ABSTRACT
BACKGROUND: In patients with coronary artery disease who are being evaluated for percutaneous coronary intervention (PCI), procedures can be guided by fractional flow reserve (FFR) or intravascular ultrasonography (IVUS) for decision making regarding revascularization and stent implantation. However, the differences in clinical outcomes when only one method is used for both purposes are unclear. METHODS: We randomly assigned 1682 patients who were being evaluated for PCI for the treatment of intermediate stenosis (40 to 70% occlusion by visual estimation on coronary angiography) in a 1:1 ratio to undergo either an FFR-guided or IVUS-guided procedure. FFR or IVUS was to be used to determine whether to perform PCI and to assess PCI success. In the FFR group, PCI was to be performed if the FFR was 0.80 or less. In the IVUS group, the criteria for PCI were a minimal lumen area measuring either 3 mm2 or less or measuring 3 to 4 mm2 with a plaque burden of more than 70%. The primary outcome was a composite of death, myocardial infarction, or revascularization at 24 months after randomization. We tested the noninferiority of the FFR group as compared with the IVUS group (noninferiority margin, 2.5 percentage points). RESULTS: The frequency of PCI was 44.4% among patients in the FFR group and 65.3% among those in the IVUS group. At 24 months, a primary-outcome event had occurred in 8.1% of the patients in the FFR group and in 8.5% of those in the IVUS group (absolute difference, -0.4 percentage points; upper boundary of the one-sided 97.5% confidence interval, 2.2 percentage points; P = 0.01 for noninferiority). Patient-reported outcomes as reported on the Seattle Angina Questionnaire were similar in the two groups. CONCLUSIONS: In patients with intermediate stenosis who were being evaluated for PCI, FFR guidance was noninferior to IVUS guidance with respect to the composite primary outcome of death, myocardial infarction, or revascularization at 24 months. (Funded by Boston Scientific; FLAVOUR ClinicalTrials.gov number, NCT02673424.).
Subject(s)
Coronary Artery Disease , Fractional Flow Reserve, Myocardial , Myocardial Infarction , Percutaneous Coronary Intervention , Ultrasonography, Interventional , Constriction, Pathologic , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/physiopathology , Coronary Artery Disease/therapy , Humans , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/physiopathology , Myocardial Infarction/therapy , Percutaneous Coronary Intervention/methods , Treatment Outcome , Ultrasonography, Interventional/methodsABSTRACT
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.
Subject(s)
Clopidogrel , Cytochrome P-450 CYP2C19 , Drug-Eluting Stents , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Proton Pump Inhibitors , Humans , Clopidogrel/therapeutic use , Clopidogrel/adverse effects , Clopidogrel/administration & dosage , Proton Pump Inhibitors/adverse effects , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Male , Female , Drug-Eluting Stents/adverse effects , Aged , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Percutaneous Coronary Intervention/adverse effects , Cytochrome P-450 CYP2C19/genetics , Treatment Outcome , Registries , East Asian PeopleABSTRACT
BACKGROUND: Both anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking. METHODS: The ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation. CONCLUSIONS: The ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04250116.
Subject(s)
Anticoagulants , Atrial Fibrillation , Clopidogrel , Drug-Eluting Stents , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Female , Humans , Male , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/therapy , Clopidogrel/administration & dosage , Clopidogrel/therapeutic use , Drug Therapy, Combination , Hemorrhage/chemically induced , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Prospective Studies , Stroke/prevention & control , Stroke/etiology , Time Factors , Randomized Controlled Trials as Topic , Multicenter Studies as TopicABSTRACT
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.
Subject(s)
Drug-Eluting Stents , Percutaneous Coronary Intervention , Ventricular Dysfunction, Left , Humans , Stroke Volume , Percutaneous Coronary Intervention/adverse effects , Prognosis , Ventricular Function, Left , Hemorrhage/etiologyABSTRACT
BACKGROUND: The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using second-generation drug-eluting stents (DESs). METHODS: Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group). RESULTS: Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639). CONCLUSION: The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03068494.
Subject(s)
Coronary Artery Disease , Drug-Eluting Stents , Percutaneous Coronary Intervention , Humans , Coronary Artery Disease/surgery , Coronary Artery Disease/etiology , Percutaneous Coronary Intervention/adverse effects , Radial Artery , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
AIMS: In patients with acute myocardial infarction (MI) and multivessel coronary artery disease, percutaneous coronary intervention (PCI) of non-infarct-related artery reduces death or MI. However, whether selective PCI guided by fractional flow reserve (FFR) is superior to routine PCI guided by angiography alone is unclear. The current trial sought to compare FFR-guided PCI with angiography-guided PCI for non-infarct-related artery lesions among patients with acute MI and multivessel disease. METHODS AND RESULTS: Patients with acute MI and multivessel coronary artery disease who had undergone successful PCI of the infarct-related artery were randomly assigned to either FFR-guided PCI (FFR ≤0.80) or angiography-guided PCI (diameter stenosis of >50%) for non-infarct-related artery lesions. The primary end point was a composite of time to death, MI, or repeat revascularization. A total of 562 patients underwent randomization. Among them, 60.0% underwent immediate PCI for non-infarct-related artery lesions and 40.0% were treated by a staged procedure during the same hospitalization. PCI was performed for non-infarct-related artery in 64.1% in the FFR-guided PCI group and 97.1% in the angiography-guided PCI group, and resulted in significantly fewer stent used in the FFR-guided PCI group (2.2 ± 1.1 vs. 2.5 ± 0.9, P < 0.001). At a median follow-up of 3.5 years (interquartile range: 2.7-4.1 years), the primary end point occurred in 18 patients of 284 patients in the FFR-guided PCI group and in 40 of 278 patients in the angiography-guided PCI group (7.4% vs. 19.7%; hazard ratio, 0.43; 95% confidence interval, 0.25-0.75; P = 0.003). The death occurred in five patients (2.1%) in the FFR-guided PCI group and in 16 patients (8.5%) in the angiography-guided PCI group; MI in seven (2.5%) and 21 (8.9%), respectively; and unplanned revascularization in 10 (4.3%) and 16 (9.0%), respectively. CONCLUSION: In patients with acute MI and multivessel coronary artery disease, a strategy of selective PCI using FFR-guided decision-making was superior to a strategy of routine PCI based on angiographic diameter stenosis for treatment of non-infarct-related artery lesions regarding the risk of death, MI, or repeat revascularization.
Subject(s)
Coronary Artery Disease , Fractional Flow Reserve, Myocardial , Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Coronary Artery Disease/therapy , Percutaneous Coronary Intervention/methods , Coronary Angiography/methods , Constriction, Pathologic , Treatment Outcome , Myocardial Infarction/therapyABSTRACT
Background: Hypertension and dyslipidemia significantly contribute to cardiovascular disease development. Their coexistence poses challenges in managing multiple medications, influencing treatment adherence. Objective: This study aimed to assess the efficacy and safety of a combined treatment approach using a fixed-dose combination therapy. Methods: This multicenter, 8-week, randomized, double-blind, Phase IV trial was named Telmisartan/Amlodipine/Rosuvastatin from Samjin Pharmaceuticals and evaluated the efficacy and safety of fixed-dose combination treatment in patients with essential hypertension and dyslipidemia. They were randomly assigned to 2 fixed-dose combination therapy groups, telmisartan 40 mg/amlodipine 5 mg/rosuvastatin 10 mg (TEL/ALD/RSV) or amlodipine 5 mg/atorvastatin 10 mg (ALD/ATV) after washout/run-in period. The primary outcomes were the change in mean sitting systolic blood pressure and the percentage change of LDL-C after 8 weeks of medical treatment. Adverse drug reactions and events were assessed. Results: Of a total of 304 patients who underwent screening, 252 were randomized to the TEL/ALD/RSV group (125 patients) and the ALD/ATV group (127 patients). The mean (SD) ages of the TEL/ALD/RSV group and the ALD/ATV group were 67.4 (11.3) and 68.2 (10.6) years, respectively (Pâ¯=â¯0.563). The least-squares mean (SE) in mean sitting systolic blood pressure changes between the 2 groups were -16.27 (0.93) mm Hg in the TEL/ALD/RSV group, -6.85 (0.92) mm Hg in the ALD/ATV group (LSM differenceâ¯=â¯-9.42 mm Hg; 95% CI, -11.99 to -6.84; P < .001). For LDL-C level changes, a significant difference was noted between the 2 groups: -50.03% (1.18%) in the TEL/ALD/RSV group, -39.60% (1.17%) in the ALD/ATV group (LSM differenceâ¯=â¯-10.43%; 95% CI, -13.70 to -7.16; P < .001). No severe adverse events were observed. Conclusions: TEL/ALD/RSV proved to be more efficient than ALD/ATV in lowering blood pressure and reducing LDL-C levels among patients with hypertension and dyslipidemia, with no notable safety concerns. (Curr Ther Res Clin Exp. 2024; XX:XXX-XXX). ClinicalTrials.gov identifier: NCT03860220.
ABSTRACT
BACKGROUND: Diabetes mellitus (DM) is associated with thrombogenicity, clinically manifested with atherothrombotic events after percutaneous cutaneous intervention (PCI). This study aimed to investigate association between DM status and platelet reactivity, and their prognostic implication in PCI-treated patients. METHODS: The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test (PTRG-PFT) cohort was established to determine the linkage of platelet function test (PFT) with long-term prognosis during dual antiplatelet therapy including clopidogrel in patients treated with drug-eluting stent (DES). We assessed platelet reactivity using VerifyNow and 'high platelet reactivity (HPR)' was defined as ≥ 252 P2Y12 reaction unit (PRU). Major adverse cardiac and cerebrovascular event (MACCE) was a composite of all-cause death, myocardial infarction, stent thrombosis or stroke. RESULTS: Between July 2003 and Aug 2018, DES-treated patients with available PFT were enrolled (n = 11,714). Diabetic patients demonstrated significant higher levels of platelet reactivity (DM vs. non-DM: 225.7 ± 77.5 vs. 213.6 ± 79.1 PRU, P < 0.001) and greater prevalence of HPR compared to non-diabetic patients (38.1% vs. 32.0%, P < 0.001). PRU level and prevalence of HPR were significantly associated with insulin requirement and HbA1c level, as well as diabetic status. DM status and HPR phenotype had a similar prognostic implication, which showed the synergistic clinical impact on MACCE. Association between PRU level and MACCE occurrence seemed higher in diabetic vs. non-diabetic patients. In non-DM patients, HPR phenotype did not significantly increase the risk of MACCE (adjusted hazard ratio [HRadj]: 1.073; 95% confidence interval [CI]: 0.869-1.325; P = 0.511), whereas HPR was an independent determinant for MACCE occurrence among diabetic patients (HRadj: 1.507; 95% CI: 1.193-1.902; P < 0.001). CONCLUSION: The levels of on-clopidogrel platelet reactivity are determined by diabetic status and the severity of DM. In addition, HPR phenotype significantly increases the risk of MACCE only in diabetic patients. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov . Unique identifier: NCT04734028.
Subject(s)
Diabetes Mellitus , Drug-Eluting Stents , Percutaneous Coronary Intervention , Humans , Clopidogrel/adverse effects , Percutaneous Coronary Intervention/adverse effects , Blood Platelets , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiologyABSTRACT
OBJECTIVE: Current guidelines recommend that patients with peripheral artery disease (PAD) should be treated with antithrombotic agents, renin-angiotensin-system blockers, and statins. However, the clinical impact of guideline-directed medical therapy (GDMT) on long-term mortality in patients with newly diagnosed PAD remains unclear. We aimed to investigate the prevalence of GDMT and evaluate 5-year mortality according to GDMT after PAD diagnosis. METHODS: This retrospective cohort study, using nationwide health insurance claims data in Korea, included patients newly diagnosed with PAD between 2006 and 2015. GDMT was defined as the use of all drugs, including antithrombotic agents, renin-angiotensin-system blockers, and statins, within 3 months of PAD diagnosis. The primary endpoint was all-cause mortality. RESULTS: We investigated 19,561 newly diagnosed patients with PAD without proven cardiovascular disease. Among the study population, 4378 patients (22.4%) were categorized in the GDMT and 15,183 (77.6%) in the non-GDMT groups. During the 5-year follow-up, GDMT showed a lower incidence of all-cause mortality than that of non-GDMT (2.8% vs 4.8%; adjusted hazard ratio, 0.329; 95% confidence interval, 0.257-0.421; P < .001). Even in the propensity-matched population, GDMT showed a lower mortality rate than non-GDMT (hazard ratio, 0.283; 95% confidence interval, 0.217-0.370; P < .001). As the number of guideline-recommended drugs increased, the mortality rate decreased proportionately. CONCLUSIONS: After PAD diagnosis, GDMT was associated with a lower incidence of mortality regardless of proven cardiovascular disease. This retrospective analysis showed an insufficient prevalence of GDMT among patients with PAD in real-world practice.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Peripheral Arterial Disease , Humans , Retrospective Studies , Fibrinolytic Agents , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Renin , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/drug therapy , AngiotensinsABSTRACT
OBJECTIVES: We aimed to investigate specific subgroups in which the benefit of transradial coronary interventions (TRIs) would be enhanced. BACKGROUND: The advantage of TRIs over transfemoral coronary interventions (TFIs) might differ according to a given clinical condition, urgency of the procedure, and operator volume pattern. METHODS: Using a cohort from the 2014 Korean Percutaneous Coronary Intervention Registry, in-hospital outcomes of the TRI group (n = 22,993) were matched to those of the TFI group (n = 15,581). After propensity score matching, the composite endpoints between the groups and subgroups for all-cause death, nonfatal myocardial infarctions (MIs), or transfusions were analyzed. RESULTS: The composite endpoints occurred less frequently in the TRI group than the TFI group [2.1% vs. 5.5%, OR 0.63, 95% CI 0.55-0.72]. The TRI group had a lower rate of death (OR 0.44, 95% CI 0.33-0.60) and nonfatal MI (OR 0.66, 95% CI 0.54-0.81) than the TFI group. The TRI group required fewer transfusions than the TFI group (OR 0.72, 95% CI 0.59-0.88). TRI benefits were consistent across subgroups except patients with chronic kidney disease and those treated in low tertile PCI volume centers. The favorable outcome of TRI was greater in the elderly (≥75 years), patients with ST-elevation MI, those who underwent emergent PCI, and those treated in high tertile PCI volume hospitals (P for the interaction <0.001 for all). CONCLUSIONS: Compared to TFI, TRI had favorable composite in-hospital outcomes. TRI benefits were pronounced in high-risk clinical settings and in high PCI volume centers.
Subject(s)
Catheterization, Peripheral , Coronary Artery Disease/therapy , Femoral Artery , Percutaneous Coronary Intervention , Radial Artery , Aged , Catheterization, Peripheral/adverse effects , Catheterization, Peripheral/mortality , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Punctures , Registries , Republic of Korea , Risk Assessment , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Cardiac remodeling characterized by cardiac fibrosis is a pathologic process occurring after acute myocardial infarction. Fibrosis can be ameliorated by interferon-gamma (IFN-γ), which is a soluble cytokine showing various effects such as anti-fibrosis, apoptosis, anti-proliferation, immunomodulation, and anti-viral activities. However, the role of IFN-γ in cardiac myofibroblasts is not well established. Therefore, we investigated the anti-fibrotic effects of IFN-γ in human cardiac myofibroblasts (hCMs) in vitro and whether indoleamine 2,3-dioxygenase (IDO), induced by IFN-γ and resulting in cell cycle arrest, plays an important role in regulating the biological activity of hCMs. After IFN-γ treatment, cell signaling pathways and DNA contents were analyzed to assess the biological activity of IFN-γ in hCMs. In addition, an IDO inhibitor (1-methyl tryptophan; 1-MT) was used to assess whether IDO plays a key role in regulating hCMs. IFN-γ significantly inhibited hCM proliferation, and IFN-γ-induced IDO expression caused cell cycle arrest in G0/G1 through tryptophan depletion. Moreover, IFN-γ treatment gradually suppressed the expression of α-smooth muscle actin. When IDO activity was inhibited by 1-MT, marked apoptosis was observed in hCMs through the induction of interferon regulatory factor, Fas, and Fas ligand. Our results suggest that IFN-γ plays key roles in anti-proliferative and anti-fibrotic activities in hCMs and further induces apoptosis via IDO inhibition. In conclusion, co-treatment with IFN-γ and 1-MT can ameliorate fibrosis in cardiac myofibroblasts through apoptosis.
Subject(s)
Cell Cycle Checkpoints/drug effects , Interferon-gamma/pharmacology , Myocardial Infarction/metabolism , Myocardium/metabolism , Myofibroblasts/metabolism , Tryptophan/analogs & derivatives , Autophagy/drug effects , Fibrosis , Gene Expression Regulation/drug effects , Humans , Muscle Proteins/biosynthesis , Myocardial Infarction/drug therapy , Myocardial Infarction/pathology , Myocardium/pathology , Myofibroblasts/pathology , Signal Transduction/drug effects , Tryptophan/pharmacologyABSTRACT
BACKGROUND: There have been few studies to evaluate the prognostic implications of guideline-directed therapy according to the temporal course of heart failure. This study assessed the relationship between adherence to guideline-directed therapy at discharge and 60-day clinical outcomes in de novo acute heart failure (AHF) and acute decompensated chronic heart failure (ADCHF) separately. METHODS: Among 5,625 AHF patients who were recruited from a multicenter cohort registry of Korean Acute Heart Failure, 2,769 patients with reduced ejection fraction were analyzed. Guideline-directed therapies were defined as the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), ß-blocker, and mineralocorticoid receptor antagonist. RESULTS: In de novo AHF, ACEI or ARB reduced re-hospitalization (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.34-0.95), mortality (HR, 0.41; 95% CI, 0.24-0.69) and composite endpoint (HR, 0.52; 95% CI, 0.36-0.77) rates. Beta-blockers reduced re-hospitalization (HR, 0.62; 95% CI, 0.41-0.95) and composite endpoint (HR, 0.65; 95% CI, 0.47-0.90) rates. In ADCHF, adherence to ACEI or ARB was associated with only mortality and ß-blockers with composite endpoint. CONCLUSION: The prognostic implications of adherence to guideline-directed therapy at discharge were more pronounced in de novo heart failure. We recommend that guideline-directed therapy be started as early as possible in the course of heart failure with reduced ejection fraction.
Subject(s)
Guideline Adherence , Heart Failure/diagnosis , Acute Disease , Adrenergic beta-Antagonists/therapeutic use , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Atrial Natriuretic Factor/analysis , Cohort Studies , Female , Heart Failure/drug therapy , Heart Failure/mortality , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Mineralocorticoid Receptor Antagonists/therapeutic use , Patient Discharge , Prognosis , Proportional Hazards Models , Prospective Studies , Protein Precursors/analysis , Registries , Survival RateABSTRACT
BACKGROUND: B-type natriuretic peptide (BNP) has prognostic significance in heart failure (HF), and reductions in BNP may predict clinical improvement. However, there are limited data regarding the prognostic value of BNP during short-term follow-up. The aim of this study was to evaluate the relationship between short-term follow-up BNP and mortality after discharge in patients with HF. METHODS: We analyzed 427 patients hospitalized with HF from the Wonju Severance Christian Hospital Heart Failure Registry from April 2011 to December 2013, with a planned follow-up period through February 2016. Of the 427 patients, 240 (mean age, 75 years; 102 males, 42.5%) had BNP measured on admission and within the short-term follow-up period (3 months). We compared all-cause mortality during the clinical follow-up period (median length of follow-up, 709.5 days) according to the median value of BNP on admission (as a baseline value) and over a short-term follow-up period after discharge. RESULTS: Median BNP at admission was 816.5 pg/ml, and median follow-up BNP was 369.7 pg/ml. Multivariate analysis revealed a positive association between risk of death and high BNP. High BNP during follow-up was significantly associated with a greater risk of all-cause mortality compared to low BNP (P < 0.001). Initial BNP was not significantly associated with all-cause mortality. A multivariate model showed that follow-up BNP and percent change in BNP were independently associated with all-cause mortality after adjustment for covariates. Of the 3 BNP measurement strategies, BNP after discharge (IDI of 0.072, P < .0001 and NRI of 0.707, P < .0001) and percent change in BNP (IDI of 0.113, P < .0001 and NRI of 0.782, P < .0001) demonstrated the greatest increase in discrimination and net reclassification for mortality. Unfortunately, we did not find any significant value with initial BNP. Kaplan-Meier survival analysis was performed to assess mortality stratified by BNP according to the median value, high median of follow-up BNP and percent change in BNP were associated with significantly higher mortality compared to the below median (log-rank, p < 0.001). CONCLUSIONS: Short-term follow-up BNP and percent change in BNP level are significant prognostic factors of all-cause mortality. These values will be clinically useful when evaluating prognosis in hospitalized patients with heart failure.
Subject(s)
Heart Failure/diagnosis , Natriuretic Peptide, Brain/blood , Patient Admission , Aged , Aged, 80 and over , Biomarkers/blood , Cause of Death , Chi-Square Distribution , Female , Heart Failure/blood , Heart Failure/mortality , Heart Failure/physiopathology , Humans , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Multivariate Analysis , Patient Discharge , Predictive Value of Tests , Prognosis , Registries , Republic of Korea , Retrospective Studies , Risk Factors , Time FactorsABSTRACT
To evaluate the pharmacodynamic efficacy of de-escalating P2Y12 inhibition from prasugrel to clopidogrel based on cytochrome P450 (CYP) 2C19 genotyping, we genotyped 50 Korean patients with AMI who underwent percutaneous coronary intervention (PCI) for CYP2C19 *2,*3, or *17 using real-time PCR. They were discharged on prasugrel 10 mg daily. A control group of 48 AMI patients who underwent PCI and were discharged on clopidogrel but did not undergo genotyping was identified retrospectively. Based on genotyping results available at 3 weeks, 12 patients found to have 2 copies of either CYP2C19 *2 or *3 loss of function alleles continued prasugrel while the remaining 38 patients switched to clopidogrel 75 mg daily. The rate of patients within the therapeutic window (TW) of on-treatment platelet reactivity (OPR), 85Subject(s)
Cytochrome P-450 CYP2C19/genetics
, Drug Substitution
, Genotype
, Myocardial Infarction/drug therapy
, Myocardial Infarction/genetics
, Pharmacogenomic Variants
, Ticlopidine/analogs & derivatives
, Aged
, Alleles
, Asian People/genetics
, Blood Platelets/drug effects
, Blood Platelets/metabolism
, Clopidogrel
, Female
, Hemorrhage/etiology
, Humans
, Male
, Middle Aged
, Myocardial Infarction/diagnosis
, Myocardial Infarction/surgery
, Percutaneous Coronary Intervention
, Platelet Activation/drug effects
, Platelet Aggregation Inhibitors/pharmacology
, Platelet Aggregation Inhibitors/therapeutic use
, Platelet Function Tests
, Polymorphism, Single Nucleotide
, Prasugrel Hydrochloride/pharmacology
, Prasugrel Hydrochloride/therapeutic use
, Purinergic P2Y Receptor Antagonists/pharmacology
, Purinergic P2Y Receptor Antagonists/therapeutic use
, Risk Factors
, Ticlopidine/pharmacology
, Ticlopidine/therapeutic use
ABSTRACT
OBJECTIVE: To evaluate the diagnostic performance of automated coronary atherosclerotic plaque quantification (QCT) by different users (expert/non-expert/automatic). METHODS: One hundred fifty coronary artery segments from 142 patients who underwent coronary computed tomography angiography (CCTA) and intravascular ultrasound (IVUS) were analyzed. Minimal lumen area (MLA), maximal lumen area stenosis percentage (%AS), mean plaque burden percentage (%PB), and plaque volume were measured semi-automatically by expert, non-expert, and fully automatic QCT analyses, and then compared to IVUS. RESULTS: Between IVUS and expert QCT analysis, the correlation coefficients (r) for the MLA, %AS, %PB, and plaque volume were excellent: 0.89 (p < 0.001), 0.84 (p < 0.001), 0.91 (p < 0.001), and 0.94 (p < 0.001), respectively. There were no significant differences in the mean parameters (all p values >0.05) except %AS (p = 0.01). The automatic QCT analysis showed comparable performance to non-expert QCT analysis, showing correlation coefficients (r) of the MLA (0.80 vs. 0.82), %AS (0.82 vs. 0.80), %PB (0.84 vs. 0.73), and plaque volume (0.84 vs. 0.79) when they were compared to IVUS, respectively. CONCLUSION: Fully automatic QCT analysis showed clinical utility compared with IVUS, as well as a compelling performance when compared with semiautomatic analyses. KEY POINTS: ⢠Coronary CTA enables the assessment of coronary atherosclerotic plaque. ⢠High-risk plaque characteristics and overall plaque burden can predict future cardiac events. ⢠Coronary atherosclerotic plaque quantification is currently unfeasible in practice. ⢠Quantitative computed tomography coronary plaque analysis software (QCT) enables feasible plaque quantification. ⢠Fully automatic QCT analysis shows excellent performance.
Subject(s)
Coronary Artery Disease/pathology , Plaque, Atherosclerotic/pathology , Aged , Algorithms , Coronary Angiography/methods , Feasibility Studies , Female , Humans , Male , Middle Aged , Observer Variation , Plaque, Atherosclerotic/diagnostic imaging , Tomography, X-Ray Computed/methods , Ultrasonography, Interventional/methodsABSTRACT
The utility of electrocardiography (ECG) in screening for left ventricular hypertrophy (LVH) in general populations is limited mainly because its low sensitivity. B-type natriuretic peptide (BNP) is released due to the remodeling processes of LVH and could improve the diagnostic accuracy for the ECG criteria for LVH. We hypothesized that addition of BNP levels to ECG criteria could aid LVH detection compared with ECG alone in a general population. We enrolled consecutive 343 subjects from a community-based cohort. LVH was defined as LV mass index > 95 g/m(2) for females and > 115 g/m(2) for males according to echocardiography. The area under the receiver operator characteristic (ROC) curve to detect LVH was 0.55 (95% confidence interval [CI], 0.50-0.61) in Sokolow-Lyon criteria and 0.53 (0.47-0.59) in the Cornell voltage criteria. After addition of N-terminal-proBNP levels to the model, the corresponding areas under the ROC were 0.63 (0.58-0.69) and 0.64 (0.59-0.69), respectively. P values for the comparison in areas under the ROC for models with and without N-terminal-proBNP levels were < 0.001. These data suggest that addition of N-terminal-proBNP levels to ECG criteria could significantly improve the diagnostic accuracy of LVH in general populations.
Subject(s)
Electrocardiography , Hypertrophy, Left Ventricular/diagnosis , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Adult , Cohort Studies , Female , Humans , Hypertrophy, Left Ventricular/blood , Male , Middle Aged , ROC CurveABSTRACT
BACKGROUND: There are conflicting data on the use of cilostazol as triple antiplatelet therapy (TAPT) for improving clinical outcomes after drug-eluting stent implantation. We aimed to evaluate whether 3-month use of cilostazol in addition to dual antiplatelet therapy (DAPT) improved clinical outcomes in patients with long or multivessel coronary artery disease (CAD) after biolimus-eluting stent (BES) implantation. METHODS: Patients (n = 630) who had been successfully treated with BES implantation for lesions with ≥28 mm in stent length or ≥2 stents for different coronary arteries were enrolled in this prospective randomized multicenter trial. All patients were randomly assigned to receive either DAPT (aspirin and clopidogrel for 12 months, n = 314) or TAPT (DAPT plus 3-month cilostazol use, n = 316). The primary end point was a device-oriented composite consisting of cardiac death, myocardial infarction (not clearly attributable to a nontarget vessel), and ischemia-driven target lesion revascularization at 1-year follow-up. RESULTS: A total of 314 patients in DAPT and 308 patients in TAPT were analyzed. Multivessel CAD was present in 65.7% of patients. Stents ≥28 mm in length were implanted in 58.1% of lesions. There were no significant differences in baseline and angiographic characteristics between the 2 groups. The primary end point was similar between the 2 groups (2.3% in DAPT vs 1.9% in TAPT, log-rank P = .799). CONCLUSIONS: In patients treated with BES implantation for long or multivessel CAD, 3 months of cilostazol use in addition to DAPT did not improve clinical outcome at 1-year follow-up.
Subject(s)
Coronary Artery Disease/therapy , Drug-Eluting Stents , Sirolimus/analogs & derivatives , Tetrazoles/administration & dosage , Ticlopidine/analogs & derivatives , Aged , Cilostazol , Clopidogrel , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Restenosis/prevention & control , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/pharmacology , Male , Middle Aged , Platelet Aggregation Inhibitors/administration & dosage , Prospective Studies , Sirolimus/pharmacology , Ticlopidine/administration & dosage , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVES: We investigated and compared the clinical outcomes between biodegradable polymer biolimus-eluting stents (BES) and durable polymer everolimus-eluting stents (EES) in a single-center prospective registry. BACKGROUND: There is limited data regarding the safety and efficacy of the biodegradable BES compared to second-generation drug-eluting stents. METHODS: From January 2010 to April 2012, a total of 1,279 patients were treated with BES (n = 647) or EES (n = 632) in a single center. We included 1,231 patients (BES = 625, EES = 606) after excluding 48 patients (BES = 22, EES = 26) with acute myocardial infarction accompanied by cardiogenic shock. The 1-year incidences of target lesion failure (TLF), patient-oriented composite outcomes (POCO), and stent thrombosis (ST) after the index procedure were compared in propensity score-matched analyses. RESULTS: Propensity score matching yielded 406 well-balanced pairs (EES = 406, BES-B = 406). In the propensity-matched population, the 1-year incidence of TLF (BES = 3.0% vs. EES = 2.5%, P = 0.666) and POCO (BES = 5.4% vs. EES = 6.4%, P = 0.552) were similar between the 2 groups. In addition, the incidence of definite or probable ST was also similar (BES = 0.74% vs. EES = 0.74%, P = 1.000). In subgroup analysis, the number of patients who reached the primary end-point did not differ significantly between the 2 groups. CONCLUSION: In a single-center registry with unrestricted use of EES and BES-B, these stents showed comparable efficacy and safety in terms of TLF, POCO, and ST at 1-year follow-up.
Subject(s)
Absorbable Implants , Drug-Eluting Stents , Everolimus/administration & dosage , Patient Outcome Assessment , Sirolimus/analogs & derivatives , Aged , Female , Humans , Male , Percutaneous Coronary Intervention , Propensity Score , Prospective Studies , Registries , Sirolimus/administration & dosageABSTRACT
Background: Our aim was to assess the relationship of the index of microvascular resistance (IMR) in left anterior descending (LAD) artery involved STEMI patients. Methods: Data of 316 STEMI patients who had undergone primary percutaneous coronary intervention (PCI) were collected from three cardiovascular centers from 2005 to 2015. In total, 246 patients with LAD STEMI were enrolled for IMR evaluation. Patients were divided into two groups respective of the cut-off IMR value of 30. All-cause mortality, left ventricular function, improvement of systolic function, and cardiac biomarkers were analyzed and compared. Results: A total of 246 patients were enrolled. The number of patients in the IMR above 30 group was 93 and below 30 was 153. The mean ages for each group were 57.91 ± 11.99 and 54 ± 10.63, respectively. The peak creatinine kinase (CK) (3936.85 ± 2827.32 IU/L vs. 2218.08 ± 2310.41 IU/L, p < 0.001) and CKmb (336.15 ± 195.08 mg/mL vs. 231.53 ± 179.53 mg/mL, p < 0.001) levels were higher for an IMR above the 30 group. The left ventricular ejection fraction (LVEF) (44.57 ± 6.685% vs. 47.35 ± 8.17%, p = 0.006) and improvement of LVEF (2.81 ± 7.135% vs. 5.88 ± 7.65%, p = 0.004) was lower in the IMR above 30 group. All-cause mortality (7.5% vs. 1.3%, p = 0.012) was higher in the IMR above 30 group, and a Cox regression analysis showed that an IMR above 30 was a poor prognostic factor regarding all-cause mortality (HR: 5.151, 95% CI 1.062-24.987, p = 0.042) even after adjusting for classical clinical risk factors. Conclusions: An elevated IMR value represented larger infarct size, more severe LV dysfunction, and higher mortality in LAD STEMI patients after successful PCI.
ABSTRACT
BACKGROUND: Quantitative flow ratio (QFR) is a method for evaluating fractional flow reserve without the use of an invasive coronary pressure wire or pharmacological hyperemic agent. OBJECTIVES: The aim of this study was to investigate the prognostic implications of QFR and plaque characteristics in patients who underwent intravascular ultrasound (IVUS)-guided treatment for intermediate lesions. METHODS: Among the IVUS-guided strategy group in the FLAVOUR (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients with Intermediate Stenosis) trial, vessels suitable for QFR analysis were included in this study. High-risk features were defined as low QFR (≤0.90), quantitative high-risk plaque characteristics (qn-HRPCs) (minimal lumen area ≤3.5 mm2, or plaque burden ≥70%), and qualitative high-risk plaque characteristics (ql-HRPCs) (attenuated plaque, positive remodeling, or plaque rupture) assessed using IVUS. The primary clinical endpoint was target vessel failure (TVF), defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization. RESULTS: A total of 415 (46.1%) vessels could be analyzable for QFR. The numbers of qn-HRPCs and ql-HRPCs increased with decreasing QFR. Among deferred vessels, those with 3 high-risk features exhibits a significantly higher risk of TVF compared with those with ≤2 high-risk features (12.0% vs 2.7%; HR: 4.54; 95% CI: 1.02-20.29). CONCLUSIONS: Among the IVUS-guided deferred group, vessels with qn-HRPC and ql-HRPC with low QFR (≤0.90) exhibited a significantly higher risk for TVF compared with those with ≤2 features. Integrative assessment of angiography-derived fractional flow reserve and anatomical and morphological plaque characteristics is recommended to improve clinical outcomes in patients undergoing IVUS-guided deferred treatment.