontology highlight
ABSTRACT:
SUBMITTER: Park K
PROVIDER: S-EPMC5846973 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ImportanceGuidelines currently recommend ticagrelor over clopidogrel for patients with acute coronary syndrome (ACS) based on randomized clinical trial data in which ticagrelor reduced major adverse coronary events (MACE) vs clopidogrel but increased bleeding and dyspnea.ObjectiveTo compare the risk of MACE with ticagrelor vs clopidogrel in patients with ACS treated with percutaneous coronary intervention (PCI), to compare major bleeding and dyspnea, and to evaluate the association between P2Y12 inhibitor adherence and MACE.Design, setting, and participantsPopulation-based cohort study using data of patients discharged alive after PCI for ACS from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry from April 1, 2012, to March 31, 2016, with follow-up to 1 year. Analysis began April 2018.ExposuresOutpatient prescription for ticagrelor or clopidogrel within 31 days after PCI. Adherence was defined as a medication refill adherence value of 80% or higher.Main outcomes and measuresMajor adverse coronary events, a composite of all-cause death, hospitalization for ACS, unplanned coronary revascularization, or stent thrombosis within 365 days after index PCI. Secondary outcomes included hospitalization for major bleeding and emergency department visit for dyspnea.ResultsOf 11 185 individuals who underwent PCI, the median (interquartile range) age was 61 (54-71) years, and 2760 (24.7%) were women. Ticagrelor users (4076 [36.4%]) were generally younger and had fewer cardiac and noncardiac comorbidities than clopidogrel users. Ticagrelor was not associated with lower risk of MACE (adjusted hazard ratio [aHR], 0.97; 95% CI, 0.85-1.10); however, it was associated with an increased risk of major bleeding (aHR, 1.51; 95% CI, 1.29-1.78) and dyspnea (aHR, 1.98; 95% CI, 1.47-2.65). A total of 3328 ticagrelor users (81.6%) were adherent during the study vs 5256 of clopidogrel users (73.9%) (P < .001; χ2 = 86.4). In the full cohort, adherence was associated with a lower MACE risk (aHR, 0.79; 95% CI, 0.69-0.90 for adherence of ≥80% vs <80%). Differences in other secondary outcomes were not statistically significant. Sensitivity and subgroup analyses were consistent with primary analyses.Conclusions and relevanceIn this population-based cohort study of patients with ACS who underwent PCI, outpatient use of ticagrelor was not associated with a statistically significant reduction in MACE vs clopidogrel; however, it was associated with more major bleeding and dyspnea.
| S-EPMC6990835 | biostudies-literature
Project description:ImportanceCurrent guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention.ObjectiveTo determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice.Design, setting, and participantsA retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record-based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019.ExposuresTicagrelor vs clopidogrel.Main outcomes and measuresThe primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis.ResultsAfter propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P < .001) were significantly higher in the ticagrelor group.Conclusions and relevanceAmong patients with ACS who underwent PCI in routine clinical practice, ticagrelor, compared with clopidogrel, was not associated with significant difference in the risk of NACE at 12 months. Because the possibility of unmeasured confounders cannot be excluded, further research is needed to determine whether ticagrelor is more effective than clopidogrel in this setting.
| S-EPMC7592033 | biostudies-literature
Project description:Diabetes mellitus (DM) is associated with enhanced platelet reactivity and impaired response to oral antiplatelet therapy, including clopidogrel. This post hoc analysis investigated the pharmacodynamic effects of ticagrelor versus clopidogrel loading dose (LD) in troponin-negative acute coronary syndrome patients with or without DM undergoing percutaneous coronary intervention in the Ad Hoc PCI study.Patients randomized (1:1) to receive ticagrelor 180 mg LD or clopidogrel 600 mg LD were assessed by diabetic status. Platelet reactivity (P2Y12 reaction units [PRU] on VerifyNow® assay) was measured pre-LD, at 0.5, 2, and 8 hours post-LD, and at the end of the percutaneous coronary intervention. The primary endpoint was PRU levels 2 hours post-LD; secondary endpoints included rates of high on-treatment platelet reactivity (PRU?208). Of 100 randomized patients, 51 received ticagrelor (DM, n=20; non-DM, n=31) and 49 clopidogrel (DM, n=16; non-DM, n=33). At 2 hours post-LD, mean (SD) PRU levels in DM patients were 130.1 (111.7) with ticagrelor versus 287.6 (71.9) with clopidogrel (mean [95%CI] difference -157.5 [-225.3, -89.8]; P<0.001); in non-DM patients, they were 75.3 (75.7) versus 243.0 (72.4) (mean difference -167.7 [-207.1, -128.3]; P<0.001). High on-treatment platelet reactivity rates at 2 hours post-LD were also significantly (P<0.001) reduced with ticagrelor versus clopidogrel in DM and non-DM patients. Between-treatment differences for PRU and high on-treatment platelet reactivity were not significant at earlier time points but were at 8 hours post-LD (P<0.001).Compared with clopidogrel, ticagrelor achieved faster, enhanced platelet inhibition and reduced high on-treatment platelet reactivity rates, in DM and non-DM patients.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603082.
| S-EPMC5533039 | biostudies-literature
Project description:BackgroundGastrointestinal bleeding (GIB) frequently occurs following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) with the prescription of P2Y12 inhibiting antiplatelet agents. Compared with clopidogrel, the newer P2Y12 inhibitors lower major adverse cardiac events with similar or possibly higher major bleeding events. The comparative GIB rates of these medications remain poorly understood.AimTo compare GIB rates associated with clopidogrel, prasugrel and ticagrelor using national medical and pharmacy claims data from privately insured and Medicare Advantage enrollees .MethodsPropensity score and inverse probability treatment weighting were used to balance baseline characteristics among treatment groups. The 1-year GIB risk was calculated using weighted Cox proportional hazard models and expressed as hazard ratios (HR) with 95% confidence intervals (CI) and number needed to harm (NNH).ResultsWe identified 37 019 patients with ACS (non-ST elevation ACS [NSTE-ACS] and ST-elevation myocardial infarction [STEMI]) within 14 days of a PCI (mean age 63 years and 70% male). Clopidogrel prescription was most common (69%) with prasugrel (16%) and ticagrelor (14%) prescribed less frequently. When compared with clopidogrel, ticagrelor was associated with a 34% risk reduction (HR 0.66; 95% CI: 0.54-0.81) in GIB overall and with NSTE-ACS, and a 37% GIB risk reduction (HR 0.63; 95% CI: 0.42-0.93) in STEMI patients. When compared with clopidogrel, prasugrel was associated with a 21% risk reduction (HR 0.79; 95% CI: 0.64-0.97) overall, a 36% GIB risk reduction (HR 0.64; 95% CI: 0.49-0.85) in STEMI patients but no reduction of GIB risk in NSTE-ACS patients.ConclusionsIn the first year following PCI, ticagrelor or prasugrel are associated with fewer GIB events than clopidogrel.
| S-EPMC8183594 | biostudies-literature
Project description:In diabetic patients a predisposed coronary microcirculation along with a higher risk of distal particulate embolization during primary percutaneous intervention (PCI) increases the risk of peri-procedural microcirculatory damage. However, new antiplatelet agents, in particular Ticagrelor, may protect the microcirculation through its adenosine-mediated vasodilatory effects.PREDICT is an original, prospective, randomized, multicenter controlled study designed to investigate the protective effect of Ticagrelor on the microcirculation during PCI in patient with diabetes mellitus type 2 or pre-diabetic status. The primary endpoints of this study aim to test (i) the decrease in microcirculatory resistance with antiplatelet therapy (Ticagrelor > Clopidogrel; mechanistic effect) and (ii) the relative microcirculatory protection of Ticagrelor compared to Clopidogrel during PCI (Ticagrelor < Clopidogrel; protective effect).PREDICT will be the first multicentre clinical trial to test the adenosine-mediated vasodilatory effect of Ticagrelor on the microcirculation during PCI in diabetic patients. The results will provide important insights into the prospective beneficial effect of this drug in preventing microvascular impairment related to PCI ( http://www.clinicaltrials.gov No. NCT02698618).
| S-EPMC5438565 | 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:BackgroundKnowledge on the pharmacodynamic effects of antiplatelet drugs including clopidogrel and ticagrelor on Asian patients is scarce. We aim to evaluate the effects of the two drugs on platelet reactivity in the treatment of Chinese patients who underwent percutaneous coronary intervention (PCI), using two platelet function tests (PFT). Meanwhile, the relationship between mean platelet volume (MPV), a routine index of platelet size, and high on-treatment platelet reactivity (HPR) is also investigated.MethodsPatients receiving dual antiplatelet therapy (DAPT) were scheduled for the assessment of platelet reactivity at 2-3 days after PCI. Two PFTs, light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP)-FCM assay, were applied in the evaluation of platelet reactivity. The MPV was measured simultaneously with EDTA plasma using a Sysmex XN 2000 automated hematology analyzer.ResultsThe final study population included the aspirin + clopidogrel group (n = 46) and the aspirin + ticagrelor group (n = 66). In the aspirin + ticagrelor group, the maximal light transmittance (LT) changes in response to 5 μM ADP assessed by LTA was obviously lower than that in the aspirin + clopidogrel group (P < 0.001). The platelet reactivity index (PRI) level in the VASP test was also markedly lower in the group given aspirin and ticagrelor (P < 0.001). There was a significant difference in HPR between the two groups. MPV showed a potent ability to predict the presence of HPR at VASP assay (AUC = 0.788, 95% CI: 0.701-0.875, P < 0.001) in receiver-operating characteristic curve analysis.ConclusionsCompared with clopidogrel, ticagrelor has dramatically greater antiplatelet effect, with a superiority in suppressing platelet function and a lower HPR rate. In addition, there existed a significant independent association between MPV and high prevalence of HPR in the VASP assay.
| S-EPMC8650403 | biostudies-literature
Project description:BackgroundDespite routine use of clopidogrel, adverse cardiovascular events recur among some patients undergoing percutaneous coronary intervention (PCI). To optimize antiplatelet therapies, we performed a meta-analysis to quantify the efficacy of high versus standard-maintenance-dose clopidogrel in these patients.MethodsRandomized controlled trials (RCTs) comparing high (>75 mg) and standard maintenance doses of clopidogrel in patients undergoing PCI were included. The primary efficacy and safety end-points were major adverse cardiovascular/cerebrovascular events (MACE/MACCE) and major bleeding. The secondary end-points were other ischemic and bleeding adverse effects. The pooled odds ratio (OR) for each outcome was estimated.Results14 RCTs with 4424 patients were included. Compared with standard-maintenance-dose clopidogrel, high-maintenance-dose clopidogrel significantly reduced the incidence of MACE/MACCE (OR 0.60; 95% CI 0.43 to 0.83), stent thrombosis (OR 0.56; 95% CI 0.32 to 0.99) and target vessel revascularization (OR 0.38; 95% CI 0.20 to 0.74), without significant decrease of the risk of cardiovascular death (OR 0.92; 95% CI 0.74 to 1.13) and myocardial infarction (OR 0.83; 95% CI 0.51 to 1.33). For safety outcomes, it did not significantly increase the risk of major bleeding (OR 0.73; 95% CI 0.41 to 1.32), minor bleeding (OR 1.29; 95% CI 1.00 to 1.66) and any bleeding (OR 1.14; 95% CI 0.91 to 1.43).ConclusionHigh-maintenance-dose clopidogrel reduces the recurrence of most ischemic events in patients post-PCI without increasing the risk of bleeding complications.
| S-EPMC3806846 | biostudies-literature
Project description:To determine the effect of adding cilostazol (100 mg b.i.d.) to standard-dose clopidogrel (75 mg/d) (TRIPLE) compared with double-dose clopidogrel (150 mg/d) (DOUBLE) and the influence of the cytochrome P450 (CYP2C19*2/*3, CYP3A5*3)and ATP-binding cassette subfamily B1(ABCB1 C3435T) genetic polymorphisms in type 2 diabetes (T2DM) patients.T2DM patients were treated with TRIPLE (n = 41) or DOUBLE (n = 39) after percutaneous coronary intervention. Conventional aggregometry and VerifyNow were performed at baseline and at 30 days. The primary end point was absolute change in 20-?M ADP-induced maximal platelet aggregation (?MPA(20)) between baseline and switching values.TRIPLE versus DOUBLE showed greater ?MPA(20) (22.9 ± 11.6 vs.12.7 ± 15.5%; difference, 10.2% [95% CI 4.2-16.3]; P < 0.001). Carriage of one (? coefficient, -5.4%; P = 0.162) and two CYP2C19 loss-of-function allele(s) (-8.3%; P = 0.007) were associated with lower ?MPA(20) in DOUBLE-treated patients, but not in TRIPLE-treated patients.Among T2DM patients, adding cilostazol achieves greater platelet inhibition compared with clopidogrel (150 mg/d), which is not influenced by genetic polymorphisms.
| S-EPMC3476883 | biostudies-literature
Project description:Although the new oral P2Y12 inhibitors, prasugrel/ticagrelor have shown greater efficacy than clopidogrel in patients with the acute coronary syndrome, but they have not shown better efficacy in Korean patients. So we evaluated the efficacy of the prasugrel/ticagrelor in patients with myocardial infarction (MI) and diabetes, a more high-risk patients group.From the Korea Acute Myocardial Infarction Registry-National Institute of Health, 3985 patients with MI and diabetes who underwent PCI were enrolled between November 2011 and December 2015. The patients were divided into 2 groups: clopidogrel (n = 2985) and prasugrel/ticagrelor (n = 1000).After propensity score matching, prasugrel/ticagrelor group showed a no significant difference in risk of the composite of cardiac death (CD), recurrent MI or stroke (hazard ratio [HR], 0.705; 95% confidence interval [CI], 0.474-1.048; P = .084). However, the risk of major bleeding was significantly higher in the prasugrel/ticagrelor group. (HR; 2.114, 95% CI; [1.027-4.353], P = .042). In subgroup analysis, major bleeding was significantly increased in the subgroup of creatinine clearance <60 ml/min/1.73 m, hypertension, underwent a trans-femoral approach and diagnosed as NSTEMI among the prasugrel/ticagrelor group.The use of prasugrel/ticagrelor did not improve the composite of CD, recurrent MI or stroke, however, significantly increased major bleeding events in Korean patients with MI and diabetes undergoing PCI.
| S-EPMC6426627 | biostudies-literature