Angiotensin Receptor Blockers In Hypertension Research Articles

Angiotensin Receptor Blockers in the Management of Hypertension: A Real-World Perspective and Current Recommendations.

Hypertension represents a major common cardiovascular risk factor. Optimal control of high blood pressure levels is recommended to reduce the global burden of hypertensive-mediated organ damage and cardiovascular (CV) events. Among the first-line drugs recommended in international guidelines, renin-angiotensin-aldosterone system antagonists [angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs)] have long represented a rational, effective, and safe anti-hypertensive pharmacological strategy. In fact, current US and European guidelines recommend ACEi and ARBs as a suitable first choice for hypertension treatment together with calcium channel blockers (CCBs) and thiazide diuretics. Different studies have demonstrated that ARBs and ACEi exert a comparable effect in lowering blood pressure levels. However, ARBs are characterized by better pharmacological tolerability. Most importantly, the clinical evidence supports a relevant protective role of ARBs toward the CV and renal damage development, as well as the occurrence of major adverse CV events, in hypertensive patients. Moreover, a neutral metabolic effect has been reported upon ARBs administration, in contrast to other antihypertensive agents, such as beta-blockers and diuretics. These properties highlight the use of ARBs as an excellent pharmacological strategy to manage hypertension and its dangerous consequences. The present review article summarizes the available evidence regarding the beneficial effects and current recommendations of ARBs in hypertension. The specific properties performed by these agents in various clinical subsets are discussed, also including an overview of their implications for the current COVID-19 pandemic.

Effect of ACEi and ARBs vs Non ACEi/ ARBs in Hypertension with Respect to Renal Outcomes in COVID-19 Infection: A Retrospective Cohort Study

Introduction: The Acute Kidney Injury (AKI) is one of the most common complications following Coronavirus Disease2019 (COVID-19) infection. The presence of high density of Angiotensin Converting Enzyme 2 (ACE2) receptors in Type 2 alveolar epithelial cells, vascular endothelium and proximal convoluted tubules explains the involvement of systemic organs in COVID-19 infection. Systemic hypertension is one of the most common co-morbidities associated with COVID19 infection with high mortality, specially in patients of severe disease with AKI. The antihypertensives, which work by Renin Angiotensin Aldosterone System (RAAS) inhibition like ACE inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs) can upregulate the enzyme ACE2, so the incidence and risk of AKI in hypertensive patients who have COVID-19 infection is common. Aim: To determine the risk of developing AKI and mortality in hypertensive patients, with COVID-19 infection, on ACEi or ARBs as compared to non ACEi and non ARBs. Materials and Methods: This was a retrospective cohort study conducted on 116 admitted hypertensive patients, who were positive for COVID-19 infection from the month of April 2021 to September 2021. The study patients were divided into two groups- group A and group B. The group A was on ACEi or ARBs and group B was on non ACEi/ARBs. The patients baseline history, clinical examination and the blood investigations like Renal Function Test (RFT), Liver Function Test (LFT), Echocardiography (ECG), Chest X-ray, 2 Dimensional ECHO (2D-ECHO), Arterial Blood Gases (ABG) were done for all the patients. The normal Blood Pressure (BP) was less than 140/90 mmHg.The normal creatinine was 0.6 to 1.5 mg/dL and normal urea was 19 to 45 mg/dL. The RFT was repeated on every day of hospital stay duration. The patients were followed-up for one month from day of starting the study. The parameters were recorded, assessed on day 7th and day 30th of the study. All parameters were compared between the final outcome of the patients by 30th day of study and the class of antihypertensives used to control hypertension. The Pearson’s Chi-square test, Fisher’s exact and Analysis of Variance (ANOVA) were used for testing the significance of relationship and outcome between group A and group B study patients. Results: The mean duration of hypertension in both the groups was 7.6 years. In group A 53 (45.7%) were on ACEi and ARBs, in group B, 63 (54.3%) were on non ACEi/ARBs. In the group A, the serum creatinine of more than >1.5 mg/dL at 7th day of study was found in 28 (52.8%) patients and on 30th day it was found in 8 (15.09%) patients (p-value=0.065). Again in the group A, blood urea of more than 45 mg/dL on 7th day of study was found in 30 (56.6%) patients and on 30th day it was found in 9 (16.98%) patients (p-value=0.064). In the group B, the serum creatinine >1.5 mg/dL on day 7th of study was found in 36 (57.14%) patients and on day 30th it was in 24 (38.09%) patients (p-value=0.061). Again in group B, the blood urea of >45 mg/dL on day 7th was found in 35 (55.55%) patients and on day 30th it was found in 16 (25.39%) patients (p-value=0.074). Of the patients on group A (ACEi and ARBs) 28 (52.83%) were on supplemental oxygen, 12 (22.6%) were on Non Invasive Ventilation (NIV), one was intubated and 12 (22.6%) did not require oxygen (p-value=0.727). Of the patients on group B (non ACEi/ARBs) 33 (52.4%) were on supplemental oxygen, 12 (19.04%) were on NIV, 5 (7.93%) were intubated and 13 (20.63%) did not require oxygen. In the patients of group A, 35 (66.03%) were recovered and 18 (33.96%) died, in the group B 40 (63.49%) cases were recovered, while 23 (36.50%) died (p-value=0.781). Conclusion: There was no significant and demonstrable association between specific groups of antihypertensives with renal outcomes and mortality in hypertensive patients with COVID-19 infection. By above observations this study concludes that, there is no specific role of ACE2 receptors in renal outcome and mortality in hypertension with COVID-19 infection.

Angiotensin II and the Cardiac Parasympathetic Nervous System in Hypertension.

The renin–angiotensin–aldosterone system (RAAS) impacts cardiovascular homeostasis via direct actions on peripheral blood vessels and via modulation of the autonomic nervous system. To date, research has primarily focused on the actions of the RAAS on the sympathetic nervous system. Here, we review the critical role of the RAAS on parasympathetic nerve function during normal physiology and its role in cardiovascular disease, focusing on hypertension. Angiotensin (Ang) II receptors are present throughout the parasympathetic nerves and can modulate vagal activity via actions at the level of the nerve endings as well as via the circumventricular organs and as a neuromodulator acting within brain regions. There is tonic inhibition of cardiac vagal tone by endogenous Ang II. We review the actions of Ang II via peripheral nerve endings as well as via central actions on brain regions. We review the evidence that Ang II modulates arterial baroreflex function and examine the pathways via which Ang II can modulate baroreflex control of cardiac vagal drive. Although there is evidence that Ang II can modulate parasympathetic activity and has the potential to contribute to impaired baseline levels and impaired baroreflex control during hypertension, the exact central regions where Ang II acts need further investigation. The beneficial actions of angiotensin receptor blockers in hypertension may be mediated in part via actions on the parasympathetic nervous system. We highlight important unknown questions about the interaction between the RAAS and the parasympathetic nervous system and conclude that this remains an important area where future research is needed.

Is the newest angiotensin-receptor blocker azilsartan medoxomil more efficacious in lowering blood pressure than the older ones? A systematic review and network meta-analysis.

Angiotensin‐receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin‐receptor blockers may be more effective than the older ones. A network meta‐analysis was performed to compare the efficacy of various angiotensin‐receptor blockers in reducing office and ambulatory blood pressure in hypertensive patients. Relevant literature was searched from English and Chinese databases for randomized controlled trials involving angiotensin‐receptor blockers in hypertension. Efficacy variables included systolic and diastolic blood pressure either in the office or on ambulatory blood pressure monitoring. Absolute blood pressure reductions at 6‐12 weeks of treatment and their credible intervals were reported. A total of 34 publications provided adequate data for analysis (n = 14 859). In 28 studies on office systolic blood pressure (n = 12 731), against the common comparator valsartan 80 mg, the differences in systolic blood pressure were in favor of azilsartan medoxomil (20‐80 mg), irbesartan (300 mg), olmesartan (20‐40 mg), telmisartan (80 mg), and valsartan (160‐320 mg), but not candesartan (8‐16 mg), losartan (50‐100 mg), irbesartan (150 mg), olmesartan (10 mg), and telmisartan (40 mg). The ranking plot shows that azilsartan medoxomil 80 mg had a possibility of 99% being the best in the class. Similar results were observed for office diastolic blood pressure and from 13 studies for 24‐hour ambulatory systolic and diastolic blood pressure. In conclusion, angiotensin‐receptor blockers had different blood pressure lowering efficacy. The newest angiotensin‐receptor blocker azilsartan medoxomil at the dose of 80 mg seemed to be most efficacious in reducing both systolic and diastolic blood pressure in the office and on ambulatory measurement.

Assessment of the utilization of angiotensin receptor blockers in hypertension

To assess the degree in which the utilization of angiotensin receptor blockers (ARBs) in our Healthcare Area fits the criteria proposed by the Autonomous Community of Madrid (CAM) before setting «Plan de Actuación de ARA-II» («Action Plan ARA-II»). To study the indications for which are prescribed and to identify those factors that can show influence in prescription. Drug utilization study of the type indication-prescription, descriptive and transversal, for which ARBs-treated and hypertensive patients admitted to a University General Hospital for a study period of 3 months were selected. Based on the clinical situations summarized in the CAM Document «Criterios para establecer el lugar en la terapéutica de los antagonistas de los receptores de la angiotensina II» («Criteria for the place of angiotensin receptor blockers in the therapeutic»), a percentage of patients with «appropriate prescription» and «inadequate prescription« of ARBs was calculated and analyzed in order to determine if the age and the sex were related to the type of prescription or the main indications for which they had been prescribed. Out of the 153 patients included in the study, 67.3% had a «inadequate prescription«, 47.6% of them due to an ARBs prescription as the first drug inhibitor of the reninangiotensin- aldosterone system and 34.0% owing to a poor control of blood pressure with angiotensin-converting enzyme inhibitors (ACEi). There were no statistically significant differences found either by age or sex in the type of prescription or in the main indications for which they were prescribed. The adequacy of the criteria for the utilisation of ARBs Document occurred in 32.7% of cases. In addition, factors such as age and sex did not seem to affect the type of prescription. Misconceptions of superiority of ARBs versus ACEi were evidenced as well.

Angiotensin receptor blockers in hypertension. New insights from Japan

Angiotensin II receptor blockers (ARBs) are widely used in the treatment of patients with hypertension, heart failure, diabetic nephropathy and other clinical conditions. Several intervention trials and systematic overviews showed that both angiotensin-converting enzyme inhibitors and ARBs effectively reduce the risk of stroke, myocardial infarction and congestive heart failure in hypertensive patients. Two recent intervention trials conducted in Japan (JIKEI and Kyoto studies) suggested that the protective effect of ARBs on major cardiovascular events might be partly independent from the degree of blood pressure (BP) reduction. Both studies used a prospective randomized open blinded end point (PROBE) design. No significant differences emerged in both studies between the ARB group (valsartan) and the control group in the achieved BP. We made a pooled analysis of the JIKEI and Kyoto studies. Overall, valsartan significantly reduced the risk of the primary composite outcome (by 42%; P<0.0001), angina pectoris (by 38%; P<0.0001), heart failure requiring hospitalization (by 43%; P=0.013) and cerebrovascular events (by 42%; P=0.002). The protective effect on the dissecting aneurysm of aorta bordered statistical significance. These data reinforce the notion that the protective effect of angiotensin II inhibition is partly independent of BP reduction.

The surge of Japanese studies supporting the use of angiotensin receptor blockers in hypertension

The surge of Japanese studies supporting the use of angiotensin receptor blockers in hypertension

Response to: Angiotensin receptor blockers in hypertension: the emerging role in diabetes mellitus

Response to: Angiotensin receptor blockers in hypertension: the emerging role in diabetes mellitus

Therapeutic potential of angiotensin receptor blockers in hypertension

The renin–angiotensin–aldosterone system plays a key role in the regulation of fluid and electrolyte balance. Angiotensin II receptor blockers (ARBs) inhibit angiotensin II type 1 receptors and large clinical trials have shown that they are effective in many cardiovascular diseases including hypertension, heart failure, myocardial infarction and diabetic nephropathy. They lower blood pressure effectively, are very well tolerated and can be used as monotherapy or in combination with other drug classes for the treatment of hypertension. ARBs are particularly suitable for hypertensive patients with co-morbities such as diabetes, microalbuminuria, proteinuria, left ventricular hypertrophy and heart failure. Unlike angiotensin-converting enzyme inhibitors, ARBs do not cause persistent dry cough. For patients in whom angiotensin-converting enzyme inhibitors are indicated but not tolerated, an ARB should be considered. Periodic monitoring of renal function and electrolytes is required in patients treated with an ARB.

Meta-analysis of large outcome trials of angiotensin receptor blockers in hypertension

Angiotensin receptor blockers (ARBs), also known as sartans, block the activation of angiotensin type 1 receptors and have a recognised role in the treatment of heart failure and nephropathy. Since 2002, there have been three major outcome trials of ARBs in hypertension. We performed a meta-analysis to evaluate the impact of ARB on major outcomes. Randomised controlled trials of ARBs in hypertensive subjects with an average follow-up of at least 2 years and at least 100 major cardiovascular events were included. For each trial, the ARB used, number and characteristics of subjects, baseline and change in blood pressure, cardiovascular and noncardiovascular outcomes were recorded. Three trials involving 29 375 subjects were included in the meta-analysis. In Losartan Intervention For Endpoint (LIFE) and Study on Cognition and Prognosis in the Elderly (SCOPE) but not in Valsartan Antihypertensive Long-term Use Evaluation trial (VALUE), an ARB reduced the occurrence of the primary end point and stroke compared to control. Compared to other antihypertensive drugs, ARB treatment was associated with no significant change in all-cause mortality (relative risk ratio (RRR) 0.96, 95% CI: 0.88-1.06, P = 0.45). There was an increase in myocardial infarction (RRR, 1.12, 95% CI: 1.01-1.26, P = 0.041), but a decrease in new-onset diabetes mellitus (RRR, 0.80, 95% CI: 0.74-0.86, P < 0.0000001). In conclusion, the reduction in new-onset diabetes partly offsets any increase in the risk of myocardial infarction. Most hypertensive patients require more than one class of drugs. Small differences in treatment outcome should not over-ride the importance of good blood pressure control.

Renin Inhibition

Experimental and clinical studies have highlighted the importance of the local renin-angiotensin system (RAS) as a pathogenetic factor in various tissues, including the kidney, heart, and eye.1 These studies have indicated that blockade of the RAS is an important therapeutic strategy in reducing cardiovascular and renal disease. However, the therapeutic response achieved with current blockers of the RAS—angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)—although efficacious, is limited. This may be partly because of the reactive rise in renin that these agents induce with the resultant increase in angiotensin peptides. Other, more effective strategies to block the RAS have, therefore, been sought. Angiotensin II, the major effector molecule of this system, is synthesized in a multistep process in which angiotensinogen is cleaved by the aspartic peptidase, renin, produced mainly in the juxtaglomerular cells of the kidney, to give to rise to angiotensin I. …

Prevention of cardiovascular events and diabetes with angiotensin-receptor blockers in hypertension: Life, scope, and value

Introduction Hypertension increases the risk for major cardiovascular events and progression of cardiovascular disease. Even modest reductions in blood pressure confer substantial reductions in risk for events. The renin-angiotensinaldosterone system (RAAS) and its principal mediator, angiotensin II, have pivotal roles in the shortand longterm regulation of blood pressure and in the prognosis of hypertension. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARB), which interfere with the vasoconstrictive and trophic effects of angiotensin II, have blood pressure-lowering effects similar to other antihypertensive agents but also have vasculoprotective properties and preserve renal function in patients with nephropathy due to diabetes and from other causes. Three trials have evaluated the effects of ARB treatment in patients with hypertension and manifestations of cardiovascular disease and/or diabetes. These trials focused on various patient populations based on age and cardiovascular risk level, used different comparator agents (eg, placebo, β-blocker, calcium antagonist), and had different primary end points.

Meta-analysis of large outcome trials of angiotensin receptor blockers in hypertension

Angiotensin receptor blockers (ARBs), also known as sartans, block the activation of angiotensin type 1 receptors and have a recognised role in the treatment of heart failure and nephropathy. Since 2002, there have been three major outcome trials of ARBs in hypertension. We performed a meta-analysis to evaluate the impact of ARB on major outcomes. Randomised controlled trials of ARBs in hypertensive subjects with an average follow-up of at least 2 years and at least 100 major cardiovascular events were included. For each trial, the ARB used, number and characteristics of subjects, baseline and change in blood pressure, cardiovascular and noncardiovascular outcomes were recorded. Three trials involving 29 375 subjects were included in the meta-analysis. In Losartan Intervention For Endpoint (LIFE) and Study on Cognition and Prognosis in the Elderly (SCOPE) but not in Valsartan Antihypertensive Long-term Use Evaluation trial (VALUE), an ARB reduced the occurrence of the primary end point and stroke compared to control. Compared to other antihypertensive drugs, ARB treatment was associated with no significant change in all-cause mortality (relative risk ratio (RRR) 0.96, 95% CI: 0.88-1.06, P = 0.45). There was an increase in myocardial infarction (RRR, 1.12, 95% CI: 1.01-1.26, P = 0.041), but a decrease in new-onset diabetes mellitus (RRR, 0.80, 95% CI: 0.74-0.86, P < 0.0000001). In conclusion, the reduction in new-onset diabetes partly offsets any increase in the risk of myocardial infarction. Most hypertensive patients require more than one class of drugs. Small differences in treatment outcome should not over-ride the importance of good blood pressure control.