Abstract Objective This study was aimed to investigate an optimal therapeutic window for platelet reactivity (PR) to predict the lowest ischemic and bleeding events in patients underwent percutaneous coronary intervention (PCI) and treated with dual antiplatelet agents. Design A total of 1709 patients who had received coronary stent implantation and had taken aspirin 100 mg in combination with clopidogrel 75 mg daily for >5 days were consecutively recruited and their platelet reactivity was determined by light transmittance aggregometry (LTA). All patients were followed up for 12 months. The primary end-point was the net adverse clinical events (NACE) of cardiovascular death, nonfatal myocardial infarction (MI), target vessel revascularization (TVR) , stent thrombosis (ST) and any bleeding. Result By using the receiver-operating curve (ROC) analysis, the optimal cutoff values were found to be 37.5% and 25.5% respectively in predicting ischemic and bleeding events. Patients were classified into 2 groups according to PR: inside the window group (IW) [adenosine diphosphate (ADP) induced platelet aggregation (PL ADP ) 25.5%-37.4%)] and outside the window group (OW) (PL ADP <25.5% or ≥37.5%). The incidence of NACE was 16.8% and 23.1% respectively in the IW and OW group. The hazard ratio of NACE in IW-group was significantly lower [0.69 (95% CI: 0.54–0.89; P = 0.004)] than that in the OW-group during 12 month follow-up. Conclusion An optimal therapeutic window of 25.5%-37.4% for PL ADP predicts the lowest risk of NACE, which could be referred for tailored antiplatelet treatment while using LTA assay. Trial and clinical registry Trial registration number: ClinicalTrials.gov NCT01968499. Registered 18 October 2013 - Retrospectively registered.
Background: Previous studies have suggested that proton pump inhibitors could impair the antiplatelet effect of clopidogrel. It is uncertain whether ilaprazole affects the antiplatelet effect of clopidogrel. This study aimed to determine the drug-drug interaction between ilaprazole and clopidogrel. Methods: A randomized crossover trial of 40 healthy subjects was performed. Clopidogrel was administered alone or in combination with ilaprazole for 7 days. The maximal platelet aggregation (MPA) to 5 μmol/L adenosine diphosphate was measured by light transmission aggregometry and the platelet reactivity index (PRI) was determined by vasodilator-stimulated phosphoprotein P2Y 12 assay. High on-treatment platelet reactivity (HOPR) was defined as a MPA of >40%. The inhibition of platelet aggregation (IPA) and PRI in the two phases were compared between two regimens after the last dosing. Results: IPA was comparable between the two regimens at 0, 10 and 24 h ( p > 0.05), but higher at 4 h in the clopidogrel alone regimen compared with that in the combined treatment regimen (75.66 ± 18.44% vs. 70.18 ± 17.67%, p = 0.031). The inhibition of PRI was comparable between the two regimens at 0 and 24 h. There were no significant differences in the area under the time-IPA% curve (AUC) or the incidence of HOPR at all time-points between the two regimens. Conclusion: In healthy subjects, ilaprazole has limited effect on the pharmacodynamics of clopidogrel and it may not be clinically relevant. Clinical Trial Registration : [ www.chictr.org.cn ], identifier [ChiCTR2000031482].
Background: Mono antiplatelet therapy (MAPT) following intended duration of dual antiplatelet therapy (DAPT) is recommended for the secondary prevention of cardiovascular events in patients after drug-eluting stent (DES) implantation. However, the optimal MAPT is uncertain. Methods: From the start of the database until November 11, 2022, the PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for all randomized trials comparing different antiplatelet therapies in patients implanted with DES and taking DAPT at least one month. The primary endpoint was net adverse clinical events (NACE), a composite of all-cause mortality, myocardial infarction, stroke, and major bleeding. The secondary efficacy endpoints were major adverse cardiac and cerebrovascular events (MACCE, a composite of all-cause mortality, myocardial infarction, and stroke), and the secondary safety endpoint was major bleeding. This study was registered with PROSPERO (CRD42022323187).Findings: A total of 14 trials including 54 477 patients were enrolled. The duration of DAPT varied from 1–48 months. There was no significant difference in NACE risk between ticagrelor and aspirin (hazard ratio [HR] 0·85, 95% credible interval 0·63–1·12), neither between ticagrelor and clopidogrel (HR 1·19, 0·79–1·79) for monotherapy. However, the risk of NACE in patients receiving clopidogrel was significantly reduced compared to patients receiving aspirin (HR 0.71, 0.53-0.94). There was no significant difference regarding the risk of MACCE or major bleeding among aspirin, clopidogrel, and ticagrelor monotherapies, except that clopidogrel had a significantly reduced risk of major bleeding compared with ticagrelor (HR 0·36, 0·13–0·99).Interpretation: For patients implanted with DES and completing DAPT, clopidogrel is superior to aspirin in reducing the risk of NACE, and superior to ticagrelor in reducing the risk of major bleeding for monotherapy.Funding This study was supported by the Special Fund for Key R & D Plans (Social Development) of Jiangsu Province (BE2019754), and the National Natural Science Funding of China (82170351).Declaration of Interests: We declare no competing interests.
It is controversial whether hemodialysis affects the efficacy of the antiplatelet agents. We aimed to investigate the impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease (CAD) patients complicated with end-stage renal disease (ESRD). 86 CAD patients complicated with ESRD requiring hemodialysis were consecutively enrolled. After 5-day treatment with aspirin and clopidogrel or ticagrelor, the platelet aggregations induced by arachidonic acid (PL
Abstract Background It is controversial whether hemodialysis affects the efficacy of the antiplatelet agents. We aimed to investigate the impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease (CAD) patients complicated with end‑stage renal disease (ESRD). Methods 86 CAD patients complicated with ESRD requiring hemodialysis were consecutively enrolled. After 5-day treatment with aspirin and clopidogrel or ticagrelor, the platelet aggregations induced by arachidonic acid (PL AA ) or adenosine diphosphate (PL ADP ), and the P2Y 12 reaction unit (PRU) were measured before and after hemodialysis. The propensity matching score method was adopted to generate a control group with normal renal function from 2439 CAD patients. Results In patients taking aspirin, the PL AA remained unchanged after hemodialysis. In patients taking clopidogrel, the PL ADP (37.26 ± 17.04 vs . 31.77 ± 16.09, p = 0.029) and corresponding clopidogrel resistance (CR) rate (23 [48.9%] vs. 14 [29.8%], p = 0.022) significantly decreased after hemodialysis, though PRU remained unchanged. Subgroup analysis indicated that PL ADP significantly decreased while using polysulfone membrane (36.8 ± 17.9 vs. 31.1 ± 14.5, p = 0.024). In patients taking ticagrelor, PL ADP , and PRU remained unchanged after hemodialysis. ESRD patients had higher incidences of aspirin resistance (AR) and CR compared to those with normal renal function (AR: 16.1% vs. 0%, p = 0.001; CR: 48.4% vs. 24.8%, p = 0.024). Conclusion Hemodialysis does not have negative effect on the efficacies of aspirin, clopidogrel and ticagrelor in ESRD patients with CAD. On the contrary, clopidogrel response may be improved while using the polysulfone membrane during hemodialysis. ESRD patients have higher incidences of AR and CR compared with those with normal renal function. Trial registration ClinicalTrials.gov Identifier: NCT03330223.
High on-treatment platelet reactivity (HOPR) is associated with increased risk of cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). We randomised post-PCI patients with HOPR after 5 days of standard dual antiplatelet therapy (DAPT) to intensified therapy with aspirin 100 mg once daily in combination with either clopidogrel 150 mg once daily, clopidogrel 75 mg once daily plus cilostazol 100 mg twice daily, ticagrelor 90 mg twice daily, or standard therapy with clopidogrel 75 mg once daily (STD) for 1 month, after which all patients were switched to standard DAPT for a further 11 months. The primary outcome was residual HOPR rate at 1 month. We screened 1724 patients with light transmission aggregation studies and randomised 434 with HOPR. At 1 month the proportion of patients with persistent HOPR was significantly lower in the intensified therapy groups compared with STD group. Compared to the group receiving STD therapy, those receiving intensified therapy had significantly lower rate of major adverse cardiovascular events (MACE) at both 1 month and 12 months with no significant increase in bleeding. In patients with post-PCI HOPR, 1 month of intensified antiplatelet therapy provides greater platelet inhibition and improves outcomes without increasing bleeding. Clinical Trial Registration URL: http://www.clinicaltrials.gov; Unique Identifier: NCT01955200.
Currently, noninvasive arteriography for the diagnosis of coronary artery disease is clinically limited to the computed tomography scanning, where patients have to be exposed to the radiation and risks associated with iodinated contrast. We aimed to investigate the diagnostic performance and safety of a novel ferumoxytol-enhanced coronary magnetic resonance angiography (CMRA) in patients with suspected coronary artery disease.Thirty patients, 19 males, with a median age of 63 years old, and 17 with renal insufficiency, who were scheduled for invasive coronary angiography, were enrolled. Ferumoxytol was administered intravenously with a dose of 3 mg/kg during CMRA. Images were acquired with an ECG-triggered, navigator-gated, inversion recovery-prepared 3D fast low-angle shot sequence, and the image quality was assessed by a 4-point scale. Eighteen-segment coronary artery model was adopted to evaluate the visibility of the coronary arteries, and the image quality and stenosis were evaluated in nine segments. The diagnostic performance of CMRA is described as sensitivity, specificity, positive and negative predictive values, and accuracy with the invasive coronary angiography results as reference. The patients' vital signs were monitored during CMRA, and their hepatic and renal functions were followed up for 3 months to evaluate the safety of ferumoxytol.Two hundred fifty-two of the 270 study segments were identified by CMRA, and their quality score reached 3.6±0.7. Referring to the invasive coronary angiography results, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ferumoxytol-enhanced CMRA reached 100.0%, 66.7%, 92.3%, 100.0%, and 93.3% respectively in patient-based analysis; 91.4%, 90.9%, 86.5%, 94.3%, and 91.1%, respectively in vessel-based analysis; and 92.3%, 96.7%, 83.7%, 98.6%, and 96.0%, respectively in segment-based analysis. No ferumoxytol-related adverse event was observed during the 3-month follow-up.Ferumoxytol-enhanced CMRA demonstrated good diagnostic performance and excellent safety in the diagnosis of significant coronary stenosis, providing an alternative to coronary computed tomography angiography for the diagnosis of coronary artery disease.URL: https://www.gov; Unique identifier: NCT05032937.
This study was aimed to determine how platelet reactivity (PR) on dual antiplatelet therapy predicts ischemic and bleeding events in patients underwent percutaneous coronary intervention (PCI).A total of 2768 patients who had received coronary stent implantation and had taken aspirin 100 mg in combination with clopidogrel 75 mg daily for > 5 days were consecutively screened and 1885 were enrolled. The recruited patients were followed-up for 12 months. The primary end-point was the net adverse clinical events (NACE) of cardiovascular death, nonfatal myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST) and any bleeding.1709 patients completed the clinical follow-up. By using the receiver operating characteristic (ROC) curve analysis, the optimal cut-off values were found to be 37.5 and 25.5% respectively in predicting ischemic and bleeding events. Patients were classified into 2 groups according to PR: inside the window group (IW) [adenosine diphosphate (ADP) induced platelet aggregation (PLADP) 25.5-37.4%)] and outside the window group (OW) (PLADP < 25.5% or ≥ 37.5%). The incidence of NACE was 16.8 and 23.1% respectively in the IW and OW group. The hazard ratio of NACE in IW group was significantly lower [0.69 (95% CI, 0.54-0.89, P = 0.004)] than that in the OW group during 12-month follow-up.An optimal therapeutic window of 25.5-37.4% for PLADP predicts the lowest risk of NACE, which could be referred for tailored antiplatelet treatment while using LTA assay.Trial registration number: ClinicalTrials.gov NCT01968499 . Registered 18 October 2013 - Retrospectively registered.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)