European Heart Journal - Cardiovascular Pharmacotherapy最新文献

Aims: Emerging evidence suggests sex-specific differences in platelet biology and clinical responses to antiplatelet agents. Light transmission aggregometry (LTA) represents the historical gold standard for the assessment of platelet reactivity but is influenced by pre-analytical and analytical variables. We analysed a large dataset of patients undergoing LTA using a standardized methodology to investigate the impact of sex on platelet reactivity with or without antiplatelet therapy.

Methods and results: Between 2004 and 2022, 11,913 patients sequentially underwent LTA assessments following stimulation with adenosine diphosphate (ADP) (2 µM), collagen (2 µg/mL), arachidonic acid (AA, 0.5 mM), and epinephrine (10 µM). After applying study entry criteria, 5687 patients were included: 428 healthy volunteers (HV, F = 273; M = 155), 1055 controls (CTR; F = 725; M = 330), 3289 aspirin-treated patients (ASA; F = 2058; M = 1231), 430 clopidogrel-treated patients (CLOP; F = 272; M = 158), and 485 patients on dual antiplatelet therapy (DAPT; F = 166; M = 319). Within each group, results were analysed and compared between males and females.Females exhibited significantly greater platelet reactivity in response to ADP compared to males in the HV (P = 0.004), CTR (P < 0.0001), ASA (P < 0.0001), and CLOP (P < 0.018) groups, but not in the DAPT group. Among aspirin-treated patients, females showed increased platelet reactivity (P < 0.0001) in response to collagen, compared with males.

Conclusion: Females exhibit heightened baseline ADP-dependent platelet reactivity and a diminished response to aspirin and clopidogrel monotherapy compared to males.

Aims: There is conflicting trial evidence on the comparative effects of dual antiplatelet therapy (DAPT) with ticagrelor vs. clopidogrel in older patients with acute coronary syndromes (ACS). We aimed to assess the risk of major adverse cardiovascular events (MACE) and major bleeding in ACS patients ≥75 years initiating ticagrelor vs. clopidogrel treatment.

Methods and results: We used healthcare data from the Stockholm region (2011-2021) to emulate a hypothetical target trial comparing ticagrelor vs. clopidogrel. MACE was defined as a composite of cardiovascular death, myocardial infarction, or stroke. Patients were followed for 12 months. Inverse probability of treatment weighting was used to adjust for 46 baseline confounders. We used weighted Cox proportional hazards regression to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) and the weighted Aalen-Johansen estimator to estimate absolute risks (AR).Among 4637 older patients [median age, 81 years (IQR, 77-85)], 49% initiated DAPT with ticagrelor and 51% with clopidogrel. After weighting, all confounders were balanced. Ticagrelor was associated with a lower one-year MACE risk than clopidogrel (11.1% vs. 14.9%), corresponding to an AR difference of -3.8% (95%CI, -6.8, -0.8). The HR for ticagrelor vs. clopidogrel was 0.73 (95%CI, 0.56-0.95). There was no difference in the risk of major bleeding with one-year absolute risks of 4.3% with ticagrelor vs. 4.8% with clopidogrel, and a HR of 0.89 (95%CI, 0.63-1.27).

Conclusion: In ACS patients aged ≥75 years, ticagrelor was associated with a lower risk of MACE than clopidogrel. There were no differences in major bleeding, although the confidence interval was wide.

Aims: Patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI) are recommended to receive double antithrombotic therapy including an antiplatelet agent and direct oral anticoagulants (DOAC). The efficacy and safety of aspirin vs. clopidogrel as a combination therapy with DOAC were compared in the present study.

Methods and results: Patient data from the Korea National Health Insurance Service from 2013 to 2020 were analysed. A total of 9157 patients with AF who received double antithrombotic therapy consisting of an antiplatelet agent and a DOAC after PCI were included. Patients were classified into the clopidogrel or aspirin group and 1:1 propensity score (PS) matching was performed. The major adverse cardiovascular event (MACE) was defined as a composite of cardiovascular death, myocardial infarction, ischaemic stroke, or systemic thromboembolism. After PS matching, the clopidogrel and aspirin groups consisted of 2882 patients each. During a median follow-up of 20.1 months, the incidence of MACE was not significantly different between the two groups (hazard ratio [HR] for clopidogrel group 0.91, 95% confidence interval [CI] 0.81-1.02). The incidence of ischaemic endpoints did not significantly differ between the two groups. A significant difference was not observed in the incidence of major bleeding events (HR 0.94, 95% CI 0.78-1.12) and net adverse clinical events (HR 0.93, 95% CI 0.84-1.03).

Conclusion: In patients with AF receiving double antithrombotic therapy after PCI, aspirin and clopidogrel showed similar efficacy and safety when used in combination with DOAC.

Background and aims: There are currently no data regarding pre-treatment with P2Y12 inhibitors in patients with acute myocardial infarction complicated with cardiogenic shock (AMI-CS). This study investigates the effectiveness and safety of pre-treatment with P2Y12 inhibitors in patients with AMI-CS.

Methods and results: Using the ACTION-SHOCK cohort, we included consecutive patients hospitalized between 2012 and 2023 with AMI-CS admitted for coronary angiography within 24 h of admission. Pretreatment was defined by the administration before angiography of an oral loading dose of a P2Y12 inhibitor. We evaluated the association between pretreatment and either major adverse cardiovascular events (MACE) or major bleeding at 30 days after admission, using an inverse probability weighting (IPW) approach. MACE was defined by the composite of all-cause death, ischaemic stroke, myocardial infarction, or stent thrombosis. Major bleeding was defined by Bleeding Academic Research Consortium grade 3, 4, or 5. Among the 421 patients with AMI-CS admitted to the catheterization laboratory within 24 h of admission, 224 (53.2%) patients received pre-treatment with a P2Y12 inhibitor. No association between pre-treatment with P2Y12 inhibitor and MACE at 30 days was found [42.1% vs. 38.8%-IPW hazard ratio (wHR): 1.11, 95% CI: 0.82-1.50]. Pre-treatment was associated with an increased risk of major bleeding (42.2% vs. 32.3%-wHR: 1.48, 95% CI: 1.05-2.08). The effect of pre-treatment on MACE or major bleeding at 30 days is consistent across STEMI/NSTEMI patients.

Conclusion: In patients with AMI-CS, pretreatment with a P2Y12 inhibitor oral load was associated with an increased risk of major bleeding without benefit on MACE.

Aims: Single antiplatelet therapy (SAPT) has been shown to be a safer alternative to dual antiplatelet therapy (DAPT) in patients without atrial fibrillation (AF) undergoing transcatheter aortic valve implantation (TAVI). However, antithrombotic therapy for TAVI patients with severe peripheral artery disease (PAD) remains an underexplored area. This study aimed to evaluate and compare the outcomes of SAPT and DAPT in this high-risk patient population.

Methods and results: The HOSTILE registry was a multicentre, international, observational study including 1707 consecutive patients with hostile femoral access undergoing TAVI in 28 international centres. Among 573 patients without AF treated through transfemoral or non-thoracic alternative approach, 144 received SAPT and 429 DAPT after TAVI. The primary efficacy endpoint was the propensity-adjusted rate of major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, stroke, or transient ischaemic attack. The primary safety endpoint was the propensity-adjusted rate of major bleeding. Outcomes were reported at 30 days and 12 months. Dual antiplatelet therapy was associated with a non-significant reduction in MACE at 30 days [hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.25-2.18; P = 0.59] and at 12 months (HR 0.89, 95% CI 0.35-2.24; P = 0.80) compared with SAPT, but with a significant interaction between antiplatelet strategy and PAD severity (P = 0.01), suggesting a greater benefit of DAPT in patients with a high PAD severity. Dual antiplatelet therapy was associated with reduced all-cause death at 12 months (HR 0.22, 95% CI 0.10-0.47; P < 0.001) but not at 30 days (HR 0.26, 95% CI 0.05-1.22; P = 0.09) compared with SAPT. There was no difference in major bleeding at 30 days (P = 0.13) or 12 months (P = 0.10) between groups. There were no differences between groups in any bleeding at 30 days (P = 0.16) or 12 months (P = 0.17).

Conclusion: In TAVI patients with severe PAD, DAPT was associated with a trend towards improved outcomes compared with SAPT, particularly in those with higher PAD severity. These findings, including the observed reduction in 1-year mortality with DAPT, warrant further investigation in prospective studies.

Dual antiplatelet therapy with acetylsalicylic acid (ASA) and an oral P2Y12 inhibitor is the standard of care to prevent thrombotic complications in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). However, the oral administration of P2Y12 inhibitors bears significant limitations in acute and high-risk PCIs, particularly in ST-elevation myocardial infarction (STEMI) patients, especially those presenting with cardiogenic shock (CS) and cardiac arrest (CA). In these cases, factors such as active vomiting, altered physiology, sedatives, mechanical ventilation, and therapeutic hypothermia can impair drug absorption, reducing the intended antiplatelet effect and increasing ischaemic risk. In these cases, intravenous antiplatelet strategies with ASA and cangrelor could guarantee adequate periprocedural platelet inhibition. Here, we discuss the role of cangrelor in acute and high-risk PCI settings. The pharmacokinetic and pharmacodynamic attributes of cangrelor are discussed first, underscoring the distinctive features that make cangrelor an attractive antiplatelet agent in acute PCI settings. The second part of the review summarizes the evidence from real-world studies that illustrate how cangrelor has been adopted in contemporary practice. Finally, we provide a practical guide to cangrelor use, including recommendations for transitioning from cangrelor to oral P2Y12 inhibitors after PCI.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D), but heterogeneity exists across cardiovascular outcome trials (CVOTs). A comprehensive search of PubMed, EMBASE, and Cochrane Library was conducted through November 2024. Eligible CVOTs compared GLP-1 RAs with placebo in T2D patients. The primary outcome was MACE, defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using I², τ², and R². Meta-regression analyses evaluated the influence of baseline covariates on cardiovascular benefits of GLP-1 RAs, contingent upon the detection of moderate to substantial heterogeneity (I² ≥ 30%). Sensitivity analyses and GRADE assessments were also performed. Ten trials (67 769 patients; 34 536 receiving GLP-1 RAs) were analyzed. GLP-1 RAs significantly reduced MACE compared with placebo (OR = 0.87, 95% CI: 0.81-0.93, P < 0.001, I² = 48.4%). Cardiovascular death (OR = 0.86, 95% CI: 0.79-0.94, P < 0.001, I² = 22.6%) and all-cause mortality (OR = 0.87, 95% CI: 0.82-0.94, P < 0.001, I² = 17.7%) were also reduced. Meta-regression revealed a greater cardiovascular benefit in patients with higher baseline body mass index (BMI; logOR = -0.098 per kg/m², P = 0.006, R² = 99.98%) and older age (logOR = -0.033 per year, P = 0.023, R² = 75.47%). Sensitivity analyses confirmed the robustness of these findings, with consistent effect sizes and no single trial unduly influencing the results. The certainty of evidence was rated as high for all outcomes based on GRADE criteria. GLP-1 RAs significantly reduce MACE, cardiovascular death, and all-cause mortality in T2D patients. Higher baseline BMI and older age were associated with greater cardiovascular benefit.