Abstract Background Dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherosclerotic and cardioprotective effects in vitro. However, the impact of DPP-4 inhibitors on coronary plaque remains ...unclear. We sought to assess the effect of sitagliptin on coronary plaque volume (PV) and stabilization in diabetic patients with acute coronary syndrome (ACS). Methods The ESPECIAL-ACS was a prospective, randomized, open-label, parallel group study at 4 Japanese centers to assess the effect of 6-month treatment with sitagliptin on coronary plaque changes in non-culprit lesion in diabetic patients with ACS using serial intravascular ultrasound (IVUS) and integrated backscatter IVUS (IB-IVUS) analysis. Results A total of 41 patients were randomly allocated to either sitagliptin group (diet and exercise with sitagliptin 50–100 mg daily, n = 21) or control group (diet and exercise, n = 20) within 72 h after percutaneous coronary intervention, and underwent volumetric IVUS and IB-IVUS analyses at baseline and 6-month follow-up. At 6-month follow-up, the percent change in PV as primary endpoint was larger in the sitagliptin group than in the control group, but the difference was not statistically significant (−4.0 ± 8.5% vs. −1.4 ± 8.8%, p = 0.35). In IB-IVUS analysis, the percent change in lipid PV significantly decreased in the sitagliptin group compared with the control group (−7.1 ± 21.5% vs. 15.6 ± 41.8%, p = 0.03). Conclusions Compared with diet and exercise therapy, sitagliptin did not significantly reduce coronary PV in diabetic patients with ACS at 6-month follow-up. However, the percent change in lipid PV significantly decreased in the sitagliptin group, suggesting that sitagliptin has a potential to stabilize the plaque vulnerability.
Background It remains controversial whether long-term clinical impact of newly diagnosed atrial fibrillation (AF) in the acute phase of acute myocardial infarction (AMI) is different from that of ...prior AF diagnosed before the onset of AMI. Methods and Results The current study population from the CREDO-Kyoto AMI (Coronary Revascularization Demonstrating Outcome Study in Kyoto Acute Myocardial Infarction) Registry Wave-2 consisted of 6228 patients with AMI who underwent percutaneous coronary intervention. The baseline characteristics and long-term clinical outcomes were compared according to AF status (newly diagnosed AF: N=489 7.9%, prior AF: N=589 9.5%, and no AF: N=5150 82.7%). Median follow-up duration was 5.5 years. Patients with newly diagnosed AF and prior AF had similar baseline characteristics with higher risk profile than those with no AF including older age and more comorbidities. The cumulative 5-year incidence of all-cause death was higher in newly diagnosed AF and prior AF than no AF (38.8%, 40.7%, and 18.7%,
<0.001). The adjusted hazard ratios (HRs) for mortality of newly diagnosed AF and prior AF relative to no AF remained significant with similar magnitude (HR, 1.31; 95% CI, 1.12-1.54;
<0.001, and HR, 1.32; 95% CI, 1.14-1.52;
<0.001, respectively). The cumulative 5-year incidence of stroke decreased in the order of newly diagnosed AF, prior AF and no AF (15.5%, 12.9%, and 6.3%, respectively,
<0.001). The higher adjusted HRs of both newly diagnosed AF and prior AF relative to no AF were significant for stroke, with a greater risk of newly diagnosed AF than that of prior AF (HR, 2.05; 95% CI, 1.56-2.69;
<0.001, and HR, 1.33; 95% CI, 1.00-1.78;
=0.048, respectively). The higher stroke risk of newly diagnosed AF compared with prior AF was largely driven by the greater risk within 30 days. The higher adjusted HRs of newly diagnosed AF and prior AF relative to no AF were significant for heart failure hospitalization (HR, 1.73; 95% CI, 1.35-2.22;
<0.001, and HR, 2.23; 95% CI, 1.82-2.74;
<0.001, respectively) and major bleeding (HR, 1.46; 95% CI, 1.23-1.73;
<0.001, and HR, 1.36; 95% CI, 1.15-1.60;
<0.001, respectively). Conclusions Newly diagnosed AF in AMI had risks for mortality, heart failure hospitalization, and major bleeding higher than no AF, and comparable to prior AF. The risk of newly diagnosed AF for stroke might be higher than that of prior AF.
Long-term clinical outcomes among patients with cardiogenic shock (CS) and heart failure (HF) who survive the early phase of acute myocardial infarction (AMI) remain uncertain. We investigated 3283 ...consecutive patients with AMI, selected from a prospective, nation-wide multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014. The 3263 eligible patients were divided into the following three groups: CS-/HF- group (n = 2467, 75.6%); CS-/HF+ group (n = 479, 14.7%); and CS+ group (n = 317, 9.7%). The thirty-day mortality rate in CS+ patients was 32.8%, significantly higher than in CS- patients. Among CS+ patients, multivariate logistic regression analysis identified statin use before admission (Odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14-0.66, P = 0.002), renal deficiency (OR 8.72, 95%CI 2.81-38.67, P < 0.0001) and final thrombolysis in myocardial infarction flow grade (OR 0.42, 95%CI 0.18-0.99, P = 0.046) were associated with 30-day mortality. Landmark Kaplan-Meier analysis showed that mortality rates after 30 days were comparable between CS+ and CS-/HF+ groups but were lower in the CS-/HF- group. Multivariate Cox hazard analysis also showed that hazard risk of mortality after 30 days was comparable between the CS+ and CS-/HF+ groups (Hazard ratio (HR) 1.03, 95%CI 0.63-1.68, P = 0.90), and significantly lower in the CS-/HF- group (HR 0.44, 95%CI 0.32-059, P < 0.0001). In conclusion, AMI patients with CS who survived 30 days experienced worse long-term outcomes compared with those without CS up to 3 years. Attention is required for patients who show HF on admission without CS to improve long-term AMI outcomes.
Previous studies have reported the prognostic value of objective nutritional indices such as the Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index (GNRI) and Prognostic ...Nutritional Index (PNI). However, the effects of these indices in patients with coronary artery disease (CAD) who have undergone percutaneous coronary intervention (PCI) remain unclear. Furthermore, there are insufficient data to combine these indices. A total of 1984 patients who underwent elective PCI were enrolled. The Combined Objective Nutritional Score was determined by assigning 1 point each for high CONUT score (3–12), low GNRI (< 98) or low PNI (< 45). Patients were grouped into normal nutritional status (0 points), mild-to-moderate malnutrition (1–2 points) and severe malnutrition (3 points). Incidences of all-cause death and cardiac death were evaluated. Among the 1984 patients, 514 (25.9%) and 244 (12.3%) had mild-to-moderate and severe malnutrition, respectively. During follow-up (median 7.4 years), 293 all-cause deaths were identified, including 92 cardiac deaths. Kaplan–Meier curves showed ongoing divergence in rates of death among nutritional statuses determined by the novel score (log rank test,
p
< 0.0001). Multivariate Cox hazard analysis showed that patients with a Combined Objective Nutritional Score of 3 showed 2.91-fold (95% confidence interval (CI) 2.10–4.00;
p
< 0.0001) and 2.16-fold (95% CI 1.15–3.92;
p
= 0.02) increases in risk of mortality and cardiac mortality compared with patients with a Combined Objective Nutritional Score of 0. In conclusion, malnutrition as evaluated by the Combined Objective Nutritional Score was significantly associated with worse long-term cardiovascular outcomes among CAD patients who underwent PCI.
Although high-sensitivity C-reactive protein (hs-CRP) has been used to predict the risk of adverse cardiac events in patients with coronary artery disease (CAD) after percutaneous coronary ...interventions (PCIs), little is known about the association between hs-CRP and long-term outcomes in patients with preserved renal function.Here, we studied 1,153 patients with stable CAD and preserved renal function (estimated glomerular filtration rate: > 60 mL/minute/1.73 m2) who underwent their first PCI between 2000 and 2011. Those with available data on preprocedural hs-CRP were included. Patients were assigned to tertiles according to preprocedural hs-CRP levels. The incidence of major adverse cardiac events (MACE), including all-cause death and nonfatal myocardial infarction, was evaluated. During a median follow-up period of 7.5 years, Kaplan-Meier curves showed ongoing divergence in the rates of MACE among the hs-CRP tertiles (hs-CRP < 0.05 mg/L, 12.1%; 0.05-0.17 mg/L, 12.1%; > 0.17 mg/L, 21.6%; log-rank P = 0.003). After adjusting for the established cardiovascular risk factors, hs-CRP levels were found to be associated with a higher incidence of MACE (hazard ratio HR: 3.65, 95% confidence interval CI: 1.77-7.07; P = 0.0008) and a higher rate of all-cause mortality (HR: 5.14, 95% CI: 2.38-10.30; P < 0.0001).In conclusion, this long-term registry showed that preprocedural hs-CRP measurement is clinically useful for long-term risk assessments in patients with stable CAD and preserved renal function.
Background:Data evaluating the effects of acute coronary syndrome (ACS) relative to stable coronary artery disease (CAD) on bleeding risk after percutaneous coronary intervention (PCI) are ...scarce.Methods and Results:From the CREDO-Kyoto Registry Cohort-3, 13,258 patients undergoing first PCI (5,521 ACS; 7,737 stable CAD) were identified. Patients were further stratified according to ACS presentation and Academic Research Consortium High Bleeding Risk (HBR): ACS/HBR: n=2,502; ACS/no-HBR: n=3,019; stable CAD/HBR: n=3,905; and stable CAD/no-HBR: n=3,832. The primary bleeding endpoint was Bleeding Academic Research Consortium 3/5 bleeding, whereas the primary ischemic endpoint was myocardial infarction (MI)/ischemic stroke. Compared with stable CAD, ACS was associated with a significantly higher adjusted risk for bleeding (hazard ratio HR 1.85; 95% confidence interval CI 1.68–2.03; P<0.0001), with a markedly higher risk within 30 days (HR 4.24; 95% CI 3.56–5.06; P<0.0001). Compared with the stable CAD/no-HBR group, the ACS/HBR, no-ACS/HBR, and ACS/no-HBR groups were associated with significantly higher adjusted risks for bleeding, with HRs of 3.05 (95% CI 2.64–3.54; P<0.0001), 1.89 (95% CI 1.66–2.15; P<0.0001), and 1.69 (95% CI 1.45–1.98; P<0.0001), respectively. There was no excess adjusted risk of the ACS relative to stable CAD group for MI/ischemic stroke (HR 1.07; 95% CI 0.94–1.22; P=0.33).Conclusions:Bleeding risk after PCI depended on both ACS presentation and HBR, with a significant effect of ACS within 30 days.
Previously we briefly reported the effect of 1-month dual antiplatelet therapy (DAPT) for patients with high bleeding risk (HBR) receiving percutaneous coronary intervention (PCI) in the STOPDAPT-2 ...trial, but full analysis data have not been available. We conducted post hoc subgroup analysis regarding the effect of very short DAPT for HBR patients in STOPDAPT-2 trial. The primary endpoint was a 1-year composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) and bleeding (TIMI major/minor bleeding) outcomes. Major secondary endpoints were 1-year cardiovascular composite endpoint and bleeding endpoint. HBR was defined by the academic research consortium (ARC) HBR criteria. Among the 3009 study patients, 1054 (35.0%) were classified as HBR and 1955 (65.0%) were as non-HBR. There were no significant interactions between HBR/non-HBR subgroups and the assigned DAPT group on the primary endpoint (HBR; 3.48% vs. 5.98%, HR 0.57, 95% CI 0.32–1.03, and non-HBR; 1.81% vs. 2.36%, HR 0.78, 95% CI 0.42–1.45;
P
for interaction = 0.48), the major secondary cardiovascular endpoint (HBR; 3.07% vs. 4.03%, HR 0.77, 95% CI 0.40–1.48, and non-HBR; 1.41% vs. 1.61%, HR 0.89, 95% CI 0.43–1.84;
P
for interaction = 0.77), and the major secondary bleeding endpoint (HBR; 0.41% vs. 2.71%, HR 0.15, 95% CI 0.03–0.65, and non-HBR; 0.40% vs. 0.85%, HR 0.48, 95% CI 0.14–1.58;
P
for interaction = 0.22). In conclusion, the effects of 1-month DAPT for the primary and major secondary endpoints were consistent in HBR and non-HBR patients without any significant interactions. The benefit of 1-month DAPT in reducing major bleeding was numerically greater in HBR patients.
Clinical trial registration
Short and optimal duration of dual antiplatelet therapy after everolimus-eluting cobalt–chromium stent-2 STOPDAPT-2; NCT02619760.
Aims
Hypoxia‐inducible factor‐prolyl hydroxylase (HIF‐PH) inhibitors have been developed for the treatment of renal anaemia; however, no study has evaluated the safety and efficacy of HIF‐PH ...inhibitors in patients with heart failure (HF). This study was designed to evaluate the safety and efficacy of daprodustat, a HIF‐PH inhibitor, in patients with HF and renal anaemia.
Methods and results
We designed a pilot, multi‐centre, open‐label, randomized controlled study, in which 50 patients with HF complicated with chronic kidney disease and anaemia will be randomized 1:1 to either the daprodustat or control group at seven sites in Japan. Study entry requires New York Heart Association Class II HF symptoms or a history of hospitalization due to HF, an estimated glomerular filtration rate of <60 mL/min/1.73 m2, and a haemoglobin level of 7.5 to <11.0 g/dl. Patients randomized to the daprodustat group will be treated with oral daprodustat, and the dose will be uptitrated according to the changes in the haemoglobin level from previous visits. In this study, we will evaluate the impact of HIF‐PH inhibitors on cardiac function using advanced cardiovascular imaging modalities, including cardiac magnetic resonance imaging. The primary outcome is the haemoglobin level at 16 weeks of randomization, and all adverse events will be recorded and evaluated for any association with daprodustat treatment.
Conclusion
Considering the hypothetical upside and downside of using HIF‐PH inhibitors in anaemic patients with HF and chronic kidney disease, and because there are virtually no safe and effective treatments for patients with anaemia not caused by iron deficiency, our study results will contribute significantly to this field.
The ultra-short dual antiplatelet therapy (DAPT) followed by P2Y
12
inhibitor monotherapy might be promising after percutaneous coronary intervention (PCI). However, CYP2C19 loss-of-function (LOF) ...alleles have been reported to diminish the effect of clopidogrel, and clopidogrel monotherapy has a concern about the increased ischemic risk for patients with such alleles. STOPDAPT-2 is the multicenter prospective open-label, but adjudicator-blinded randomized control study comparing 1-month DAPT followed by clopidogrel monotherapy with the standard 12-month DAPT after PCI with cobalt–chromium everolimus-eluting stents. Among the participants of STOPDAPT-2, selected patients participated in a substudy of the CYP2C19 gene test. Patients with two CYP2C19*2 or *3 alleles were defined as the poor metabolizer (PM), one allele as the intermediate metabolizer (IM), and no allele as the extensive metabolizer (EM). The primary endpoint was the composite of cardiovascular and bleeding events, as defined in STOPDAPT-2. Among 750 (24.9%) patients with known CYP2C19 genotypes, 129 (17.2%) were PM, 367 (49.0%) were IM, and 254 (33.9%) were EM. The hazard ratios of 1-month DAPT relative to 12-month DAPT for the primary endpoint in PM, IM, and EM strata were 0.66 (95% CI 0.11–3.94), 1.94 (95% CI 0.60–6.31), and 0.21 (95% CI 0.02–1.78), respectively (
P
interaction = 0.17), and those for cardiovascular composite endpoint were 1.00 (95% CI 0.14–7.10), 6.10 (95% CI 0.75–49.55), and 0.26 (95% CI 0.03–2.34), respectively (
P
interaction = 0.12). In conclusion, for the selected patients in STOPDAPT-2 trial, CYP2C19 LOF alleles had no significant, consistent interaction with the effect of 1-month DAPT relative to 12-month DAPT for clinical outcomes, although the study was overtly underpowered.
Trial registry
STOPDAPT-2 ClinicalTrials.gov number, NCT02619760.
A poor nutritional status has been gathering intense clinical interest recently as it has been suggested to associate with adverse outcomes in patients in the intensive care unit (ICU). However, ...there is still no established nutritional index dominantly used in clinical practice. We have previously proposed a novel nutritional index, which can be calculated using serum levels of triglycerides, total cholesterol, and body weight (TCBI). In this study, to expand the application of TCBI for critical patients, we investigated the usefulness of TCBI to predict prognosis in hemodynamically unstable patients with percutaneously implantable mechanical circulatory support (MCS) devices in the ICU.
This is a retrospective analysis of a multicenter registry consisting of three Juntendo University hospitals in Japan involving patients who received MCS devices, including intra-aortic balloon pumping (IABP) with or without veno-arterial extracorporeal membrane oxygenation (VA-ECMO), between 2012 and 2016 (
= 439). The median follow-up period was 298 days.
Spearman's correlation coefficient between TCBI and the geriatric nutritional risk index (GNRI) was 0.44 (
< 0.0001), indicating a moderate positive correlation for these two variables. Unadjusted Kaplan-Meier analysis demonstrated reduced risks of all-cause and cardiovascular mortalities in patients with higher tertiles of TCBI. Furthermore, adjusted multivariate Cox proportional hazard analyses revealed that the highest tertile TCBI was an independent predictor for the reduced risk of all-cause mortality (hazard ratio (HR): 0.22, 95% confidence interval: 0.10-0.48,
< 0.0001) and cardiovascular mortality (0.20, 0.09-0.45,
< 0.0001).
A novel and simple to calculate nutritional index, TCBI, can be applicable as a prognostic indicator in hemodynamically unstable patients requiring MCS devices.
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