Efficacy and Safety of Esaxerenone in Hypertensive Patients with Diabetes Mellitus Undergoing Treatment with Sodium-Glucose Cotransporter 2 Inhibitors (EAGLE-DH).

INTRODUCTION: The EAGLE-DH study assessed the efficacy and safety of esaxerenone in hypertensive patients with diabetes mellitus receiving sodium-glucose cotransporter 2 (SGLT2) inhibitors. METHODS: In this multicenter, open-label, prospective, interventional study, esaxerenone was started at 1.25 or 2.5 mg/day and could be gradually increased to 5 mg/day on the basis of blood pressure (BP) and serum potassium levels. Oral hypoglycemic or antihypertensive medications prior to obtaining consent was continued. Data were evaluated in the total population and creatinine-based estimated glomerular filtration rate (eGFR) subcohorts (eGFR ≥ 60 mL/min/1.73 m2 [G1-G2 subcohort] and 30 to < 60 mL/min/1.73 m2 [G3 subcohort]). RESULTS: In total, 93 patients were evaluated (G1-G2, n = 49; G3, n = 44). Morning home systolic/diastolic BP values (SBP/DBP) were significantly reduced from baseline to week 12 (- 11.8 ± 10.8/- 5.1 ± 6.3 mmHg, both P < 0.001) and week 24 (- 12.9 ± 10.5/- 5.7 ± 6.3 mmHg, both P < 0.001). Similar results were observed in both eGFR subcohorts. The urinary albumin-to-creatinine ratio significantly decreased from baseline to week 24 in the total population (geometric percentage change, - 49.1%, P < 0.001) and in both eGFR subcohorts. The incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 45.2% and 12.9%, respectively; most were mild or moderate. Serum potassium levels increased over the first 2 weeks of esaxerenone treatment, gradually decreased by week 12, and remained constant to week 24. One patient in the G1-G2 subcohort had serum potassium levels ≥ 5.5 mEq/L. No patients had serum potassium ≥ 6.0 mEq/L. CONCLUSION: Esaxerenone effectively lowered BP, was safe, and showed renoprotective effects in hypertensive patients with diabetes mellitus receiving treatment with SGLT2 inhibitors. Esaxerenone and SGLT2 inhibitors did not interfere with either drug's efficacy and may reduce the frequency of serum potassium elevations, suggesting they are a compatible combination. CLINICAL TRIAL REGISTRATION: jRCTs031200273.

Predictive Value of Combining the Ankle-Brachial Index and SYNTAX Score for the Prediction of Outcome After Percutaneous Coronary Intervention (from the SHINANO Registry).

The Synergy Between PCI With TAXUS and Cardiac Surgery (SYNTAX) score is effective in predicting clinical outcome after percutaneous coronary intervention (PCI). However, its prediction ability is low because it reflects only the coronary characterization. We assessed the predictive value of combining the ankle-brachial index (ABI) and SYNTAX score to predict clinical outcomes after PCI. The ABI-SYNTAX score was calculated for 1,197 patients recruited from the Shinshu Prospective Multi-center Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention (SHINANO) registry, a prospective, observational, multicenter cohort study in Japan. The primary end points were major adverse cardiovascular and cerebrovascular events (MACE; all-cause death, myocardial infarction, and stroke) in the first year after PCI. The ABI-SYNTAX score was calculated by categorizing and summing up the ABI and SYNTAX scores. ABI ≤ 0.49 was defined as 4, 0.5 to 0.69 as 3, 0.7 to 0.89 as 2, 0.9 to 1.09 as 1, and 1.1 to 1.5 as 0; an SYNTAX score ≤ 22 was defined as 0, 23 to 32 as 1, and ≥ 33 as 2. Patients were divided into low (0), moderate (1 to 2), and high (3 to 6) groups. The MACE rate was significantly higher in the high ABI-SYNTAX score group than in the lower 2 groups (low: 4.6% vs moderate: 7.0% vs high: 13.9%, p = 0.002). Multivariate regression analysis found that ABI-SYNTAX score independently predicted MACE (hazards ratio 1.25, 95% confidence interval 1.02 to 1.52, p = 0.029). The respective C-statistic for the ABI-SYNTAX and SYNTAX score for 1-year MACE was 0.60 and 0.55, respectively. In conclusion, combining the ABI and SYNTAX scores improved the prediction of 1-year adverse ischemic events compared with the SYNTAX score alone.

Lean body mass index prognostic value for cardiovascular events in patients with coronary artery disease.

OBJECTIVE: Little is known about the relationship between body composition indicators, including body mass index (BMI), fat mass index (FMI) and lean BMI (LBMI), and adverse outcomes after percutaneous coronary intervention (PCI) in Asian populations. The aim of this study was to clarify this relationship. METHODS: The SHINANO registry is a prospective, observational, multicenter cohort registry that enrolled 1923 consecutive patients with coronary heart disease (CHD) from August 2012 to July 2013; 66 patients were excluded because of missing data. We evaluated 1857 patients with CHD who underwent PCI (aged 70±11 years; 23% women; BMI 23.8±3.5 kg/m2; LBMI 18.3±1.8 kg/m2; FMI 5.4±2.2 kg/m2). Patients were divided into three groups, based on BMI, LBMI and FMI tertiles, to assess the prognostic value of the three indicators. The primary endpoint was major adverse cardiac events (MACE), including all cause death, non-fatal myocardial infarction and ischaemic stroke at 1 year. RESULTS: Over a 1 year follow-up period (1776 patients, 95.6%), the cumulative MACE incidence was 8.7% (161 cases). Using Kaplan-Meier analysis, the MACE incidence was significantly higher in patients with lower BMI values (13.4-22.2 kg/m2) (p=0.002) and lower LBMI values (11.6-17.6 kg/m2) (p<0.001); this trend was not observed for FMI. Multivariate Cox regression analysis showed that lower LBMI but not lower BMI values were predictive of a higher MACE incidence (HR 1.55; 95% CI 1.05 to 2.30). CONCLUSIONS: Lower LBMI values are associated with adverse outcomes in an Asian population with CHD undergoing PCI. LBMI is a better predictor of MACE than BMI or FMI. CLINICAL TRIAL REGISTRATION: UMIN-ID; 000010070.

In-hospital clinical outcomes of elderly patients (≥80 years) undergoing percutaneous coronary intervention.

BACKGROUND: The clinical outcomes of elderly patients (≥80 years old) undergoing percutaneous coronary intervention (PCI) has not been well established, despite recent advances in both devices and techniques. METHODS AND RESULTS: We recruited patients from the SHINANO Registry, a prospective, observational, multicenter, cohort study. From August 2012 to July 2013, a total of 1,923 consecutive patients with 2,250 elective/urgent PCIs (2,105 admissions) (mean age, 71±11 years; ≥80 years, 23%; men, 77%) were enrolled. The primary endpoint was procedural success. The secondary endpoints were in-hospital death and in-hospital major adverse cardiovascular events (MACE). The procedural success rate was significantly lower (83.7% vs. 89.1%, P=0.0001), and the rates of in-hospital mortality and MACE were significantly higher in elderly than in non-elderly patients (3.6% vs. 1.5%, P=0.005; 4.4% vs. 2.3%, P=0.016, respectively). For elective PCI, the rates of procedural success and in-hospital MACE were similar between groups (90.3% vs. 91.3%, P=0.65, 2.3% vs. 1.2%, P=0.2, respectively). On multivariate analysis, being elderly was not an independent predictor of procedural failure (OR, 1.15; CI, 0.81-1.61; P=0.43). CONCLUSIONS: In elderly patients, PCI is safe and feasible. The presence of comorbidities is a more important factor than age alone.

A critical increase in right-to-left shunt after acute myocardial infarction in a 68-year-old male with tetralogy of Fallot.

A male patient with tetralogy of Fallot accompanied by aortic regurgitation had maintained sufficient exercise capacity for a number of decades with the status of acyanotic tetralogy of Fallot. When he was 67 years old, he suffered a posterior wall acute myocardial infarction and direct percutaneous coronary angioplasty successfully revascularised the target lesion in the left circumflex artery. However, a few months after the onset of the myocardial infarction, his shortness of breath became clinically significant and was associated with increased right-to-left shunt and increased right ventricular end-diastolic pressure, as well as hypoxia. At 68 years old, therefore, total corrective repair of the tetralogy with replacement of the aortic and pulmonary valves was performed. The patient was asymptomatic after the successful operation. This report suggests that coronary artery disease can be one of the potential factors in inducing critical hemodynamic changes in aging patients with congenital heart disease, especially those who have a shunt between the right and left chambers. The unique clinical course is described with some discussion of the repair of tetralogy in adults.