Renin-angiotensin Inhibitors Research Articles

Prediction of mortality and heart failure admission with the mitraScore after percutaneous mitral valve repair: an external validation study

Abstract Background Prediction of events is critical in decision-making for transcatheter edge-to-edge mitral valve repair (TEER). A new score has been reported for this aim, the MitraScore, that showed adequate performance for predicting death and heart failure rehospitalization in an external validation cohort described in the original publication. Purpose Our aim was to perform an external validation of this prognostic score in an independent sample. Methods The MitraScore assigned 1 point to each independent predictor of mortality found in the validation cohort: age ≥75 years, anemia, glomerular filtrate rate <60 mL/min/1.73 m2, left ventricular ejection fraction <40%, peripheral artery disease, chronic obstructive pulmonary disease, high diuretic dose, and no therapy with renin-angiotensin inhibitors. We calculated the MitraScore in every subject of a prospective cohort of patients treated with TEER in a single institution from November 2011 to January 2024. Association of the score with mortality and the combined end-point of heart failure admission or death was assessed by the Cox proportional hazard method and Kaplan Meier curves. Discrimination was studied by receiver operating characteristics (ROC) curve. Results A total of 191 consecutive patients (median age [p25-75] 74 [64-80] years, 33% female) were included in the study. Our sample differed significantly from the original derivation and validation cohorts in several baseline variables (figure 1). After a median follow up of 24 [9-50] months, 92 patients (48.4%) had 160 admissions for heart failure and 73 patients died (38.2%). MitraScore, as a continuous variable, had a significant association with mortality and the combined end-point in follow-up, either by univariate Cox analysis (HR 1.36 [1.11-1.66] per each score point, p=0.003 for all-cause mortality, and HR 1.35 [1.11-1.65] per each score point, p=0.003 for the combined end-point), and Kaplan Meier analysis (figure 2). Discrimination by ROC analysis was nearly significant for both end-points (C statistics 0.58 [0.50-0.67], p=0.052 for all-cause mortality, and HR 0.58 [0.49-0.66], p=0.068 for the combined end-point). Conclusion The MitraScore, considered as a continuous variable, was significantly associated with mortality and the combined end-point of heart failure admission or death in follow-up in the present external validation study. These data support the use of this prognostic index in risk stratification for patients treated with TEER.

Abstract 4120131: Absence of standard modifiable risk factors (SMuRF-less) among 5002 Middle Eastern patients with atherosclerotic cardiovascular disease: (Interim analysis from the Jo-SMuRF Study)

Introduction: A growing number of patients develop atherosclerotic cardiovascular disease (ASCVD) despite the absence of standard modifiable risk factors i.e. hypertension (HTN), type 2 diabetes (T2D), dyslipidemia (DSL), and cigarette smoking (SMuRF-less). There is scarcity of studies on prevalence and clinical profiles of SMuRF-less patients in the Middle Ease (ME). Aim: To study the prevalence and clinical features of ME patients with ASCVD who are SMuRF-less vs. those with ≥ 1 SMuRFs, presence of other risk factors and utilization of secondary preventive medications in the 2 groups, and one year survival. Methods: Clinical details of adult patients with ASCVD who participated in 5 previous registries were analyzed according to the absence or presence of ≥ 1 SMuRFs. Results: Of the 5002 patients included in the analysis, 676 (13.5%) were SMuRF-less and 4326 (86.5%) had ≥ 1 SMuRFs. Prevalence of the 4 SMuRFs in the whole cohort was 53.5% HTN, 47.8% T2D, 40.2% smoking, and 37.5% DSL, and the SMuRF group was 61.9%, 55.2%, 46.5%, and 43.4%, respectively. Compared with the SMuRFs group, patients in the SMuRFless group were younger (mean age 52±11.4 years vs. 56.3±11.5 years, respectively, p<0.001) and more likely to be women than men (38.6% vs. 27.9%, p<0.0001). Furthermore, SMuRF-less patients had lower mean body mass index, and less prevalence of metabolic syndrome, heart failure, and family history of ASCVD. Utilization of secondary cardiovascular prevention medications was significantly less in the SMuRF -less group than those with SMuRFs; dual antiplatelet therapy (36.4% vs. 69.5%), statins (66.3% vs. 87.4%), B blockers (57.5% vs. 70.5%), and renin-angiotensin inhibitors (35.2% vs. 55.3%, respectively, all p<0.001. Of the subgroup with one year follow up after percutaneous coronary intervention (N=2641), mortality rate was not different in the 2 groups; 1.4% vs. 1.8%, p=0.98. Conclusions: In this first study of SMuRFs in ASCVD patients in the Middle East, SMuRF-less patients account for nearly 14% of the studied cohort. These patients were younger, had less comorbid disease, received less guidelines-recommended prevention medication, and had same one year event rate compared with patients who have SMuRFs.

Synergistic effects of calcium channel blockers and renin-angiotensin inhibitors with gemcitabine-based chemotherapy on the survival of patients with pancreatic cancer

PurposePancreatic cancer remains a significant public health challenge, with poor long-term outcomes due to the lack of effective treatment options. Repurposing commonly used clinical drugs, such as ACE inhibitors, ARBs, CCBs, and metformin, may enhance the efficacy of chemotherapy and offer a promising therapeutic strategy for improving patient outcomes.MethodsA retrospective analysis of concomitant treatment with ACE-Is, ARBs, CCBs, and metformin alongside gemcitabine chemotherapy in patients with pancreatic cancer was conducted. Treatment responses were evaluated, with overall survival (OS) estimated using the Kaplan–Meier method. Additionally, the Cox proportional hazards model was employed to assess the impact of these specific agents on patient survival.Results4628 patients with various stages of pancreatic cancer were identified in the database between 2007 and 2016. The estimated overall survival (OS) in the analyzed group was 6.9 months (95% CI 6.4–7). The use of any of the analyzed drugs was associated with a significant improvement in mOS of 7.5 months (95% CI 6.8–7.8) vs. 6.7 months (95% CI 6.4–7.0) for patients who did not have additional treatment (p < 0.0001). ARBs, ACE-Is, CCBs, and metformin varied in their effectiveness in prolonging mOS among patients. The longest mOS of 8.9 months (95% CI 7.7–11.6) was observed in patients receiving additional therapy with ARBs, while the shortest mOS of 7.7 months (95% CI 6.5–8.9) was achieved by patients receiving metformin. In the adjusted Cox analysis, metformin was associated with a significantly weaker effect on mOS (p = 0.029). A particularly interesting trend in prolonging 5-year survival was demonstrated by ARBs and CCBs with 14.1% (95% CI 9–22%) and 14.8% (95% CI 11.1–19.6%), respectively, compared to patients not taking these drugs, who achieved a 5-year OS of 3.8% (95% CI 3.2–4.4%).ConclusionOur results demonstrate a significant positive impact of ARBs, ACE inhibitors, and CCBs on survival in patients with pancreatic cancer treated with gemcitabine. The addition of these inexpensive and relatively safe drugs in patients with additional comorbidities may represent a potential therapeutic option in this indication. However, prospective clinical trials to evaluate the optimal patient population and further studies to determine the potential impact of these agents on chemotherapy are necessary.

Prevalence of heart failure and trends in its pharmacological treatment between 2000 and 2017 among very old people

PurposeThe aim of this study was to describe a population of very old people with heart failure (HF), to analyse the use of cardiovascular drugs over time, and to explore factors influencing cardiovascular drug treatment for this group.MethodsAll participants with information regarding HF diagnosis were selected from the Umeå 85+/Gerontological Regional Database (GERDA). The people in GERDA are all ≥85 years old. Trained investigators performed structured interviews and assessments. Information regarding medications and diagnoses was obtained from the participants and from medical records. Medical diagnoses were reviewed and confirmed by an experienced geriatrician.ResultsIn this very old population, the prevalence of HF was 29.6% among women and 30.7% among men. Between 2000 and 2017, there was an increase in the use of renin-angiotensin (RAS) inhibitors (odds ratio [OR] 1.107, 95% confidence interval [CI] 1.072–1.144) and beta-blockers (BBs) (OR 1.123, 95% CI 1.086–1.161) among persons with HF, whereas the prevalence of loop diuretics (OR 0.899, 95% CI 0.868–0.931) and digitalis (OR 0.864, 95% CI 0.828–0.901) decreased (p < 0.001 for all drug classes). Higher age was associated with lower use of RAS inhibitors and BBs.ConclusionIn this HF population, the use of evidence-based medications for HF increased over time. This may be a sign of better awareness among prescribers regarding the under-prescribing of guidelines-recommended treatment to old people. Higher age associated with a lower prevalence of RAS inhibitors and BBs. This might indicate that further improvement is possible but could also represent a more cautious prescribing among frail very old individuals.

Contemporary review of IgA nephropathy.

IgA nephropathy (IgAN) is considered the most common primary glomerulonephritis worldwide with a predilection for Asian-Pacific populations and relative rarity in those of African descent. Perhaps 20%-50% of patients progress to kidney failure. The pathogenesis is incompletely understood. Mesangial deposition of immune complexes containing galactose-deficient IgA1 complexed with anti-glycan IgG or IgA antibodies results in mesangial cell activation and proliferation, inflammatory cell recruitment, complement activation, and podocyte damage. Diagnosis requires a biopsy interpreted by the Oxford criteria. Additional pathologic features include podocytopathy, thrombotic microangiopathy, and C4d staining. Biomarkers predicting adverse outcomes include proteinuria, reduced GFR, hypertension, and pathology. Acceptable surrogate endpoints for therapeutic trials include ongoing proteinuria and rate of eGFR decline. The significance of persisting hematuria remains uncertain. The mainstay of therapy is supportive, consisting of lifestyle modifications, renin-angiotensin inhibition (if hypertensive or proteinuric), sodium-glucose-transporter 2 inhibition (if GFR reduced or proteinuric), and endothelin-receptor antagonism (if proteinuric). Immunosuppression should be considered for those at high risk after maximal supportive care. Corticosteroids are controversial with the most positive results observed in Chinese. They carry a high risk of serious side effects. Similarly, mycophenolate may be most effective in Chinese. Other immunosuppressants are of uncertain benefit. Tonsillectomy appears efficacious in Japanese. Active areas of investigation include B-cell inhibition with agents targeting the survival factors BAFF and APRIL and complement inhibition with agents targeting the alternate pathway (Factors B and D), the lectin pathway (MASP-2), and the common pathway (C3 and C5). Hopefully soon, the who and the how of immunosuppression will be clarified, and kidney failure can be forestalled.

Role of renin angiotensin system inhibitors and metformin in Glioblastoma Therapy: a review.

Glioblastoma multiforme (GBM) is a highly aggressive and incurable disease accounting for about 10,000 deaths in the USA each year. Despite the current treatment approach which includes surgery with chemotherapy and radiation therapy, there remains a high prevalence of recurrence. Notable improvements have been observed in persons receiving concurrent antihypertensive drugs such as renin angiotensin inhibitors (RAS) or the antidiabetic drug metformin with standard therapy. Anti-tumoral effects of RAS inhibitors and metformin have been observed in in vitro and in vivo studies. Although clinical trials have shown mixed results, the potential for the use of RAS inhibitors and metformin as adjuvant GBM therapy remains promising. Nevertheless, evidence suggest that these drugs exert multimodal antitumor actions; by particularly targeting several cancer hallmarks. In this review, we highlight the results of clinical studies using multidrug cocktails containing RAS inhibitors and or metformin added to standard therapy for GBM. In addition, we highlight the possible molecular mechanisms by which these repurposed drugs with an excellent safety profile might elicit their anti-tumoral effects. RAS inhibition elicits anti-inflammatory, anti-angiogenic, and immune sensitivity effects in GBM. However, metformin promotes anti-migratory, anti-proliferative and pro-apoptotic effects mainly through the activation of AMP-activated protein kinase. Also, we discussed metformin's potential in targeting both GBM cells as well as GBM associated-stem cells. Finally, we summarize a few drug interactions that may cause an additive or antagonistic effect that may lead to adverse effects and influence treatment outcome.

Dose and Time Effects of Renin-Angiotensin Inhibitors on Patients With Advanced Stages 4 to 5 of Diabetic Kidney Disease.

Limited evidence exists regarding the cumulative dosing and duration impact of renin-angiotensin system inhibitors (RASis) on cardiorenal and mortality outcomes in patients with advanced stages (predominantly in stage 5 and a minority in stage 4) of diabetic kidney disease (DKD). To retrospectively investigate whether there are dose- and time-dependent relationships between RASis and cardiorenal and mortality outcomes in this population. Using Taiwan's national health insurance data in 2000-2017, we analyzed 2196 RASi users and 2196 propensity-matched nonusers among 8738 patients living with diabetes and newly diagnosed with advanced chronic kidney disease (23% stage 4, 77% stage 5). Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CI. RASi use was significantly associated with reduced risks of all-cause mortality (aHR, 0.53; 95% CI 0.47-0.60) and cardiovascular mortality (0.68; 0.56-0.83) with the degree of benefit depending on therapeutic dosage and duration, despite a nonsignificant increase in acute kidney injury risk (1.16; 0.98-1.38) and a significant increase in hyperkalemia risk (1.45; 1.19-1.77). Significant differences in proteinuria risk (1.32; 1.21-1.43) were observed, while there were no significant differences in end-stage renal disease risk (1.01; 0.88-1.15) and no dose- or time-response relationships for either end-stage renal disease or proteinuria risks. Sensitivity analyses confirmed cardiovascular and survival benefits, even in patients with stage 5 DKD. This real-world study suggests that RASi use in advanced stages 4 to 5 DKD may provide dose- and time-dependent cardioprotection and improved survival, without excess renal harms.

THU-386-YI Renin-angiotensin inhibitor intake is associated with improved survival in patients with chronic hepatitis C viral infection following SVR-data from the german hepatitis C-registry (DHC-R)

THU-386-YI Renin-angiotensin inhibitor intake is associated with improved survival in patients with chronic hepatitis C viral infection following SVR-data from the german hepatitis C-registry (DHC-R)

#3104 Adequacy of nephroprotective prescription in an elderly diabetic population in a primary care setting

Abstract Background and Aims The prevalence of chronic kidney disease (CKD) has been increasing and one of the main risk factors is diabetes mellitus (DM). The addition of sodium-glucose cotransporter 2 inhibitors (SGLT2i) to the renin-angiotensin inhibitors (RASi) is recommended in patients with DM and CKD due to the benefits in metabolic control, decrease in proteinuria, and in delaying glomerular filtration decline. Method A retrospective cohort was performed and included a sample of patients with diabetes registered and monitored in a primary care facility. A random sample was selected, calculated for an expected prevalence of 40%, error of 4%, and alpha of 0.05. The primary outcome was to assess the adequacy of nephroprotective prescription. Secondary outcomes were to determine the prevalence of CKD (and associated factors) in the sample, and to assess the percentage of patients with correct CKD diagnosis. Demographic and analytical data of patients (glomerular filtration rates and values of albuminuria) were collected from their electronic health records. Statistical analysis was performed using SPSS v28.0. A p-value &amp;lt; 0.05 was considered statistically significant. The study protocol was approved by the Ethics Committee. Results 338 patients were included, 58% were men, and with a mean age of 71.4 years. 22.2% [95% CI 16.2-29.7%] of patients had the pathology properly coded in the problem list. The prevalence of CKD found was 42.6% [95% CI 37.4-48.0%]. Most patients were in stages G2 (33.3%), G3a (30.6%) and G3b (14.6%). Concerning albuminuria, most were in stage A2 (68.8%). Of the patients with CKD, 77.1% [95% CI 69.6%-83.2%], 60.4% [95% CI 52.3%-68.0%] and 43.1 [95% CI 35.3–51.2%] were medicated with RASi, SGLT2i and both, respectively. Conclusion In this primary setting study, the majority of this elderly population was under nephroprotective therapies (RASi and/or SGLT2i). The relatively low coding suggests underdiagnosis. Further optimization of nephroprotective therapies can be made in order to avoid renal failure, as long as the pathology is properly recognized.

#145 Subgroup and secondary endpoint evaluation of a phase 2 randomized placebo-controlled trial of ravulizumab in IgA nephropathy

Abstract Background and Aims The pathogenesis of IgA nephropathy (IgAN) involves immune complex deposition and activation of the complement system, causing formation of the terminal pathway components C5a and C5b-9, leading to inflammation and glomerular damage. Elevated levels of activated C3 in plasma are associated with proteinuria and renal function decline in patients with IgAN [1]; mesangial C3 deposition is also associated with progression of disease [2]. Ravulizumab is a humanized monoclonal antibody that immediately and completely inhibits complement component C5. Primary endpoint (week 26) data from the phase 2 randomized controlled trial (RCT) (NCT04564339) were previously reported and demonstrated a 30% and 33% treatment effect of ravulizumab compared to placebo on 24-hour urine protein and 24-hour urine protein-to-creatinine ratio (UPCR) reduction, respectively [3]. This analysis reports prespecified subgroup and secondary endpoints as well as post hoc exploration of treatment response by baseline serum C3 and C4 quartiles through week 26. Method The SANCTUARY RCT evaluated ravulizumab (IV; weight-based dosing Q8W) vs placebo in adults with primary IgA nephropathy. Randomized patients (2:1) were stratified by mean proteinuria (1–2 vs &amp;gt;2 g/day). Patients (18–75 years) with biopsy-confirmed IgA nephropathy, proteinuria ≥1g/day, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, and on stable maximally tolerated renin angiotensin inhibition were enrolled. The primary endpoint was proteinuria reduction at week 26 based on 24-hour urine collection. Secondary endpoints at week 26 included the proportion of patients with &amp;gt;50% reduction in proteinuria (absolute urine protein) and the percentage with &amp;lt;1g/day proteinuria. The percentage change in proteinuria (absolute urine protein) among subgroups of sex, race, duration of disease, baseline proteinuria and eGFR, and baseline serum C3 and C4 levels were also evaluated, as were safety data. Results 66 patients entered the 26-week initial evaluation period (n = 43, ravulizumab arm; n = 23, placebo arm); 71.2% were White and 21.2% were Asian. Overall, 41.5% and 18.2% of ravulizumab- and placebo-treated patients, respectively, achieved &amp;gt;50% proteinuria reduction (Fig. 1). Proteinuria reduction to &amp;lt;1g/day was achieved in 26.8% and 18.2% in the ravulizumab and placebo arms, respectively. Subgroup analysis indicated a treatment effect across subgroups of sex, race, disease duration, and baseline proteinuria and eGFR (Fig. 2). With ravulizumab, there were reductions of 41.9% and 41.0% in proteinuria for those with the lowest quartile of baseline serum C3 and C4, respectively. Similarly, reductions of 40.4% and 40.8% were observed in those with baseline serum C3 and C4 levels above the lowest quartile. In the ravulizumab arm, two patients had low serum C3 at baseline and there were no patients with low serum C4 at baseline; there was no change in mean serum C3 and C4 levels over time. Treatment with ravulizumab was well-tolerated. Conclusion In this phase 2 trial of ravulizumab in IgAN, proteinuria was significantly reduced with ravulizumab vs placebo through week 26. A reduction in proteinuria was also observed across subgroups of patients. As is typical in IgAN, serum C3 and C4 levels at baseline were normal, and there was no difference in proteinuria reduction by baseline serum C3 and C4 levels with ravulizumab through 6 months.

Renin-Angiotensin Inhibitor, Captopril, Attenuates Growth of Patient-Derived Colorectal Liver Metastasis Organoids.

The recurrence of colorectal liver metastasis (CRLM) following liver resection is common; approximately 40% of patients will experience tumor recurrence post-surgery. Renin-angiotensin inhibitors (RASis) have been shown to attenuate the growth and progression of CRLM in pre-clinical models following liver resection. This study examined the efficacy of the RASi captopril on patient-derived colorectal liver metastasis organoids. Patient-derived organoids (PDOs) were established using fresh samples of colorectal liver metastasis from appropriately consented patients undergoing liver resection. To mimic the regenerating liver post-CRLM liver resection, PDOs were cultured under hepatocyte regeneration conditions in vitro. CRLM PDOs were established from three patients' parent tissue. CRLM PDOs and parent tissue expressed markers of colorectal cancer, CDX2 and CK20, consistently. Furthermore, CRLM PDOs treated with captopril showed a dose dependent reduction in their expansion in vitro. In conclusion, CRLM PDOs recapitulate in vivo disease and displayed a dose-dependent response to treatment with captopril. RASis may be an additional viable treatment for patients with CRLM.

Pre-operative withdrawal of renin-angiotensin inhibitors: time to re-visit current guidelines.

Pre-operative withdrawal of renin-angiotensin inhibitors: time to re-visit current guidelines.

Role of renal function in patients with advanced heart failure: insights from the help-hf registry

Abstract Background Chronic kidney disease (CKD) and heart failure (HF) strongly interact in determining patients prognosis. However, the prevalence and impact of CKD in advanced HF is still poorly characterized. Objective To determine the prevalence and prognostic impact of CKD and how estimated glomerular filtration rate (eGFR) might limit the use of guideline directed medical therapy in a large cohort of HF patients with at least one high-risk I NEED HELP marker. Methods 1120 patients enrolled in the HELP-HF registry were included in the analysis; eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration formula. Patients were stratified according to eGFR into three categories (&amp;gt; 60 ml/min, 30-60 ml/min, &amp;lt;30 ml/min). The primary endpoint was a composite of all-cause death and HF-hospitalization. Secondary endpoints were all-cause death, HF-hospitalization and cardiovascular death. Results 291 patients (25.98%) had an eGFR&amp;gt;60 ml/min, whereas 497 (44.37%) had eGFR between 30 and 60 ml/min and 332 (29.64%) had &amp;lt;30 ml/min. The risk of the primary endpoint was increased in patients with worse renal function (eGFR 30-60, HR 1.34, 95%CI 1.05-1.71, p = 0.017; eGFR&amp;lt;30, HR 1.88, 95%CI 1.47-2.42, p&amp;lt;0.001), whereas only patients with eGFR&amp;lt;30 ml/min demonstrated higher risk of all-cause death (HR = 2.36, 95%CI 1.68-3.31, p&amp;lt;0.001) and CV death (HR = 3.08, 95%CI 2.00-4.75, p&amp;lt;0.001). No difference in HF hospitalizations was seen with respect to patients with eGFR&amp;gt;60 ml/min. Once analyzed as a continuous variable, eGFR was significantly associated with each outcome. The impact of CKD was also confirmed in patients fulfilling the 2018 ESC-HFA definition of advanced HF. Logistic regression showed that patients with lower eGFR and with HF with reduced (HFrEF) and mildly reduced ejection fraction (HFmrEF) were less frequently discharged on maximal tolerated dose of mineral corticoid receptor antagonists (p= 0.001 for HrEF, p= 0.013 for HFmrEF), while lower eGFR was associated with less frequent use of maximal tolerated dose of a renin-angiotensin inhibitors (including angiotensin receptor-neprilysin inhibitors) only among patients with HFmrEF (p = 0.018). Conclusions Chronic kidney disease is highly prevalent among patients with advanced HF and impacts on patients’ prognosis and survival. The use of GDMT was significantly limited in patients with lower eGFR only in patients with HFrEF and HFmrEF.

Albuminuria and Serum Tumor Necrosis Factor Receptor Levels in Patients with Type2 Diabetes on SGLT2 Inhibitors: A Prospective Study.

Large-scale clinical trials of sodium-glucose cotransporter2 inhibitors (SGLT2i) demonstrate proteinuria-reducing effects in diabetic kidney disease, even after treatment with renin-angiotensin inhibitors. The precise mechanism for this favorable effect remains unclear. This prospective open-label single-arm study investigated factors associated with a reduction in proteinuria after SGLT2i administration. Patients with type2 diabetes (T2DM) who had glycated hemoglobin (HbA1c) levels ≥ 6.5% despite dietary and/or oral hypoglycemic monotherapy were recruited and administered the recommended daily dose of SGLT2i for 4months. Dual primary outcomes were changes in the urine albumin-to-creatinine ratio (uACR) and urine liver-type fatty acid-binding protein (L-FABP)-to-creatinine ratio (uL-FABPCR) at month4 from baseline. Changes in kidney injury, inflammation, and oxidative stress biomarkers were investigated as secondary endpoints to examine the effects of this treatment on the kidney. The correlation between renal outcomes and clinical indicators, including circulating tumor necrosis factor receptors (TNFR) 1 and 2, was evaluated using univariate and multivariate analyses. Participants (n = 123) had a mean age of 64.1years (SD 13.4), with 50.4% being male. The median BMI was 25.8 kg/m2 (interquartile range (IQR) 23.1-28.9), and the median HbA1c level was 7.3% (IQR 6.9-8.3). After SGLT2i administration, the uACR declined from 19.2mg/gCr (IQR 7.1-48.7) to 13.3mg/gCr (IQR 7.5-31.6), whereas the uL-FABPCR was not influenced. In univariate analysis, the change in log-transformed uACR due to SGLT2i administration showed a positive correlation with the change in serum TNFR1 level (R = 0.244, p < 0.01). Multivariate regression analysis, including confounding factors, showed that the changes in serum TNFR1 level were independently associated with the changes in the log-transformed uACR (independent t = 2.102,p < 0.05). After the 4-month SGLT2i administration, decreased albuminuria level was associated with decreased serum TNFR level in patients with T2DM. UMIN000031947.

Effects of renin–angiotensin inhibitors on renal function and the clinical course in patients with decompensated cirrhosis

Patients with decompensated cirrhosis are at risk of developing acute kidney injury (AKI). Studies have suggested that inhibition of the Renin-Angiotensin System (RAS) has certain nephro- and hepatoprotective effects in patients with compensated liver disease. This study aimed to investigate the clinical impact of RAS-Inhibitors in individuals with decompensated liver cirrhosis. Overall, 1181 consecutive hospitalized patients with ascites that underwent paracentesis were considered for this retrospective study. In total, 667 patients with decompensated cirrhosis fulfilled the inclusion criteria and were finally analyzed. RAS-Inhibitor intake was documented in 41 patients (7%). First, 28-day incidences of AKI and grade III AKI of all patients with RAS-Inhibitors were compared to those without intake. Afterwards, propensity score matching was conducted in a 3:1 manner. Here, incidence of further renal endpoints such as need of hemodialysis were analyzed in detail. In the unmatched setting, intake of RAS-Inhibitors was not associated with an increased 28 day-incidence of AKI (P = 0.76) or LTx-free survival (P = 0.60). However, 28 day-incidence of grade III AKI was significantly lower in patients with RAS-Inhibitor intake (P < 0.001). In the matched setting, 28 day-incidence of AKI did not differ (P = 0.81), while grade III AKI was significantly less frequent in the RAS-Inhibitor group (P < 0.001). Need for hemodialysis was also significantly lower in patients with RAS-Inhibitors (P = 0.03) and LTx-free survival was comparable between both groups (P = 0.52). Thus, this study suggests that intake of RAS-Inhibitors is associated with decreased incidences of grade III AKI and need of hemodialysis in patients with decompensated liver disease.

Factores asociados al tratamiento crónico no justificado con digoxina en pacientes con insuficiencia cardiaca aguda y relación con el pronóstico a corto plazo

ObjectivesTo analyze the factors related to inadequate chronic treatment with digoxin and whether the inadequacy of treatment has an impact on short-term outcome. MethodPatients diagnosed with AHF who were in chronic treatment with digoxin were selected. Digoxin treatment was classified as adequate or inadequate. We investigated factors associated to inadequacy and whether such inadequacy was associated with in-hospital and 30-day mortality, prolonged hospital stay (>7 days) and combined adverse event (re-consultation to the ED or hospitalization for AHF or death from any cause) during the 30 days after discharge. ResultsWe analyzed 2366 patients on chronic digoxin treatment (median age=83 years, women=61%), which was considered adequate in 1373 cases (58.0%) and inadequate in 993 (42.0%). The inadequacy was associated with older age, less comorbidity, less treatment with beta-blockers and renin–angiotensin inhibitors, better ventricular function, and worse Barthel index. In-hospital and 30-day mortality was higher in patients with inadequate digoxin treatment (9.9% vs. 7.6%, p=0.05; and 12.6% vs. 9.1%, p<0.001, respectively). No differences were recorded in prolonged stay (35.7% vs. 33.8%) or post-discharge adverse events (32.9% vs. 31.8%). In the model adjusted for baseline and decompensation episode differences, inadequate treatment with digoxin was not significantly associated with any outcome, with an odds ratio of 1.31 (95% CI=0.85-2.03) for in-hospital mortality; 1.29 (0.74-2.25) for 30-day mortality; 1.07 (0.82-1.40) for prolonged stay; and 0.88 (0.65-1.19) for post-discharge adverse event. ConclusionThere is a profile of patients with AHF who inadequately receive digoxin, although this inadequateness for chronic digitalis treatment was not associated with short-term adverse outcomes.

Factors associated with unjustified chronic treatment with digoxin in patients with acute heart failure and relationship with short-term prognosis

ObjectivesTo analyze the factors related to inadequate chronic treatment with digoxin and whether the inadequacy of treatment has an impact on short-term outcome. MethodPatients diagnosed with AHF who were in chronic treatment with digoxin, were selected. Digoxin treatment was classified as adequate or inadequate. We investigated factors associated to inadequacy and whether such inadequacy was associated with in-hospital and 30-day mortality, prolonged hospital stay (>7 days) and combined adverse event (re-consultation to the ED or hospitalization for AHF or death from any cause) during the 30 days after discharge. ResultsWe analyzed 2,366 patients on chronic digoxin treatment (median age = 83 years, women = 61%), which was considered adequate in 1,373 cases (58.0%) and inadequate in 993 (42.0%). The inadequacy was associated with older age, less comorbidity, less treatment with beta-blockers and renin-angiotensin inhibitors, better ventricular function, and worse Barthel index. In-hospital and 30-day mortality was higher in patients with inadequate digoxin treatment (9.9% versus 7.6%, p = 0.05; and 12.6% versus 9.1%, p < 0.001, respectively). No differences were recorded in prolonged stay (35.7% versus 33.8%) or post-discharge adverse events (32.9% versus 31.8%). In the model adjusted for baseline and decompensation episode differences, inadequate treatment with digoxin was not significantly associated with any outcome, with an odds ratio of 1.31 (95%CI = 0.85−2.03) for in-hospital mortality; 1.29 (0.74–2.25) for 30-day mortality; 1.07 (0.82−1.40) for prolonged stay; and 0.88 (0.65−1.19) for post-discharge adverse event. ConclusionThere is a profile of patients with AHF who inadequately receive digoxin, although this inadequateness for chronic digitalis treatment was not associated with short-term adverse outcomes.

Abstract P403: Prevalence And Incidence Of Dyskalemia In Adults With Hypertension Initiating Fixed-dose Combination Treatment Of Telmisartan And Amlodipine In Bangladesh: Findings From The OK Study

Introduction: WHO recommends fixed-dose combination (FDC) pills for treating hypertension. All FDC pills include renin-angiotensin inhibitor (RASi) or diuretics and are considered to require blood tests for checking dyskalemia, a significant barrier for implementation in resource-limited settings. However, the need for blood tests may be overemphasized if dyskalemia is uncommon. Methods: In 2022-2023, a community-based screening program in Dhaka, Bangladesh, recruited adults who were candidates for hypertension treatment (SBP ≥140 and/or DBP &gt; 90 mmHg). We examined the prevalence of dyskalemia, and of those free of prevalent dyskalemia, the incidence of dyskalemia at 2 months of initiating a daily FDC of telmisartan 40mg and amlodipine 5mg. Secondary outcomes were BP change, medication adherence, and symptoms. Results: Of 1,075 participants (mean age 54 yrs, 71% men, mean baseline BP 157/94 mmHg), hypo- (K &lt;3 mmol/L) and hyperkalemia (&gt;5 mmol/L) were present 1.6% each. Of 1,017 patients without hyperkalemia or creatinine clearance &lt;30 who initiated FDC, 866 had the follow-up blood test. The incidence of hypokalemia (K&lt;3) and hyperkalemia (&gt;5.5) was 1.5% and none, respectively (Figure). Mean SBP change was -29.8 mmHg, 92% self-reported taking the medication every day, and 1% self-reported mild symptoms (e.g., leg swelling). There was one death of undetermined cause. Conclusions: In Bangladeshi adults with hypertension, the prevalence of dyskalemia was 3.2%. Of those who initiated FDC of telmisartan and amlodipine, 1.5% developed incident hypokalemia and none developed hyperkalemia. Our study suggests that this FDC can be safely used without follow-up blood test.

Renin-angiotensin inhibitors reduce thrombotic complications in Essential Thrombocythemia and Polycythemia Vera patients with arterial hypertension

Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are chronic myeloproliferative neoplasms (MPNs) characterized by thrombotic and hemorrhagic complications, leading to a high risk of disability and mortality. Although arterial hypertension was found to be the most significant modifiable cardiovascular (CV) risk factor in the general population, little is known about its role in MPNs as well as a possible role of renin-angiotensin system inhibitors (RASi) in comparison with other anti-hypertensive treatments. We investigated a large cohort of 404 MPN adult patients, 133 diagnosed with PV and 271 with ET. Over half of the patients (53.7%) reported hypertension at MPN diagnosis. The 15-year cumulative incidence of thrombotic-adverse events (TAEs) was significantly higher in patients with hypertension (66.8 ± 10.3% vs 38.5 ± 8.4%; HR = 1.83; 95%CI 1.08–3.1). Multivariate analysis showed that PV diagnosis and hypertension were independently associated with a higher risk of developing TAEs (HR = 3.5; 95%CI 1.928–6.451, p < 0.001 and HR = 1.8; 95%CI 0.983–3.550, p = 0.05, respectively). In multivariate analysis, the diagnosis of PV confirmed a significant predictive role in developing TAEs (HR = 4.4; 95%CI 1.92–10.09, p < 0.01), also considering only MPN patients with hypertension. In addition, we found that the use of RASi showed a protective effect from TAEs both in the whole cohort of MPN with hypertension (HR = 0.46; 95%CI 0.21–0.98, p = 0.04) and in the subgroup of thrombotic high-risk score patients (HR = 0.49; 95%CI 0.24–1.01, p = 0.04). In particular, patients with ET and a high risk of thrombosis seem to benefit most from RASi treatment (HR = 0.27; 95%CI 0.07–1.01, p = 0.03). Hypertension in MPN patients represents a significant risk factor for TAEs and should be adequately treated.

DO RENIN-ANGIOTENSIN SYSTEM INHIBITORS HAVE ANY EFFECT ON THE SEVERITY OF COVID-19 IN HYPERTENSIVE SUBJECTS?

Objective: An increase in angiotensin-converting enzyme (ACE) type 2 levels would stimulate the infection by SARS-Cov-2. On the other hand, the inhibition of the effect of angiotensin II could decrease the inflammatory and oxidative response related to the severity of the disease. Our purpose is to assess the effect of renin-angiotensin inhibitors (RASi) on the severity of COVID-19 in a primary care population of hypertensives. Design and method: Multicenter, observational, cross-sectional, retrospective and analytical study. The subjects were enrolled by a random sampling from 10 autonomous regions in Spain, among patients over 18 years-old with treated hypertension and COVID-19 (PCR positive), within the framework of primary health care (119 physicians). Patients were treated 6 months prior data collection (May 2021–February 2022) in the third wave. Multivariate logistic regression analysis adjusted by age, sex, smoking, and obesity was performed to assess the relationship of COVID-19 severity with anti-hypertensive therapy. Results: 1372 patients were enrolled, mean age 67.1±13.6 years, women 50.8%, smoking 12.5%, obesity 43.9%, diabetes 27.5%, controlled arterial hypertension 55.9% (office BP &lt;140 /90). The severity of COVID-19 was: mild-asymptomatic 971 (70.8%), hospital admission 401 (29.2%), ICU admission 74 (5.4%) and death 48 (Fatality rate, 4%). 64.3% of patients were treated with RASi alone or as add-on therapy during COVID-19. Comparing the progression of COVID-19 between those patients who required hospitalisation versus mild-asymptomatic, we found statistically significant differences (Figure 1): RASi vs Diuretics(D)+Calcium channel blockers(CCB)+RASi (OR = 0.36; 95%CI: 0.22-0.57; p&lt;0.001) and D+RASi vs D (OR = 0.49; 95%CI: 0.28-0.93; p&lt;0.05). RASi alone or in combination vs other anti-hypertensives only showed a non-significant trend for fewer hospitalizations (OR = 0.87; 95%CI: 0.68-1.12; p = 0.274). There were no differences between survivors vs non-survivors treated with RASi: 63.2% vs 58.3% (p = 0.496). Conclusions: RASi do not worsen the severity of COVID-19 among hypertensive patients. Regarding its possible protective effect on the progression of the disease, the results are not conclusive, although there could be a trend in this sense, especially when RASi are compared with some antihypertensive combinations.