Use Of Renin-angiotensin-aldosterone System Inhibitors Research Articles

Economic burden of recurrent hyperkalemia in patients with chronic kidney disease.

Hyperkalemia is a common complication of chronic kidney disease (CKD) and can become recurrent in half of cases. However, the incremental economic burden associated with recurrent hyperkalemia is unknown. To evaluate all-cause health care resource utilization (HRU) and medical costs in patients with stage 3/4 CKD with recurrent hyperkalemia vs normokalaemia and vs nonrecurrent hyperkalemia. Data were from Optum's de-identified Market Clarity Data (January 1, 2016, to August 1, 2022). This retrospective observational cohort study compared patients with stage 3/4 CKD with recurrent hyperkalemia (≥2 hyperkalemia events within 1 year [hyperkalemia event: hyperkalemia diagnosis or potassium [K+]>5 mmol/l]; index was the first hyperkalemia event) with an exact- and propensity score-matched cohort of patients with normokalemia (K+ ≥3.5 to ≤5 mmol/l; random K+ as index) and separately with a matched cohort of patients with nonrecurrent hyperkalemia (1 hyperkalemia event within 1 year; index was hyperkalemia event). Patient characteristics, medication use, HRU, and medical costs were compared between cohorts using standardized mean differences during the 12-month baseline period. All-cause HRU and medical costs during the 12-month follow-up were compared using Wilcoxon rank sum tests for continuous variables and McNemar tests for categorical variables. Substudies of recurrent hyperkalemia vs normokalemia were conducted for patients with Medicare coverage and renin-angiotensin-aldosterone system inhibitor (RAASi) use. The recurrent hyperkalemia vs normokalemia sample comprised 4,549 matched pairs (Medicare substudy: 3,151; RAASi substudy: 3,535) and the recurrent hyperkalemia vs nonrecurrent hyperkalemia sample comprised 1,599 matched pairs. Baseline characteristics, HRU, and medical costs of the cohorts were similar after matching. During follow-up, patients with recurrent hyperkalemia had a mean of 11.2 more health care encounters (0.5 more inpatient admissions, 0.3 more emergency department visits, and 7.2 more outpatient visits) than patients with normokalemia. Patients with recurrent hyperkalemia also had double the total annual medical costs vs normokalemia ($34,163 vs $15,175; P < 0.001), mainly driven by inpatient costs ($21,250 vs $7,392), which accounted for 62.2% and 48.7% of total costs, respectively. Results were similar in the RAASi and Medicare substudies. Recurrent hyperkalemia was associated with a mean 4.3 more all-cause health care encounters and $14,057 higher medical costs (both P < 0.001) than nonrecurrent hyperkalemia. Recurrent hyperkalemia in patients with stage 3/4 CKD was associated with higher all-cause HRU and medical costs compared with normokalemia (including in patients with Medicare coverage and RAASi use) and nonrecurrent hyperkalemia. Research is needed to understand if long-term treatment strategies aimed at preventing hyperkalemia recurrence may alleviate this economic burden.

Influence of sodium/glucose cotransporter-2 inhibitors on the incidence of acute kidney injury: a meta-analysis.

Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are associated with cardiovascular benefits. The aim of this systematic review and meta-analysis is to summarize the influence of SGLT2i on the incidence of acute kidney injury (AKI), and to ascertain whether it is affected by confounding variables such as age, baseline renal function and concurrent use of renin-angiotensin-aldosterone system inhibitors (RAASi) or mineralocorticoid receptor antagonists (MRA). PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials comparing the influence of SGLT2i versus placebo/blank treatment on AKI in the adult population. A fixed-effect model was used if the heterogeneity was not significant; otherwise, a randomized-effect model was used. Eighteen studies comprising 98,989 patients were included. Compared with placebo/blank treatment, treatment with SGLT2i significantly reduced the risk of AKI (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.71 to 0.84, p < 0.001; I 2 = 0%). Subgroup analysis suggested consistent results in patients with diabetes, chronic kidney disease, and heart failure (for subgroup difference, p = 0.32). Finally, univariate meta-regression suggested that the influence of SGLT2i on the risk of AKI was not significantly modified by variables such as age (coefficient: 0.011, p = 0.39), baseline estimated glomerular filtration rate (coefficient: -0.0042, p = 0.13) or concomitant use of RAASi (coefficient: 0.0041, p = 0.49) or MRA (coefficient: -0.0020, p = 0.34). SGLT2i may be effective in reducing the risk of AKI, and the effect might not be modified by age, baseline renal function and concurrent use of RAASi or MRA.

#493 CKDG4/5 with K-elevated metabolic acidosis under RAAS inhibitor use show a slow renal decline and preservation of response to alkalizing therapy

Abstract Background and Aims Renin-angiotensin-aldosterone system inhibitors (RAASi) are well-established renoprotective agents, but can induce serum potassium (K) elevation and metabolic acidosis (MA). MA contributes to the progression of chronic kidney disease (CKD), thus the renoprotective potential of RAASi is unknown in advanced CKD with MA due to the use of RAASi. MA with elevated serum K may discourage the use of RAASi. In highly advanced CKD, besides factors such as age, proteinuria, and diabetes, it is still debatable under what conditions the continued use of RAASi is favorable for renal prognosis. Furthermore, no studies have focused on the relationship between the response to alkalizing therapy for MA and renal prognosis in advanced CKD with MA and serum K elevation under RAASi use. Method In this single-center retrospective observational study, CKDG4 or G5 outpatients with MA ([HCO3−] &amp;lt; 22 mM) and elevated K (serum [K]≥5.0 mEq/L) at our center and who had started alkalinizing therapy (i.e., sodium bicarbonate and/or low-dose trichlormethiazide plus fludrocortisone) for MA were included. A total of 45 patients were selected, excluding those who had already been prepared for renal replacement therapy at the start of treatment. The RAASi group (Ri group, N = 39) and the non-RAASi group (non-Ri group, N = 16) were divided by the presence or absence of continued RAASi use prior to alkalizing therapy for MA, and the two groups were followed and compared up to 2 years after treatment. Background factors including age, sex, cause of CKD, estimated glomerular filtration rate (eGFR), CKD stage, diabetes, urinary protein (g/gCr), serum [K]/ [HCO3−]/[Na]/[CL]/albumin/phosphate, hemoglobin levels, and the use of K binders, diuretics were investigated. The endpoints were rapid response to alkalizing therapy (i.e., changes in serum [HCO3−], [K], [Na]-[CL] levels 2 months after the start of alkalinizing therapy, and percentage of patients achieving [HCO3−] ≥22 mM at 2 months after the start of alkalizing therapy) and incidence of renal events (&amp;gt;30% reduction in eGFR or renal replacement therapy). Results In all 45 subjects, the mean age was 71.3±11.8 years, 84% were male, mean eGFR was 18.3 ± 5.6 mL/min/1.73 m2, G4 67%/G5 33%, primary disease was diabetic nephropathy 31%, nephrosclerosis 40%, K binders and diuretics use was 25% and 24%, respectively. Mean serum [HCO3−] was 17.9 ± 2.3 mM and mean serum [K] was 5.5 ± 0.4 mEq/L. Comparison of background factors showed no significant difference between the two groups. The changes in serum [K], [HCO3−], [Na]-[CL] 2 months after the start of alkalinizing therapy and the percentage of patients achieving [HCO3−] ≥22 mM after 2 months of starting alkalizing therapy did not differ at all between the Ri and non-Ri groups (Table 1). Cumulative renal survival (non-renal events) was significantly higher in the Ri group than in the non-Ri group(p = 0.010) (Figure 1). None of the rapid responses to alkalizing therapy (i.e., changes in serum[HCO3−], [K], [Na]-[CL], and the percentage of patients achieving [HCO3−] ≥22 mM) were significantly associated with cumulative renal survival (p = 0.186, p = 0.266, p = 0.65, p = 0.114). In a Cox proportional hazards multivariate model adjusted for age, sex, eGFR, cause of CKD, diabetes, urinary protein(g/gCr), method of alkalizing therapy, and rapid response to alkalizing therapy, the risk of renal events without RAASi use was significantly higher (Table 2). Conclusion In CKDG4/5 with MA with elevated serum K under RAASi use, renal function declines more slowly than with non-RAASi use, ensuring a rapid response to alkalizing therapy for MA.

#1395 Management of CKD patients and HK, as its main complication: degree of adoption of the multi-society consensus on CKD and HK in Spain

Abstract Background and Aims The high incidence, morbidity and mortality of Chronic Kidney Disease (CKD) makes it a public health problem, due to the difficulties in its early detection and management. Hyperkalemia (HK) is a common complication of CKD, also associated with high morbidity and mortality, impacting on the management of patients with CKD and leading sometimes to deoptimization of their treatment. It has been shown that the development of multidisciplinary consensus contributes to improving patient management. With this objective, the multi-society consensus documents –Information and consensus document for the detection and management of chronic kidney disease (2022)- and –Recommendations for the management of hyperkalemia in the emergency department (2022)- have been published. The aim of this study is to analyze the degree of adoption of the recommendations of both consensus in clinical practice in Spain, in order to identify potential areas of improvement in the management of CKD patients with HK. Method This study is based on the perceptions obtained through the discussion on the applicability of the national consensus documents for the management of CKD and HK. To this end, two medical education programs focused on CKD and HK, respectively, were carried out to discuss the applicability of both consensuses. In total, 41 meetings were held (14 from ERC and 27 from HK) from April 2022 to April 2023, involving a total of 542 healthcare professionals (HCPs) (nephrologists and emergency physicians). The main hypothesis was that neither the consensuses are being followed regularly in Spanish clinical practice. All responses were coded numerically, and a national mean was created based on the meeting means. Results The majority of nephrologists who participated in the discussion of the consensus analysis consider that CKD is underdiagnosed (77%), and that the detection of albuminuria is not routinely performed in Primary Care (PC) (72%). Furthermore, half of the nephrologists point out that referrals from PC do not meet the recommended criteria. In relation to treatment, almost 90% of nephrologists would follow the recommendations for the use of RAASi (renin angiotensin aldosterone system inhibitors) and Dapagliflozin very frequently. Regarding HK (a complication of CKD), 42% of HCPs considered that 30-40% of patients with CKD and/or HF suffered a second episode of HK. In relation to its management, only 21% of HCPs considered that the recommendations to maintain treatment with RAASis were followed. Of those who modified it, more than 50% did not consider reintroducing it or considered it little. 33% of HCPs did not show willingness to use the new antihyperkalemia treatments upon discharge. 50% of the participants said they did not have access to them. Regarding follow-up, 54% considered that it should be done by PC specialists. Conclusion The recommendations specified in the CKD and HK management consensuses are being applied less than desired in Spanish clinical practice. Especially highlighting the lack of detection of albuminuria and non-compliance with the referral criteria in patients with CKD, which is consistent with the high underdiagnosis described in Spain. Furthermore, the recommendation of not to modifying the RAASi treatment for the management of HK is not regularly adopted, despite of its impact on the morbidity and mortality of these patients. This information could help to guide future interventions that aim to improve the diagnosis and management of patients with CKD and/or HK.

#356 Low-dose thiazide/fludrocortisone use in advanced CKD can rapidly improve potassium-elevated metabolic acidosis with renal and cardiovascular safety

Abstract Background and Aims Advanced chronic kidney disease (CKD) is often complicated by metabolic acidosis(MA) with elevated serum potassium(K). MA is a risk factor for CKD progression, and elevated serum K forces dietary K restriction, which is also undesirable in CKD, stalling the use and escalation of renin-angiotensin-aldosterone system inhibitors (RAASi). Sodium bicarbonate(SB) and K binders, which are not well tolerated due to gastrointestinal symptoms, are often used to correct MA and hyperkalemia. On the other hand, the concurrent use of thiazide and fludrocortisone to promote urinary excretion of K and hydrogen ions has been reported in the type IV renal tubular acidosis, but its efficacy and safety in advanced CKD is unclear. Method This single-center, retrospective, observational study included CKDG3b-G5 outpatients with MA([HCO3−]&amp;lt;22 mM) and elevated K (serum [K]≥ 5.0 mEq/L) at our center. A total of 59 patients were selected, excluding those who had already been prepared for renal replacement therapy at the start of treatment. Patients who continued to receive trichlormethiazide (1 mg, at 1-3 day intervals) plus fludrocortisone (0.1 mg, at 1-3 day intervals) (low-T/F group, N = 10) or SB(0.5 g-5 g/day) alone (SB group, N = 49) were followed up until 2 years after the start of treatment and the two groups were compared. Background factors including age, sex, cause of CKD, estimated glomerular filtration rate (eGFR), CKD stage, urinary protein(g/gCr),serum [K]/ [HCO3−]/[Na]/[CL]/albumin/phosphate, hemoglobin levels, and the use of RAASi/K binders/diuretics were investigated. Efficacy and safety comparisons between the two groups were evaluated based on changes in serum [HCO3−]and [K] levels before and after starting of treatment (at 2, 6, 12, 18, and 24 months), percentage of patients achieving [HCO3−] ≥22 mM, change in eGFR, incidence of renal events (&amp;gt;30% reduction in eGFR or renal replacement therapy), the incidence of cardiovascular events, and the incidence of treatment-modified events such as initiation or increase of antihypertensive, K-binding, and uric acid-lowering agents. Results In all 59 subjects, the mean age was 72.0±11.7 years, 81% were male, mean eGFR was 19.6 ± 7.2 mL/min/1.73 m2, CKDG4/5 account for 92% (G4 60%/G5 32%), primary disease was diabetic nephropathy 30%, nephrosclerosis 43%, RAASi use 68%, mean [K] was 5.5 ± 0.4 mEq/L and mean [HCO3−] was 18.1 ± 2.2 mM. The low-T/F group consisted of patients who switched due to prior SB intolerance or in whom SB was ineffective, and included 5 patients who received concomitant SB. Comparison of background factors showed no significant difference between the two groups. The changes in the serum [HCO3−] and [K] levels 2 months after starting the treatment were significantly larger in the low-T/F group compared with the SB group ([K]after - [K]before (mEq/L):median −1.2, IQR-1.6 to −0.48 vs −0.57, −0.80 to −0.10, p = 0.036; {[K]after -[K]before}×100/[K]before(%): median −20.3, IQR −26.4 to −9.2 vs −9.3, −14.8 to −1.85, p = 0.032; [HCO3−]after-[HCO3−]before (mM):median +5.2, IQR +3.75 to +8.23 vs +3.2, +1.7 to +5.1, p = 0.022) . The percentage of patients achieving [HCO3−] ≥22 mM at 2 months after treatment was significantly higher in the low-T/F group at 88.9% (SB group 38.8%, p = 0.007). There were no renal events in the low-T/F group, and cumulative renal survival (no renal events) tended to be higher in the low-T/F group than in the SB group in the all conditions such as unadjusted condition, presence of RAASi, CKDG4/5 and matched for age, sex, primary cause of CKD and eGFR (p = 0.06, p = 0.265, p = 0.16, p = 0.14, respectively) (Figure). In patients with no renal events, the low-T/F group had a significantly better mean eGFR change of +4.2% at 6 months (SB group: −11.0%, p = 0.019). There were also no cardiovascular events in the low-T/F group, and there were no significant differences between the two groups in either cardiovascular events or treatment-modified events (Table). Conclusion Even in advanced CKD, the low-dose combination of thiazide and fludrocortisone can rapidly improve K-elevating MA and continue without adverse renal or cardiovascular outcomes.

#1481 Renin-angiotensin-aldosterone system inhibitor (RAASi) optimisation after initiating outpatient SZC therapy: the GALVANIZE RAASi real-world study

Abstract Background and Aims Hyperkalaemia often occurs in patients with comorbidities that are treated with renin-angiotensin-aldosterone system inhibitors (RAASi), e.g., chronic kidney disease (CKD), heart failure or resistant hypertension. However, RAASi use can exacerbate hyperkalaemia. The GALVANIZE RAASi real-world study evaluated RAASi dose optimisation or maximisation following initiation of sodium zirconium cyclosilicate (SZC) therapy in the outpatient setting. Method A large US insurance claims database (from HealthVerity), spanning July 2018–December 2022, was used to identify adults initiating SZC therapy in the outpatient setting, who had an overlapping RAASi prescription fill (≥7 days; index date) and another RAASi prescription fill, within 90 days following the end of the index RAASi episode, during the 6-month follow-up period. Exclusion criteria included patients with a diagnosis of CKD Stage 5 or end-stage kidney disease, treatment with haemodialysis, or the absence of 6 months of continuous insurance coverage prior to, and after, the index date. During a 6-month follow-up period, the proportions of patients with an optimised (≥50% maximum dose; primary endpoint) or maximised (≥100% maximum dose; secondary endpoint) RAASi dose, per label indication, were assessed in the overall population and in sub-studies of patients with a diagnosis of CKD, heart failure, or hypertension (International Classification of Diseases, tenth revision). Diagnosis of hypertension with ≥3 classes of antihypertensive medications (including a diuretic) was defined as resistant hypertension. Multivariable logistic regression was used to identify factors associated with optimised or maximised doses of RAASi. Results Among 2973 eligible patients, mean age was 66.3 years and 41.6% of the population was female. Most patients had Stage 1 to 4 CKD (85.7%), including 46.2% with stage 3 CKD, and 33.0% with stage 4 CKD. Heart failure or resistant hypertension was present in 29.6% and 30.4% of patients, respectively. In the overall population, almost two-thirds of patients (63.7%) optimised their RAASi dose and over a quarter of patients maximised their RAASi dose (27.2%) during follow-up. Factors associated with optimised or maximised doses of RAASi are shown in Figs 1 and 2, respectively. In the sub-studies of patients with CKD (n = 2549), heart failure (n = 879) or resistant hypertension (n = 903), RAASi optimisation was achieved in 63.5%, 63.9% and 72.6% of patients, respectively, and RAASi maximisation was reached in 27.0%, 27.5% and 36.1% of patients, respectively. Conclusion In this real-world study of patients with hyperkalaemia who were receiving RAASi treatment, most individuals who initiated outpatient SZC therapy achieved RAASi dose optimisation overall and across the comorbidity-defined sub-studies evaluated, and more than a quarter of patients achieved dose maximisation within 6 months.

Hyperkalemia in chronic kidney disease patients with and without heart failure: an Italian economic modelling study

BackgroundHyperkalemia (HK) is frequently present in chronic kidney disease (CKD). Risk factors for HK among CKD patients include comorbidities and renin–angiotensin–aldosterone system inhibitor (RAASi) treatment. Current standard of care (SoC) often necessitates RAASi down-titration or discontinuation, resulting in poorer cardiorenal outcomes, hospitalization and mortality. This study evaluates the cost-effectiveness of patiromer for HK in CKD patients with and without heart failure (HF) in an Italian setting.MethodsA lifetime Markov cohort model was developed based on OPAL-HK to assess the health economic impact of patiromer therapy in comparison to SoC after accounting for the effects of HK and RAASi use on clinical events. Outcomes included accumulated clinical events, number needed to treat (NNT) and the incremental cost-effectiveness ratio (ICER). Subgroup analysis was conducted in CKD patients with and without HF.ResultsPatiromer was associated with an incremental discounted cost of €4,660 and 0.194 quality adjusted life years (QALYs), yielding an ICER of €24,004. Per 1000 patients, patiromer treatment prevented 275 moderate/severe HK events, 54 major adverse cardiovascular event, 246 RAASi discontinuation and 213 RAASi up-titration/restart. Subgroup analysis showed patiromer was more effective in preventing clinical events in CKD patients with HF compared to those without; QALY gains were greater in CKD patients without HF versus those with HF (0.267 versus 0.092, respectively). Scenario analysis and sensitivity analysis results support base-case conclusions.ConclusionPatiromer is associated with QALY gains in CKD patients with and without HF compared to SoC in Italy. Patiromer prevented HK events, enabled RAASi therapy maintenance and reduced cardiovascular event risk.

Impact of Angiotensin Blockade on Development of Chronic Lung Allograft Dysfunction.

Background: The renin-angiotensin-aldosterone system (RAAS) is responsible for a multitude of physiological functions, including immunological effects such as promotion of TGF-β and upregulation of IL-6 and IL-8 which are also implicated in the development of chronic lung allograft dysfunction (CLAD). Blockade of the RAAS pathway in pre-clinical models has demonstrated a decrease in these cytokines and pulmonary neutrophil recruitment. Objective: This study sought to evaluate whether use of RAAS inhibitor (RAASi) in lung transplant recipients impacted CLAD-free survival. Methods: In this retrospective, single-center study, 35 lung transplant recipients who received a RAASi post-transplant were compared to 70 lung transplant recipients not exposed to a RAASi and were followed for up to 5years post-transplant. Results: The incidence of CLAD did not differ based on RAASi treatment (34.3% in RAASi vs 38.6%, P-value .668). This was confirmed with a multivariable Cox proportional hazards model with RAASi initiation as a time-varying covariate (RAASi hazard ratio of 1.01, P-value .986). Incidence of hyperkalemia and acute kidney injury were low in the RAASi group. Conclusions: This study demonstrated no association between post-transplant RAASi use and decreased risk of CLAD development. RAASi were also well tolerated in this patient population.

Management of Hyperkalemia in Patients with Chronic Kidney Disease Using Renin Angiotensin Aldosterone System Inhibitors.

Use of renin-angiotensin-aldosterone system (RAAS) inhibiting medications is critical in the prevention of cardiovascular disease and kidney function decline in patients with chronic kidney disease (CKD); however, these agents can lead to hyperkalemia, an electrolyte disorder associated with risk of arrythmia, conduction disorders, and increased overall mortality. Discontinuation, or reduction of dose, of RAAS inhibitor therapy in hyperkalemic patients with CKD can lead to loss of kidney and cardiovascular protection afforded by these medications. Given the high prevalence of hyperkalemia among patients with CKD utilizing RAAS inhibitors, clear management principles are critical to minimize risk and maximize benefit when facing this clinical dilemma. Strategies to mitigate hyperkalemia that do not interfere with optimal RAAS inhibitor therapy should be prioritized when managing potassium elevation in patients with CKD. These strategies include discontinuing non-RAAS inhibitor medications known to cause hyperkalemia, correction of metabolic acidosis, and maximization of medication therapies that lower serum potassium, including diuretics and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Initiation of potassium exchange resins should also be considered to allow for sustained RAAS inhibitor utilization. An approach which employs multiple strategies concurrently is important to mitigate hyperkalemia and maintain long-term use of RAAS-inhibitors. Persistence of RAAS inhibitor use in patients with CKD is important to slow kidney function decline, delay onset of dialysis or the need for kidney transplant, and prevent adverse cardiovascular outcomes. When hyperkalemia develops among patients with CKD utilizing a RAAS inhibitor, a deliberate effort to reduce serum potassium levels using an approach that allows for continuation of maximally dosed RAAS inhibitor therapy is important. Patient education and engagement in the potassium management process is important for sustained success.

Effects of renin-angiotensin-aldosterone-system inhibitors on coronary atherosclerotic plaques: The PARADIGM registry

Background and aimsInhibition of Renin-Angiotensin-Aldosterone-System (RAAS) has been hypothesized to improve endothelial function and reduce plaque inflammation, however, their impact on the progression of coronary atherosclerosis is unclear. We aim to study the effects of RAAS inhibitor on plaque progression and composition assessed by serial coronary CT angiography (CCTA). MethodsWe performed a prospective, multinational study consisting of a registry of patients without history of CAD, who underwent serial CCTAs. Patients using RAAS inhibitors were propensity matched to RAAS inhibitor naïve patients based on clinical and CCTA characteristics at baseline. Atherosclerotic plaques in CCTAs were quantitatively analyzed for percent atheroma volume (PAV) according to plaque composition. Interactions between RAAS inhibitor use and baseline PAV on plaque progression were assessed in the unmatched cohort using a multivariate linear regression model. ResultsOf 1248 patients from the registry, 299 RAAS inhibitor taking patients were matched to 299 RAAS inhibitor naïve patients. Over a mean interval of 3.9 years, there was no significant difference in annual progression of total PAV between RAAS inhibitor naïve vs taking patients (0.75 vs 0.79%/year, p = 0.66). With interaction testing in the unmatched cohort, however, RAAS inhibitor use was significantly associated with lower non-calcified plaque progression (Beta coefficient −0.100, adjusted p = 0.038) with higher levels of baseline PAV. ConclusionsThe use of RAAS inhibitors over a period of nearly 4 years did not significantly impact on total atherosclerotic plaque progression or various plaque components. However, interaction testing to assess the differential effect of RAAS inhibition based on baseline PAV suggested a significant decrease in progression of non-calcified plaque in patients with a higher burden of baseline atherosclerosis, which should be considered hypothesis generating.

Renin-Angiotensin-Aldosterone System Inhibitors Are Associated With Favorable Outcomes Compared to Beta Blockers in Reducing Mortality Following Abdominal Aneurysm Repair.

Background The best medical therapy to control hypertension following abdominal aortic aneurysm repair is yet to be determined. We therefore examined whether treatment with renin-angiotensin-aldosterone system inhibitors (RAASIs) versus beta blockers influenced postoperative and 1-year clinical end points following abdominal aortic aneurysm repair in a Medicare-linked database. Methods and Results All patients with hypertension undergoing endovascular aneurysm repair and open aneurysm repair in the Vascular Quality Initiative Vascular Implant Surveillance and Interventional Outcomes Network database between 2003 and 2018 were included. Patients were divided into 2 groups based on their preoperative and discharge medications, either RAASIs or beta blockers. Our cohort included 8789 patients, of whom 3523 (40.1%) were on RAASIs, and 5266 (59.9%) were on beta blockers. After propensity score matching, there were 3053 matched pairs of patients in each group. After matching, RAASI use was associated with lower risk of postoperative mortality (odds ratio [OR], 0.3 [95% CI, 0.1-0.6]), myocardial infarction (OR, 0.1 [95% CI, 0.03-0.6]), and nonhome discharge (OR, 0.6 [95% CI, 0.5-0.7]). Before propensity score matching, RAASI use was associated with lower 1-year mortality (hazard ratio [HR], 0.4 [95% CI, 0.4-0.5]) and lower risk of aneurysmal rupture (HR, 0.7 [95% CI, 0.5-0.9]). These results persisted after propensity score matching for mortality (HR, 0.4 [95% CI, 0.4-0.5]) and aneurysmal rupture (HR, 0.7 [95% CI, 0.5-0.9]). Conclusions In this large contemporary retrospective cohort study, RAASI use was associated with favorable postoperative outcomes compared with beta blockers. It was also associated with lower mortality and aneurysmal rupture at 1 year of follow-up.

Differences in prevalence and management of chronic kidney disease among T2DM inpatients at the grassroots in Beijing and Taiyuan: a retrospective study

PurposeChronic kidney disease (CKD) has been one of the most common complications in type 2 diabetes mellitus (T2DM) patients. This retrospective study aimed to investigate the regional differences in the prevalence and management of CKD in T2DM inpatients from two grassroots hospitals in Beijing and Taiyuan.MethodsThe sociodemographic status, health history, lifestyle information, biochemical parameters and drug choices of the patients were collected from the Diabetes Care Information System using a retrospective cross-sectional analysis. The presence of CKD was defined as albuminuria (urine albumin-to-creatinine ratio of ≥ 30 mg/g) and/or as a reduced estimated glomerular filtration rate (< 60 ml/min/1.73 m2).Results858 patients with T2DM in Beijing and 1,085 patients with T2DM in Taiyuan were included, with a median age of 61.0 and 61.9 years, respectively. The duration of diabetes was 10.5 and 10.3 years, respectively. The prevalence of CKD in Beijing (39.2%) was significantly higher than in Taiyuan (22.4%). The overall ABC control (A = haemoglobin A1c; B = blood pressure; C = cholesterol) in both the Beijing and Taiyuan groups were not ideal. Patients with CKD tended to use insulin, renin–angiotensin–aldosterone system (RAAS) inhibitors, sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and dyslipidaemia therapy in Taiyuan than in Beijing. The actual proportion of carbohydrate, fat and protein in calories was 49.6%:35.4%:14.4% in Beijing and 61.5%:27.8%:10.8% in Taiyuan.ConclusionsThe higher prescription rates of RAAS inhibitors, SGLT-2i and dyslipidaemia therapy may underlie the fluctuations in the prevalence of CKD in Beijing or Taiyuan. Intensive insulin therapy and personal nutritional guidance, along with the extensive use of RAAS inhibitors, SGLT-2i and dyslipidaemia therapy during follow-up, can all play a positive role in the management of CKD in patients with T2DM in both Beijing and Taiyuan.

Electronic health record based population health management to optimize care in CKD: Design of the Kidney Coordinated HeAlth Management Partnership (K-CHAMP) trial

Primary care physicians (PCPs) provide the majority of medical care to patients with non-dialysis dependent CKD. However, PCPs report numerous limitations to providing expert CKD care, including poor patient education, inadequate diagnostic evaluation, suboptimal use of medications, and time limitations. The Kidney Coordinated HeAlth Management Partnership (Kidney CHAMP) trial is a cluster randomized controlled trial to evaluate the effectiveness of a novel centralized electronic health records (EHR)-delivered population health management (PHM) strategy for high-risk CKD patients on patient care, safety, and other outcomes of interest to patients, providers, and payors. Over a 42-month period, the trial will compare the effectiveness of a multifaceted intervention that combines early identification of high-risk patients, timely nephrology guidance, pharmacist-led medication management services, and CKD patient education to usual care and enroll 1650 high-risk CKD patients from 100 primary care practices. The primary outcome will be ≥40% decline in estimated glomerular filtration rate (eGFR) or end stage kidney disease. Key secondary outcomes will include blood pressure, renin-angiotensin aldosterone system inhibitors use, and exposure to potentially unsafe medications. If successful, our treatment approach could improve CKD care delivery and safety, resource allocation, and adoption of evidence-based CKD guideline-concordant care.

#5507 ANTIHYPERTENSIVE PRESCRIBING PATTERNS IN CKD: FINDINGS FROM THE SALFORD KIDNEY STUDY

Abstract Background and Aims Hypertension is the second leading cause of chronic kidney disease (CKD) following diabetes and occurs in most patients with CKD. Finding an optimal treatment regime for hypertension remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD, and hypertensive CKD patients may require treatment with multiple antihypertensive drugs. Database studies and practice guidelines have continued to demonstrate international variability in antihypertensive treatment practices. We analysed data from the Salford Kidney Study (SKS) database in relation to antihypertensive prescribing patterns amongst study patients. Method The SKS is an ongoing prospective study recruiting patients with CKD since the year 2002. Data including patient demographics, comorbidities, physical parameters, concurrent medications, and biochemical results are collected at baseline (study enrolment). All patients are followed up annually until they reach their endpoints [reaching end-stage kidney disease (ESKD), death, or discharge from follow-up] individually, with updates in their medical records including a list of medications. We have used Cox regression analysis and Kaplan Meier charts to investigate the associations between Renin-Angiotensin-Aldosterone System inhibitor (RAASi) use and the number of antihypertensive agents (binary groups of ≤3 or &amp;gt;3), and clinical outcomes (ESKD and all-cause mortality). Results A total of 3230 patients recruited between October 2002 and December 2019 were included in this analysis. At baseline, the median age of the cohort was 67 years with a predominance of males (62%) and those of white ethnicity (96%). 90% had a history of hypertension and 32% were diabetic. The median blood pressure was 138/75 mmHg. Previous myocardial infarction was recorded in 15%, congestive cardiac failure in 17% and cerebrovascular disease in 7.7% of the patients. The median estimated glomerular filtration rate (eGFR) was 30 ml/min/1.73 m2 and the median urine protein creatinine ratio (uPCR) was 33 mg/mmol. RAASi agents (ACEi &amp; ARB) (56%) were the most common antihypertensive medications to be prescribed, followed by diuretics (50%), calcium channel blockers (45%), and beta blockers (34%). The proportion of patients prescribed RAASi was associated with greater proteinuria (43 vs 33%, p&amp;lt;0.001). CKD patients with preexisting cardiovascular comorbidities were more likely to be prescribed beta blockers (44 vs 27%, p&amp;lt;0.001), diuretics (58 vs 39%, p&amp;lt;0.001) and mineralocorticoid antagonists (6.4 vs 1.85%, p&amp;lt;0.001). An increasing number of CKD patients were being prescribed ARBs over 24-month follow-up (34 vs 28%, p = 0.02). In a multivariable Cox-regression analysis, RAASi intake was not associated with reaching ESKD (HR 0.91; p = 0.49) but was associated with a significant survival benefit (HR 0.84; p = 0.001) (Figure 1). Use of a higher number of antihypertensive agents (i.e. &amp;gt;3) was associated with both greater mortality (HR 1.28; p = 0.02) and worse dialysis-free survival (HR 1.46; p = 0.007) (Figure 2). Conclusion Antihypertensive prescribing patterns in the SKS were consistent with current guidelines in the U.K. (e.g. NICE guidance 2022), with RAASi being predominantly prescribed as the first-line antihypertensive agent. An overall survival benefit was noted with RAASi use, although there was no signal for reducing progression towards ESRD. Outcomes were poor in patients with resistant hypertension needing multiple antihypertensive agents. Considering existing variations between the U.K. and other international guidelines regarding antihypertensive treatment in CKD, continued research is indicated to bridge the gaps between these recommendations and optimise patient outcomes.

The impact of renin-angiotensin-aldosterone system inhibitors on immune checkpoint inhibitor-associated adverse cardiovascular events.

2605 Background: Immune checkpoint inhibitors (ICIs) are associated with adverse cardiovascular events that impair patient outcomes. Previous observational studies showed that renin-angiotensin-aldosterone system inhibitors (RAASi) may mitigate the cardiotoxicity associated with chemotherapeutic agents. However, the effects of RAASi on ICI-associated adverse cardiovascular events are unknown. Methods: We conducted a 1:1 propensity score-matched cohort study involving ICI-treated patients at two tertiary referral centers in Taiwan. The propensity score matching model includes age, sex, hypertension, diabetes mellitus, chronic kidney disease, Eastern Cooperative Oncology Group (ECOG) Performance Scale, cancer stage, and cancer type. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of myocardial infarction (MI), ischemic stroke, peripheral arterial occlusive disease (PAOD), pulmonary embolism (PE), deep venous thrombosis (DVT), heart failure, pericardial disease, myocarditis, and cardiac arrhythmias. The secondary outcomes were arterial thrombotic events (MI, ischemic stroke, PAOD) and venous thrombotic events (PE and DVT). Results: We identified 684 patients eligible for inclusion, from which 164 patients who received RAASi were matched to patients who did not receive RAASi. Over a median follow-up of 9.1 months, the incidence rate of MACE for RAASi and non-RAASi recipients was 6.5 and 13.9 per 100 patient-years, respectively, resulting in an incidence rate ratio of 0.47 [95% CI: 0.21–1.00] (p = 0.038). In a multivariate Cox proportional hazard model adjusting for cancer therapy, RAASi recipients had an approximately 60% reduction in the risk for MACE (HR, 0.37 [95% CI: 0.16-0.86], p = 0.021). In the secondary analysis, RAASi were associated with a reduction in venous thrombotic events (HR, 0.11 [95% CI: 0.02-0.63], p = 0.013), but not for arterial thrombotic events (HR, 0.47 [95% CI: 0.06-3.38], p = 0.45). Conclusions: In patients receiving ICI therapy, the use of RAASi is associated with a decreased cardiovascular risk, particularly for venous thrombotic events. [Table: see text]

Renin-angiotensin System Antagonists and Beta-blockers in Prevention of Anthracycline Cardiotoxicity: a Systematic Review and Meta-analysis.

The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is controversial. We performed a meta-analysis to assess the effectiveness of these drugs in preventing cardiotoxicity. The meta-analysis included prospective, randomized studies in adults receiving anthracycline chemotherapy and compared the use of RAAS inhibitors or beta-blockers versus placebo with a follow-up of 6 to 18 months. The primary outcome was change in left ventricular ejection fraction (LVEF) during chemotherapy. Secondary outcomes were the incidence of heart failure, all-cause mortality, and changes in end-diastolic measurement. Heterogeneity was assessed by stratification and meta-regression. A significance level of p < 0.05 was adopted. The search resulted in 17 studies, totaling 1,530 patients. The variation (delta) in LVEF was evaluated in 14 studies. Neurohormonal therapy was associated with a lower delta in pre- versus post-therapy LVEF (weighted mean difference 4.42 [95% confidence interval 2.3 to 6.6]) and higher final LVEF (p < 0.001). Treatment resulted in a lower incidence of heart failure (risk ratio 0.45 [95% confidence interval 0.3 to 0.7]). There was no effect on mortality (p = 0.3). For analysis of LVEF, substantial heterogeneity was documented, which was not explained by the variables explored in the study. The use of RAAS inhibitors and beta-blockers to prevent anthracycline-induced cardiotoxicity was associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. (CRD PROSPERO 42019133615).

Effect of renin-angiotensin-aldosterone system inhibitors on survival outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

Effect of renin-angiotensin-aldosterone system inhibitors (RAASIs) in combination with immune checkpoint inhibitors (ICIs) on prognoses in cancer patients remains controversial. This study systematically evaluated the effect of RAASIs on survival outcomes in cancer patients receiving ICIs treatment and provided an evidence-based reference for the rational use of RAASIs and ICIs combination therapy in clinical practice. Studies evaluating the prognosis of RAASIs-used versus RAASIs-free in cancer patients receiving ICIs treatment from inception to 1 November 2022 were retrieved by searching PubMed, Cochrane Library, Web of Science, Embase, and major conference proceedings. Studies in English reporting hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS) were included. Statistical analyses were conducted using the software Stata 17.0. A total of 12 studies containing 11739 patients were included, comprising ~4861 patients in the RAASIs-used and ICIs-treated group and ~6878 patients in RAASIs-free and ICIs-treated group. The pooled HR was 0.85 (95%CI, 0.75-0.96; P = 0.009) for OS and 0.91 (95%CI, 0.76-1.09; P = 0.296) for PFS, indicating a positive effect of RAASIs concomitant with ICIs on cancer patients. This effect was observed especially in patients with urothelial carcinoma (HR, 0.53; 95%CI, 0.31-0.89; P = 0.018) and renal cell carcinoma (HR, 0.56; 95%CI, 0.37-0.84; P = 0.005) on OS. Concomitant use of RAASIs and ICIs enhanced the efficacy of ICIs and this combination regimen was associated with significantly improved OS and a trend towards better PFS. RAASIs can be considered as adjuvant drugs when hypertensive patients receive ICIs treatment. Our results provide an evidence-based reference for the rational use of the RAASIs and ICIs combination therapy to improve the efficacy of ICIs in clinical practice. https://www.crd.york.ac.uk/prospero/, identifier CRD42022372636; https://inplasy.com/, identifier INPLASY2022110136.

Renin-Angiotensin-Aldosterone System Inhibitors and Development of Gynecologic Cancers: A 23 Million Individual Population-Based Study.

The chronic receipt of renin-angiotensin-aldosterone system (RAAS) inhibitors including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been assumed to be associated with a significant decrease in overall gynecologic cancer risks. This study aimed to investigate the associations of long-term RAAS inhibitors use with gynecologic cancer risks. A large population-based case-control study was conducted from claim databases of Taiwan's Health and Welfare Data Science Center (2000-2016) and linked with Taiwan Cancer Registry (1979-2016). Each eligible case was matched with four controls using propensity matching score method for age, sex, month, and year of diagnosis. We applied conditional logistic regression with 95% confidence intervals to identify the associations of RAAS inhibitors use with gynecologic cancer risks. The statistical significance threshold was p < 0.05. A total of 97,736 gynecologic cancer cases were identified and matched with 390,944 controls. The adjusted odds ratio for RAAS inhibitors use and overall gynecologic cancer was 0.87 (95% CI: 0.85-0.89). Cervical cancer risk was found to be significantly decreased in the groups aged 20-39 years (aOR: 0.70, 95% CI: 0.58-0.85), 40-64 years (aOR: 0.77, 95% CI: 0.74-0.81), ≥65 years (aOR: 0.87, 95% CI: 0.83-0.91), and overall (aOR: 0.81, 95% CI: 0.79-0.84). Ovarian cancer risk was significantly lower in the groups aged 40-64 years (aOR: 0.76, 95% CI: 0.69-0.82), ≥65 years (aOR: 0.83, 95% CI: 0.75-092), and overall (aOR: 0.79, 95% CI: 0.74-0.84). However, a significantly increased endometrial cancer risk was observed in users aged 20-39 years (aOR: 2.54, 95% CI: 1.79-3.61), 40-64 years (aOR: 1.08, 95% CI: 1.02-1.14), and overall (aOR: 1.06, 95% CI: 1.01-1.11). There were significantly reduced risks of gynecologic cancers with ACEIs users in the groups aged 40-64 years (aOR: 0.88, 95% CI: 0.84-0.91), ≥65 years (aOR: 0.87, 95% CI: 0.83-0.90), and overall (aOR: 0.88, 95% CI: 0.85-0.80), and ARBs users aged 40-64 years (aOR: 0.91, 95% CI: 0.86-0.95). Our case-control study demonstrated that RAAS inhibitors use was associated with a significant decrease in overall gynecologic cancer risks. RAAS inhibitors exposure had lower associations with cervical and ovarian cancer risks, and increased endometrial cancer risk. ACEIs/ARBs use was found to have a preventive effect against gynecologic cancers. Future clinical research is needed to establish causality.

RAAS inhibitors are associated with a better chance of surviving of inpatients with Covid-19 without a diagnosis of diabetes mellitus, compared with similar patients who did not require antihypertensive therapy or were treated with other antihypertensives.

The effect of renin-angiotensin-aldosterone system (RAAS) inhibitors in combination with COVID-19 and diabetes mellitus (DM) remains unknown. We assessed the risk of death in COVID-19 inpatients based on the presence or absence of DM, arterial hypertension (AH) and the use of RAAS inhibitors or other antihypertensives. The results of treatment of all adult PCR-confirmed COVID-19 inpatients (n = 1097, women 63.9%) from 02/12/2020 to 07/01/2022 are presented. The presence of DM at the time of admission and the category of antihypertensive drugs during hospital stay were noted. Leaving the hospital due to recovery or death was considered as a treatment outcome. Multivariable logistic regression analysis was used to assess the risk of death. Patients with COVID-19 without AH were considered the reference group. DM was known in 150 of 1,097 patients with COVID-19 (13.7%). Mortality among DM inpatients was higher: 20.0% vs. 12.4% respectively (p=0.014). Male gender, age, fasting plasma glucose (FPG) and antihypertensives were independently associated with the risk of dying in patients without DM. In DM group such independent association was confirmed for FPG and treatment of AH. We found a reduction in the risk of death for COVID-19 inpatients without DM, who received RAAS inhibitors compared with the corresponding risk of normotensive inpatients, who did not receive antihypertensives: OR 0.22 (95% CI 0.07-0.72) adjusted for age, gender and FPG. This result raises a question about the study of RAAS inhibitors effect in patients with Covid-19 without AH.

Clinical impact of suboptimal RAASi therapy following an episode of hyperkalemia

BackgroundHyperkalemia (HK) is a barrier to optimization of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy in heart failure (HF) and chronic kidney disease (CKD). We investigated cardiorenal risk associated with changes in RAASi regimen after an episode of HK in patients with HF and/or CKD.MethodsThis observational study utilized data from hospital records, claims, and health registers from the US (Optum’s de-identified Market Clarity Data) and Japan (Medical Data Vision). Included patients had an index episode of HK between July 2019 and September 2021 (US), or May 2020 and September 2021 (Japan), with prior diagnosis of HF or CKD (stage 3 or 4), and RAASi use. Risk of a cardiorenal composite outcome (HF emergency visit, HF hospitalization, or progression to end-stage kidney disease) was determined in patients who discontinued RAASi, down-titrated their dose by > 25%, or maintained or up-titrated their dose following the HK episode.ResultsA total of 15,488 and 6020 patients were included from the US and Japan, respectively. Prior to the episode of HK, 59% (US) and 27% (Japan) of patients had achieved > 50% target RAASi dose. Following the episode of HK, 33% (US) and 32% (Japan) of patients did not fill a new RAASi prescription. Risk of the cardiorenal outcome at 6 months was higher in patients who discontinued or down-titrated versus maintained or up-titrated RAASi treatment both in the US (17.5, 18.3, and 10.6%; p < 0.001) and in Japan (19.7, 20.0, and 15.1%; p < 0.001).ConclusionHK-related RAASi discontinuation or down-titration was associated with higher risk of cardiorenal events versus maintained or up-titrated RAASi.