An Aspirin-Free Versus Dual Antiplatelet Strategy for Coronary Stenting: STOPDAPT-3 Randomized Trial.

BACKGROUND: Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials. METHODS: We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin. RESULTS: The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; Psuperiority=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; Pnoninferiority=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group. CONCLUSIONS: The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.

Long-term observation of estimated fluid volume reduction after the initiation of ipragliflozin in patients with type 2 diabetes mellitus: a sub-analysis from a randomized controlled trial (PROTECT).

BACKGROUNDS/AIM: Recent studies have shown that the addition of sodium-glucose co-transporter 2 (SGLT2) inhibitors gradually reduces the estimated fluid volume parameters in a broad range of patient populations, suggesting that this mediates the clinical benefits of SGLT2 inhibitors in preventing heart failure. Here, we sought to examine the long-term (24 months) effect of the SGLT2 inhibitor ipragliflozin on the estimated fluid volume parameters in patients with type 2 diabetes mellitus (T2DM). METHODS: In this prespecified sub-analysis of the PROTECT (Prevention of Atherosclerosis by SGLT2 Inhibitor: Multicenter, Randomized Controlled Study) trial, which was an investigator-initiated, multicenter, prospective, randomized, open-label, clinical trial primarily designed to evaluate the effect of ipragliflozin treatment administered for 24 months on carotid atherosclerosis in patients with T2DM, we evaluated serial changes in estimated plasma volume (ePV, %) calculated using the Straus formula and estimated extracellular volume (eEV, mL) calculated by the body surface area by 24 months following the initiation of 50-mg ipragliflozin once daily and compared them with those following standard care for T2DM (non-SGLT2 inhibitor use). RESULTS: This sub-analysis included 464 patients (ipragliflozin, n = 232; control, n = 232), a full analysis set of the PROTECT trial. In an analysis using mixed-effects models for repeated measures, relative to the control group, ipragliflozin significantly reduced ePV by - 10.29% (95% confidence interval [CI] - 12.47% to - 8.11%; P < 0.001) at 12 months and - 10.76% (95% CI - 12.86% to - 8.67%; P < 0.001) at 24 months. Additionally, ipragliflozin significantly reduced eEV by - 190.44 mL (95% CI - 249.09 to - 131.79 mL; P < 0.001) at 12 months and - 176.90 mL (95% CI - 233.36 to - 120.44 mL; P < 0.001) at 24 months. The effects of ipragliflozin on these parameters over 24 months were mostly consistent across various patient clinical characteristics. CONCLUSIONS: This prespecified sub-analysis from the PROTECT trial demonstrated that ipragliflozin treatment, compared with the standard care for T2DM, reduced two types of estimated fluid volume parameters in patients with T2DM, and the effect was maintained for 24 months. Our findings suggest that SGLT2 inhibitor treatment regulates clinical parameters incorporated into the calculating formulas analyzed and consequently fluid volume status for the long-term, and this may be at least partly associated with clinical benefits from chronic use of SGLT2 inhibitors. Trial registration Japan Registry of Clinical Trials, ID jRCT1071220089.

The potential of dynamic 99mTc-sestamibi cadmium zinc telluride-single-photon emission computed tomography camera assessing myocardial flow reserve in patients with heart failure with preserved ejection fraction.

Aims: Coronary microvascular dysfunction (CMD) is related to the pathophysiology, mortality, and morbidity of heart failure with preserved ejection fraction (HFpEF). A novel single-photon emission computed tomography (SPECT) camera with cadmium zinc telluride (CZT) detectors allows for the quantification of absolute myocardial blood flow and myocardial flow reserve (MFR) in patients with coronary artery disease. However, the potential of CZT-SPECT assessing for CMD has never been evaluated in patients with HFpEF. Methods and results: The clinical records of 127 consecutive patients who underwent dynamic CZT-SPECT were retrospectively reviewed. Rest and stress scanning were started simultaneously with 3 and 9 MBq/kg of 99mTc-sestamibi administration, respectively. Dynamic CZT-SPECT imaging data were analysed using a net-retention model with commercially available software. Transthoracic echocardiography was performed in all patients. The MFR value was significantly lower in the HFpEF group (mean ± SEM = 2.00 ± 0.097) than that in the non-HFpEF group (mean ± SEM = 2.74 ± 0.14, P = 0.0004). A receiver operating characteristic analysis indicated that if a cut-off value of 2.525 was applied, MFR could efficiently distinguish HFpEF from non-HFpEF. Heart failure with preserved ejection fraction had a consistently low MFR, regardless of the diastolic dysfunction score. Heart failure with preserved ejection fraction patients with MFR values lower than 2.075 had a significantly higher incidence of heart failure exacerbation. Conclusion: Myocardial flow reserve assessed by CZT-SPECT was significantly reduced in patients with HFpEF. A lower MFR was associated with a higher hospitalization rate in these patients. Myocardial flow reserve assessed by CZT-SPECT has the potential to predict future adverse events and stratify the severity of disease in patients with HFpEF.

Long-term outcomes of percutaneous revascularization for internal mammary artery-left anterior descending artery bypass failure.

Despite the excellent long-term results of internal mammary artery (IMA)-left anterior descending (LAD) bypass, percutaneous revascularization of IMA is sometimes required for IMA-LAD bypass failure. However, its clinical outcomes have not been fully elucidated. The aim of this study was to investigate the long-term clinical outcomes, including target lesion revascularization (TLR) following contemporary percutaneous revascularization of failed IMA bypass graft. We examined data of 59 patients who had undergone percutaneous revascularization of IMA due to IMA-LAD bypass failure at nine hospitals. Patients with IMA graft used for Y-composite graft or sequential bypass graft were excluded. The incidence of TLR was primarily examined, whereas other clinical outcomes including cardiac death, myocardial infarction, and target vessel revascularization were also evaluated. Mean age of the enrolled patients was 67.4 ± 11.3 years, and 74.6% were men. Forty patients (67.8%) had anastomotic lesions, and 17 (28.8%) underwent revascularization within three months after bypass surgery. Procedural success was achieved in 55 (93.2%) patients. Stent implantation was performed in 13 patients (22.0%). During a median follow-up of 1401 days (interquartile range, 282-2521 days), TLR was required in six patients (8.5% at 1, 3, and 5 years). Patients who underwent percutaneous revascularization within 3 months after surgery tended to have a higher incidence of TLR. Clinical outcomes of IMA revascularization for IMA-LAD bypass failure were acceptable.

Assessment of appropriate body mass index cut-off points for long-term mortality among ST-elevation myocardial infarction survivors in Asian population using machine learning algorithm.

Low body mass index (BMI) is a predictor of adverse events in patients with ST-elevated myocardial infarction (STEMI) in Western countries. Because the average BMI of Asians is significantly lower than that of the Western population, the appropriate cut-off BMI value and its role in long-term mortality are unclear in Asian patients. Between January 2006 and December 2017, 1215 patients who underwent percutaneous coronary intervention (PCI) for acute STEMI and were alive at discharge (mean age, 67.7 years; male, 75.4%) were evaluated. The cut-off BMI value, which could predict all-cause mortality within 10 years, was detected using a survival classification and regression tree (CART) model. The causes of death according to the BMI value were evaluated in each group. Based on the CART model, the patients were divided into three groups (BMI < 18 kg/m2: 54 patients, 18 kg/m2 ≤ BMI ≤ 20 kg/m2: 109 patients, and BMI > 20 kg/m2: 1052 patients). The BMI decreased with age; with an increased BMI, patients with dyslipidemia, diabetes mellitus, and smoking habit increased. During the study period (median, 4.9 years), 194 patients (26.8%) died (cardiac death, 59 patients; non-cardiac death, 135 patients). All-cause mortality was more frequent as the BMI decreased (BMI < 18 kg/m2; 72.8%, 18 kg/m2 ≤ BMI ≤ 20 kg/m2; 40.5%, and BMI > 20 kg/m2; 22.8%; log-rank p < 0.001). Non-cardiac deaths were more frequent than cardiac deaths in all groups, and the dominance of non-cardiac death was highest in the lowest BMI group. Cut-off BMI values of 18 kg/m2 and 20 kg/m2 can predict long-term mortality after PCI in Asian STEMI survivors, whose cut-off value is lower than that in the Western populations. The main causes of death in this cohort differed according to the BMI values.

Ten-Year Mortality in Patients With ST-Elevation Myocardial Infarction.

Knowledge of the long-term prognosis (>10 years) and mortality predictors of ST-elevation myocardial infarction (STEMI) patients who have undergone primary percutaneous coronary intervention (p-PCI) is scarce. Therefore, this study evaluated the long-term prognosis and determined the predictors of long-term outcomes for STEMI patients after p-PCI. Between January, 2006 and December, 2010, we collected data and analyzed 459 consecutive patients with acute STEMI who underwent p-PCI and were discharged from the hospital (mean age, 66.8 years; male, 75.2%; peak creatine phosphokinase level, 2,292.5 IU/L). The primary endpoint was 10-year all-cause mortality. The cumulative 10-year incidence of all-cause death was 23.8%. The Cox multivariate regression analysis identified age ≥ 65 years (adjusted hazard ratio [aHR], p <0.001), body mass index (aHR, 0.93, p = 0.033), presence of atrial fibrillation (aHR, 1.69, p = 0.038), mineralocorticoid receptor antagonist use (aHR, 1.95, p = 0.008), ejection fraction <40% (aHR, 2.14, p = 0.005), and albumin <3.5 g/dL (aHR, 2.01, p = 0.005) as independent predictors of all-cause mortality. In conclusion, a post-discharge 10-year survival rate of 76.2% was identified for STEMI patients who underwent p-PCI.

Myocardial salvage after ST-segment-elevation myocardial infarction: comparison between prasugrel and clopidogrel in the presence or absence of high-residual platelet reactivity.

BACKGROUND: The effect of prasugrel over clopidogrel on myocardial salvage in ST-segment-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (p-PCI) is not fully elucidated. METHODS: Among 854 consecutive STEMI patients who underwent p-PCI, 446 patients were evaluated by two-phase (7 days and 3 months) single-photo emission computed tomography (SPECT). Patients were divided into two groups based on the loading P2Y12 inhibitor. The clopidogrel group was further divided based on the result of platelet function testing. Thus, the prasugrel group included 227 patients; the clopidogrel without high-residual platelet reactivity (HRPR) group, 109 patients; and the clopidogrel with HRPR group, 107 patients. The primary endpoint was the Myocardial Salvage Index (MSI), determined by SPECT. RESULTS: The incidence of final TIMI 0/1 and TIMI myocardial perfusion grade 0/1 was higher in the clopidogrel with HRPR group (0.9%, 1.8%, and 7.5%, P =  .002; 19.8%, 29.4%, and 41.1%, P = .0002, in the prasugrel, clopidogrel without HRPR, and clopidogrel with HRPR groups, respectively). The MSI was significantly lower in the clopidogrel with HRPR group (48% [27-66], 44% [30-72], and 36% [15-55], P =  .006, respectively). CONCLUSIONS: Prasugrel in STEMI patients was associated with an increased MSI compared with clopidogrel in the presence of HRPR.

Heparin 'flush' induced thrombocytopenia triggered by total hip replacement: a case report.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) typically responds to heparin termination. Some types of HIT can persist after heparin discontinuation. CASE SUMMARY: A 95-year-old woman was referred to the cardiology from orthopaedics because of acute limb ischaemia (ALI) 1 day after surgery of a femoral neck fracture. Despite thrombectomy, ALI relapsed the next day. She had been treated with intravenous antibiotics with a diagnosis of aspiration pneumonia for 1 week until 3 days before surgery, together with heparin flush twice a day. Of note, no intra-/post-operative heparin was administered, no cell salvage device, central venous, nor arterial catheters were used before development of ALI. The patient and her family refused reattempting invasive therapies; consequently, the patient continued to worsen and died on post-operative day 3. Diagnosis of autoimmune HIT, which was prompted by surgery without re-exposure to heparin, was confirmed posthumously. DISCUSSION: This case emphasizes the significance of suspecting autoimmune HIT in any patient presenting with thrombosis, even if the heparin exposure dates back more than a few days or even without heparin exposure.