Predictors and long-term outcomes of in-hospital switching from clopidogrel to ticagrelor among patients with acute coronary syndrome undergoing percutaneous coronary intervention.

This study evaluated clinical outcomes of switching from clopidogrel to ticagrelor in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). The clinical benefit of in-hospital switching from clopidogrel to ticagrelor in these patients remains unclear. Among patients with ACS initially receiving clopidogrel, logistic regression was used to identify independent predictors of switching to ticagrelor. Multivariable Cox regression was used to compare efficacy and safety between switching to ticagrelor and continuing clopidogrel. The primary endpoint was net adverse clinical events (NACEs) at 12 months, a composite of major adverse cardiovascular events (MACE) and Bleeding Academic Research Consortium (BARC) type 2/3/5 bleeding. Among 10,519 patients initially receiving clopidogrel, 1405 (13.4%) were switched to ticagrelor at discharge. Stent number, left main artery lesions, diabetes, male sex, age, estimated glomerular filtration rate of <45 ml/min/1.73 m2 , and history of PCI or stroke were identified as independent predictors of switching to ticagrelor. The rate of NACE (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.18-1.91) or BARC type 2/3/5 bleeding (HR: 2.01; 95% CI: 1.52-2.66) was significantly higher in patients switching to ticagrelor than in those continuing clopidogrel. The risk of MACE was comparable between both the groups (HR: 0.71; 95% CI: 0.41-1.22). In real-world practice, in-hospital switching from clopidogrel to ticagrelor was independently associated with several clinical factors. Patients switching to ticagrelor had a higher rate of NACE or BARC type 2/3/5 bleeding than those continuing clopidogrel, without any reduction in the MACE rate.

Impact of 6- versus 12-month dual antiplatelet therapy on clinical prognosis in patients with high bleeding risk: Insights from the 4-year results of the I LOVE IT 2 study.

OBJECTIVES: To explore the impact of 6- versus 12-month dual antiplatelet therapy (DAPT) on the clinical prognosis of high bleeding risk (HBR) patients. BACKGROUND: The optimal DAPT duration after percutaneous coronary intervention (PCI) in HBR patients is unclear. METHODS: This study is a post hoc analysis of the 4-year clinical follow-up results of the I LOVE IT 2 study. Prevalence and prognosis of HBR patients were explored, and clinical outcomes of HBR patients who underwent 6- versus 12-month DAPT were compared. The primary outcome was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. The secondary outcomes were BARC type 2-5 bleeding and net clinical adverse events (NACE), defined as a composite of all-cause death, myocardial infarction (MI), ischemia-driven revascularization, stroke, stent thrombosis, or any bleeding events. RESULTS: HBR occurred in 440 of 2,737 patients (16.0%). HBR patients were associated with a higher risk of BARC type 3 or 5 bleeding (2.95 vs. 1.52%, p = .03), NACE (31.82 vs. 25.99%, p = .01), all-cause death (5.68 vs. 3.13%, p = .008) and stroke (9.09 vs. 3.83%, p < .001) than non-HBR patients at 4 years. There were no significant differences in BARC type 3 or 5 bleeding (3.07 vs. 2.76%, p = 1.00) or NACE rate (31.9 vs. 33.8%, p = .72) between patients who underwent 6- and 12-month DAPT. CONCLUSIONS: HBR patients are at a higher risk of long-term bleeding and ischemic events than non-HBR patients. The safety and efficacy of 6- and 12-month DAPT were comparable in HBR patients.

Impact of extended dual antiplatelet therapy on long-term prognosis in patients with acute coronary syndrome complicated with anemia: A sub-analysis of the real-world OPT-CAD study.

OBJECTIVES: To evaluate the impact of extended dual antiplatelet therapy (DAPT) beyond 12 months on long-term prognosis in acute coronary syndrome (ACS) patients complicated with anemia undergoing percutaneous coronary intervention (PCI). BACKGROUND: Anemia is frequent among ACS patients and is associated with increased risk of adverse clinical outcomes. METHODS: A total of 6,953 patients were enrolled from the Optimal anti Platelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) study. A landmark analysis comparing extended DAPT versus single antiplatelet therapy (SAPT) at 12-24 months were performed in anemia patients without premature discontinuation of DAPT before 9 months and major clinical adverse events within 12 months. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of all-cause death, myocardial infarction, and stroke. RESULTS: Patients with anemia (n = 1,728) had higher rates of MACCE, all-cause mortality, and BARC type 2, 3, 5 bleeding (p < .05) compared to those without anemia (n = 5,225). Anemia patients received extended DAPT (n = 1,010) were associated with a lower risk of stroke (0.3% vs. 1.8%; HR, 0.14; 95% CI, 0.03-0.71; p = .018) compared to those received SAPT (n = 342). The rates of MACCE and all revascularization were lower in patients with extended DAPT, but the differences were not statistically significant. Risk of all-cause mortality and bleeding were comparable between the two groups. CONCLUSIONS: Extended DAPT beyond 12 months may reduce the incidence of stroke without increasing the risk of bleeding in anemic ACS patients who tolerate 12-month DAPT.

Efficacy and Safety of Potent Oral P2Y12 Inhibitors in Medically Managed ACS Patients: a Meta-analysis.

PURPOSE: Although current guidelines recommend ticagrelor in addition to aspirin as the antiplatelet strategy for medically managed acute coronary syndrome (MMACS) patients, clinical evidence specific to this special population is lacking. Whether potent oral P2Y12 inhibitors should be used in MMACS patients is still under debate. METHODS: We conducted a comprehensive search in PubMed, Embase, Web of Science, and Cochrane Library to identify studies exploring the efficacy or safety of ticagrelor and prasugrel versus clopidogrel or placebo in MMACS patients. The primary efficacy endpoint was major adverse cardiovascular events (MACE) defined by each study, and the safety endpoint was TIMI non-CABG major bleeding. RESULTS: A total of 6102 records were screened, and 4 studies including 46,346 patients were finally included. The use of potent oral P2Y12 inhibitors significantly lowers the risk of MACE compared with clopidogrel (HR: 0.90; 95% CI: 0.82-0.98; P = .018; I2 = 0%). A significant reduction in risks of all-cause death and myocardial infarction was also observed with the use of potent oral P2Y12 inhibitors compared with clopidogrel. No significant difference in risks of stroke or TIMI non-CABG major bleeding (HR: 1.24; 95% CI: 0.90-1.73; P = .191; I2 = 0%) was observed between potent oral P2Y12 inhibitors and clopidogrel. CONCLUSION: Potent oral P2Y12 inhibitors, especially ticagrelor, decrease the risk of ischemic events in MMACS patients as compared with clopidogrel, without significantly increasing major bleeding.

Clonal hematopoiesis of indeterminate potential in patients with acute coronary syndrome undergoing percutaneous coronary intervention in the absence of traditional risk factors.

AIMS: To investigate the frequency of clonal hematopoiesis of indeterminate potential (CHIP) and evaluate its impacts on outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the absence of traditional cardiovascular risk factors (CVRFs). METHODS: Whole-exome sequencing was performed to detect the presence of CHIP in 183 patients underwent PCI for the treatment of ACS. The association between CHIP-related mutations and major adverse cardiac or cerebral events (MACCEs, a composite of all-cause mortality, coronary revascularization, myocardial infarction, or stroke) was analyzed in such cohort. RESULTS: Of 179 patients [median age, 65 years; 84 female (46.9%)] included in this analysis, CHIP-related mutations were detected in 36 (20.1%) patients. The somatic mutations most frequently occurred in the genes DNMT3A (17 mutations), TET2 (6 mutations), and ASXL1 (4 mutations). Clinical outcomes at median 635 follow-up days showed that DNMT3A/TET2/ASXL1-CHIP mutations were associated with significantly higher risk of MACCEs, compared with non-CHIP carriers in the CVRFs-absent ACS cohort (26.1% vs. 4.2%, log-rank P = 0.001). Multivariable regression showed that DNMT3A/TET2/ASXL1-CHIP driver mutations (HR 4.015; 95% CI 1.236-13.046; P = 0.021) were independent predictors of adverse clinical outcomes. CONCLUSION: The most frequent CHIP-related mutations, DNMT3A, TET2, and ASXL1 are significantly associated with increased risk of recurrent cardiovascular events. Our study may be valuable target to reduce residual risk in patients with ACS carrying specific mutations.

Correction to: Dual Antiplatelet Therapy Duration in Medically Managed Acute Coronary Syndrome Patients: Sub-Analysis of the OPT-CAD Study.

In the original article, t.

Dual Antiplatelet Therapy Duration in Medically Managed Acute Coronary Syndrome Patients: Sub-Analysis of the OPT-CAD Study.

INTRODUCTION: Optimal dual antiplatelet therapy (DAPT) duration for medically managed acute coronary syndrome (ACS) (MMACS) patients is still unknown. We explored the efficacy and safety of ≥ 12-month DAPT among MMACS patients. METHODS: In this sub-analysis of the optimal antiplatelet therapy for Chinese Patients with Coronary Artery Disease study (NCT01735305), clinical outcomes among MMACS patients were compared between the < 12-month and ≥ 12-month DAPT groups. The primary efficacy endpoint was a composite of cardiac death, myocardial infarction, and stroke. Safety endpoints included the Bleeding Academic Research Consortium (BARC) 2-5, BARC 3-5, and all bleeding events. Propensity score matching (PSM) was used to compare baseline characteristics between the < 12-month and ≥ 12-month DAPT groups. RESULTS: In this cohort of ACS patients (n = 10,016), MMACS patients (n = 2967) were less likely to use DAPT at 12 (31.64% vs. 67.47%, P < 0.0001) and 24 (13.82% vs. 18.71%, P < 0.0001) months and experienced more ischemic events at 12 (4.55% vs. 3.40%, P = 0.006) and 24 (6.88% vs. 5.08%, P = 0.0004) months than those treated with percutaneous coronary intervention (n = 7049). Among MMACS patients, the rate of primary efficacy endpoint occurring within the second year was significantly higher in the < 12-month DAPT group than in the ≥ 12-month group both before (2.88% vs. 1.60%, P = 0.040) and after (3.19% vs. 1.71%, P = 0.045) PSM. After PSM, no significant differences in all bleeding, BARC 2-5, and BARC 3-5 bleeding were found between the groups. CONCLUSION: MMACS patients with insufficient DAPT management experienced relatively more ischemic events. DAPT for at least 1 year may be beneficial to this special population without significantly increasing the bleeding risks. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01735305.

Effect of Clopidogrel vs Ticagrelor on Platelet Aggregation and Inflammation Markers After Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

BACKGROUND: Patients with acute coronary syndrome show an inflammatory response that is known to affect platelet aggregation. We aimed to clarify the relationship between the inflammation severity and the effect of antiplatelet therapy after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). METHODS: This retrospective, single-center study included 203 patients with STEMI who underwent primary PCI and were stratified on the basis of the antiplatelet therapy on admission (clopidogrel vs ticagrelor). Inflammation levels were defined as low, intermediate, and high, based on the tertiles of the distribution of high-specificity C-reactive protein levels pre-PCI. Platelet aggregation function during hospitalization and follow-up was quantified as residual adenosine diphosphate-induced platelet reactivity on light transmittance aggregometry. Inflammation markers were measured on admission and at 1 year post-PCI. RESULTS: At intermediate and high levels of inflammation, residual adenosine diphosphate-induced platelet aggregation was significantly higher among clopidogrel users than among ticagrelor users. In the clopidogrel group, statistically significant differences in platelet aggregation function were observed among the 3 levels of inflammation. At 1 year post-PCI, ticagrelor users had significantly lower levels of interleukin-1ß and higher levels of interleukin-35 and transforming growth factor-ß. CONCLUSION: At different inflammation levels, ticagrelor provides more potent platelet inhibition than clopidogrel, suggesting that ticagrelor might exert a more stable antiplatelet effect at higher levels of systemic inflammation. Furthermore, ticagrelor is associated with reduced indices of inflammation on follow-up after PCI, suggesting that anti-inflammatory effects might play a role in the clinical benefit observed with antiplatelet therapy, which would provide an additional rationale for using ticagrelor in patients with STEMI undergoing primary PCI.