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Ticagrelor vs. Clopidogrel in Acute Coronary Syndrome Patients With Chronic Kidney Disease After New-Generation Drug-Eluting Stent Implantation.

ABSTRACT: Background: The impact of ticagrelor-based dual antiplatelet therapy (DAPT) on acute coronary syndrome (ACS) in patients with chronic kidney disease (CKD) remains unclear. Methods: Data on a total of 1,067 ACS patients with CKD including end-stage renal disease (ESRD) who underwent new-generation drug-eluting stent implantation were extracted from a multicenter registry. This study aimed to compare outcomes of patients treated with ticagrelor- (n = 449) and those treated with clopidogrel-based (n = 618) DAPT. Outcomes of interest included major adverse cardiac and cerebrovascular events (MACCEs) and bleeding (Bleeding Academic Research Consortium grade 3 or 5) at 12 months. Propensity-score matching (346 pairs) analysis was performed. Results: The patients with ESRD showed the highest MACCE and bleeding rates (P < 0.001). There was no difference in the rate of MACCEs between the treatment groups (7.8% vs. 8.4%; hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.56-1.61, P = 0.855); however, a trend toward an increased bleeding rate was observed in the ticagrelor-based DAPT group (6.8% vs. 3.8%, HR = 1.84, 95% CI = 0.93-3.63, P = 0.079). Among patients with CKD stage III/IV but without ESRD (277 pairs), the ticagrelor-based DAPT group showed a reduced MACCE rate (3.6% vs. 8.7%, HR = 0.41, 95% CI = 0.19-0.86, P = 0.018) and a similar bleeding rate (5.1% vs. 3.2%, HR = 1.61, 95% CI = 0.70-3.71, P = 0.267), compared with those of the clopidogrel-based DAPT group. Conclusion: The effects of ticagrelor-based DAPT on ischemic and bleeding outcomes of ACS patients with CKD varied according to CKD stage; in ACS patients with CKD without ESRD, ticagrelor-based DAPT reduced MACCE risk without increasing bleeding risks, relative to those observed with clopidogrel-based DAPT.

SUBMITTER: Roh JW

PROVIDER: S-EPMC8785207 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Early generation drug-eluting stents (DESs) showed a high grade of coronary endothelial dysfunction that was attributed to lack of stent reendothelialization. Endothelium-dependent vasomotor response of current DESs and bioresorbable scaffolds (BRSs) remains unknown. This study sought to assess the device-related endothelial function of current devices and to correlate neointima healing with endothelial function. Methods and Results A total of 206 patients from 4 randomized trials treated with the durable-polymer everolimus-eluting Xience (n=44), bioresorbable-polymer sirolimus-eluting Orsiro (n=35), polymer-free biolimus-eluting Biofreedom (n=24), bioactive endothelial-progenitor cell-capturing sirolimus-eluting Combo DES (n=25), polymer-based everolimus-eluting Absorb (n=44), and Mg-based sirolimus-eluting Magmaris BRS (n=34) underwent endothelium-dependent vasomotor tests and optical coherence tomography imaging, as per protocol, at follow-up. Crude vasomotor responses of distal segments to low-dose acetylcholine (10-6 mol/L) were different between groups: bioresorbablepolymer DEShad the worst (-8.4%±12.6%) and durable-polymer DES had the most physiologic (-0.4%±11.8%; P=0.014). High-dose acetylcholine (10-4 mol/L) showed similar responses between groups (ranging from -10.8%±11.6% to -18.1%±15.4%; P=0.229). Device healing was different between devices. Uncovered struts ranged from 6.3%±7.1% (bioresorbable-polymer DES) to 2.5%±4.5% (bioactive DES; P=0.056). In multivariate models, endothelium-dependent vasomotor response was associated with age, bioresorbable-polymer DES, and angiographic lumen loss, but not with strut coverage nor plaque type. Endothelial dysfunction (defined as ≥4% vasoconstriction) was observed in 46.6% of patients with low-dose and 68.9% with high-dose acetylcholine, without differences between groups. Conclusions At follow-up, endothelial dysfunction was frequently observed in distal segments treated with current stents without remarkable differences between devices. Although neointima healing was different between devices, poor healing was not associated with endothelial dysfunction.

Project description:Clopidogrel use after drug-eluting stent (DES) coronary artery implantation is essential for the prevention of early in-stent thrombosis, but clopidogrel use among older DES recipients has not been widely studied. We sought to identify characteristics associated with failure to fill a clopidogrel prescription and to examine the relationship between a clopidogrel prescription fill and hospitalization for acute myocardial infarction (AMI) or death.This study was a retrospective analysis of administrative data (20% sample) of 15 996 Medicare Part D enrollees who received a DES in 2006 to 2007. We modeled the adjusted probability and odds of clopidogrel prescription fill within 7 and 90 days of discharge and its association with AMI hospitalization or death. Of the study sample, 19.7% did not fill a clopidogrel prescription within 7 days of discharge, falling to 13.3% by day 90. The adjusted probability of filling a clopidogrel prescription within 7 or 90 days of discharge was lower for patients with dementia (20.2% less likely; 95% CI, 10.4%-30.1%), depression (10.7% less likely; 95% CI, 6.9%-14.5%), age >84 years compared to age 65 to 69 years (10.6% less likely; 95% CI, 8.6%-12.7%), black race (6.6% less likely; 95% CI, 4.2%-9.0%), intermediate levels of medication cost share (5.2% less likely; 95% CI, 2.9%-7.6%), and female sex (3.3% less likely; 95% CI, 2.1%-4.5%). It was higher for patients initially hospitalized for an AMI (12.5% more likely; 95% CI, 11.3%-13.6%). Failure to fill a clopidogrel prescription within 7 days of discharge was associated with a higher adjusted odds ratio of death during days 8 to 90 (2.44; 95% CI, 1.76-3.38) but was not associated with an increased risk of hospitalization for AMI.One in 5 patients failed to fill a prescription for clopidogrel at 7 days after DES placement, and 1 in 7 failed to do so by 3 months. Individual characteristics available at the time of hospital discharge were associated with a clopidogrel prescription fill. Those characteristics most strongly associated with nonadherence, including age >84 years, not having an AMI, depression, and dementia, may guide clinicians and health systems seeking to target this high-risk population and improve health outcomes after percutaneous coronary intervention.

Project description:BackgroundEnd-stage renal disease yields susceptibility to both ischemia and bleeding. The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is not established in dialysis patients, who are usually excluded from randomized studies. Since recent studies implied the benefits of prolonged DAPT >12 months in chronic kidney disease, we investigated the effectiveness and safety of prolonged DAPT in dialysis patients with higher cardiovascular risks.MethodsIn this nationwide population-based study, we analyzed dialysis patients who underwent DES implantation from 2008 to 2015. Continued DAPT was compared with discontinued DAPT using landmark analyses, including free-of-event participants at 12 (n = 2246), 15 (n = 1925) and 18 months (n = 1692) after DES implantation. The primary outcome was major adverse cardiovascular events (MACEs): a composite of mortality, nonfatal myocardial infarction, coronary revascularization and stroke. Major bleeding was a safety outcome. Inverse probability of treatment weighting Cox regression was performed.ResultsMean follow-up periods were 278.3-292.4 days, depending on landmarks. Overall, incidences of major bleeding were far lower than those of MACE. Continued DAPT groups showed lower incidences of MACE and higher incidences of major bleeding, compared with discontinued DAPT groups. In Cox analyses, continued DAPT reduced the hazards of MACE at the 12- [hazard ratio (HR) = 0.74, 95% confidence interval (CI) 0.61-0.90; P = 0.003], 15- (HR = 0.78, 95% CI 0.64-0.96; P = 0.019) and 18-month landmarks (HR = 0.79, 95% CI 0.63-0.99; P = 0.041), but without a significant increase in major bleeding at 12 (HR = 1.39, 95% CI 0.90-2.16; P = 0.14), 15 (HR = 1.13, 95% CI 0.75-1.70; P = 0.55) or 18 months (HR = 1.27, 95% CI 0.83-1.95; P = 0.27).ConclusionsProlonged DAPT reduced MACE without significantly increasing major bleeding in patients who were event-free at 12 months after DES implantation. In deciding on DAPT duration, prolonged DAPT should be considered in dialysis patients.

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Ticagrelor vs. Clopidogrel in Acute Coronary Syndrome Patients With Chronic Kidney Disease After New-Generation Drug-Eluting Stent Implantation.

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