Effect of Luseogliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, and Dipeptidyl-Peptidase 4 Inhibitors on the Quality-of-Life and Treatment Satisfaction of Patients With Type 2 Diabetes Mellitus: A Subanalysis of a Multicenter, Open-Label, Randomized-Controlled Trial (J-SELECT Study).

INTRODUCTION: The effects of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) on quality of life (QOL) and treatment satisfaction have not been directly compared. This sub-analysis of a randomized-controlled trial with an SGLT2i, luseogliflozin, and DPP-4is compared their effects on QOL and treatment satisfaction of patients. METHODS: This study recruited 623 patients with type 2 diabetes mellitus who were drug-naïve or treated with antidiabetic agents other than SGLT2is and DPP-4is. The patients were randomized into luseogliflozin or DPP-4i group and followed for 52 weeks. This sub-analysis assessed QOL and treatment satisfaction using Oral Hypoglycemic Agent Questionnaire (OHA-Q) version 2 in the drug-naïve subgroup who were drug-naïve at baseline and with monotherapy with luseogliflozin or DPP-4i throughout the observation period (256 patients) at 24 and 52 weeks and in the add-on subgroup who were treated with OHAs other than SGLT2is and DPP-4is (204 patients) at baseline, 24 and 52 weeks. RESULTS: In the drug-naïve subgroup, total (50.8 ± 8.2 in luseogliflozin group and 53.1 ± 10.0 in DPP-4i group, p = 0.048) and somatic symptom scores (22.4 ± 5.0 in luseogliflozin group and 24.4 ± 5.8 in DPP-4i group, p = 0.005) at 52 weeks (but not at 24 weeks) were significantly higher in DPP-4i group than in luseogliflozin group. In add-on subgroup, changes in total (3.3 ± 7.8 in luseogliflozin group and 0.9 ± 7.6 in DPP-4i group, p = 0.030) and treatment convenience (1.2 ± 3.9 in luseogliflozin group and - 0.6 ± 4.2 in DPP-4i group, p = 0.002) from baseline to 24 weeks (but not at 52 weeks) were significantly greater in luseogliflozin group than in DPP-4i group. The QOL related to safety or glycemic control was comparable between the groups. CONCLUSIONS: Physicians should pay attention to side effects of SGLT2is to maintain the patients' QOL when SGLT2is are initiated or added-on. Add-on of luseogliflozin increased patients' QOL more than DPP-4is. Considering patients' QOL and treatment satisfaction is important for selecting SGLT2is or DPP-4is. TRIAL REGISTRATION: UMIN000030128 and jRCTs031180241.

Characteristics and Related Factors of One-year Transition in Exercise Tolerance Following an Emergency Declaration due to the Coronavirus Disease 2019 Pandemic in Patients on Phase III Cardiac Rehabilitation.

OBJECTIVE: This study aimed to understand the long-term transition of exercise tolerance in patients on phase III cardiac rehabilitation (CR) and clarify the characteristics of patients with a high risk of declined exercise tolerance during the first emergency declaration. METHODS: Patients who participated in phase III outpatient CR before the first emergency declaration and those who performed cardiopulmonary exercise testing were at ≥2-time points: before and at 3 or 12 months post-emergency declaration. Exercise tolerance transition at 3-time points was analyzed, and whether different social background factors affected the peak oxygen uptake (V̇O2) transition method remains to be examined. RESULTS: A total of 101 (median age 74.0 years, 69% men), and both peak V̇O2 and anaerobic threshold (AT) significantly declined from pre-declaration to 3 months post-declaration but recovered to levels likely similar from pre-declaration at 12 months (peak V̇O2: from 17.3 to 16.7 to 18.7 mL/min/kg; AT: from 11.8 to 11.2 to 11.6 mL/min/kg). Further, patients with multiple comorbidities at pre-declaration had a significantly lower peak V̇O2 at 3 months (-1.0 mL/min/kg, p = 0.025) and it remained significantly low in those with a slower gait speed at 12 months after lifting the emergency declaration (-2.5 mL/min/kg, p = 0.009). CONCLUSION: The emergency declaration declined the exercise tolerance in patients on phase III CR but improved to pre- declaration levels over time, but more likely declined in patients with multiple comorbidities during pre-declaration and those with low-gait speeds were less likely to improve their declined exercise tolerance.

Overall Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitor Luseogliflozin Versus Dipeptidyl-Peptidase 4 Inhibitors: Multicenter, Open-Label, Randomized-Controlled Trial (J-SELECT study).

INTRODUCTION: Evidence of a direct comparison between dipeptidyl-peptidase 4 inhibitors (DPP-4is) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) remains lacking, and no clear treatment strategy or rationale has been established using these drugs. This study aimed to compare the overall efficacy and safety of DPP-4is and the SGLT2i luseogliflozin in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients with T2DM who had not used antidiabetic agents or who had used antidiabetic agents other than SGLT2is and DPP-4is were enrolled in the study after written informed consent had been obtained. The enrolled patients were subsequently randomly assigned to either the luseogliflozin or DPP-4i group and followed up for 52 weeks. The primary (composite) endpoint was the proportion of patients who showed improvement in ≥ 3 endpoints among the following five endpoints from baseline to week 52: glycated hemoglobin (HbA1c), weight, estimated glomerular filtration rate (eGFR), systolic blood pressure, and pulse rate. RESULTS: A total of 623 patients were enrolled in the study and subsequently randomized to either the luseogliflozin or DPP-4i groups. The proportion of patients who showed improvement in ≥ 3 endpoints at week 52 was significantly higher in the luseogliflozin group (58.9%) than in the DPP-4i group (35.0%) (p < 0.001). When stratified by body mass index (BMI) (< 25 or ≥ 25 kg/m2) or age (< 65 or ≥ 65 years), regardless of BMI or age, the proportion of patients who achieved the composite endpoint was significantly higher in the luseogliflozin group than in the DPP-4i group. Hepatic function and high-density lipoprotein-cholesterol were also significantly improved in the luseogliflozin group compared with the DPP-4i group. The frequency of non-serious/serious adverse events did not differ between the groups. CONCLUSION: This study showed the overall efficacy of luseogliflozin compared with DPP-4is over the mid/long term, regardless of BMI or age. The results suggest the importance of assessing multiple aspects regarding the effects of diabetes management. TRIAL REGISTRATION NUMBER: jRCTs031180241.

Impact of the COVID-19 pandemic on exercise tolerance and patient outcomes with Phase III cardiac rehabilitation in Japan: A multicenter study.

This study aimed to determine how behavioural restrictions due to the emergency declaration following the coronavirus disease 2019 (COVID-19) pandemic affect exercise tolerance and its outcomes in patients in Phase III cardiac rehabilitation programme. This is a multicenter retrospective cohort study. Participants in outpatient cardiac rehabilitation programmes and cardiopulmonary exercise testing before and after the emergency declarations were included. A total of 90 participants were included (median age 75.0 years, 69% male), and the changes in physical function and exercise tolerance were compared before and after the emergency declaration. Patients were divided into a decline-in-peak oxygen uptake (VO2 ) group and a nondecline-in-peak VO2 group. Comparison before and after the emergency declaration showed that the anaerobic threshold declined significantly and peak VO2 exhibited a downward trend. The decline-in-peak VO2 group consisted of 16 patients (17%) with better exercise tolerance, multiple comorbidities, and declined lower extremity muscle strength. These patients also had a higher rate of subsequent composite events (hazard ratio, 5.2; 95% confidence interval, 1.4-18.8, p = 0.01). Before and after the emergency declaration, the patient's exercise tolerance may decline, leading to a poor prognosis. This study suggests the importance of maintaining exercise tolerance during the COVID-19 pandemic.

Validity of the Low-Impact Dance for exercise-based cardiac rehabilitation program.

PURPOSE: The aim of this study was to evaluate the oxygen uptake in patients with cardiovascular disease during the low-impact dance program and to compare the findings with the values at peak oxygen uptake (VO2) and aerobic threshold (AT). METHODS: The study included 19 patients with cardiovascular disease [age, 68.3±8.7 years; left-ventricular ejection fraction, 60.3%±8.7%; peak VO2, 6.6±1.1 metabolic equivalents (METs)] who were receiving optimal medical treatment. Their heart rate and VO2 were monitored during cardiopulmonary exercise testing (CPET) and during the low impact dance. The dance involved low-impact dynamic sequences. The patients completed two patterns of low-impact dance, and metabolic gas exchange measurements were obtained using a portable ergospirometry carried in a backpack during the dance sessions. RESULTS: The mean values of VO2 (4.0±0.2 METs and 3.9±0.3 METs) and those of heart rate (105.2±2.9 bpm and 96.8±2.6 bpm) during the dance program were not significantly differ from the AT value (4.5±0.2 METs) obtained in CPET. The median (and interquartile range) RPE reported after the dance exercise trials was 11 (9-13). No signs of overexertion were observed in any of the patients during either dance exercise trial. CONCLUSIONS: The results suggest that it is reasonable to consider the low-impact dance program as an aerobic exercise program in cardiac rehabilitation. Our findings have important implications for exercise training programs in the cardiac rehabilitation setting and for future studies.

Impact of Serum Phosphorus Levels on Outcomes After Implantation of Drug-Eluting Stents in Patients on Hemodialysis.

BACKGROUND: Elevated serum phosphorus level is an important risk factor for cardiovascular death in general patients on hemodialysis (HD). However, the effect of serum phosphorus levels on outcomes after drug-eluting stent (DES) implantation in HD patients is unknown.Methods and Results:This was a post-hoc study of the OUCH study series, a series of prospective multicenter registries of HD patients who underwent DES implantation comprising 359 patients from 31 centers in Japan. Patients were categorized into 3 groups according to their preprocedural serum phosphorus levels. The 1-year clinical outcomes of the 336 patients treated for de novo lesions were evaluated. Compared with patients with high (>5.5 mg/dL; n=65) or normal (3.5-5.5 mg/dL; n=219) serum phosphorus levels, those with low serum phosphorus levels (<3.5 mg/dL; n=52) had significantly fewer target lesion revascularization events (13.9% vs. 16.9% vs. 1.9%; P=0.0090) and major adverse cardiac and cerebrovascular events (29.2% vs. 31.1% vs. 13.5%; P=0.032). Multivariate logistic regression analysis revealed that low serum phosphorus level was an independent negative predictor for major adverse cardiac and cerebrovascular events (adjusted odds ratio, 0.31; 95% confidence interval, 0.12-0.70; P=0.0036). CONCLUSIONS: Lowering of serum phosphorus levels beyond the current recommended range may be considered in HD patients who undergo DES implantation.

Cardiovascular Outcomes in Patients With Previous Myocardial Infarction and Mild Diabetes Mellitus Following Treatment With Pioglitazone: Reports of a Randomised Trial From The Japan Working Group for the Assessment Whether Pioglitazone Protects DM Patients Against Re-Infarction (PPAR Study).

BACKGROUND: Secondary prevention in patients with myocardial infarction (MI) is critically important to prevent ischaemic heart failure and reduce social burden. Pioglitazone improves vascular dysfunction and prevents coronary atherosclerosis, mainly via anti-inflammatory and antiatherogenic effects by enhancing adiponectin production in addition to antihyperglycemic effects, thus suggesting that pioglitazone attenuates cardiovascular events in patients with mild (HbA1c levels < 6·5%) diabetes mellitus (DM). Therefore, we evaluated the effects of pioglitazone on cardiovascular events in patients with both previous MI and mild DM. METHODS: In this multicentre, prospective, randomised, open, blinded-endpoint trial, we randomly assigned 630 patients with mild DM with a history of MI to undergo either DM therapy with (pioglitazone group) or without (control group) pioglitazone. DM was diagnosed using the 75-g oral glucose tolerance test, and mild DM was defined if HbA1c level was < 6·5%. The primary endpoint was the composite of cardiovascular death and hospitalisation caused by acute MI, unstable angina, coronary revascularisation (including percutaneous coronary intervention and cardiac bypass surgery), and stroke. FINDINGS: HbA1C levels were 5·9 and 5·8% (p = 0·71) at baseline and 6·0 and 5·8% (p < 0·01) at 2 years for the control and pioglitazone groups, respectively.The primary endpoint was observed in 14·2% and 14·1% patients in the control and pioglitazone groups during two years (95% confidential interval (CI):0.662-1·526, p = 0·98), respectively; the incidence of MI and cerebral infarction was 0·3% and 2·2% (95%CI: 0·786-32·415, p = 0·09) and 1·0% and 0·3% (95%CI: 0·051-3·662, p = 0·44), respectively. Post-hoc analyses of the 7-year observation period showed that these trends were comparable (21·9% and 19·2% in the control and pioglitazone groups, 95%CI: 0.618-1·237, p = 0·45). INTERPRETATION: Pioglitazone could not reduce the occurrence of cardiovascular events in patients with mild DM and previous MI.

Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?

PURPOSE: We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). METHODS: This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. RESULTS: The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints. CONCLUSION: Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00212017.

[Percutaneous transluminal angioplasty using Filtrap to capture thrombus for chronic total occlusion of superficial femoral artery: a case report].

A 75-year-old female was admitted for cerebral infarction and arteriosclerosis obliterans. Computed tomography with contrast medium revealed occlusion of the superficial femoral artery (SFA). Percutaneous transluminal angioplasty (PTA)was performed for the SFA (length 30 cm), but massive thrombus was seen in the SFA. PTA was continued using a Filtrap deployed at the popliteal artery to prevent distal embolism and the thrombus was captured by the Filtrap. Finally antegrade blood flow was observed. However, the following day, acute stent thrombosis occurred and emergent PTA was performed. Suboptimal stent expansion and dissection were found. Balloon angioplasty was performed using a Filtrap and another stent was deployed. Final angiography revealed good blood flow in the SFA. Filtrap may reduce the risk of distal embolism during PTA for the lower limb.