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Efficacy and safety of ticagrelor versus clopidogrel with different dosages in acute coronary syndrome patients with high GRACE and CRUSADE scores.

ABSTRACT:

Objective

To investigate the efficacy and safety of ticagrelor and different dosages of clopidogrel after acute coronary syndrome.

Methods

We compared different antiplatelet strategies for the prevention of cardiovascular events in 1939 patients admitted to the hospital with an acute coronary syndrome undergoing percutaneous coronary intervention (PCI).

Results

At 24 months, a survival analysis showed that ticagrelor and double-dose clopidogrel decreased the incidence of MACCE (a composite of all-cause death, myocardial infarction (MI), target vessel revascularization and stroke) (p < 0.001, p = 0.012, respectively). Although double-dose clopidogrel obviously increased the risk of major bleeding (p < 0.001), a similar result was not observed in the ticagrelor group (p = 0.398). These two stronger antiplatelet strategies also decreased the incidence of myocardial infarction (p = 0.004 and 0.045, respectively). The advantages of ticagrelor are also evident in the endpoints of all cause death and target vessel revascularization. The NACCE (a composite of all-cause death, MI, stroke and major bleeding) rate was also reduced in the ticagrelor group (p = 0.004).

Conclusions

In PCI patients with a high ischemic and bleeding risk, the ticagrelor antiplatelet strategy significantly reduced the MACCE rate without increasing the risk of major bleeding. A decreased MACCE rate was also observed in patients administered the double dosage of clopidogrel, but the bleeding risk was increased compared with the control group.

SUBMITTER: Xiao P

PROVIDER: S-EPMC8322751 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Dual antiplatelet therapy combining aspirin with a P2Y12 adenosine diphosphate receptor inhibitor is a therapeutic mainstay for acute coronary syndrome (ACS). However, the optimal choice of P2Y12 adenosine diphosphate receptor inhibitor in elderly (aged ≥65 years) patients remains controversial. We conducted a meta-analysis to compare the efficacy and safety of ticagrelor and clopidogrel in elderly patients with ACS. Methods: We comprehensively searched in Web of Science, EMBASE, PubMed, and Cochrane databases through 29th March, 2021 for eligible randomized controlled trials (RCTs) comparing the efficacy and safety of ticagrelor or clopidogrel plus aspirin in elderly patients with ACS. Four studies were included in the final analysis. A fixed effects model or random effects model was applied to analyze risk ratios (RRs) and hazard ratios (HRs) across studies, and I2 to assess heterogeneity. Results: A total number of 4429 elderly patients with ACS were included in this analysis, of whom 2170 (49.0%) patients received aspirin plus ticagrelor and 2259 (51.0%) received aspirin plus clopidogrel. The ticagrelor group showed a significant advantage over the clopidogrel group concerning all-cause mortality (HR 0.78, 95% CI 0.63-0.96, I2 = 0%; RR 0.79, 95% CI 0.66-0.95, I2 = 0%) and cardiovascular death (HR 0.71, 95% CI 0.56-0.91, I2 = 0%; RR 0.76, 95% CI 0.62-0.94, I2 = 5%) but owned a higher risk of PLATO major or minor bleeding (HR 1.46, 95% CI 1.13-1.89, I2 = 0%; RR 1.40, 95% CI 1.11-1.76, I2 = 0%). Both the groups showed no significant difference regarding major adverse cardiovascular events (MACEs) (HR 1.06, 95% CI 0.68-1.65, I2 = 77%; RR 1.04, 95% CI 0.69-1.58, I2 = 77%). Conclusion: For elderly ACS patients, aspirin plus ticagrelor reduces cardiovascular death and all-cause mortality but increases the risk of bleeding. Herein, aspirin plus ticagrelor may extend lifetime for elderly ACS patients compared with aspirin plus clopidogrel. The optimal DAPT for elderly ACS patients may be a valuable direction for future research studies.

Project description:BACKGROUND:The dose and time point for switching from clopidogrel to ticagrelor remain controversial, especially for Chinese acute coronary syndrome (ACS) patients with complicated coronary artery disease (CAD). Hence, the purpose of this study was to further explore the optimal dose and time point for the switching strategy to balance the increase in platelet inhibition and the decrease in adverse events in Chinese ACS patients with complicated CAD managed by percutaneous coronary intervention (PCI). METHODS:From July 2017 to December 2017, the prospective, randomized, open-label study (the SwitcHIng from clopidogrel to ticagrelor study) assigned the eligible Chinese ACS patients with complicated CAD managed by PCI (n = 102) for 90 mg of ticagrelor at 12 h (T-90 mg-12 h), 90 mg of ticagrelor at 24 h (T-90 mg-24h) or 180 mg ticagrelor at 24 h (T-180 mg-24 h) after the last dose of clopidogrel. The primary endpoint was the comparison of maximal platelet aggregation (MPA) values at 2 h after switching strategies among the three groups. In addition, the MPA values at baseline, 8 h and before discharge and the rates of high on-treatment platelet reactivity were evaluated, the incidences of bleeding episodes and dyspnea during hospitalization and at 30-day follow-up in our study were also recorded. The MPA was measured by light transmittance aggregometry in our study. A repeated-measures analysis of variance (ANOVA) model and one-way ANOVA were used to compare data for the primary endpoint. RESULTS:The MPA values were significantly decreased in the T-180 mg-24 h group compared with the T-90 mg-12 h group (P = 0.017) and decreased numerically compared with the T-90 mg-24 h group (P = 0.072) at 2 h. In particular, the MPA values were markedly reduced in the T-90 mg-24 h group compared with the T-90 mg-12 h group at 8 h after switching treatment (P = 0.002). There was no significant difference among the three groups in all bleedings and dyspnea events. CONCLUSIONS:The optimal treatment strategy recommended in this study for Chinese ACS patients with complicated CAD managed by PCI is 180 or 90 mg of ticagrelor at 24 h after the last dose of clopidogrel. In addition, a negative interaction was detected in this study between the overlap for clopidogrel and ticagrelor at 12 h after the last dose of clopidogrel. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03577652; http://clinicaltrials.gov/ct2/show/NCT03577652.

Project description:Background Current guidelines recommend the new-generation P2Y12-inhibitor ticagrelor for patients with acute ST-segment-elevation myocardial infarctions (STEMIs). The aim of the present study was to assess efficacy and safety of ticagrelor for elderly patients with STEMI (?75 years) in an all-comers STEMI registry. Methods and Results Patients with STEMI, aged ?75 years, treated with primary percutaneous coronary intervention and documented in the Bremen STEMI Registry between 2006 and 2017 entered analysis. The primary efficacy outcome, major adverse cardiac and cerebrovascular events, was defined as a composite of death, myocardial reinfarction, and stroke. The safety outcome was defined as any significant bleeding event within 1 year. To estimate benefit/risk ratio, net adverse clinical events (major adverse cardiac and cerebrovascular events+bleedings) were calculated. Outcomes were estimated in propensity score-matched cohorts to adjust for possible confounders. Of a total of 7466 patients with STEMI, 1087, aged ?75 years, were selected, of which 552 (51%) received clopidogrel and 535 (49%) received ticagrelor, with similar age (80.9±4.6 versus 80.9±4.6 years) and sex (51% versus 50% female) distributions between treatment arms. The primary efficacy outcome occurred in 32.4% of patients treated with clopidogrel versus 25.5% treated with ticagrelor (P=0.015), with the 1-year mortality rate at 26.8% versus 21.1% (P=0.035). Because there was no difference in the safety outcome (clopidogrel versus ticagrelor, 4.9% versus 5.1%; not significant), net adverse clinical events were higher for clopidogrel than for ticagrelor: 37.3% versus 30.6% (P=0.028). In a propensity score-matched model, the advantage for ticagrelor on major adverse cardiac and cerebrovascular events remained significant (hazard ratio, 0.69; 95% CI, 0.49-0.97; P=0.03), whereas 1-year-mortality (hazard ratio, 0.89; 95% CI, 0.67-1.27; P=0.5) and 1-year bleeding events (hazard ratio, 1.1; 95% CI, 0.4-2.3; P=0.8) did not differ. Conclusions These results from propensity score-matched registry data show that for elderly patients with STEMI, ticagrelor compared with clopidogrel was associated with a reduction in major adverse cardiac and cerebrovascular events without a significant increase in bleeding events within 1 year.