Mean platelet volume and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor

Objective: High on-treatment platelet reactivity (HRPR) is associated with a two- to ninefold increased risk of recurrent ischemic events among patients receiving dual antiplatelet therapy (DAPT) for coronary artery disease. However, its determinants are still poorly understood. The aim of the present study was to assess the impact of mean platelet volume (MPV) on platelet reactivity in patients receiving DAPT after an acute coronary syndrome or PCI.

Methods: Patients treated with DAPT (acetylsalicylic acid [ASA] and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30 – 90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test > 862 aggregation units (AU)*min (for ASA) and ADP test values ≥ 417 AU*min (for ADP-antagonists).

Results: Our population is represented by a total of 487 patients on DAPT, divided according to MPV tertiles (< 10.4 fl; 10.4 – 11.29 fl; ≥ 11.3 fl). Larger-sized platelets were associated with use of statins (p < 0.001) and beta-blockers (p = 0.03), higher hemoglobin levels (p = 0.002) and lower platelets count (p < 0.001). Higher platelet reactivity was observed at ASPI test in patients with higher MPV (r = 0.12, p = 0.008), but not for ADP-mediated aggregation (r = -0.007, p = 0.88). However, a low prevalence of HRPR was observed with ASA, with no impact of MPV tertiles (1.2 vs 1.1 vs 1.6%, p = 0.70, adjusted OR [95% CI] = 1.05 [0.51 – 1.77], p = 0.87). MPV did not influence the prevalence of HRPR for ADP-antagonists (25.9 vs 1 vs 26.5%, p = 0.89; adjusted OR [95% CI] = 1.1 [0.84 – 1.45], p = 0.50) with similar results among the 259 patients receiving clopidogrel (adjusted OR [95% CI] = 1.15 [0.82 – 1.62], p = 0.43) and the 228 patients on ticagrelor (adjusted OR [95% CI] = 1.46 [0.84 – 2.55], p = 0.18).

Conclusion: In patients receiving DAPT, MPV does not affect the response to major antiplatelet therapies. In fact, MPV elevation does not influence the risk of HRPR with clopidogrel, ticagrelor or ASA.     

替格瑞洛在高龄急性非ST段抬高型心肌梗死患者早期介入治疗中的疗效及安全性

目的评价替格瑞洛在高龄(≥75岁)急性非ST段抬高型心肌梗死(NSTEMI)患者早期(发病24 h内)介入治疗(PCI)中的有效性及安全性。方法连续入选85例资料齐全行早期PCI的高龄NSTEMI的患者,随机分为替格瑞洛组和氯吡格雷组。随访6个月,比较2组患者术中无复流或慢血流的发生情况,发生典型心绞痛、非致死性心肌梗死、心力衰竭和心源性死亡等主要心脏不良事件(MACE)的发生率,出血、药物不良反应情况,以及左室舒张末期内径(LVDD)、左室射血分数(LVEF)等指标变化情况。结果替格瑞洛组术中发生梗死溶栓试验血流分级(TIMI)2级、TIMI心肌灌注分级(TMP)3级的比例显著低于氯吡格雷组(P0.05)。随访6个月,替格瑞洛组总MACE发生率显著低于氯吡格雷组(P0.05)。2组患者术后严重出血发生率无显著差异(P0.05)。2组发生呼吸困难等药物不良反应情况有显著差异(P0.05)。替格瑞洛组LVEF优于氯吡格雷组。结论对于高龄NSTEMI患者早期行PCI时,替格瑞洛可以获得更好的心肌水平再灌注,且不增加严重出血情况的发生,降低总心脏不良事件的发生。     

替格瑞洛治疗急性冠状动脉综合征疗效观察

目的 探讨替格瑞洛治疗急性冠状动脉综合征(acute coronary syndrome,ACS)的疗效及安全性.方法 ACS患者281例随机分为替格瑞洛组140例和氯吡格雷组141例,替格瑞洛组经皮冠状动脉介入术(percutaneous coronary intervention,PCI)前口服负荷剂量替格瑞洛180mg,PCI术后给予替格瑞洛90 mg/次,2次/d,口服;氯吡格雷组PCI前口服负荷剂量氯吡格雷300mg,PCI术后给予氯吡格雷75 mg/次,1次/d,口服.比较2组术后24 h血肌酐、肌红蛋白、肌钙蛋白、肌酸激酶同工酶-MB水平,并随访8个月观察2组终点事件、支架内再狭窄、出血、呼吸困难、造影剂肾病等发生情况.结果 替格瑞洛组术后24 h血肌酐水平((119.41±22.10) μmol/L)高于氯吡格雷组((99.03±19.14)μmol/L)(P＜0.05),肌红蛋白水平((15.67±5.61)μg/L)低于氯吡格雷组((20.22±7.31)μg/L)(P＜0.05),2组肌钙蛋白T、肌酸激酶同工酶-MB水平比较差异无统计学意义(P＞0.05);随访结果显示,替格瑞洛组终点事件发生率(5.71％)低于氯吡格雷组(10.64％),支架再狭窄率(2.14％)低于氯吡格雷组(3.55％),轻度出血发生率(5.71％)高于氯吡格雷组(2.13％)(P＜0.05),2组严重出血、呼吸困难、造影剂肾病发生率比较差异无统计学意义(P＞0.05).结论 应用替格瑞洛可有效降低ACS患者再发心肌梗死或心绞痛等终点事件发生率,并有较高安全性.     

Prediction of Ticagrelor and its Active Metabolite in Liver Cirrhosis Populations Using a Physiologically Based Pharmacokinetic Model Involving Pharmacodynamics

Ticagrelor, a P2Y₁₂ receptor antagonist, has been highly recommended for use in acute coronary syndrome. The major active metabolite (AM) is similar to the parent drug, which exhibits antiplatelet activity. The inhibition of platelet aggregation (IPA) is used as an assay to demonstrate the anticoagulant efficacy of ticagrelor. In this study, we developed a physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics of ticagrelor and its AM and combined this model with a pharmacodynamics model to reflect potential pharmacodynamic alterations in liver cirrhosis populations. The simulated results obtained using the PBPK model were validated by fold error values, which were all smaller than 2. Comparisons of exposure in different classifications of liver cirrhosis indicated that exposure to ticagrelor increased significantly with an increase in the degree of cirrhosis severity, whereas exposure to AM was decreased. The total concentration of ticagrelor and AM was related to the IPA included in the Sigmoid E_max model. The PBPK model of ticagrelor and AM could predict the pharmacokinetics of all populations, and a combination of PD models was used to extrapolate for predicting unknown scenarios. Liver cirrhosis may result in prolonged IPA, depending on the severity degree of this disease. The combined PBPK model including IPA can reveal changes in pharmacokinetics and pharmacodynamics in populations affected by liver cirrhosis and indicate the risk potential.     

Mild Hypertension

PREVIEW

Rheumatoid arthritis can cause joint erosion and deformity, pain, stiffness, and decreased function and range of motion. Early diagnosis is crucial to prevent permanent joint damage. In this article, Drs Williams and Fye discuss articular and extra articular manifestations of rheumatoid arthritis as well as the evolving treatment approaches to this complex disease.     

Effects (MACE and bleeding events) of ticagrelor combined with omeprazole on patients with acute myocardial infarction undergoing primary PCI

BackgroundThis study aimed to investigate the effect of ticagrelor combined with omeprazole on patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI).MethodsEighty-six patients with AMI who underwent primary PCI in Xinxiang Central Hospital between July 2015 and December 2016 were included and divided randomly into the observation group and the control group by the draw, with 43 patients in each group. All patients were routinely treated with dual antiplatelet therapy with aspirin plus ticagrelor. Omeprazole was used in the observation group and placebo was used in the control group. Data of baseline patient characteristics, platelet response index (PRI), ADP-induced platelet aggregation (ADP-Ag), major adverse cardiac events (MACE), and incidence of bleeding events were recorded and compared between both groups.ResultsPRI and ADP-Ag at 7 days, 1 month, and 6 months after operation in both groups were significantly lower than those in the same group before administration (p < 0.017). Incidence of bleeding events in the observation group was significantly lower than that in the control group (p < 0.05).ConclusionFor patients with AMI undergoing primary PCI, omeprazole was found to reduce the incidence of gastrointestinal bleeding without reducing the antiplatelet aggregation effect of ticagrelor or increasing the risk of MACE, which is worthy of clinical promotion.