Renin-angiotensin System Inhibitors Group Research Articles

Impact on clinical outcomes of renin-angiotensin system inhibitors against doxorubicin-related toxicity in patients with breast cancer and hypertension: A nationwide cohort study in South Korea.

Although doxorubicin (DOX) is a commonly used potent chemotherapeutic agent in patients with breast cancer, its cardiotoxic effect is a concern, particularly in patients with hypertension. Antihypertensive renin-angiotensin system (RAS) inhibitors may potentially play a role in preventing overt heart failure (HF) due to DOX toxicity. This study aimed to evaluate whether the use of RAS inhibitors improves clinical outcomes in patients with hypertension and breast cancer undergoing DOX-containing chemotherapy. A total of 54,344 female patients who were first diagnosed with breast cancer and initiated into DOX therapy between 2008 and 2015 were recruited from a nationwide Korean cohort. Patients were divided into two groups: with and without hypertension (HT, n = 10,789; non-HT, n = 43,555), and the RAS inhibitor group (n = 1,728) was sub-classified from the HT group. Two propensity score-matched cohorts were constructed to compare the clinical outcomes between non-HT and HT groups and between non-HT and RAS inhibitor groups. The primary outcome was the composite of HF and death. After propensity score matching, the HT group had a higher risk for HF (adjusted hazard ratio [HR] = 1.30, 95% confidence intervals [95% CI] = 1.09-1.55) compared to the non-HT group, but there was no significant difference in primary outcome between the two groups. The RAS inhibitor group had a lower risk for primary outcome (adjusted HR = 0.78, 95% CI = 0.65-0.94) and death (adjusted HR = 0.81, 95% CI = 0.66-0.99) compared to the non-HT group. Hypertension is a risk factor for HF in patients with breast cancer undergoing DOX chemotherapy. However, the RAS inhibitors used to treat hypertension may contribute to decreased mortality and improved clinical outcomes.

Long-Term Impact of Renin-Angiotensin System Inhibitors for Secondary Prevention in Patients with Chronic Kidney Disease Who Underwent Percutaneous Coronary Intervention

Introduction: The long-term impact of renin-angiotensin system (RAS) inhibitors for secondary prevention in patients with chronic kidney disease (CKD) and coexisting coronary artery disease remains unclear. Methods: Altogether, 1,160 consecutive patients with CKD (mean age, 70 ± 9 years; 78% men) who underwent their first percutaneous coronary intervention (PCI) between 2000 and 2018 were included and analyzed. Based on their RAS inhibitor use, 674 patients (58%) were allocated to the RAS inhibitor group, and 486 patients (42%) were allocated to the non-RAS inhibitor group. This study evaluated the incidence of 3-point major adverse cardiovascular events (3P-MACE), including cardiovascular death, nonfatal acute coronary syndrome and nonfatal stroke, admission for heart failure (HF), target vessel revascularization (TVR), and all-cause death. Results: During a median follow-up duration of 7.8 years, 280 patients (24.1%) developed 3P-MACE, 134 patients (11.6%) were hospitalized for HF, 171 patients (14.7%) underwent TVR, and 348 patients (30.0%) died of any causes. The cumulative incidence rate of 3P-MACE in the RAS inhibitor group was significantly lower than in the non-RAS inhibitor group (31.7% vs. 39.0%, log-rank test, p = 0.034); however, that of admission for HF in the RAS inhibitor group was significantly higher than in the non-RAS inhibitor group (28.1% vs. 13.3%, log-rank test, p < 0.001). The subgroup of preserved ejection fraction, non-acute myocardial infarction, and non-proteinuria tended to promote the onset of HF rather than cardiovascular prevention by RAS inhibitors. Conclusion: The long-term RAS inhibitor use for patients with CKD after PCI might prevent cardiovascular events but increase the risk of HF.

Decreased risk of radiation pneumonitis with concurrent use of renin-angiotensin system inhibitors in thoracic radiation therapy of lung cancer.

Radiation pneumonitis (RP) is the primary dose-limiting toxicity associated with radiotherapy. This study aimed to observe the effects of renin-angiotensin system inhibitors in Chinese patients with lung cancer who received thoracic radiation. Patients with lung cancer who received thoracic radiation at a total dose of ≥45 Gray between October 2017 and December 2022 were enrolled in this study. We retrospectively evaluated the factors influencing grade 2 or higher RP. A total of 320 patients were enrolled in this study; 62 patients were identified as angiotensin receptor blockers or angiotensin-converting enzyme inhibitor users. Additionally, 99 patients (30.9%) had grade 2 or higher RP, and the incidence in the renin-angiotensin system inhibitor group was 17.7% (11 out of 62 patients). Patients in the renin-angiotensin system inhibitors (RASi) group were older and had a higher percentage of males, lower percentage of ECOG score 0, higher percentage of hypertension, and higher percentage of adenocarcinoma than those in the non-RASi group. ECOG score [hazard ratio (HR) = 1.69, p = 0.009], history of smoking (HR = 1.76, p = 0.049), mean dose (HR = 3.63, p = 0.01), and RASi (HR = 0.3, p = 0.003) were independent predictive factors for RP. All subgroups benefited from RASi. This study showed that oral RASi administration has the potential to mitigate the incidence of grade 2 or higher RP in patients with lung cancer undergoing thoracic radiotherapy. To validate and further substantiate these findings, additional prospective research is warranted.

425-P: Renin-Angiotensin System Inhibition in Combination with Glucagon-Like Peptide 1 Receptor Agonist Treatment Improve Levels of a Kidney Fibrosis Biomarker in Persons with Type 2 Diabetes

Background: The drug combinations for rewriting trajectories of renal pathologies in type 2 diabetes (DC-ren) study focuses on DKD, a complication of diabetes often accompanied by cardiovascular disease. Novel biomarkers for identifying persons at increased risk of disease progression and predicting treatment response are currently needed. Levels of urinary C3M, a marker of type III collagen degradation, have been shown to correlate with CKD progression, and dulaglutide treatment improved levels of this biomarker compared with insulin glargine in persons with type 2 diabetes (T2D). We investigated the effect of combination therapy on urinary C3M in persons with T2D. Method: We measured urinary C3M in urine collected at baseline and after years 1, 2, and 3 from 229 individuals with T2D enrolled in the DC-ren study. All persons were on renin-angiotensin system inhibitor (RASi) treatment at baseline and during follow-up. While some persons remained on RASi treatment (n = 184), others received glucagon-like peptide-1 receptor agonist (GLP-1 RA) on top of RASi (n = 45). Results: The cohort consisted of 48% males (age of 66 ± 8 years and eGFR was 65 ± 17 ml/min/1.73 m2). Lower baseline levels of urinary C3M were associated with lower eGFR, and this relation remained consistent over time. Levels of urinary C3M were higher in persons after treatment with GLP-1 RA in combination with RASi compared to RASi alone (P = 0.034). In adjusted linear models (for the RASi group), an association of current urinary C3M with future eGFR was found (P &amp;lt; 0.01), indicating that urinary C3M is a prognostic risk marker for kidney function decline. Conclusion: RASi in combination with GLP-1 RA treatment was associated with increased type III collagen degradation, suggesting a potential effect to reduce kidney fibrosis. This anti-fibrotic effect could be a mechanism for the beneficial effects observed with GLP-1 RA treatment on CKD in T2D. Disclosure A.Møller: None. S.Thöni: None. C.F.G.Laursen: None. M.A.Karsdal: Speaker's Bureau; Pfizer Inc. F.Genovese: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. D.Rasmussen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S.

Abstract 6755: The impact of renin-angiotensin system inhibitors on survival outcomes of pancreatic adenocarcinoma patients

Abstract Introduction Pancreatic adenocarcinoma (PDAC) is a highly aggressive malignancy with significant morbidity and mortality. RAS (renin-angiotensin system) inhibitors have been used for hypertension, and the potential role of using RAS inhibitors in pancreatic adenocarcinoma have been investigated in pre-clinical models by enhancing drug delivery and reducing hypoxia. However, the clinical benefit of RAS inhibitors in pancreatic cancer patients was still unclear. Methods We retrospectively investigated the impact of RAS inhibitors on survival outcomes of pancreatic adenocarcinoma patients in Taichung Veterans General Hospital between January 2014 and July 2021. Patients with histologically proven pancreatic adenocarcinoma were included in the study. Clinical feature with drugs exposure and survival outcome were analyzed. Results A total of 384 pancreatic cancer patients were analyzed. Among them, 70 patients had concurrent use of RAS inhibitors and 314 patients had no concurrent medication use. Among patients with RAS inhibitors use, the diagnosed age was significantly older (70.0 vs. 68.0, p = 0.023), and a higher proportion of hypertension (100.0% vs. 51.0%, p &amp;lt; 0.0001), chronic kidney disease (27.5% vs. 9.1%, p &amp;lt; 0.0001), and diabetes (64.3% vs 39.5%, p &amp;lt; 0.0001) than those without RAS inhibitors use. The 12-month progression-free survival were 22.9% and 13.7% in the RAS inhibitors and control group (p = 0.008), respectively. The Overall survival was not significantly different in the both groups (p = 0.356). In the multivariate analysis, the use of RAS inhibitors had a significantly better progression-free survival outcome (Hazard ratio = 0.025, CI:0.52-0.96). The advanced disease status, poor ECOG performance status and the elevated level of CA19-9 were correlated with poor progression-free survival. Conclusion In our study, although higher percentage of existed comorbidities in the RAS inhibitor group, we demonstrated that the use of RAS inhibitors among pancreatic cancer patients might provide a better progression-free survival outcome. Further prospective study and investigation are warranted. Citation Format: Kuan-Yu Tseng, Cheng-Wei Chou. The impact of renin-angiotensin system inhibitors on survival outcomes of pancreatic adenocarcinoma patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6755.

S-28-2: EFFECT OF ESAXERENONE ON NOCTURNAL BLOOD PRESSURE COMBINED WITH RENIN-ANGIOTENSIN SYSTEM INHIBITOR OR CALCIUM CHANNEL BLOCKER IN UNCONTROLLED HYPERTENSION

Objective: To evaluate the nighttime blood pressure(BP)-lowering effects of esaxerenone with different concomitant antihypertensive treatments, we conducted a post hoc analysis of a multicenter, open-label, long-term phase 3 study (NCT02722265) of esaxerenone, a highly selective mineralocorticoid receptor blocker, alone or in combination with a calcium channel blocker (CCB) or a renin-angiotensin system (RAS) inhibitor in patients with essential hypertension. Design and method: Patients had previously untreated essential hypertension, or had received only one RAS inhibitor or CCB as a baseline antihypertensive agent at the start of the study. All patients had a sitting systolic BP of 140 to &lt; 180 mmHg and a sitting diastolic BP of 90 to &lt; 110 mmHg, a 24-h ambulatory BP of ≧130/80 mmHg. In this post hoc analysis, patients were classified into 3 treatment groups; esaxerenone monotherapy, combination with a CCB and combination with RAS inhibitor and targeted on the patient without any additional antihypertensive treatment at Week 28. For these 3 groups, mean changes in 24-hour, early morning, daytime, and nighttime systolic BP in 24-h ambulatory BP, mean changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and changes in dipping pattern (extreme dippers, dippers, non-dippers, risers) were evaluated at 28 Week to include as many patients as possible available for analysis. Results: Of the total 368 patients in the study, 248 patients were included in this analysis and there were 153 in esaxerenone monotherapy, 48 in combination with a CCB and 48 in combination with a RAS inhibitor. Nighttime systolic BP statistically significantly decreased in all groups at Week 28 compared to baseline, with combination with a RAS inhibitor group showing the greatest change (-20.6 mmHg). Those changes were numerically greater than the daytime systolic blood pressure in all groups. The decrease in NT-proBNP from baseline to Week 28 was statistically significant in all group (p &lt; 0.001, respectively) and the decrease in combination with RAS inhibitor was numerically greater than that of monotherapy. A statistically significant shift in dipping pattern and changes from riser/non-dipper to dipper/extreme dipper pattern were found at Week 28 in Monotherapy (p &lt; 0.05) and the same trend of shifting was shown in combination with RAS inhibitor (p = 0.1615). The prevalence of riser/non-dipper pattern was decreased from 58.2% to 47.7% in monotherapy and from 54.2% to 39.6% in combination with RAS inhibitor. Conclusions: Esaxerenone would provide a useful treatment option for nocturnal hypertension, especially in combination with RAS inhibitor, in uncontrolled hypertension.

Adherence and persistence to pharmacotherapy in patients with heart failure: a nationwide cohort study, 2014-2020.

We aimed to study initiation, adherence, and long-term persistence to beta-blockers (BB), renin-angiotensin system inhibitors (RASi), and mineralocorticoid receptor antagonists (MRA) in a nationwide cohort of patients with heart failure (HF). Patients aged 18-80years in Norway with a first diagnosis of HF from 2014 until 2020 that survived ≥30days were identified from the Norwegian Patient Registry and linked to the Norwegian Prescription Database. We collected information about BB, RASi [angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and angiotensin receptor-neprilysin inhibitors (ARNI)], and MRA. Dual HF therapy was defined as taking at least two out of three drug classes, whereas triple HF therapy was defined as taking all three. Initiation (time to initiation) and persistence (time to discontinuation using a grace period of 30days) of HF drugs was calculated by the Kaplan-Meier method, followed to outcome of interest, death, or December 2020. One-year adherence was measured as proportion of days covered (PDC) using a cut-off at 80%. For adherence and persistence measurements, we allowed for maximum 60days of stockpiling and switching within drug groups. We performed sensitivity analyses to test the robustness of our findings. Out of 54 899 patients included in the cohort, 75%, 69%, and 21% initiated a BB, RASi, and MRA, respectively, whereas 13% did not receive any. Dual and triple HF therapy was prescribed to 61% and 16%, respectively. The proportion of adherent patients during the first year following initiation was 83%, 81%, 84%, and 61% for BB, RASi, ARNI, and MRA, whereas 42% and 5% were adherent to dual and triple HF therapy, respectively. From 2 to 5years following initiation, persistence decreased from 58% to 38%, 57% to 37%, and 31% to 15% for BB, RASi, and MRA, respectively. Within the RASi group, persistence was higher for ARNI than for ACEI and ARB. There were no major changes in either initiation or adherence of the drug classes from 2014 to 2019, except for an increase in initiation and adherence of MRA. We found low adherence to dual and triple HF therapies in this nationwide cohort study of newly diagnosed HF patients. Efforts are needed to increase adherence and persistence to HF therapies into clinical practice, emphasizing maintenance of multiple drug therapies in patients with such an indication.

Renin-angiotensin system inhibitors may have an advantage over calcium channel blockers in reducing proteinuria in gastric cancer patients receiving ramucirumab.

This study aimed to investigate whether renin-angiotensin system inhibitors (RAS-I) have an advantage over calcium channel blockers (CCB) for suppression of proteinuria in hypertensive patients with gastric cancer receiving ramucirumab (RAM) treatment. Adult Japanese patients with gastric cancer who were outpatients at Asahikawa Medical University Hospital, National Hospital Organization Hokkaido Cancer Center, and Iwate Medical University Hospital between July 1, 2015, and March 31, 2021, were included in this study. Of these patients, those who had received first-time RAM treatment, and those treated with antihypertensive agents including RAS-I or a CCB at initial RAM administration were included. A total of 36 patients were analyzed in this study. Of these patients, 17 patients were classified into the RAS-I group and the remaining 19 into the CCB group. After 12 weeks of RAM administration, the prevalence of proteinuria in the RAS-I group was significantly lower than that in the CCB group. Additionally, Kaplan-Meier analysis showed that the cumulative occurrence of proteinuria in the RAS-I group over 12 weeks following RAM administration was significantly lower than that in the CCB group. Furthermore, simulation of the time course of RAM blood concentrations based on the O'Brien model showed that there may not be differences in the RAM blood concentration profiles over 12 weeks between the two groups. RAS-I may have an advantage over CCB for suppressing proteinuria in hypertensive patients with gastric cancer treated with blood pressure antihypertensive agents. Our results provide useful information to healthcare professionals involved in the administration of RAM treatment.

The Effect of Hydroxychloroquine on Residual Proteinuria in Patients With Immunoglobulin A Nephropathy: A Retrospective Study Based on Propensity Score Matching.

BackgroundThere is insufficient evidence to support the use of hydroxychloroquine (HCQ) in Immunoglobulin A nephropathy (IgAN) patients with high residual proteinuria in spite of 6-month supportive treatment combined with corticosteroids (P) and/or immunosuppressives (IM). This study aims to explore the effect of HCQ on residual proteinuria in IgAN.Materials and MethodsThis is a retrospective study. IgAN patients who had residual proteinuria ≥0.3 g/24 h after 6-month treatment by renin-angiotensin system inhibitors (RASI) + P ± IM were included. Groups were divided based on the different regimens and then matched by the propensity score matching method. The primary outcome was defined as the cumulative frequency of residual proteinuria reduction ≥30%.ResultsRASI (n = 183), HCQ + RASI (n = 59), RASI + P ± IM (n = 145), and HCQ + RASI + P ± IM (n = 38) groups were included. HCQ + RASI group had a higher level of residual proteinuria and a worse renal function than those in the RASI group. The renal function was worse in the HCQ + RASI + P ± IM group than that in the control group, but residual proteinuria levels were similar. After matching, there were 40 patients in the first two groups and 29 patients in the latter two groups, respectively. The cumulative frequency of residual proteinuria reduction ≥30% in HCQ + RASI + P ± IM group was higher than that in control group (86.2% vs. 62.1%, χ2 = 6.397, p = 0.011). HCQ combination treatment was one of independent factors.ConclusionThe addition of HCQ treatment can effectively reduce the residual proteinuria in IgAN patients previously treated with supportive treatment combined with P and IM treatment and the cumulative frequency of effective reduction of residual proteinuria can reach 86.2%.

Renin-Angiotensin-System Inhibitors for the Prevention of Chemotherapy-Induced Peripheral Neuropathy: OncoToxSRA, a Preliminary Cohort Study.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting adverse side effect of treatment. CIPN affects the oncological prognosis of patients, as well as their quality of life. To date, no specific pharmacological therapy has demonstrated effectiveness in preventing CIPN. Accumulating preclinical evidence suggests that renin-angiotensin system (RAS) inhibitors may have neuroprotective effects. One hundred and twenty patients were included in this observational study and were followed from the beginning of their neurotoxic chemotherapy schedule until their final assessment, at least one month after its cessation. The National Cancer Institute’s common toxicity criteria 4.0 (NCI-CTC 4.0) were used to grade the severity of adverse events. Follow-ups also included electrochemical skin conductance and scales for pain, quality of life and disability. Among patients receiving a platinum-based regimen, the mean grade of sensory neuropathy (NCI-CTC 4.0) was significantly lower in the RAS inhibitor group after the end of their anticancer treatment schedule. Because of the observational design of the study, patients in the RAS inhibitor group cumulated comorbidities at risk of developing CIPN. Randomized controlled trials in platinum-based regimens would be worth conducting in the future to confirm the neuroprotective potential of RAS inhibitors during chemotherapy.

Low serum chloride level gives renin-angiotensin system inhibitor a prognostic impact in heart failure patients with preserved ejection fraction

Abstract Background Hypochloremia is associated with a poor prognosis of heart failure (HF) patients. This phenomenon is sustained even in HF with preserved ejection fraction (HFpEF). Serum chloride level is known to be affected by serum renin secretion; however, this relationship is one of the least investigated field in HF patients. Renin-angiotensin system (RAS) inhibitor is recommended as a first-line medication for HF patients with reduced left ventricular ejection fraction, but no prior studies of RAS inhibitors have achieved to improve the prognosis of HFpEF patients. Purpose We investigated the relationship between baseline serum chloride level and the prognostic impact of RAS inhibitor in HFpEF patients. Methods This is an observational study including 1,913 consecutive patients who admitted to hospital due to worsening of HF and discharged alive in a single university hospital. After excluding patients who received regular hemodialysis and whose left ventricular ejection fraction were under 50%, 506 HFpEF patients were ultimately analyzed. They were categorized into tertiles by serum chloride levels at discharge (T1: −100 mEq/L, T2: 101–104 mEq/L, T3: 105- mEq/L), and patients in each category were further divided into subgroups depending on the prescription of RAS inhibitor at discharge (RAS inhibitor group and Non-RAS inhibitor group). The primary endpoint of this study was death from any cause. Results During the observation period with 479 days of median follow-up, 77 (15.2%) died. Patients in the RAS inhibitor group had significantly better prognosis than those in the Non-RAS inhibitor group in T1 category (Log-rank: p=0.003, Figure). In contrast, there was no statistical difference in the mortality between the RAS inhibitor group and Non-RAS inhibitor group in T2 and T3 categories (Log-rank: p=0.15, p=0.81, respectively, Figure). Multivariate Cox regression analysis in T1 category revealed that taking RAS inhibitor at discharge was independently associated with a lower mortality rate, even after the adjustment of diverse covariates (hazard ratio: 0.40, 95% confidence interval: 0.20–0.80). Conclusion In this observational study, the administration of RAS inhibitor was associated with an improved prognosis of HFpEF patients only in low serum chloride level at discharge. Therapeutic strategy focusing on the chloride level may be one of the promising options to find the light on a unintervenable prognosis of HFpEF. Funding Acknowledgement Type of funding sources: None.

Renin-angiotensin system inhibitors can be a first choice drug for hypertension in patients treated with vascular endothelial growth factor inhibitors

Abstract Background Vascular endothelial growth factor Signaling Pathway (VSP) inhibitor suppresses tumor growth in solid cancers with disorganized tumor vasculature.1 However, VSP inhibitor often provokes hypertension as an adverse effect.2 The VSP inhibitor-induced hypertension may lead to a dose reduction or discontinuation of the treatment, which cause to poor prognosis. Therefore, it is important to investigate the appropriate anti-hypertensive treatment during cancer therapy. Although renin-angiotensin system (RAS) inhibitor or calcium channel blocker (CCB) is recommended to first-line anti-hypertensive drugs for cancer patients,3 it has not been well-elucidated whether RAS inhibitor or CCB is a beneficial impact for clinical outcome. Purpose The aim of this study is to clarify whether RAS inhibitor or CCB would be an effective drug as the first antihypertensive drug during VSP inhibitor therapy. Method From the LIFE Study database which consisted of 14 municipality-level information from claims data between 2016 and 2020, 1,263 cancer patients treated with VSP inhibitors were retrospectively reviewed. All patients were stratified into two groups according to hypertensive drugs: (1) RAS inhibitors alone (n=512) and (2) CCBs alone (n=751) (Figure 1). The time to treatment failure (TTF) was substituted as an alternative clinical indicator of overall survival. The Kaplan-Meier survival method with the log-rank test was conducted to compare the TTF between the two groups. In addition, Cox proportional hazard model adjusted with baseline clinical characteristics was performed to analyze determinant factors for TTF. Results There were no difference in baseline characteristics including age, sex, primary cancer site, the type of VSP inhibitors, and past medical histories between the two groups, excepted for renal failure. The rate of renal failure was significantly higher in the RAS inhibitor group than in the CCB group (p=0.013). TTF in the patients treated with RAS inhibitors were significantly longer than that with CCB (median TTF [25th–75th percentile]: 183 [61–455] vs. 153 [61–351] days, p=0.020) (Figure 2). In Cox proportional hazard analysis adjusted with age, sex, past medical history, primary cancer lesion, and type of VSP inhibitors, RAS inhibitor was a significantly independent favorable factor to TTF, compared to CCB (Hazard ratio 0.86, 95% confidence interval [0.77–0.97], p=0.011). Conclusion RAS inhibitor is associated with a favorable clinical outcome than CCB, and can be a first choice for treating hypertension during cancer therapy with VSP inhibitors. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) Figure 1. Patient screening and enrollmentFigure 2. Antihypertensive drugs &amp; TTF

Impact of renin angiotensin system inhibitor on 3-year clinical outcomes in acute myocardial infarction patients with preserved left ventricular systolic function: a prospective cohort study from Korea Acute Myocardial Infarction Registry (KAMIR)

BackgroundPatients with acute myocardial infarction (AMI) are usually treated with angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) if ACEIs are not tolerated. However, there is no data regarding the impact of switching from ACEIs to ARBs on long-term clinical outcomes in AMI patients with preserved left ventricular (LV) systolic function especially beyond 1 year. To investigate the effectiveness of treatment with ACEIs or ARBs on clinical outcomes over 3 years in AMI patients with preserved LV systolic function following percutaneous coronary intervention.MethodIt is a prospective cohort study using data from a nationwide large scale registry with 53 hospitals involved in treatment of acute myocardial infarction (AMI) in Korea. Between March 2011 and September 2015, we enrolled 6236 patients with AMI who underwent primary percutaneous coronary intervention and had a left ventricular ejection fraction ≥ 50%. Main outcome measures composite of total death or recurrent AMI over 3 years after AMI. Patients were divided into an ACEI group (n = 2945), ARB group (n = 2197), or no renin-angiotensin system inhibitor (RASI) treatment (n = 1094). We analyzed patients who changed treatment. Inverse probability of treatment weighting (IPTW) analysis was also performed.ResultsAfter the adjustment with inverse probability weighting, the primary endpoints at 1 year, AMI patients receiving ACEIs showed overall better outcomes than ARBs [ARBs hazard ratio (HR) compared with ACEIs 1.384, 95% confidence interval (CI) 1.15–1.71; P = 0.003]. However, 33% of patients receiving ACEIs switched to ARBs during the first year, while only about 1.5% switched from ARBs to ACEIs. When landmark analysis was performed from 1 year to the end of the study, RASI group showed a 31% adjusted reduction in primary endpoint compared to patients with no RASI group (HR, 0.74; 95% CI 0.56–0.97; P = 0.012).ConclusionsThis result suggests that certain patients got benefit from treatment with ACEIs in the first year if tolerated, but switching to ARBs beyond the first year produced similar outcomes. RASI beyond the first year reduced death or recurrent AMI in AMI patients with preserved LV systolic function.CRIS Registration number: KCT0004990.

Does renin-angiotensin system inhibition have impacts on muscle mass and bone mineral density in heart failure patients?

AimsResults of experimental studies have indicated the possibility of muscle and bone mass being negatively regulated by renin‐angiotensin system (RAS) activation, but that possibility has not been analysed in patients with heart failure (HF).Methods and resultsData for HF patients who received a dual‐energy X‐ray absorptiometry scan in our hospital were reviewed. Propensity scores for the use of RAS inhibitors (RASIs) were calculated using a multivariate logistic regression model to minimize selection bias. One hundred sixty pairs of patients were extracted. Plasma aldosterone concentration was significantly lower in the RASIs group than in the no‐RASIs group (119 [IQR 71–185] vs. 94 [IQR 60–131] pg/mL, P = 0.003), confirming RAS inhibition in the RASIs group. Skeletal muscle mass index tended to be higher in the RASIs group than in the non‐RASIs group (15.6 [IQR 14.0–17.2] vs. 15.0 [IQR 13.3–16.6] pg/mL, P = 0.065). The proportion of patients with muscle wasting, defined as appendicular skeletal muscle mass indexes of <7.00 and <5.40 kg/m2 for males and females, respectively, was significantly lower in the RASIs group than in the non‐RASIs group (53% vs. 64%, P = 0.041). Multivariate logistic regression analysis showed that the no use of RASIs was associated with presence of muscle wasting independently of age, presence of diabetes, renal function, and severity of HF. Bone mineral densities and proportions of patients with osteoporosis were similar in the two groups.ConclusionsRenin‐angiotensin system inhibition is associated with a lower prevalence of muscle wasting in HF patients independently of established risk factors.

Renin Angiotensin System Inhibitors Reduce Aortic Stiffness and Flow Reversal After a Cryptogenic Stroke

Blood flow reversal is a possible mechanism for retrograde embolism in the setting of high-risk atherosclerotic plaques in the descending aorta (DAo). Evidence suggests that pulse wave velocity (PWV) is a determinant of blood flow reversal and can be reduced by the destiffening effect of renin-angiotensin system inhibitors (RASI). To evaluate the impact of antihypertensive therapy on in vivo changes in PWV and flow reversal in patients with cryptogenic stroke. Prospective. Sixteen patients (69 ± 9 years; 10 males) included after cryptogenic stroke. 3T. 4D flow sequence (temporal resolution = 19.6 msec) ASSESSMENT: Patients underwent aortic MRI at baseline and at 6-month follow-up. Patients received standard-of-care antihypertensive therapy that were classified as RASI vs. non-RASI medications (ie, destiffening vs. nondestiffening).We compared aortic PWV, flow reversal fraction (FRF), aortic measurements, cardiac function, and other aortic and cardiac measurements in the antihypertensive therapy groups. Two-tailed paired or unpaired Student's t-tests (normal distributions) or Wilcoxon tests (nonnormal distribution). Univariate correlations using Pearson correlation coefficients. There was a significant decrease in PWV in the RASI (n = 10) group (9.4 ± 1.6 m/s vs. 8.3 ± 1.9 m/s; P < 0.05), as well as FRF (18.6% ± 4.1% vs. 16.3% ± 4.0%; P < 0.05) between baseline and the 6-month MRI studies. There were no changes in PWV or FRF in the non-RASI (n = 6) group (P = 0.146 and P = 0.32). A decrease in FRF was significantly correlated with a decrease in PWV (r = 0.53; P < 0.05). The findings of our study suggest that RASI therapy after cryptogenic stroke resulted in a decrease of blood flow reversal and aortic stiffness. 1 TECHNICAL EFFICACY STAGE: 4.

Impacto de los inhibidores del sistema renina-angiotensina en el pronóstico tras recambio valvular aórtico quirúrgico o percutáneo. Metanálisis

Introduction and objectivesTo determine whether renin-angiotensin system inhibitor (RASi) prescription is associated with better outcomes after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). MethodsAll comparative studies of RASi vs no RASi prescription in patients undergoing TAVI/SAVR were gathered from PubMed, Web of Science, and Google Scholar through August, 2019. We extracted hazard ratios (HRs) with their confidence intervals (CIs) for mortality from each study and combined study-specific estimates using inverse variance-weighted averages of logarithmic HRs in the random effects model. ResultsWe identified 6 eligible studies with a total of 21 390 patients (TAVI: 17 846; SAVR: 3544) and included them in the present meta-analysis. The 6 studies were observational comparative studies (including 3 propensity score matched and 3 cohort studies) of RASi vs no RASi prescription. The analysis demonstrated that RASi prescription was associated with significantly lower mortality in the whole group of patients undergoing aortic valve intervention (HR, 0.64; 95%CI, 0.47-0.88; P <.001). However, subgroup analysis suggested differences according to the selected therapy, with TAVI showing better mortality rates in the RASi group (HR, 0.67; 95%CI, 0.49-0.93) but not in the SAVR group (HR, 0.61; 95%CI, 0.29-1.30). No funnel plot asymmetry was identified, suggesting minimum publication bias. Sensitivity analyses sequentially eliminating dissimilar studies did not substantially alter the primary result favoring RASI prescription. ConclusionsThese findings suggest a mortality benefit of RASi in patients with AS treated with aortic valve replacement that might be particularly relevant following TAVI. Future randomized studies are warranted to confirm this relevant finding.

Impact of renin-angiotensin system inhibitors on outcomes after surgical or transcatheter aortic valve replacement. A meta-analysis

Introduction and objectivesTo determine whether renin-angiotensin system inhibitor (RASi) prescription is associated with better outcomes after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). MethodsAll comparative studies of RASi vs no RASi prescription in patients undergoing TAVI/SAVR were gathered from PubMed, Web of Science, and Google Scholar through August, 2019. We extracted hazard ratios (HRs) with their confidence intervals (CIs) for mortality from each study and combined study-specific estimates using inverse variance-weighted averages of logarithmic HRs in the random effects model. ResultsWe identified 6 eligible studies with a total of 21 390 patients (TAVI: 17 846; SAVR: 3544) and included them in the present meta-analysis. The 6 studies were observational comparative studies (including 3 propensity score matched and 3 cohort studies) of RASi vs no RASi prescription. The analysis demonstrated that RASi prescription was associated with significantly lower mortality in the whole group of patients undergoing aortic valve intervention (HR, 0.64; 95%CI, 0.47-0.88; P <.001). However, subgroup analysis suggested differences according to the selected therapy, with TAVI showing better mortality rates in the RASi group (HR, 0.67; 95%CI, 0.49-0.93) but not in the SAVR group (HR, 0.61; 95%CI, 0.29-1.30). No funnel plot asymmetry was identified, suggesting minimum publication bias. Sensitivity analyses sequentially eliminating dissimilar studies did not substantially alter the primary result favoring RASI prescription. ConclusionsThese findings suggest a mortality benefit of RASi in patients with AS treated with aortic valve replacement that might be particularly relevant following TAVI. Future randomized studies are warranted to confirm this relevant finding.

Renin-angiotensin inhibitors were associated with improving outcomes of hepatocellular carcinoma with primary hypertension after hepatectomy.

The activation of the renin-angiotensin system (RAS) promotes tumor progression. In this study, we aimed to assess whether RAS inhibitors (RASIs) could improve the outcome of hepatocellular carcinoma (HCC) patients with primary hypertension after curative liver resection. Data on 387 consecutive patients with primary hypertension who underwent curative liver resection for HCC were reviewed. The study population was divided into two groups based on the type of anti-hypertensive medications: the RASI group (patients using RASIs) and the non-RASI group (patients using other anti-hypertensive drugs but not RASIs). Kaplan-Meier curves, log-rank tests and cox proportional hazards regression models were used to analyze time to recurrence (TTR) and overall survival (OS). There were 144 (37.2%) patients in RASI group and 243 (62.8%) in non-RASI group. The preoperative clinicopathological features were comparable between the two groups. Kaplan-Meier curves demonstrated HCC patients with RASIs had a longer TTR and OS than the patients with non-RASIs (both P<0.001). On multivariate analysis, RASIs administration was identified as an independent prognostic factor for TTR [hazard ratio (HR) =0.52, 95% confidence interval (CI), 0.38-0.70, P<0.001] and OS (HR =0.50, 95% CI, 0.34-0.74, P<0.001). Patients in the RASI group had lower rates of extrahepatic metastases than patients in the non-RASI group (2.8% vs. 7.8%, P<0.042). Targeting the RAS was associated with a reduced risk of recurrence, decreased rate of extrahepatic metastases and prolonged survival of HCC patients with primary hypertension after curative liver resection.

Calcium channel blocker monotherapy versus combination with renin-angiotensin system inhibitors on the development of new-onset diabetes mellitus in hypertensive Korean patients.

BackgroundIn real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibitors (RASI), with calcium channel blockers (CCB) over CCB monotherapy on the development of new-onset diabetes mellitus (NODM) in Korean patients during four-year follow-up periods.MethodsA total of 3208 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled from January 2004 to December 2012. These patients were divided into the two groups according to the additional use of RASI (the RASI group, n = 1221 and the no RASI group, n = 1987). Primary endpoint was NODM, defined as a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, myocardial infarction (MI) and percutaneous coronary intervention (PCI).ResultsAfter propensity score-matched (PSM) analysis, two propensity-matched groups (939 pairs, n = 1878, C-statistic = 0.743) were generated. The incidences of NODM (HR = 1.009, 95% CI: 0.700–1.452, P = 0.962), MACE (HR = 0.877, 95% CI: 0.544–1.413, P = 0.589), total death, MI, PCI were similar between the two groups after PSM during four years.ConclusionsThe use of RASI in addition to CCB showed comparable incidences of NODM and MACE compared to CCB monotherapy in non-diabetic hypertensive Korean patients during four-year follow-up period. However, large-scaled randomized controlled clinical trials will be required for a more definitive conclusion.

The beneficial effects of renin-angiotensin system inhibitors (RASI) on IgA nephropathy with tubulointerstitial lesions categorized by Oxford classification.

Global sclerosis has been reported as the risk factor of IgAN. In Oxford classification, global sclerosis was correlated with tubulointerstitial (T) lesions. Therefore, in patients with T lesions, renin-angiotensin system inhibitors (RASI) might be effective by decreasing glomerular hyperfiltration and hypertension. However, these beneficial effects of RASI have not been reported. In this retrospective cohort study, we divided 87 IgAN patients with T1/2 lesions into two groups: RASI group (n = 47, treated with RASI) and APA group (n = 40, treated with anti-platelet agents). We analyzed the background of each group, the serial changes of blood pressure and the amount of proteinuria (U-Prot), progression to end-stage renal disease, and the risk factors for progression. After propensity score matching, 22 cases from each group were selected, and clinical and histological characteristics were similar. Serial changes of blood pressure had been significantly decreased in RASI group (p = 0.0029), but not in the APA group. Proteinuria was tended to decrease in RASI group, though it was not significant (1.14-0.47g/gCre) and it was similar in APA group (0.95-0.85g/gCre). 20year renal survival rate was 59.5% in RASI group, whereas 21.3% in APA group (p = 0.0119). In multivariate Cox regression analysis, RASI was an independent factor to prevent from progression to ESRD (HR 5.91, p = 0.0039). RASI has shown a significant beneficial effect on histologically advanced IgAN patients with T lesions. These results are compatible with the previous studies that reported the beneficial effects of RASI on clinically advanced IgAN patients.