ARBs In Patients Research Articles

Patient Adherence and Duration of Continuous Treatment With Various Arbs in Patients With Uncomplicated Arterial Hypertension in the USA Based on The Analysis of the Truven Health Analytics MarketScan Database.

To discuss two aspects that can be used to improve the adherence to therapy in patients with arterial hypertension (AH): 1) which of the angiotensin II receptor blockers (ARBs) provides the highest adherence rates; 2) how various factors influence adherence rates. An analysis of one of the world's largest clinical practice databases, Truven Health Analytics MarketScan (currently Merative MarketScan), was performed. The analysis included data on patients of both sexes aged 30 to 65 years who had been diagnosed with uncomplicated AH (at least once between March 1, 2012 and January 1, 2018) and prescribed monotherapy with one of ARBs. The exclusion criteria were heart failure and the treatment with two or more ARBs (simultaneously or sequentially) during the treatment period. Ultimately, the study included 717,099 patients with uncomplicated AH, who were divided into four groups based on the prescribed drug: azilsartan (n=4276), candesartan (n=6023), losartan (n=586,857), and valsartan (n=119,943). Adherence to treatment was evaluated by two parameters: duration of continuous therapy and medication possession ratio (MPR). The individual effect of each factor (specific ARB used for therapy, patient gender, age, initial ARB dose, patient co-payment per day of treatment) on the adherence to treatment was assessed using a regression analysis. The adherence to the ARB therapy was generally high. The MPR was the lowest in the azilsartan group and the highest in the candesartan group. However, the parameters that potentially influenced both the MPR and the duration of continuous therapy (patient's gender and age, initial ARB dose, co-payment size) differed significantly between the groups receiving different ARBs. The regression analysis showed that both adherence parameters and the duration of continuous therapy were higher in patients receiving candesartan than in patients receiving azilsartan, losartan or valsartan, when the effect on the adherence of other factors available for study (age, gender, initial dose of the drug, and the absolute size of co-payment for a day of therapy) was excluded. The lowest adherence to therapy was observed in the azilsartan treatment group (p<0.01). The study provided data for comparing the adherence of patients with uncomplicated AH to the therapy with different ARBs. Further study of adherence to treatment will provide additional data that will allow an optimal selection of drugs for the treatment of AH in patients with potentially poor adherence.

The role of angiotensin receptor blockers in treating epilepsy: a review.

Epilepsy is a chronic brain disease with a global prevalence of 70 million people. According to the World Health Organization, roughly 5 million new cases are diagnosed every year. Anti-seizure drugs are the treatment of choice. However, in roughly one third of the patients, these drugs fail to produce the desired effect. As a result, finding novel treatments for epilepsy becomes inevitable. Recently, angiotensin receptor blockers have been proposed as a treatment to reduce the over-excitation of neurons in epilepsy. For this purpose, we conducted a review using Medline/PubMed and Google Scholar using the relevant search terms and extracted the relevant data in a table. Our review suggests that this novel approach has a very high potential to treat epilepsy, especially in those patients who fail to respond to conventional treatment options. However, more extensive and human-based trials should be conducted to reach a decisive conclusion. Nevertheless, the use of ARBs in patients with epilepsy should be carefully monitored keeping the adverse effects in mind.

Initiation of ACE Inhibitor and ARBs in Patients with Advanced CKD

Initiation of ACE Inhibitor and ARBs in Patients with Advanced CKD

СПИРОНОЛАКТОН В СОСТАВЕ АНТИГИПЕРТЕНЗИВНОЙ ТЕРАПИИ ПЕРВОЙ ЛИНИИ: ВЛИЯНИЕ НА СОСУДИСТОЕ РЕМОДЕЛИРОВАНИЕ

Introduction. Previously, clinical studies have proven a pronounced antihypertensive effect of spironolactone in patients with true resistant hypertension. The effectiveness of spironolactone as part of first-line therapy, as well as the effect on vascular wall remodeling, has not been studied. Target. To study the effect of spiroconolactone as part of the first line of therapy when added to telmisartan on indicators of vascular wall stiffness in patients with hypertension at high/very high cardiovascular risk. Materials and methods 32 patients (54 (45; 59) years old) were randomly divided into two groups: in the main group receiving spironolactone at a dose of 25 mg in addition to telmisartan (ARB/spironolactone) and in the group receiving hydrochlorothiazide/ARB combination (control). group). Inclusion criteria: age of patients (30-65 years), hypertension at high/very high cardiovascular risk without antihypertensive therapy, no contraindications to prescribed drugs. At baseline and 6 months later, all patients underwent clinical (office) blood pressure (BP) measurements, ABPM, endothelium-dependent vasodilation (EDVD), vascular remodeling indicators: central blood pressure (CAP), augmentation index, pulse wave velocity (PWV). In patients in the ARB/spironolactone group, serum potassium levels were assessed at baseline and after 4 weeks of treatment. Results. In both groups, a significant decrease in clinical and average daily blood pressure was revealed, as well as a decrease in the augmentation index and CAP. PWV in the carotid-radial segment (CWCR) did not significantly decrease in both groups, while PWV in the carotid-femoral area (CWCF) decreased in the ARB/spironolactone group from 9.8 (9.0; 10.6) m/s to 8.6 (8.0; 10.2) m/s (p = 0.0007). The dynamics of SPWcr was 0.9 (1.3;-0.5) m/s in the ARB/HCT group. In all patients, blood potassium was within reference values. Conclusions. Spironolactone as part of first-line therapy, when added to ARBs in patients with hypertension at high/very high cardiovascular risk, led to a significant decrease in clinical and mean daily blood pressure, as well as a decrease in PWCF.

Managing patients with diabetes and chronic kidney disease

In late 2020, the nonprofit organization Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline in the Annals of Internal Medicine on management of patients with diabetes and chronic kidney disease (CKD). The new guidance focuses on comprehensive care needs, glycemic monitoring and targets, and educational and integrated care approaches. “The 2020 KDIGO clinical practice guideline on diabetes management incorporates recent kidney outcome data to provide specific recommendations on use of glucose-lowering agents to mitigate kidney and cardiovascular risk,” said Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP, vice-chair and Allen I. White Distinguished Associate Professor in the College of Pharmacy and Pharmaceutical Sciences at Washington State University in Pullman. “Recommendations from KDIGO complement current guidance from the endocrine and cardiology communities, but provides a succinct resource related to the specific care needs of patients with diabetes and CKD. Particularly important to pharmacists is the guideline's discussion of risk mitigation strategies and important counseling points to optimize patient safety,” said Neumiller. Patients with diabetes and CKD often have other comorbidities and a higher cardiovascular burden, so a comprehensive management approach is needed. KDIGO recommends use of an ACE inhibitor (ACEi) or an ARB in patients with diabetes, hypertension, and albuminuria, with these medications titrated to the highest approved dose that is tolerated. Use may also be considered in patients with diabetes, albuminuria, and normal blood pressure. Only one of these agents should be used at a time, as combination therapy with an ACEi and an ARB or one of these agents with a direct renin inhibitor may be potentially harmful. Close monitoring of blood pressure, potassium levels, and serum creatinine is needed within 2 to 4 weeks of initiation of therapy or when there is a dose increase. KDIGO recommends that hyperkalemia be managed by implementing measures to reduce potassium levels (e.g., moderating potassium intake, initiating diuretics) rather than by decreasing or discontinuing the ACEi or ARB immediately. In addition, KDIGO recommends continuation of the ACEi or ARB unless creatinine levels increase by more than 30%. The ACEi or ARB dose should be reduced or withdrawn in patients who develop symptomatic hypotension, uncontrolled hyperkalemia (despite interventions), and acute kidney injury. The guideline discusses tobacco cessation as part of the comprehensive care plan, with patients encouraged to avoid using any tobacco products and to reduce their exposure to secondhand smoke. A section on lifestyle intervention is also included, and clinicians are encouraged to review those recommendations in the full publication. KDIGO recommends that A1C levels be used to monitor glycemic control in patients with diabetes and CKD, with an individualized target ranging from <6.5% to <8.0% for those not treated with dialysis. Assessment twice per year is reasonable, but assessments as often as 4 times per year may be needed if glycemic targets are not met or after a change in antihyperglycemic therapy. For antihyperglycemic therapy, KDIGO recommends metformin in combination with a sodium–glucose cotransporter-2 inhibitor for patients with type 2 diabetes, CKD, and an eGFR of 30 mL/min/1.73 m2 or greater. If patients do not reach their individualized glycemic target or are unable to use those medications, the guideline recommends use of a glucagon-like peptide-1 receptor agonist as the next preferred agent. Other antihyperglycemic agents are also listed with a figure (i.e., Figure 4) that helps guide appropriate selection based on patient and provider preferences (e.g., weight loss, avoid injections, avoid hypoglycemia, potent glucose lowering needed), comorbidities (e.g., high-risk atherosclerotic cardiovascular disease, heart failure), eGFR (e.g., dialysis), and cost. KDIGO recognizes that data on use of newer agents in patients with type 1 diabetes and CKD receiving insulin are sparse and makes no special recommendations for these patients. KDIGO discusses the importance of both a self-management education program and a team-based integrated approach to care. The self-education program should consider local context, cultures, and availability of resources and be tailored to individual preferences and learning styles. These programs can be delivered one-on-one or as a group-based model. The team-based approach should include both physician and nonphysician personnel and focus on regular assessments, control of multiple risk factors, and self-management to protect kidney function and reduce the risk for complications.

The Use of ACE Inhibitors and ARBs in Patients Admitted for COVID-19

The Use of ACE Inhibitors and ARBs in Patients Admitted for COVID-19

P1839GLOMERULAR HYPERFILTRATION: THEORY AND APPLICATIONS

Abstract Background and Aims The role of glomerular hyperfiltration in the development and progression of diabetic and non-diabetic chronic kidney disease (CKD) was established during the 80’s of the last century and represented a paradigm shift in current nephrology practice. Method A web-based review of relevant bibliography: articles and textbooks, reporting the development of hyperfiltration theory and its clinical applications was conducted. Results In 1982, after a series of animal studies, Brenner and colleagues proposed that glomerular hyperfiltration, in diabetic and other glomerulopathies, contributes to intrarenal hypertension and predispose to progressive glomerular sclerosis and deterioration of renal function. Clinical trials during late 80’s and early 90’s then focused on inhibition of Renin Angiotensin Aldosteron system (RAAS) to reverse glomerular hyperfiltration, and suggested that ACE inhibitors can be anti-proteinuric independent of their blood pressure-lowering effect in non-diabetic and diabetic nephropathies. In 1993, a randomized controlled trial (RCT) by Lewis and colleagues proved a beneficial effect of captopril in patients with nephropathy caused by type 1 diabetes. Few years later, the results of Ramipril Efficacy in Nephropathy (REIN) study proved the renoprotective role of ACE inhibition in patients with non-diabetic nephropathies with nephrotic and non-nephrotic proteinuria in 2 Lancet articles in 1997 and 1999 respectively. The renoprotective role of RAAS inhibition with ARBs in patients with type 2 diabetes was proven in 3 RCTs published in the New England Journal of Medicine in 2001: Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA) Study, Irbesartan Diabetic Nephropathy Trial (IDNT), and Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. Dual blockade with an ACE inhibitor and an ARB was then attempted to further ameliorate glomerular hyperfiltration. Yet this approach was faced by an increased risk of hyperkalemia and acute kidney injury in 2 RCTs: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) in 2008 and The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) study in 2013. It was until 2014 when evidence appeared for a potential role of SGLT2 inhibition in attenuating glomerular hyperfiltration. The 1st clinical evidence of renoprotective effect of SGLT2i appeared in 2016 when the results of the EMPA-REG OUTCOME study found that empagliflozin was associated with lower rates of renal events. Subsequently, the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program trials and the Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial found similar reductions in composite renal endpoints. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial published in 2019 was the first study designed to assess the effects of a SGLT2i, canagliflozin, on renal outcomes in patients with type 2 diabetes and albuminuric CKD, and proved significant reduction in the composite renal outcome with canagliflozin. The potentiality for renoprotective role of SGLT2i in patients with non-diabetic CKD has stimulated a number of ongoing clinical trials: DIAMOND and Dapa-CKD using Dapagliflozin and EMPATHY and EMPA-KIDNEY using Empagliflozin. Conclusion The hyperfiltration theory represents the basis for current therapeutic interventions in diabetic and non-diabetic CKD. Current guidelines recommend using RAAS blockers in diabetic and non-diabetic proteinuric CKD and SGLT2i in patients with type 2 diabetes and CKD. Whether SGLT2i could be considered in patients with CKD independent of the diabetic state awaits the results of ongoing studies which might change the management practice of CKD.

Hypertension and coronavirus disease 2019 mortality.

The number of deaths because of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to increase around the world, with Italy and China being the countries with the highest mortality. The main comorbidity found in these patients was hypertension: In Italy, the National Institute of Health reported such condition in 73.8% of the deceased [1], whereas in China it was 39.7% according to the Centers of Disease Control and Prevention (CDC), which agrees with the study by Guan et al. [2] where 35.8% of patients with a history of hypertension, were admitted to ICU or required mechanical ventilation or died. A possible cause of this unusual association between hypertension and COVID-19, is explained as SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) as a cell entry receptor, which is expressed mainly in alveolar, intestinal and renal epithelial cells, as well as in the vascular endothelium. Thus, it is proposed that the expression of ACE2 is increased in patients with hypertension because of an imbalance in the renin--angiotensin system, increasing their susceptibility to infection and complications by SARS-CoV-2, particularly in patients on treatment with either angiotensinogen-converting enzyme (ACE) inhibitors or angiotensin II type I receptor blockers (ARBs) [3]. However, at the present time, there is not enough data to discontinue the use of ACE inhibitors and ARBs in patients with COVID-19, further studies are needed. Likewise, another hypothesized causative mechanism is that in the presence of long-term hypertension, there is an inflammatory endothelial dysfunction that can lead to an increased risk of an overreacting immune response, triggering a cytokine storm in the context of a potent viral infection, such as SARS-CoV-2, especially in the elderly, where in turn immunosuppression exists, causing a more severe condition as multiple organ failure or acute respiratory distress syndrome [4]. The low prevalence of COVID-19 in children could be because of a better innate inflammatory response and a lower expression of ACE2 in the lower respiratory tract [5]. Therefore, we suggest having more careful monitoring in the management and follow-up of the elderly patient with COVID-19 and cardiovascular disease as hypertension, because of its greater probability of complications and mortality, either in the outpatient or inpatient setting; similarly, in the upcoming clinical trials that are performed with cardiotoxic drugs, such as hydroxychloroquine and azithromycin, which are currently being studied as a possible treatment for COVID-19. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be harmful in patients with diabetes during COVID-19 pandemic

The novel coronavirus disease 2019 (COVID-19) outbreak once again demonstrated the importance of the renin-angiotensin system (RAS) in patients with diabetes. Activation of the RAS increases in patients with diabetes. The virus attaches to the ACE2 enzyme at low cytosolic pH values and enters into the cell and causes infection. Especially in the presence of diabetes mellitus and accompanying comorbid conditions such as hypertension, obesity, old age, and smoking, cytosolic pH is low, thus the virus easily may enter the cell by attaching to ACE2. ACEIs and ARBs lead to a reduction in angiotensin II level by increasing the ACE2 level, thus they cause a low cytosolic pH. Increased cardiac ACE2 levels due to ACEIs and ARBs can trigger cardiac arrhythmias and myocarditis by causing the virus to easily enter the heart tissue. There is ACE2 activity in the rostral ventrolateral medulla in the brain stem. The release of angiotensin 1-7 in the brain stem leads to the activation of the sympathetic nervous system. This activation causes systemic vasoconstriction and the patient’s blood pressure increases. The most important event is the increased sympathetic activity via the central stimulation, this activity increases pulmonary capillary leaking, causing the ARDS. As the cytosolic pH, which is already low in patients with diabetes will decrease further with the mechanisms mentioned above, the viral load will increase and the infection will be exacerbated. As a result, the use of ACEIs and ARBs in patients with diabetes can lead to increased morbidity and mortality of COVID-19.

КЛИНИЧЕСКИЕ АССОЦИАЦИИ КОРОНАВИРУСНОЙ ИНФЕКЦИИ COVID-19 И АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИ: ПАТОГЕНЕТИЧЕСКИЕ МЕХАНИЗМЫ И ДИСКУССИОННЫЕ ВОПРОСЫ ПРИМЕНЕНИЯ ИНГИБИТОРОВ РЕНИН-АНГИОТЕНЗИН-АЛЬДОСТЕРОНОВОЙ СИСТЕМЫ

A review of current publications suggests that patients with arterial hypertension (AH) are at increased risk for severe course and fatal outcome of COVID-19. The main pathogenetic mechanisms explaining the association of AH with COVID-19 include the effect of coronavirus on the functioning of the renin-angiotensin-aldosterone system (RAAS), which is involved in the development and progression of AH. The review presents the results of a number of studies evaluating the effect of the use of ACE inhibitors / ARBs on the development and course of COVID-19 in patients with cardiovascular diseases. The results of international data analysis showed that the use of ACE inhibitors / ARBs in patients with AH and COVID-19 is associated with lower rates of total mortality, and the use of ACE inhibitors, statins and the female sex are associated with a greater likelihood of patient survival. The data on the promising development of new drugs affecting the functioning of RAAS are presented.

P833Two-year clinical outcomes between statin with ACE inhibitor or ARB in patients with ST-segment elevation myocardial infarction after successful PCI with DES

Abstract Background Limited comparative data are available. Purpose We decided to compare 2-year major clinical outcomes between statin with ACEI and statin ARB therapy in patients with STEMI after PCI with drug-eluting stents (DES). Methods A total 11706 STEMI patients who underwent PCI with DES and who prescribed statin were enrolled and they were divided into two groups, the statin with ACEI group (n=8705) and the statin with ARB group (n=3001). The primary endpoint was the major adverse cardiac events (MACE) defined as all-cause death, recurrent myocardial infarction (re-MI), target lesion revascularization (TLR), target vessel revascularization (TVR), non-TVR. The secondary endpoints were the cumulative incidences of individual components of MACE and target vessel failure (TVF), a composite of death related to the target vessel, re-MI, or clinically driven TVR. Results Two PSM groups (2835 pairs, n=5670, C-statistic = 0.680) were generated. The relative risk of MACE was higher in the statin with ARB group compared to statin with ACEI groups after propensity score-matched (PSM) analysis (hazard ratio [HR]: 1.323, 95% confidence interval [CI]: 1.085–1.613, p=0.006). The relative risks of cardiac death (HR: 1.831, 95% CI: 1.199–2.740, p=0.005), total repeat revascularization (HR: 1.487, 95% CI: 1.133–1.950, p=0.004), and non-TVR (HR: 1.696, 95% CI: 1.122–2.564, p=0.012) were also higher in the statin with ARB group after PSM. Outcomes Cumulative Events at 2-year (%) Hazard Ratio (95% CI) p value Statin + ACEI Statin + ARB Log-rank Propensity score matched Patients MACE 173 (6.5) 225 (8.5) 0.006 1.323 (1.085–1.613) 0.006 All-cause death 58 (2.2) 80 (3.0) 0.054 1.391 (0.992–1.950) 0.056 Cardiac death 35 (1.3) 63 (2.3) 0.004 1.831 (1.199–2.740) 0.005 Re-MI 39 (1.5) 44 (1.7) 0.548 1.141 (0.742–1.756) 0.548 Total repeat revascularization 88 (3.4) 128 (4.9) 0.004 1.487 (1.133–1.950) 0.004 TLR 26 (1.0) 40 (1.5) 0.075 1.561 (0.953–2.558) 0.077 TVR 53 (2.0) 71 (2.8) 0.086 1.364 (0.955–1.946) 0.088 Non-TVR 36 (1.4) 60 (2.3) 0.011 1.696 (1.122–2.564) 0.012 TVF 140 (5.3) 173 (6.6) 0.050 1.249 (1.000–1.561) 0.050 Conclusions In this study, we suggest that the combination of statin with ACEI may be beneficial for reducing the cumulative incidences of MACE, total repeat revascularization rate, and non-TVR rather than the statin with ARB after PCI with DES in STEMI patients.

EFEK HIPOTENSIF DARI ACEi DAN ARB PADA PASIEN DIABETES MELLITUS DAN HIPERTENSI DI RSUD. ABDUL WAHAB SYAHRANIE SAMARINDA

More than two-thirds of patients with type 2 diabetes also experience hypertension whose development coincides with hyperglycemia, where each disease has a tendency to influence the increased risk of other diseases. Sundry new guidelines, such as the National Joint Committee 8, the American Diabetes Association recommend blood pressure targets in the diabetic population of &lt;140/90 mmHg to reduce cardiovascular risk and prevent the progression of nephropathy. This study aims to determine whether there is a difference in achieving blood pressure target &lt; 140/90 mmHg according to Join National Committee 8 between ACEi and ARB in patients with type 2 diabetes with hypertension. This research was conducted using a retrospective at internist clinic of Abdul Wahab Syahranie hospital, by taking secondary data from the medical record from blood pressure o 49 outpatients received a single antihypertensive either drug ACEi 29 people or ARB 34 people. This study showed that the achievement of target blood pressure by &lt;140/90 mmHg (JNC 8 guideline) between ACEi 7 (28%) and ARB 5 (20,8%) group and it can be concluded that between ACEi and ARB drugs(P=0.5) there was no differsignificantly in achievement blood pressure target on type 2 diabetes with hypertension.

Kidney Function, ACE-Inhibitor/Angiotensin Receptor Blocker Use, and Survival Following Hospitalization for Heart Failure: A Cohort Study

Background:Angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (ACE-I/ARB) improve outcomes in patients with heart failure and reduced left-ventricular (LV) systolic function. However, these medications can cause a rise in serum creatinine and their benefits in patients with HF accompanied by kidney disease are less certain.Objective:To characterize associations between estimated glomerular filtration rate (eGFR), patterns of ACE-Is and ARBs use, and 1-year survival following hospitalization for heart failure (HF).Design:We formed a retrospective cohort study of patients admitted with HF and followed HF medication prescriptions using the pharmaceutical information network, stratified by discharge eGFR.Setting:Cardiology services in 3 centers in Southern Alberta, Canada.Patients:The study cohort included patients admitted to hospital with a clinical diagnosis of HF.Measurements:eGFR was determined from inpatient laboratory data prior to discharge. Outpatient prescription data prior to and following the index hospitalization was obtained using the Pharmaceutical Information Network of Alberta and survival was determined from provincial vital statistics.Methods:Characteristics of the HF cohort were obtained from the Admissions Module of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. Multivariable Cox proportional hazards models were used to evaluate the association between time-varying ACE-I/ARB use, and mortality, and to test whether eGFR modified this association.Results:Totally, 1404 patients were included. Within the first 3 months following discharge, ACE-I/ARBs were used in 71%, 67%, 62%, and 52% for those with eGFR > 90, 45-89, 30-44, and < 30 mL/min/1.73 m2, respectively, with differences in use persisting after 1 year of follow-up. Patients with eGFR < 45 mL/min/1.73 m2 had significantly lower rates of ACE-I/ARB use following hospitalization. In adjusted models, ACE-I/ARB use following discharge was associated with 25% lower risk of mortality (Hazard Ratio [HR]: 0.75, 95% confidence interval [CI]: 0.61-0.92; P < 0.01), without evidence that this association differed by eGFR (P = 0.75).Limitations:LV function measurements were not available for the cohort. Due to the observation design of the study, treatment-selection bias may be present.Conclusion:Patients with HF and reduced eGFR at time of hospital discharge were less likely to receive ACE-I/ARB despite these medications being associated with lower mortality independent of eGFR. These findings demonstrate the need for further research on strategies for safe use of ACE-I and ARB in patients with HF and kidney disease.

A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis.

IntroductionNon-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide. Experimental and small clinical trials have demonstrated that angiotensin II blockers (ARB) may be anti-fibrotic in the liver. The aim of this randomised controlled trial was to assess whether treatment with Losartan for 96 weeks slowed, halted or reversed the progression of fibrosis in patients with non-alcoholic steatohepatitis (NASH).MethodsDouble-blind randomised-controlled trial of Losartan 50 mg once a day versus placebo for 96 weeks in patients with histological evidence of NASH. The primary outcome for the study was change in histological fibrosis stage from pre-treatment to end-of-treatment.ResultsThe study planned to recruit 214 patients. However, recruitment was slower than expected, and after 45 patients were randomised (median age 55; 56% male; 60% diabetic; median fibrosis stage 2), enrolment was suspended. Thirty-two patients (15 losartan and 17 placebo) completed follow up period: one patient (6.7%) treated with losartan and 4 patients (23.5%) in the placebo group were “responders” (lower fibrosis stage at follow up compared with baseline). The major reason for slow recruitment was that 39% of potentially eligible patients were already taking an ARB or angiotensin converting enzyme inhibitor (ACEI), and 15% were taking other prohibited medications.ConclusionsDue to the widespread use of ACEI and ARB in patients with NASH this trial failed to recruit sufficient patients to determine whether losartan has anti-fibrotic effects in the liver.Trial registrationISRCTN 57849521

The Effectiveness of Combination Antihypertensive Therapy in Women With Hypothyroidism and the Metabolic Syndrome

Evaluating the effectiveness of the various options of combination antihypertensive therapy (AHT) in women with arterial hypertension (AH) and metabolic syndrome (MS) and hypothyroidism. The study included 163 women with hypertension, metabolic syndrome, and hypothyroidism, the median age of 53.5 (48-60) years; in 73 (44.8%) women were diagnosed with subclinical hypothyroidism (SH), 90 (55.2%) - overt hypothyroidism (OH). Patients with both SH and OH, depending on the source of the heart rate (HR) was appointed as one of the following combination of AHT. If heart rate <75 beats/min, patients (n=100) received a combination of the dihydropyridine calcium antagonist (AA) amlodipine 5 mg/day, and angiotensin receptor blockers II (ARB) losartan 50 mg/day, with heart rate >75 beats/min (n=63) - a combination of amlodipine 5 mg/day and imidazoline receptor agonist (IRA) moxonidine 200 micrograms/day. The failure to achieve target blood pressure (BP) after 4 weeks of dose drugs doubled with subsequent evaluation of the effectiveness even after 4 weeks. At baseline and after 6 months of therapy, all patients underwent daily blood pressure monitoring (DBPM). At 8 weeks, the use of a combination of AA+ARB target BP level was registered in 26 (59%) of 44 women with SH and 34 (60.7%) of the 56 - OH. In the group of women who took the AA+IRA, after 8 weeks of the target blood pressure was observed in 24 (82.8%) of 29 patients with SH and 28 (82.4%) of 34 - to OH. Register the target blood pressure was observed significantly more frequently (p<0,05) when using a combination of AA+IRA compared with AA+ARBs as with SH and OH. As a result of the combination of DBPM AA and ARBs in patients with SH and OG provided a significant reduction in average daily, daytime and nighttime systolic and diastolic blood pressure (SBP and DBP), the time index of SBP and DBP during the day and night hours. The therapy of AA and IRA regardless of the severity of hypothyroidism, there was a significant improvement in all indicators DBPM: average daily, daytime and nighttime SBP and DBP, time index and variability in SBP and DBP during the day and at night. Furthermore, as in the SH and OH significantly more pronounced positive changes most DBPM parameters were recorded using IRA in combination with AA compared with a combination AA+ARB. Significant increase in the number of women with optimal BP daily profile "dipper" observed only when using amlodipine and moxonidine. In women with hypertension, hypothyroidism and MS, regardless of the severity of decline of thyroid function and combination of the dihydropyridine AA IRA had an advantage over the AA combination with ARBs, since most patients provided achieving target blood pressure and clinically significant positive impact on BPM indicators. The results can be used in selecting the optimal AHT in patients with hypertension, MS, and the manifest subclinical hypothyroidism.

Abstract 17683: LCZ696 vs. ACEI/ARB for Hypertension: A Meta-analysis of Randomized Controlled Trials

Introduction: LCZ696 is a first-in-class inhibitor of the angiotensin II receptor and Neprilysin. The use of LCZ696 in Heart Failure is promising compared to ACEI or ARB. The use of LCZ696 for blood pressure has been studied but controversial. We performed a meta-analysis of randomized controlled trials (RCTs) comparing LCZ696 to ACEI/ARB for lowering systolic blood pressure effect. Objectives: To assess the efficacy of LCZ696 on systolic blood pressure in comparison to angiotensin-converting-enzyme inhibitor (ACEI)/Angiotensin II receptor antagonist (ARB). Methods: We searched PubMed, Medline, Embase and Cochrane for prospective RCTs that compared LCZ696 versus ACEI or ARB in patients with established diagnosis of essential hypertension. Trials that included patients with essential hypertension with or without heart failure were randomized to either LCZ696 or ACEI or ARB, and that also reported at least one of the studied outcomes were included. Study quality was assessed using the Jadad score. Heterogeneity of the studies was analyzed by Cochran’s Q statistics. Mean differences were calculated using the random effect model. Results: Three RCTs met our inclusion criteria and included 8996 patients who had mild-moderate essential hypertension and were between18-75 years. They were randomized to LCZ696 versus ACEI or ARB. The use of LCZ696 was associated with improved systolic blood pressure control when compared to the control group (MD -3.89; 95% CI -7.75, -0.04; P=0.05). Conclusions: Our findings suggest that the use of LCZ696 in hypertensive patients provides better reduction of blood pressure when compared to an ACEI or an ARB.

The Risk of Hypertension after Preoperative Discontinuation of Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Antagonists in Ambulatory and Same-Day Admission Patients

The continued use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II subtype I receptor antagonists (ARBs) medications in the preoperative period has been reported to be associated with intraoperative hypotension that can be unresponsive to pressor drugs. As a result, several investigators suggested discontinuation of these medications before scheduled surgery but did not report on unintended consequences that might result from discontinuation. We conducted a prospective, single-blind, randomized trial to observe the effect of the medications on preoperative arterial blood pressure recordings in patients presenting for ambulatory and same-day surgery. Six hundred forty-four patients presenting for ambulatory and same-day surgery were enrolled prospectively between 2006 and 2011 and randomly assigned to 2 groups based on continuation or discontinuation of ACEIs and ARBs. An intention-to-treat analysis was performed. The primary outcome was presence of hypertension (HTN) immediately before surgery. Secondary outcomes included surgical cancellations due to HTN, prolongation of hospitalization, adverse clinical events, and HTN in the postoperative period. Data for 526 patients were analyzed. There were 262 patients in the discontinuation group and 264 patients in the continuation group. Discontinuation of ACEIs and ARBs on the day of surgery was not associated with increased prevalence of preoperative HTN (P = 0.775). The upper bound of a 95% confidence interval for the difference in prevalence of Stage 1 and 2 HTN between study arms indicates that discontinuation of study medication is unlikely to be associated with an increase in Stage 1 HTN of >4.8 percentage points and in Stage 2 HTN of no >5.8 percentage points. Discontinuation was not associated with an increase in postoperative HTN, with prolongation of hospitalization or with adverse clinical events. Discontinuing ACEIs and ARBs in patients on the day of surgery did not result in a substantively increased incidence of pre- or postoperative HTN compared with patients who continued these medications on the day of surgery. The results provide an evidentiary basis for the safety of discontinuing ACEIs and ARBs on the day of surgery without increasing adverse hemodynamic outcomes.

Economic evaluations of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in type 2 diabetic nephropathy: a systematic review

BackgroundStructured comparison of pharmacoeconomic analyses for ACEIs and ARBs in patients with type 2 diabetic nephropathy is still lacking. This review aims to systematically review the cost-effectiveness of both ACEIs and ARBs in type 2 diabetic patients with nephropathy.MethodsA systematic literature search was performed in MEDLINE and EMBASE for the period from November 1, 1999 to Oct 31, 2011. Two reviewers independently assessed the quality of the articles included and extracted data. All cost-effectiveness results were converted to 2011 Euros.ResultsUp to October 2011, 434 articles were identified. After full-text checking and quality assessment, 30 articles were finally included in this review involving 39 study settings. All 6 ACEIs studies were literature-based evaluations which synthesized data from different sources. Other 33 studies were directed at ARBs and were designed based on specific trials. The Markov model was the most common decision analytic method used in the evaluations. From the cost-effectiveness results, 37 out of 39 studies indicated either ACEIs or ARBs were cost-saving comparing with placebo/conventional treatment, such as amlodipine. A lack of evidence was assessed for valid direct comparison of cost-effectiveness between ACEIs and ARBs.ConclusionThere is a lack of direct comparisons of ACEIs and ARBs in existing economic evaluations. Considering the current evidence, both ACEIs and ARBs are likely cost-saving comparing with conventional therapy, excluding such RAAS inhibitors.

Comparative assessment of angiotensin ii type 1 receptor blockers in the treatment of acute myocardial infarction: surmountable vs. insurmountable antagonist

BackgroundThe mechanisms of antagonism vary between the angiotensin II type 1 receptor blockers (ARBs): insurmountable antagonism and surmountable antagonism. Recent retrospective observational studies suggest that ARBs may not have equivalent benefits in various clinical situations. The aim of this study was to compare the effect of two categories of ARBs on the long-term clinical outcomes of patients with acute myocardial infarction (AMI). MethodsWe analyzed the large-scale, prospective, observational Korea Acute Myocardial Infarction Registry study, which enrolled 2740 AMI patients. They divided by the prescription of surmountable ARBs or insurmountable ARBs at discharge. Primary outcome was major adverse cardiac events (MACEs), defined as a composite of cardiac death, nonfatal MI, and re-percutaneous coronary intervention, coronary artery bypass graft surgery. ResultsIn the overall population, the MACEs rate in 1year was significantly higher in the surmountable ARB group (14.3% vs. 11.2%, p=0.025), which was mainly due to increased cardiac death (3.3% vs. 1.9%, p=0.031). Matching by propensity-score showed consistent results (MACEs rate: 14.9% vs. 11.4%, p=0.037). In subgroup analysis, the insurmountable ARB treatment significantly reduced the incidence of MACEs in patients with left ventricular ejection fraction greater than 40%, with a low killip class, with ST segment elevation MI, and with normal renal function. ConclusionsIn our study, insurmountable ARBs were more effective on long-term clinical outcomes than surmountable ARBs in patients with AMI.

Tolerability of Angiotensin-Receptor Blockers in Patients with Intolerance to Angiotensin-Converting Enzyme Inhibitors

Between 5% and 20% of patients treated with angiotensin-converting enzyme inhibitors (ACE inhibitors) develop intolerance. Angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) can be used as an alternative treatment. In this study we aimed to evaluate the tolerability of ARBs in patients with intolerance to ACE inhibitors. The electronic databases PubMed, MEDLINE/EMBASE via Dialog, CENTRAL, and ISI Web of Knowledge were searched. Randomized controlled trials (RCTs) evaluating ARBs in patients with intolerance to ACE inhibitors were selected. Risk ratio (RR) and 95% confidence intervals (CIs) were estimated assuming the random effects method. We found 11 RCTs comparing ARBs with ACE inhibitors, diuretics, or placebo, and one RCT comparing high-dose versus low-dose ARB. ARBs had fewer cough events versus ACE inhibitors (RR 0.37; 95% CI 0.28, 0.48). ARBs had drug discontinuation (RR 0.99; 95% CI 0.84, 1.17) and cough risk (RR 1.01; 95% CI 0.74, 1.39) rates similar to placebo. Angioedema risk with ARBs was also similar to placebo (RR 1.62; 95% CI 0.17, 15.79). Compared with placebo, hypotension (RR 2.63; 95% CI 1.77, 3.92), renal dysfunction (RR 2.07; 95% CI 1.45, 2.95) and hyperkalemia (RR 3.37; 95% CI 1.60, 7.11) were more frequent with ARBs. ACE inhibitor rechallenge should be discouraged in patients with previous intolerance to ACE inhibitors due to a higher risk of cough. ARBs had cough and angioedema incidences similar to placebo. Despite a significantly higher incidence of hypotension, renal dysfunction and hyperkalemia, discontinuation of ARBs was similar to placebo.