Impact of proton pump inhibitor use on clinical outcomes in East Asian patients receiving clopidogrel following drug-eluting stent implantation.

BACKGROUND: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. METHODS: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3-5) and gastrointestinal (GI) bleeding (BARC types 3-5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. RESULTS: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18-8.78). The incidence of major bleeding and GI bleeding (BARC types 3-5) was comparable between PPI users and non-users in the PS-matched cohort. CONCLUSIONS: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

Prognostic Implication of Platelet Reactivity According to Left Ventricular Systolic Dysfunction Status in Patients Treated With Drug-Eluting Stent Implantation: Analysis of the PTRG-DES Consortium.

BACKGROUND: Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated. METHODS: From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography. Platelet reactivity was measured using VerifyNow P2Y12 assay and high platelet reactivity (HPR) was defined as PRU ≥ 252. The major adverse cardiac and cerebrovascular events (MACCEs) were a composite of death, myocardial infarction, stent thrombosis and stroke at 5 years after PCI. Major bleeding was defined as Bleeding Academic Research Consortium bleeding types 3-5. RESULTS: A total of 13,160 patients from PTRG-DES, 9,319 (79.6%) patients with the results of both PRU and LVEF were analyzed. The incidence of MACCE and major bleeding was higher in REF group as compared with PEF group (MACCEs: hazard ratio [HR] 2.17, P < 0.001, 95% confidence interval [CI] 1.85-2.55; major bleeding: HR 1.78, P < 0.001, 95% CI 1.39-2.78). The highest rate of MACCEs was found in patients with REF and HPR, and the difference between the groups was statistically significant (HR 3.14 in REF(+)/HPR(+) vs. PEF(+)/HPR(-) group, P < 0.01, 95% CI 2.51-3.91). The frequency of major bleeding was not associated with the HPR in either group. CONCLUSION: LV dysfunction was associated with an increased incidence of MACCEs and major bleeding in patients who underwent PCI. The HPR status further exhibited significant increase of MACCEs in patients with LV dysfunction in a large, real-world registry. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04734028.

Effect of diabetes mellitus on 3-year outcomes in patients with acute myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: Diabetes mellitus (DM) is a significant factor in increased mortality rates among patients with acute myocardial infarction (AMI), but research on its impact on the long-term outcomes in patients with MI with nonobstructive coronary arteries (MINOCA) is limited. Thus, a comparison of the 3-year clinical outcomes between the DM and non-DM groups among patients with MINOCA was undertaken. METHODS: From the Korea AMI Registry-National Institute of Health dataset, 10,774 AMI patients were enrolled. After applying the exclusion criteria, 379 patients with MINOCA were included. The primary clinical outcomes were major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction (MI), repeat coronary revascularization, and stroke. The secondary outcomes were the individual components of MACCE. RESULTS: The adjusted hazard ratios for 3-year MACCE (2.287, p = 0.010), all-cause death (2.845, p = 0.004), and non-cardiac death (non-CD, 3.914, p = 0.008) were higher in the DM group than in the non-DM group. It is speculated that the higher non-CD rate in the MINOCA group is attributable to a higher proportion of patients with non-ST-segment elevation MI in the total study population. The CD, recurrent MI, revascularization, and stroke rates were similar between the DM and non-DM groups. DM, advanced age, cardiopulmonary resuscitation on admission, and non-use of statin medications were significant predictors of MACCE. CONCLUSIONS: In this study involving patients with MINOCA, the DM group exhibited a higher 3-year mortality rate than the non-DM group. Thus, DM demonstrated a hazardous effect even in patients with MINOCA.

Renin-angiotensin system inhibitors and non-ST-elevation myocardial infarction outcomes based on left ventricular ejection fraction.

BACKGROUND: We assessed left ventricular ejection fraction (LVEF) to compare the effects of renin-angiotensin system inhibitors (RASI) in patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: We categorized 4558 patients with NSTEMI as either RASI users (3752 patients) or non-users (806 patients). The 3-year patient-oriented composite outcomes (POCO), which included all-cause death, recurrent MI, any repeat revascularization, or hospitalization for heart failure (HF), were the primary outcomes. To compare clinical outcomes, a multivariable-adjusted hazard ratio (aHR) was calculated after performing multicollinearity tests on all significant confounding variables (P <0.05) RESULTS: Among RASI users, the aHRs for POCO, all-cause death, and cardiac death were significantly higher in the HF with reduced EF (HFrEF) subgroup than in the HF with mildly reduced EF (HFmrEF; 1.610, 2.120, and 2.489, respectively; P <0.001, <0.001, and <0.001, respectively) and HF with preserved EF (HFpEF; 2.234, 3.920, 5.215, respectively; P <0.001, <0.001, and <0.001, respectively) subgroups. The aHRs for these variables were significantly higher in the HFmrEF subgroup than the HFpEF subgroup (1.416, 1.843, and 2.172, respectively). Among RASI non-users, the aHRs for these variables were significantly higher in the HFrEF subgroup than the HFmrEF (2.573, 3.172, and 3.762, respectively) and HFpEF (2.425, 3.805, and 4.178, respectively) subgroups. In three LVEF subgroups, RASI users exhibited lower aHRs for POCO and all-cause death than RASI non-users. CONCLUSIONS: In the RASI users group, the aHRs for POCO and mortality were highest in the HFrEF subgroup, intermediate in the HFmrEF subgroup, and lowest in the HFpEF subgroup.

Prognostic Implication of Platelet Reactivity According to Procedural Complexity After PCI: Subanalysis of PTRG-DES Consortium.

Background: Complex percutaneous coronary intervention (C-PCI) and high platelet reactivity (HPR) have been proposed as representative risk factors for the high ischemic phenotype. Uncertainty remains regarding the relative prognostic importance of these factors. Objectives: This study aimed to investigate the prognostic implication of HPR according to procedural complexity. Methods: Patients treated with drug-eluting stent implantation (PTRG-PFT cohort; N = 11,714) were classified according to procedural complexity. HPR criteria were determined using VerifyNow (≥252 P2Y12 reaction units). The major adverse cardiac and cerebrovascular events (MACCE) (the composite of all-cause death, myocardial infarction, definite stent thrombosis, or stroke) and major bleeding were assessed for up to 3 years. Results: C-PCI was performed in 3,152 patients (26.9%). C-PCI significantly increased the risk of MACCE (HRadjusted: 1.21; 95% CI: 1.01-1.44; P = 0.035), driven by a higher rate of all-cause death (HRadjusted: 1.45; 95% CI: 1.15-1.83; P = 0.002), although it did not increase the risk of major bleeding. Irrespective of procedural complexity, the HPR phenotype was significantly associated with MACCE (Pinteraction = 0.731) and all-cause mortality (Pinteraction = 0.978), in which the prognostic implication appeared prominent within 1 year. The HPR phenotype did not show a significant interaction with any type of C-PCI. In addition, the number of complexity features per procedure did not proportionally increase the risk of MACCE. Conclusions: C-PCI was significantly associated with 3-year risk of MACCE and all-cause death. The HPR phenotype appears to have a similar prognostic implication irrespective of the type and extent of procedural complexity. (Platelet Function and Genotype-Related Long-Term Prognosis in DES-Treated Patients [PTRG-DES]; NCT04734028).

High platelet reactivity strongly predicts early stent thrombosis in patients with drug-eluting stent implantation.

Stent thrombosis (ST) is a fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence remains unclear. Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were analyzed. We sought to identify the predictors of early stent thrombosis (EST) and compared the primary outcome, a composite of cardiac death, myocardial infarction, and revascularization, between EST and non-EST groups. EST, defined as definite ST within 1 month after index PCI, occurred in 51 patients. PRU values were significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p < 0.001). In multivariable analysis, PRU ≥ 252 (OR, 5.10; 95% CI 1.58-16.46; p = 0.006) and aspirin reaction unit ≥ 414 (OR 4.85; 95% CI 1.07-21.97; p = 0.040) were independent predictors of EST. The cumulative incidence of primary composite outcome at one year was significantly higher in the EST group (38.2% vs. 3.9%, Log-rank p < 0.001). In patients treated with clopidogrel after successful DES implantation, EST was associated with higher platelet reactivities, and a greater risk of cardiovascular events.Trial Registration: clinicaltrials.gov Identifier: NCT04734028.

Different association of atherogenic index of plasma with the risk of high platelet reactivity according to the presentation of acute myocardial infarction.

This study evaluated the association of atherogenic index of plasma (AIP) with platelet reactivity and clinical outcomes according to acute myocardial infarction (AMI). The composite of 3-year adverse outcomes of all-cause death, myocardial infarction, and cerebrovascular accident was evaluated in 10,735 patients after successful percutaneous coronary intervention with drug-eluting stents. AIP was defined as the base 10 logarithm of the ratio of triglyceride to high-density lipoprotein cholesterol concentration. High platelet reactivity (HPR) was defined as ≥ 252 P2Y12 reactivity unit. An increase of AIP (per-0.1 unit) was related to the decreased risk of HPR [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96-0.99; P = 0.001] in non-AMI patients, not in AMI patients (OR 0.98, 95% CI 0.96-1.01; P = 0.138). The HPR was associated with the increased risk of composite outcomes in both non-AMI and AMI patients (all-P < 0.05). AIP levels were not independently associated with the risk of composite outcomes in both patients with non-AMI and AMI. In conclusion, an inverse association between AIP and the risk of HPR was observed in patients with non-AMI. This suggests that the association between plasma atherogenicity and platelet reactivity may play a substantial role in the development of AMI.Trial registration: NCT04734028.

Association of Age- and Body Mass Index-Stratified High On-Treatment Platelet Reactivity With Coronary Intervention Outcomes in East Asian Patients.

BACKGROUND: Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on-treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. METHODS AND RESULTS: The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (<67 years of age or ≥67 years of age) and BMI (≤22.6 kg/m2 or >22.6 kg/m2). Patients <67 years of age with HPR had increases in both MACCEs (adjusted hazard ratio [HR], 1.436 [95% CI, 1.106-1.867]; P=0.007) and major bleeding (adjusted HR, 1.584 [95% CI, 1.095-2.290]; P=0.015) compared with the those with non-HPR, respectively. In patients ≥67 years of age with HPR, there were no differences in MACCEs, but there was a decrease in major bleeding (adjusted HR, 0.721 [95% CI, 0.542-0.959]; P=0.024). Meanwhile, patients with HPR with BMI >22.6 kg/m2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140-1.688]; P=0.001). No differences were shown in major bleeding. CONCLUSIONS: HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.

Prognostic Impact of CYP2C19 Genotypes on Long-Term Clinical Outcomes in Older Patients After Percutaneous Coronary Intervention.

BACKGROUND: Carriers of CYP2C19 loss-of-function alleles have increased adverse events after percutaneous coronary intervention, but limited data are available for older patients. We aimed to evaluate the prognostic impact of CYP2C19 genotypes on clinical outcomes in older patients after percutaneous coronary intervention. METHODS AND RESULTS: The study included 1201 older patients (aged ≥75 years) who underwent percutaneous coronary intervention and received clopidogrel-based dual antiplatelet therapy in South Korea. Patients were grouped on the basis of CYP2C19 genotypes. The primary outcome was 3-year major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, and stent thrombosis. Older patients were grouped into 3 groups: normal metabolizer (36.6%), intermediate metabolizer (48.1%), and poor metabolizer (15.2%). The occurrence of the primary outcome was significantly different among the groups (3.1, 7.0, and 6.2% in the normal metabolizer, intermediate metabolizer, and poor metabolizer groups, respectively; P=0.02). The incidence rate of all-cause death at 3 years was greater in the intermediate metabolizer and poor metabolizer groups (8.1% and 9.2%, respectively) compared with that in the normal metabolizer group (3.5%, P=0.03) without significant differences in major bleeding. In the multivariable analysis, the intermediate metabolizer and poor metabolizer groups were independent predictors of 3-year clinical outcomes. CONCLUSIONS: In older patients, the presence of any CYP2C19 loss-of-function allele was found to be predictive of a higher incidence of major adverse cardiac events within 3 years following percutaneous coronary intervention. This finding suggests a need for further investigation into an optimal antiplatelet strategy for older patients. REGISTRATION: URL: https://clinicaltrials.gov. Identifier: NCT04734028.