Angiotensin Aldosterone System Blockers Research Articles

Uncovering patients’ preferences for brand among essential classes of coronary heart disease medications using a discrete choice experiment

Patient preferences for medications strongly correlate with adherence; one area of interest is the choice between branded and generic drugs. Despite extensive research about brand-versus-generic drug preferences, few studies have explored severe-illness patients like those with coronary heart disease (CHD). We could not locate studies measuring preference weights of branded drugs in different classes within guideline-recommended regimens using discrete choice experiments (DCE). We aimed to explore the preference for branded medications used for secondary prevention of CHD events among patients receiving treatment at one of the largest Egyptian health insurance clinics. Patients with CHD were interviewed to choose between various therapy regimens containing brand-name and generic versions of aspirin, beta-blockers, statins, and renin–angiotensin–aldosterone system blockers (RAAS blockers). The study employed a DCE technique and followed the recommendations of the International Society of Pharmacoeconomics and Outcomes Research (ISPOR). Seventy-two percent (149) of the 208 patients questioned were dissatisfied with at least one of their generic medications. The majority of unsatisfied patients displayed brand preferences across the four medicine classes, primarily due to the notion that generics may be less effective. Patients preferred the RAAS blocker brand the most (adjusted odds ratio [AOR]: 3.14; 95% confidence interval [CI] 2.83 to 3.48), followed by beta-blockers (AOR: 2.06; 95% CI 1.88 to 2.27) and statins (AOR: 1.5; 95% CI 1.50 to 1.61). The relative importance of each class from the patient’s perspective showed the highest importance with RAAS blockers (22.2%) and beta-blockers (14.1%), while statins and aspirin had minor importance (7.8% and 6.6%, respectively). In the present study, branded drugs for secondary CHD prevention were preferred over generic alternatives. This finding has two implications for clinical practice. Firstly, physicians and pharmacists need to assure patients about the quality of generics to insure patient satisfaction and adherence to medication. Secondly, health insurance providers need to confirm the effectiveness of generics through observational studies. Despite the well-proven protective effects of aspirin and statins, they had minor importance from the patient’s perspective, highlighting the need to enhance patient knowledge. DCE was demonstrated to be a useful tool for eliciting the genuine preferences of patients treated within the setting of health insurance.

Prescription of quadruple therapy in heart failure with reduced ejection fraction during hospitalization

BackgroundHospitalization of patients with heart failure makes it possible to optimize drug therapy, considerably improving the prognosis of this serious condition.MethodsWe conducted a retrospective descriptive study of patients with reduced left ventricular ejection fraction (≤ 40%) in the Cardiology Department of a community hospital center in France to measure the prescription rate of heart failure medications in hospitalized patients with reduced ejection fraction heart failure and identify their limiting factors. The primary endpoint was the prescription on the discharge prescription of the following four drug classes: beta-blockers, renin–angiotensin–aldosterone system blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter inhibitors.ResultsFrom September 1, 2022, to March 31, 2023, 73 patients were included in the study. About one-third of patients were discharged with the recommended four drug classes. Those discharged with all 4 drug classes were younger and had preserved renal function.ConclusionsThe low rate of prescription of heart failure medications after hospitalization is a reminder of the need to develop a specialized follow-up structure to optimize the drug treatment of reduced ejection fraction heart failure, even in the most fragile patients.

Assessment of effects of combination of SGLT2 inhibitors and renin–angiotensin–aldosterone system blockers on the renal functions of patients of diabetic kidney disease (SGRASS-DKD study)

Abstract Introduction: With the advent of the novel class of drug, SGLT-2-I, there are many speculations about the combined use of this class of drug with renin–angiotensin–aldosterone system inhibitors (RAAS-I) and their effects on DKD. In spite of the fact, that there is a huge prevalence of DM in India, there is hardly any Indian study regarding their combined use. Therefore, with this in mind, the present study has been conceived and conducted in the southern part of West Bengal, India. Materials and Methods: A total of 279 patients of DKD were recruited from different private clinics in this region over a period of 12 weeks and followed up for about a year. All the patients were initiated on RAAS-I (ACE-I, ARB, or ARNI) and SGLT-2-I was added on second visit. Statistical analysis was done after the completion of the study and significance was tested using Student t test with P value of <0.05. Results: The study showed a slight male preponderance and a significant decrease in FBG, PPBG, HbA1C, and ACR and an increase in serum sodium with no significant change of serum urea, creatinine, and eGFR. A slight but clinically insignificant increase in serum potassium was also noted. Conclusion: Combination of RAAS-I and SGLT-2-I retard the progression of DKD by their composite effects on glycemic control, albuminuria, and blood pressure in this study population. Whether combining these two classes of drugs have any synergistic effects on DKD, will have to be determined by larger studies.

13-LB: Treatment Patterns of Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease in Colombia

Aim: Describe treatment patterns of patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in outpatient setting from Colombia. Methods: We conducted a cross-sectional study characterizing treatment patterns of T2DM and CKD using the Audifarma S.A. drug dispensing database and included all patients with both diagnoses using ICD-10 codes and at least one disease-related prescription from April 1st 2019 to March 31st 2020. Sociodemographic variables, comorbidities, treatment received and combinations were evaluated. Drugs were classified as those for management of T2DM (oral antidiabetic agents, insulins, SGLT2i, GLP-1 analogs (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i)), and others including renin angiotensin aldosterone system blockers (angiotensin converting enzyme inhibitors-ACEI, angiotensin receptor antagonists-ARBs) and mineralocorticoid receptor antagonists (MRAs). A descriptive analysis with frequencies and proportions, means and standard deviation was carried out. Results: Of a total of 194,023 patients with a primary diagnosis of T2DM, it was possible to identify that 14,722 (7.5%) had concomitant CKD, during the observation period. A total of 7513 (51%) were men, and the mean age was 74.7±10.9 years. The main comorbidities were hypertension (n=10665; 72.4%) and hypothyroidism (n=1138; 7.7%). The most used drugs were metformin (n=9901; 67.3%) alone or associated with some other antidiabetic, followed by 52.2% used DPP4i (n=7691), 17.0% an SGLT2i (n=2500), and 5.2% GLP-1a (n=766). Additionally, 67.2% (n=9895) of patients were under treatment with ARBs, 15.8% (n=2325) with ACEIs and 10.9% (n=1598) with MRAs. Conclusions: This contemporary study from Colombia further highlights the complexity and heterogeneity of treating patients with T2DM and CKD, which could be improved if the beneficial properties of newer agents that have shown positive anti-hyperglycemic and renal outcomes were implemented in the local treatment strategy. Disclosure M. Machado: Research Support; Bayer Inc., Pfizer Inc. A. Gaviria-mendoza: Employee; Audifarma S. A, Research Support; Bayer Inc., Pfizer Inc. J. S. Franco: Employee; Bayer Inc. M. D. R. Forero: Employee; Bayer Inc. D. Vizcaya: Employee; Bayer Inc. L. F. Valladales restrepo: Research Support; Bayer Inc., Pfizer Inc. J. E. Machado-alba: None. Funding Bayer AG

Effectiveness of renin-angiotensin-aldosterone system blockers in patients with Alport syndrome: a systematic review and meta-analysis.

Though renin-angiotensin-aldosterone system (RAAS) blockers have been considered the primary treatment for patients with Alport syndrome (AS) for a decade, there is no comprehensive review with evidence-based analysis evaluating the effectiveness of RAAS blockers in AS. A systematic review and meta-analysis was performed of published studies that compared outcomes related to disease progression between patients with AS receiving RAAS blockers with those taking non-RAAS treatment. Outcomes were meta-analyzed using the random effects models. Cochrane risk-of-bias, Newcastle-Ottawa Scale and GRADE assessment determined the certainty of evidence. A total of eight studies (1182 patients) were included in the analysis. Overall, the risk of bias was low to moderate. Compared with non-RAAS treatment, RAAS blockers could reduce the rate of progression to end-stage kidney disease (ESKD) (four studies; HR: 0.33; 95% CI: 0.24-0.45; moderate certainty evidence). After stratified by genetic types, a similar benefit was detected: male X-linked Alport syndrome (XLAS) (HR: 0.32; 95% CI: 0.22-0.48), autosomal recessive Alport syndrome (HR: 0.25; 95% CI: 0.10-0.62), female XLAS and autosomal dominant Alport syndrome (HR: 0.40; 95% CI: 0.21-0.75). In addition, RAAS blockers showed a clear gradient of benefit depending on the stage of disease at the initiation of treatment. This meta-analysis suggested that RAAS blockers could be considered as a specific therapy to delay of ESKD for AS with any genetic type, especially at the early stage of the disease, and every further more-effective-therapy would be advised to be applied on top of this standard of care.

Association of outpatient use of renin–angiotensin–aldosterone system blockers on outcomes of acute respiratory illness during the COVID-19 pandemic: a cohort study

ObjectivesEvaluate the associations between patients taking ACE inhibitors and angiotensin receptor blockers (ARBs) and their clinical outcomes after an acute viral respiratory illness (AVRI) due to COVID-19.DesignRetrospective cohort.SettingThe USA; 2017–2018...

Pregnancy in women with dilated cardiomyopathy.

Only a few studies describe the pathophysiology and outcomes of dilated cardiomyopathy (DCM) in pregnancy, which the authors aim to review here. DCM causes enlargement of the ventricles and reduced systolic function. Fluid overload and raised cardiac output in pregnancy may contribute to cardiac complications that lead to cardiac remodeling and heart failure, a common cause of maternal mortality. The risk of cardiac complications is higher in women with New York Heart Association class III and IV. Fetal and neonatal complications are common with coexisting obstetric risk factors. Hence, prepregnancy counseling and a multi-disciplinary approach are essential. Renin-angiotensin-aldosterone system blockers prevent cardiac remodeling but are teratogenic. Drugs, such as β-blockers to control cardiac remodeling, thiazide diuretics to reduce preload, hydralazine and nitrates to reduce afterload and digoxin to increase inotropy, are safe and should be used to manage DCM in pregnancy.

MO680: Association of Systemic Inflammation with Changing Peritoneal Membrane Characteristics

Abstract BACKGROUND AND AIMS Increasing transport status with ultrafiltration (UF) and solute-removal inadequacy is among the most challenging issues in peritoneal dialysis (PD) continuity. Decreased transport status is less frequent but also results in solute clearance. Although the current incidence of peritonitis has reduced considerably, defined membrane disruptions are still frequently observed. Our study examines the relationship between different types of membrane disruptions and the course of systemic inflammation in incident PD patients. METHOD This is a retrospective, single-site, cohort study of incident adult PD patients (n = 202) sampled between January 2000 and January 2020. An increase or decrease in transport status is defined as two or more categories of a rise or decline in peritoneal equilibration test (PET) from their baseline during follow-up. The 4-h dialysate/plasma creatinine ratio was used to classify PET categories. C-reactive protein (CRP) values were obtained from the annual tests in the routine controls of the patients. RESULTS Baseline demographics, diabetes frequency, residual renal function, baseline laboratory, frequency of renin–angiotensin–aldosterone system blockers, high glucose–containing dialysate and icodextrin use were similar among the groups. Total episodes of peritonitis and peritonitis rates within the first 5 years of follow-up was higher in patients with stable transport status with a median rate of 0 (min:0 to max:5) than patients with increased transport status [median rate of 0 (min:0 to max:3)] and decreased transport status [median rate of 0 (min:0 to max:1)] (P = 0.009). The main time-dependent effect of CRP was statistically significant [Wilks’ λ = 0.76, F (5, 127) = 7.75, P < 0.001]. The joint effect of the mean CRP value depending on time and group was also significant [Wilks’ λ = 0.91, F (10, 254) = 1.10, P = 0.36]. The effect of CRP and time was significantly different between the groups [F (2, 131) = 3.49, P = 0.03; partial η2 = 0.05]. While there was a significant difference between stable and increased transporters in the post-hoc analysis, no similar significance was found between stable and decreased transporters (P = 0.03 and P = 0.99, respectively). CONCLUSION Our study shows that the peritoneal membrane kinetics may change into different characteristics in many patients over time, despite the very low frequency of peritonitis episodes and similar baseline characteristics, and may be significantly affected by systemic inflammation. Systemic inflammation, in particular, appears to be related to increased transport status, which is most often responsible for the deterioration of UF and solute clearance over time.

Clinical case of fibronectin glomerulopathy

Fibronectin glomerulopathy (FNGP) is an extremely rare glomerulopathy with an autosomal dominant pattern of inheritance. Sporadic cases of the disease are also described. Currently, several types of FN1 gene mutations are known that underlie conformational changes in the fibronectin molecule and lead to its deposition in the renal tissue. The clinical manifestations of FNGP may be very heterogeneous, but in most cases are characterized by proteinuria, microscopic hematuria, arterial hypertension, and long-term progressive renal failure. Renal biopsy is the main method for diagnosing the disease. Histologically, GFND is characterized by a lobular glomerular architecture with mesangial expansion and obliteration of capillary loops due to the accumulation of an acellular, periodic acid–Schiff positive, silver Jones-negative material. Immunofluorescence is usually negative. Electron microscopy shows finely granular or fibrillary mesangial and subendothelial electron-dense deposits. At higher magnifications, the fibrils have a diameter of 12-16 nm and are randomly arranged. Standard protocols for the etiopathogenetic therapy of FNGP are not currently developed. Improvement of clinical status and prognosis can be achieved by optimizing blood pressure and proteinuria control by renin–angiotensin–aldosterone system blockers. The recurrence risk of FNGP after renal transplantation remains uncertain due to the rare prevalence of the pathology. In this article, we report a 25-year-old man with nephrotic syndrome, which occurred after a previous upper respiratory tract infection. Histological changes specific to FNGP were found in the kidney biopsy. Genetic analysis was not performed. The absence of a family history of kidney disease suggests that this is a sporadic case of FNGP.

Investigation of the effects of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on anemia in patients with normal or mildly low glomerular filtration rate.

The relationship between the activation of the renin-angiotensin system and the increase in erythropoiesis has been shown in many studies. In addition, the use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARB) has been reported to reduce hemoglobin levels in various patient groups at risk for secondary erythrocytosis/polycythemia. The aim of our study is to investigate whether there is a change in hemoglobin levels after starting ACEIs or ARBs in patients who have not used them before. Three hundred and fifty-one patients who were started on renin angiotensin aldosterone system (RAAS) blockers were evaluated retrospectively. None of the patients had anemia before starting RAAS blockers. A median of 6 (4-12) months after the start of the drug, complete blood count and kidney function tests were evaluated. Hemoglobin values before and after the start of the drug were compared statistically. A statistically significant decrease in mean Hb value was found after starting ACEIs or ARBs (14.39 ± 1.29 g/dL vs 13.98 ± 1.36 g/dL, p < 0.001). The decrease in control Hb values was higher in the ARB group than in the ACEI group (-0.53 ± 0.06 g/dL vs -0.29 ± 0.06 g/dL, p < 0.001). A significant decrease in mean Hb level was detected in the first year following the first administration of ACEIs or ARBs.

Single, Double and Triple Blockade of RAAS in Alport Syndrome: Different Tools to Freeze the Evolution of the Disease.

Background: The goal of the treatment of Alport syndrome (AS) is to delay the progression of kidney damage. The current standard of care is the use of Renin Angiotensin Aldosterone System (RAAS) blockers: angiotensin-converting enzyme inhibition (ACEi), angiotensin receptor blockade, and, recently, spironolactone (SP). Aim of the study: the purpose of this retrospective study is to evaluate the efficacy (reduction of proteinuria and changes of glomerular function) and safety of a sequential introduction of RAAS blockers up to a triple RAAS blockade in pediatric proteinuric patients with AS. Methods: in this retrospective study (1995 to 2019), we evaluated proteinuria values in AS patients, during the 12 months following the beginning of a new RAAS blocker, up to a triple blockade. ACEi was always the first line of treatment; then ARB and SP were sequentially added if uPCR increased by 50% from the basal level in 2 consecutive samples during a 3-months observation period, or when uPCR ratio was >2 mg/mg. Results: 26 patients (mean age at treatment onset was 10.55 ± 5.02 years) were enrolled. All patients were on ACEi, 14/26 were started on a second drug (6/14 ARB, 8/14 SP) after a mean time of 2.2 ± 1.7 years, 7/26 were on triple RAAS blockade after a further period of 5.5 ± 2.3 years from the introduction of a second drug. Repeated Measure Anova analysis of log-transformed data shows that the reduction of uPCR values after Time 0 from the introduction of the first, second and third drug is highly significant in all three cases (p values = 0.0016, 0.003, and 0.014, respectively). No significant changes in eGFR were recorded in any group, apart from a 15-year-old boy with X-linked AS, who developed kidney failure. One patient developed mild hyperkaliemia, and one gynecomastia and symptomatic hypotension. No life-threatening events were recorded. Conclusions: double and triple RAAS blockade is an effective and safe strategy to reduce proteinuria in children with AS. Nevertheless, we suggest monitoring eGFR and Kaliemia during follow-up.

Effectiveness of Management of Type 2 Diabetes Mellitus Through Telephone Consultation During COVID-19 Lockdown in Lagos Nigeria

Aim: The aim of the study was to explore the impact of the coronavirus disease 19 (COVID-19) lockdown on the clinical outcome of patients with Type 2 diabetes mellitus (DM) attending a primary care Diabetes Clinic in Lagos State, Nigeria, in terms of their compliance with medication intake, blood pressure (BP), and glycemic control and ability to modify medication through telephone consultation. Methodology: A retrospective review of the clinical characteristics of patients was carried out. Telephone calls were made to patients with Type 2 DM who attended the chronic medical disorder clinic of the Family Medicine Department, Lagos State University Teaching Hospital, Lagos, Nigeria. The information obtained included questions on demographic data, type of medications used, and medication compliance, use of self-monitoring devices for BP, and blood glucose levels. Data analysis was performed using SPSS program version 26. Results: A total of 178 patients were eligible. Most (87%) reported using their medication as prescribed, 74% of patients had self-monitoring of blood glucose (SMBG) during lockdown, though only 29% checked glucose level regularly and 54% practiced home monitoring of BP (HMBP). Medication was modified in 34% of patients by the doctor who called in. Biguanides and Sulfonylureas were the most prescribed oral antidiabetic medications, while Renin Angiotensin Aldosterone System (RAAS) blockers were the most prescribed antihypertensive class. The HMBP was associated with lower systolic BP (t-test 3.49,P= 0.0008). Conclusions: Type 2 diabetic patients managed through telephone during the COVID-19 lockdown reported good level of drug compliance, while improved practice of SMBG, and HMBP resulted in better level of control. The findings of this review suggest that the use of e-consultation can play a role in patient management of Type 2 diabetes even beyond the COVID-19 era including reaching patients in distant locations who are unable to come to the hospital. There is a need for further studies on e-medicine role on various aspects of medical care.

Marine Natural Products and Coronary Artery Disease.

Coronary artery disease is the major cause of mortality worldwide, especially in low- and middle-income earners. To not only reduce angina symptoms and exercise-induced ischemia but also prevent cardiovascular events, pharmacological intervention strategies, including antiplatelet drugs, anticoagulant drugs, statins, and other lipid-lowering drugs, and renin–angiotensin–aldosterone system blockers, are conducted. However, the existing drugs for coronary artery disease are incomprehensive and have some adverse reactions. Thus, it is necessary to look for new drug research and development. Marine natural products have been considered a valuable source for drug discovery because of their chemical diversity and biological activities. The experiments and investigations indicated that several marine natural products, such as organic small molecules, polysaccharides, proteins, and bioactive peptides, and lipids were effective for treating coronary artery disease. Here, we particularly discussed the functions and mechanisms of active substances in coronary artery disease, including antiplatelet, anticoagulant, lipid-lowering, anti-inflammatory, and antioxidant activities.

Clinical characteristics and treatment of outpatients with chronic heart failure in the Moscow Region

Aim: To perform clinical characterization of patients with chronic heart failure (CHF) in the Moscow Region and to assess if their current treatments meet the current clinical guidelines.Materials and methods: Based on the information submitted from 11 outpatient clinics in the Moscow Region in December 2019, we analyzed retrospective data on 286 patients with CHF, including their concomitant diseases, types of assessments and their results, as well as current treatments.Results: The most common concomitant disease was arterial hypertension (95.1% of the patients). 53.8% of the patients had previous myocardial infarction, 37.8%, diabetes mellitus, and 34.6%, atrial fibrillation. Chronic kidney disease was present in 18.5% of the patients, valvular heart disease in 11.9%, and past stroke in 10.5%. Of non-cardiovascular diseases, the most common were gastrointestinal disorders (25.2%), chronic obstructive pulmonary disease or asthma (9.8%), and anemia (5.2%). Only 8% of the patients had one concomitant disease, whereas 72% had 2 to 3 diseases, and 20% had at least 4 concomitant diseases. Mean number of comorbidities per patient was 2.7. Echocardiography had been performed in 82.9% of the cases. Mean left ventricular ejection fraction was 51.0±10.11%; in 11.5% of the patients it was≤40%. Glomerular filtration rate (GFR) was calculated in 58.7% of the patients. 35.9% of the patients had a GFR of less than 60 mL/min/1.73 m2 , in 3.6% it was≤30 mL/min/1.73 m2 . 83.2% of the patients were treated with renin angiotensin aldosterone system blockers (angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, sacubitril/valsartan), 79.0% with beta-blockers, 53.1% with mineralocorticoid receptor antagonists. Glycosides had been administered to 6.9% of the patients, and diuretics, to 51.1%. In most cases, the doses administered were below those recommended by the international clinical guidelines.Conclusion: We have confirmed the need to increase the adherence of doctors to the clinical guidelines on assessment and management of CHF patients.

FDA approval of dapagliflozin for chronic kidney disease: a remarkable achievement?

Chronic kidney disease (CKD) affects 12% of the population worldwide,1 is a major cause of morbidity and mortality, and consumes health-care resources.2 A primary therapeutic goal for the treatment of CKD is prevention of kidney failure and cardiovascular disease (CVD).3,4 Healthy lifestyle behaviours, blood pressure (BP) lowering, maintaining glucose control (in people with diabetes), and renin and angiotensin aldosterone system (RAAS) blockers have been the cornerstone of therapy for patients with CKD since the late 1990s.

Investigation of the effects of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on anemia in patients with normal or mildly low glomerular filtration rate

The relationship between the activation of the renin-angiotensin system and the increase in erythropoiesis has been shown in many studies. In addition, the use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARB) has been reported to reduce hemoglobin levels in various patient groups at risk for secondary erythrocytosis/polycythemia. The aim of our study is to investigate whether there is a change in hemoglobin levels after starting ACEIs or ARBs in patients who have not used them before. Three hundred and fifty-one patients who were started on renin angiotensin aldosterone system (RAAS) blockers were evaluated retrospectively. None of the patients had anemia before starting RAAS blockers. A median of 6 (4–12) months after the start of the drug, complete blood count and kidney function tests were evaluated. Hemoglobin values before and after the start of the drug were compared statistically. A statistically significant decrease in mean Hb value was found after starting ACEIs or ARBs (14.39± 1.29 g/dL vs 13.98 ± 1.36 g/dL, p < 0.001). The decrease in control Hb values was higher in the ARB group than in the ACEI group (–0.53 ± 0.06 g/dL vs –0.29 ± 0.06 g/dL, p < 0.001). A significant decrease in mean Hb level was detected in the first year following the first administration of ACEIs or ARBs.

Renin-angiotensin-aldosterone system blockers and region-specific variations in COVID-19 outcomes: findings from a systematic review and meta-analysis.

Background and aims: Coronavirus disease 2019 (COVID-19) has been observed to cause a high mortality in people with cardiometabolic diseases. Renin–angiotensin–aldosterone system (RAAS) blockers enhance the expression of ACE2, the binding receptor of SARS-CoV-2, and can enhance viral infectivity. We aim to provide a pooled estimate of the effect of RAAS blockers on COVID-19 outcomes.Methods:A literature search was performed using MEDLINE/PubMed, Google Scholar and preprint servers. All clinical studies analyzing the effect of RAAS blockers on clinical outcomes in COVID-19 patients were included in this study. Newcastle–Ottawa scale was used for quality assessment of studies. MOOSE checklist was followed. Mortality and severity outcomes were recorded as pooled odds ratio (OR) with 95% Confidence Intervals (CIs) and level of heterogeneity (I2). Odds of mortality was the primary outcome. Odds of severity, hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV), steroid use and acute kidney injury were the secondary outcomes. Severity outcomes were chosen depending upon the definition used by respective authors. Country-specific variations and effects of individual class of RAAS blockers were also explored.Results:In total 47 published studies were included in the final analysis, with a total of 26,432 patients from 31 studies in mortality analysis and 20,127 patients from 23 studies in severity analysis. No increased risk of mortality [Pooled OR 0.91 (0.65–1.26), I2 = 89%] or severity [Pooled OR 1.08 (0.79–1.46), I2 = 88%] was seen with RAAS blockers. The drug class was protective in hypertension [pooled OR 0.63 (0.46–0.86), I2 = 58%]. Severity of COVID-19 outcomes was high for Europeans [Pooled OR 2.08 (1.52–2.85), I2 = 77%] and US patients [Pooled OR 1.87 (1.62–2.17)]. Nearly 4 times higher risk of hospitalization and 2 times higher risk of ICU admission and MV were observed in US patients. Class-wise, angiotensin receptor blocker use was associated with 1.6 times higher odds of severity, mainly in Europeans.Conclusion:RAAS blockers are not associated with increased mortality in COVID-19 patients and should be continued in hypertensives. US and European patients are at higher risk of severe outcomes. Pharmacogenetic differences may explain the ethnicity-related variations.Plain language summary Effect of RAAS-blocking medicines on COVID-19 Background and aims: Higher deaths have been observed in COVID-19 patients who have other long-term diseases such as heart disease, diabetes, and high blood pressure. Many of these patients are prescribed a class of medicines called RAAS blockers (ramipril, telmisartan, etc). We studied whether the use of these medicines worsens the course of COVID-19 disease in these patients or causes excess deaths.Methods: We conducted a pooled analysis of 47 observational studies on the use of RAAS blocker drugs in COVID-19 patients.Results: We found that RAAS blockers do not cause excess deaths in patients with COVID-19. On the contrary, they have benefits if prescribed to those with high blood pressure. We also found that whereas European and US patients of COVID-19 taking these medicines had higher disease severity, this was not the case for Chinese patients.Conclusion: Theremay be some genetic and other factors responsible for differences by ethnicity.

Increasing prescription of renin-angiotensin-aldosterone system blockers associated with improved kidney prognosis in Korean IgA nephropathy patients.

BackgroundWe aimed to describe the characteristics of immunoglobulin A nephropathy (IgAN) in Korea with assessment for time trends.MethodsWe performed a multicenter retrospective observational cohort study including biopsy-confirmed native IgAN cases from four tertiary hospitals in Korea. Time eras of diagnosis were stratified into 1979–2003, 2004–9 and 2010–17. The prognostic variable was progression to end-stage kidney disease (ESKD) analyzed by multivariable Cox regression analysis.ResultsWe included 1366 (from 1979 to 2003), 1636 (from 2004 to 2009) and 1442 (from 2010 to 2017) IgAN patients in this study. In the recent periods, IgAN had relatively better clinical characteristics, as patients had higher estimated glomerular filtration rates and lower baseline blood pressures than before. The use of renin–angiotensin–aldosterone system (RAAS) blockers increased from 57.7% in 1979–2003 to 80.0% in 2010–17. During a median follow-up duration of 11.3 years, 722 patients progressed to ESKD with an incidence rate of 12.5 per 1000 person-years. The 10-year risk of progression to ESKD was lower in 2010–17 compared with that of 1979–2003 [adjusted hazard ratio 0.692 (95% confidence interval 0.523–0.915)], even after adjustment for multiple clinicopathologic characteristics. The use of RAAS blockers was a significant mediator (P < 0.001) for the association between time trends and lower 10-year ESKD risk.ConclusionsClinicopathologic characteristics of IgAN in Korea have changed over time. Although the limitation of a retrospective observational study remains, the result showed that the prognosis of IgAN has improved over the study period, possibly related to increased prescription of RAAS blockers.

Does dietary potassium intake associate with hyperkalemia in patients with chronic kidney disease?

Dietary potassium restriction is a strategy to control hyperkalemia in chronic kidney disease (CKD). However, hyperkalemia may result from a combination of clinical conditions. This study aimed to investigate whether dietary potassium or the intake of certain food groups associate with serum potassium in the face of other risk factors. We performed a cross-sectional analysis including a nondialysis-dependent CKD (NDD-CKD) cohort and a hemodialysis (HD) cohort. Dietary potassium intake was assessed by 3-day food records. Underreporters with energy intake lower than resting energy expenditure were excluded. Hyperkalemia was defined as serum potassium >5.0 mEq/L. The NDD-CKD cohort included 95 patients {median age 67 [interquartile range (IQR) 55-73] years, 32% with diabetes mellitus (DM), median estimated glomerular filtration rate 23 [IQR 18-29] mL/min/1.73 m2} and the HD cohort included 117 patients [median age 39 (IQR 18-67) years, 50% with DM]. In NDD-CKD, patients with hyperkalemia (36.8%) exhibited lower serum bicarbonate and a tendency for higher serum creatinine, a higher proportion of DM and the use of renin-angiotensin-aldosterone system blockers, but lower use of sodium bicarbonate supplements. No association was found between serum and dietary potassium (r = 0.01; P = 0.98) or selected food groups. Conditions associated with hyperkalemia in multivariable analysis were DM {odds ratio [OR] 3.55 [95% confidence interval (CI) 1.07-11.72]} and metabolic acidosis [OR 4.35 (95% CI 1.37-13.78)]. In HD, patients with hyperkalemia (50.5%) exhibited higher serum creatinine and blood urea nitrogen and lower malnutrition inflammation score and a tendency for higher dialysis vintage and body mass index. No association was found between serum and potassium intake (r = -0.06, P = 0.46) or food groups. DM [OR 4.22 (95% CI 1.31-13.6)] and serum creatinine [OR 1.50 (95% CI 1.24-1.81)] were predictors of hyperkalemia in multivariable analyses. Dietary potassium was not associated with serum potassium or hyperkalemia in either NDD-CKD or HD patients. Before restricting dietary potassium, the patient's intake of potassium should be carefully evaluated and other potential clinical factors related to serum potassium balance should be considered in the management of hyperkalemia in CKD.

RAAS Blockers and Region-Specific Variations in COVID-19 Outcomes: Findings from a Systematic Review and Meta-Analysis

Background: Coronavirus disease 2019 (COVID-19) has evolved as a global crisis with high mortality seen in elderly and people with cardiometabolic diseases. The use of renin angiotensin aldosterone system (RAAS) blockers in these patients is known to enhance the expression of ACE-2, the chief binding receptor of SARS-CoV-2 and may potentially enhance infectivity.Objective: To provide a pooled estimate of the effect of RAAS blocker usage on COVID-19 outcomes.Data Sources: An electronic literature search was performed for published (using MEDLINE/PubMed and Google Scholar) and preprint (using bioRxiv and medRxiv) studies of interest. The last search was conducted on 9th July 2020.Study Selection: Studies reporting data on RAAS blocker use and COVID-19 mortality and severity were included in the review.Data Extraction and Synthesis: Mortality data and severity data including hospitalization, intensive care unit (ICU) admission, invasive ventilation, steroid use and acute kidney injury (AKI) were recorded. Pooled Odds ratio (OR) estimates were reported with 95% CIs and level of heterogeneity (I2).Main Outcomes and Measures: Odds of mortality in users of RAAS blockers with respect to non-users was the primary outcome. Odds of severity, hospitalization, ICU admission, mechanical ventilation, steroid use, and AKI in users with respect to non-users of RAAS blockers were the secondary outcomes.Results: Of 1348 articles identified, 48 published studies were included in the final analysis, with a total of 26432 patients from 31 studies included in mortality analysis and 20127 patients from 23 studies included in severity analysis. Majority of the studies (41.6%) were from China. No increased risk of mortality (Pooled OR 0.91 (0.65-1.26), I2 =89%) or severity (Pooled OR 1.08 (0.79-1.46), I2 =88%) was seen with RAAS blockers. The drug class was protective in hypertension (pooled OR 0.63 (0.46-0.86), I2 =58%). Severity of COVID-19 outcomes was found to be high for Europeans (Pooled OR 2.08 (1.52-2.85), I2 =77%) and US patients (Pooled OR 1.87 (1.62-2.17) in users of RAAS-blockers. A nearly 4 times higher risk of hospitalization, two times higher risk of ICU admission and mechanical ventilation was observed in US patients on RAAS blockers. No net effect on mortality and severity outcomes was seen in Chinese patients. RAAS blocker usage did not have any effect on corticosteroid use and AKI in Chinese patients.Conclusions and Relevance: Use of RAAS blockers is not associated with increased risk of mortality in COVID-19 patients. Reduced mortality is seen in hypertensive patients with COVID-19 and therefore the drugs should be continued in this subset. US and European patients are at higher risk of severe outcomes. Pharmacogenomic differences may explain the ethnicity related variations.Funding Statement: None.Declaration of Interests: None.