Hospitalization Rates, Prevalence of Cardiovascular Manifestations, and Outcomes Associated With Sarcoidosis in the United States

Background: Recent trends of hospitalizations and in‐hospital mortality are not well defined in sarcoidosis. We examined aforementioned trends and prevalence of cardiovascular manifestations and explored rates of implantable cardioverter‐defibrillator implantation in hospitalizations with sarcoidosis. Methods and Results: Using data from the National Inpatient Sample, a retrospective population cohort from 2005 to 2014 was studied. To identify sarcoidosis, an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) diagnosis code was used. We excluded hospitalizations with myocardial infarction, coronary artery disease, and ischemic cardiomyopathy. Cardiovascular manifestations were defined by the presence of diagnosis codes for conduction disorders, arrhythmias, heart failure, nonischemic cardiomyopathy, and pulmonary hypertension. A total of 609 051 sarcoidosis hospitalizations were identified, with an age of 55±14 years, 67% women, and 50% black. The number of sarcoidosis hospitalizations increased from 2005 through 2014 (138 versus 175 per 100 000, P trend<0.001). We observed declining trends of unadjusted in‐hospital mortality (6.5 to 4.9 per 100 sarcoidosis hospitalizations, P trend<0.001). Overall ≈31% (n=188 438) of sarcoidosis hospitalizations had coexistent cardiovascular manifestations of one or more type. Heart failure (≈16%) and arrhythmias (≈15%) were the most prevalent cardiovascular manifestations. Rates of implantable cardioverter‐defibrillator placement were ≈7.5 per 1000 sarcoidosis hospitalizations (P trend=0.95) during the study period. Black race was associated with 21% increased risk of in‐hospital mortality (odds ratio, 1.21; 95% confidence interval, 1.16–1.27 [P<0.001]). Conclusions: Sarcoidosis hospitalizations have increased over the past decade with a myriad of coexistent cardiovascular manifestations. Black race is a significant predictor of in‐hospital mortality, which is declining. Further efforts are needed to improve care in view of low implantable cardioverter‐defibrillator rates in sarcoidosis

Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status:A Prespecified Analysis From the DAPA-CKD Trial

OBJECTIVE: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) study demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status. RESEARCH DESIGN AND METHODS: We enrolled participants with CKD, estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2, and urinary albumin-to-creatinine ratio 200-5,000 mg/g. The primary composite end point was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. RESULTS: Of 4,304 participants, 738 had normoglycemia, 660 had prediabetes, and 2,906 had type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (P for interaction = 0.19) in normoglycemia (hazard ratio [HR] 0.62 [95% CI 0.39, 1.01]), prediabetes (HR 0.37 [0.21, 0.66]), and type 2 diabetes (HR 0.64 [0.52, 0.79]). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes. CONCLUSIONS: Dapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Comparison of Relative Waist Circumference between Asian Indian and US Adults

Background. Relative to Europeans, Asian Indians have higher rates of type 2 diabetes and cardiovascular disease. Whether differences in body composition may underlie these population differences remains unclear. Methods. We compared directly measured anthropometric data from the Chennai Urban Rural Epidemiology Study (CURES) survey of southern Indians (I) with those from three US ethnic groups (C: Caucasians, A: African Americans, and M: Mexican Americans) from NHANES III (Third National Health and Nutrition Examination Survey). A total of 15,733 subjects from CURES and 5,975 from NHANES III met inclusion criteria (age 20–39, no known diabetes). Results. Asian Indian men and women had substantially lower body mass index, waist circumference, hip circumference, waist-to-hip ratio, and body surface area relative to US groups (P values <0.0001). In contrast, the mean (±se) waist-weight ratio was significantly higher (P<0.001) in I (men 1.35 ± 0.002 and women 1.45 ± 0.002) than in all the US groups (1.09, 1.21, and 1.14 in A, M, and C men; 1.23, 1.33, and 1.26 in A, M, and C women (se ranged from 0.005 to 0.006)). Conclusions. Compared to the US, the waist-weight ratio is significantly higher in men and women from Chennai, India. These results support the hypothesis that Southeast Asian Indians are particularly predisposed toward central adiposity

Comparison of Relative Waist Circumference between Asian Indian and US Adults

Background. Relative to Europeans, Asian Indians have higher rates of type 2 diabetes and cardiovascular disease. Whether differences in body composition may underlie these population differences remains unclear. Methods. We compared directly measured anthropometric data from the Chennai Urban Rural Epidemiology Study (CURES) survey of southern Indians (I) with those from three US ethnic groups (C: Caucasians, A: African Americans, and M: Mexican Americans) from NHANES III (Third National Health and Nutrition Examination Survey). A total of 15,733 subjects from CURES and 5,975 from NHANES III met inclusion criteria (age 20-39, no known diabetes). Results. Asian Indian men and women had substantially lower body mass index, waist circumference, hip circumference, waist-to-hip ratio, and body surface area relative to US groups ( values &lt;0.0001). In contrast, the mean (±se) waist-weight ratio was significantly higher ( &lt; 0.001) in I (men 1.35 ± 0.002 and women 1.45 ± 0.002) than in all the US groups (1.09, 1.21, and 1.14 in A, M, and C men; 1.23, 1.33, and 1.26 in A, M, and C women (se ranged from 0.005 to 0.006)). Conclusions. Compared to the US, the waist-weight ratio is significantly higher in men and women from Chennai, India. These results support the hypothesis that Southeast Asian Indians are particularly predisposed toward central adiposity

Efficacy and safety of once-weekly semaglutide 2.0 mg versus 1.0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial

Background Semaglutide is an effective treatment for type 2 diabetes; however, 20-30% of patients given semaglutide 1.0 mg do not reach glycaemic treatment goals. We aimed to investigate the efficacy and safety of once-weekly semaglutide 2.0 mg versus 1.0 mg in adults with inadequately controlled type 2 diabetes on a stable dose of metformin with or without a sulfonylurea. Methods We did a 40-week, randomised, active-controlled, parallel-group, double-blind, phase 3B trial (SUSTAIN FORTE) at 125 outpatient clinics in ten countries. Participants (&gt;= 18 years) with inadequately controlled type 2 diabetes (HbA1c 8.0-10.0%) with metformin and with or without sulfonylurea were randomly assigned (1:1) by an interactive web-response system to 2.0 mg or 1.0 mg once-weekly semaglutide. Participants, site personnel, the clinical study group, and investigators were masked to the randomised treatment. Outcomes included change from baseline at week 40 in HbA1c (primary outcome) and bodyweight (secondary confirmatory outcome), evaluated through trial product estimand (no treatment discontinuation or without rescue medication) and treatment policy estimand (regardless of treatment discontinuation or rescue medication) strategies. This study is registered with ClinicalTrials.gov, NCT03989232; EudraCT, 2018-004529-96; and WHO, U1111-1224-5162. Findings Between June 19 and Nov 28, 2019, of 1515 adults assessed for eligibility, 961 participants (mean age 58.0 years [SD 10.0]; 398 [41%] women) were included. Participants were randomly assigned to once-weekly semaglutide 2.0 mg (n=480 [50%]) or 1.0 mg (n=481 [50%]); 462 (96%) patients in the semaglutide 2.0 mg group and 471 (98%) in the semaglutide 1.0 mg group completed the trial. Mean baseline HbA1c was 8.9% (SD 0.6; 73.3 mmol/mol [SD 6.9]) and BMI was 34.6 kg/m2 (SD 7.0). Mean change in HbA1c from baseline at week 40 was -2.2 percentage points with semaglutide 2.0 mg and -1.9 percentage points with semaglutide 1.0 mg (estimated treatment difference [ETD] -0.23 percentage points [95% CI -0.36 to -0.11]; p=0.0003; trial product estimand) and -2.1 percentage points with semaglutide 2.0 mg and -1.9 percentage points with semaglutide 1.0 mg (ETD -0.18 percentage points [-0.31 to -0.04]; p=0.0098; treatment policy estimand). Mean change in bodyweight from baseline at week 40 was -6.9 kg with semaglutide 2.0 mg and -6.0 kg with semaglutide 1.0 mg (ETD -0.93 kg [95% CI -1.68 to -0.18]; p=0.015; trial product estimand) and -6.4 kg with semaglutide 2.0 mg and -5.6 kg with semaglutide 1.0 mg (ETD -0.77 kg [-1.55 to 0.01]; p=0.054; treatment policy estimand). Gastrointestinal disorders were the most commonly reported adverse events (163 [34%] in the 2.0 mg group and 148 [31%] in the 1.0 mg group). Serious adverse events were similar between treatment groups, reported for 21 (4%) participants given semaglutide 2.0 mg and 25 (5%) participants given semaglutide 1.0 mg. Three deaths were reported during the trial (one in the semaglutide 1.0 mg group and two in the semaglutide 2.0 mg group). Interpretation Semaglutide 2.0 mg was superior to 1.0 mg in reducing HbA1c, with additional bodyweight loss and a similar safety profile. This higher dose provides a treatment intensification option for patients with type 2 diabetes treated with semaglutide in need of additional glycaemic control. Copyright (C) 2021 Elsevier Ltd. All rights reserved