The influence of carvedilol posology timing on clinically significant portal hypertension: insights from elastography measurements.

BACKGROUND AND AIMS: Carvedilol has emerged as the preferred ß-blocker for treating portal hypertension. However, there is still a debate in dosing regimen, with a potential lower bioavailability in once-daily regimens. The aim of this study is to assess the acute effects of carvedilol posology in patients with clinically significant portal hypertension (CSPH), as a surrogate marker of bioavailability. METHODS: In this experimental study, 34 patients with CSPH receiving carvedilol twice daily were asked to suppress the night dose of carvedilol, creating a standardized 24-hour dose interval. Spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by transient elastography (TE) were performed, with the exact interval between the last carvedilol administration and TE measurements consistently maintained at 24 hours and compared with values prior and under treatment. RESULTS: Thirty-four patients were included, predominantly male (82.9%). SSM after suspending carvedilol for 24 hours [mean, 73.9kPa (SD, 17.0)] was significantly higher ( P < 0.001) than under treatment [mean, 56.3kPa (SD, 13.2)] and was not significantly different ( P = 0.908) from SSM prior to introduction of carvedilol [mean, 74.5kPa (SD, 12.4)]. Differences were also found in stratified analysis for carvedilol dosage, D'Amico classification stages, MELDNa scores, MELD3.0 scores, Child-Pugh class A and CSPH due to alcoholic cirrhosis. LSM after suspension was not significantly different from both under treatment and prior to treatment. CONCLUSION: The differences in SSM after skipping one dose of carvedilol show both the importance of strict adherence to the prescribed dosing regimen to achieve the expected therapeutic benefits and the impact of twice daily prescription in bioavailability throughout the day.

Premature Mortality in Type 2 Diabetes Mellitus Associated with Heart Failure and Chronic Kidney Disease: 20 Years of Real-World Data.

INTRODUCTION: Type 2 diabetes mellitus (T2D) increases the risk of heart failure (HF) and chronic kidney disease (CKD). Nonetheless, evidence of cardiovascular (CV) prognosis is relatively scarce in young T2D patients. PURPOSE: To estimate the risk of all-cause death, CV death, and non-fatal major CV events (MACEs) in T2D patients younger than 65 years old. METHODS: We designed a retrospective cohort study using incident cases of either T2D, HF, or CKD in the population aged 40-65 years, from 1st January 2000 to 31st December 2019. Each individual was followed for up to one year. The primary analysis consisted of survival analysis with Cox proportional hazards to compare one-year risk of all-cause death, CV death, and MACEs between T2D without HF or CKD (T2D), T2D with HF (T2D-HF), and T2D with CKD (T2D-CKD) groups. RESULTS: A total of 14,986 incident adult diabetic patients from the last two decades in our institution were included with an average age at cohort inclusion of 55-58 years old. Glycemic control was similar among groups. The adjusted hazard ratio (HR) of one-year all-cause death was 2.77 (95% CI: 2.26-3.40) for T2D-HF and 3.09 (2.77-3.45) for T2D-CKD compared with the baseline T2D risk. The highest event rate (T2D-CKD) was 0.15 per person-year. The adjusted HR of one-year CV death was 2.75 (95% CI: 2.19-3.46) for T2D-CKD and 2.59 (1.72-3.91) for T2D-HF. The non-fatal MACE risk was significantly increased in T2D-HF or T2D-CKD compared with T2D (2.82 (CI95%: 2.34-3.41) for T2D-CKD vs. 1.90 (CI95%: 1.66-2.17) for T2D-CKD) with a 32% event rate in non-fatal MACEs. CONCLUSIONS: Coexistence of HF or CKD is associated with increased premature mortality as well as non-fatal CV events in T2D patients under 65 years old.