Hypertension Management and End Organ Protection: Focus on Aliskiren

2009 ◽  
Vol 1 ◽  
pp. CMT.S1980
Author(s):  
Toshio Imanishi ◽  
Hiroto Tsujioka ◽  
Takashi Akasaka
Keyword(s):  
Ace Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Renin Inhibitor ◽  
Organ Protection ◽  
Renin Inhibitors ◽  
Direct Renin Inhibitor ◽  
Key Factor ◽  
Receptor Blockers

The renin-angiotensin system (RAS) activity is a key factor in the pathophysiology and development of hypertension, atherosclerosis, heart failure, and renal disease. It is unclear whether angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) have fully delivered the expected reductions in cardiovascular risk. In fact, the optimized RAS suppression is difficult to achieve with these agents, partly because ACE inhibitors and ARBs both activate compensatory feedback mechanisms that result in renin release and increase plasma renin activity (PRA). Molecular modeling was used to develop aliskiren, a potent, low-molecular-weight, nonpeptide, direct renin inhibitor with sufficient bioavailability to produce sustained suppression of PRA after oral administration. This report discusses the mechanisms of action of oral renin inhibitors and their pharmacokinetic properties. In addition, the report also evaluates the available data regarding the effects of the renin inhibitor aliskiren in the treatment of hypertension and related cardiovascular disorders.

scholarly journals Safety and Tolerability of Initiating Maximum-Dose Sacubitril-Valsartan in Patients on Target Dose Renin-Angiotensin System Inhibitors

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Helena Norberg ◽  
Ellinor Bergdahl ◽  
Krister Lindmark
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Ace Inhibitors ◽  
Maximum Dose ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Target Dose ◽  
Reduced Ejection Fraction ◽  
Receptor Blockers

Aim. Sacubitril-valsartan has proven beneficial in heart failure with reduced ejection fraction. Guidelines recommend initiating half-dose sacubitril-valsartan before up-titration even to patients already on target dose angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). To reduce the number of titration steps needed in order to simplify for the patient as well as the clinic, we aimed to investigate the safety and tolerability of switching patients on target dose ACE inhibitors or ARBs directly to maximum-dose sacubitril-valsartan. Methods. This prospective cohort study was conducted between April 2016 and November 2017. A total of 66 patients with heart failure and reduced ejection fraction already on guideline-recommended target dose ACE inhibitors or ARBs (equivalent to enalapril 10 mg twice daily) were switched to maximum-dose sacubitril-valsartan (200 mg twice daily). The patients were followed for twelve months. Results. Patients had a mean age of 72 ± 10 years, mean systolic blood pressure of 121 ± 17 mmHg, and 92% were male. At 12-month follow-up, nine patients (14%) had discontinued sacubitril-valsartan, four patients (6%) had a dose reduction, and 17 patients (26%) had developed symptomatic hypotension. No angioedema occurred within the 12-month follow-up and there were no hospitalizations or emergency room visits within the first 14 days. Conclusions. Switching directly from target dose ACE inhibitors or ARBs to maximum-dose sacubitril-valsartan was safe and generally well tolerated.

scholarly journals The dual blockade of the renin-angiotensin system in Internal Medicine: after ONTARGET trial

2013 ◽  
pp. 30-36
Author(s):  
F. Rondoni ◽  
F. Rossetti
Keyword(s):  
Heart Failure ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Renin Inhibitors ◽  
Direct Renin Inhibitors ◽  
Receptor Blockers ◽  
Dual Blockade ◽  
New Discovery

BACKGROUND In the increasing progress of scientific knowledge, every new discovery is a basis for new problems. In fact, after the success of Angiotensin-Converting Enzyme (ACE)-inhibitors in different cardiovascular diseases, the evidence of the “escape” of ACE and the discovery of Angiotensin- Receptor Blockers (ARBs) became the basis for a new question: is a dual blockade of the Renin-Angiotensin System (RAS) correct? DISCUSSION The different trials carried out (also the latest ONTARGET) didn’t give reliable answers, because differences were found both in the various diseases (hypertension, heart failure, coronary disease, nephropathy, diabetic or not), and between the single drugs of the class. We can say that this combination treatment didn’t show reliable clinical efficacy yet, except in heart failure and in some subgroups of hypertensive patients, checking carefully serum electrolytes and renal function. But even though we haven’t got certain outcomes, the research goes on quickly and some other sites of modulation of RAS were identified, from its first phases (aliskiren as prototype of direct renin inhibitors).

Telmisartan in High Cardiovascular Risk Patients

2012 ◽  
Vol 8 (1) ◽  
pp. 10 ◽  
Author(s):  
Roland Asmar ◽  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Ace Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
High Cardiovascular Risk ◽  
Raas Blockade ◽  
Risk Patients ◽  
Receptor Blockers ◽  
Current Guidelines

The worldwide morbidity and mortality burden of cardiovascular disease (CVD) is overwhelming and caused by increasing life expectancy and an epidemic of risk factors, including hypertension. Therapeutic options targeting different areas of the renin–angiotensin–aldosterone system (RAAS) to disrupt pathophysiological processes along the cardiovascular continuum are available. Angiotensin-converting enzyme (ACE) inhibitors are first-line treatments for CVD and angiotensin receptor blockers (ARBs) are suitable alternatives. Both ACE inhibitors and ARBs prevent CVD by lowering blood pressure (BP). Additionally, several studies have demonstrated that RAAS blockade can reduce cardiovascular risk beyond what might be expected from BP lowering alone. However, the ARBs are not all equally effective. Telmisartan is a long-lasting ARB that effectively controls BP over the full 24-hour period. Recently, the Ongoing telmisartan alone and in combination with ramipril global endpoint trial (ONTARGET) study showed that telmisartan reduces cardiovascular events in high cardiovascular risk patients similarly to the gold standard ACE inhibitor ramipril beyond BP lowering alone, but with a better tolerability. Based on the results of the ONTARGET and Telmisartan randomized assessment study in ACE intolerant subjects with cardiovascular disease (TRANSCEND) studies, telmisartan is indicated for the reduction of cardiovascular morbidity. This article aims to review current guidelines for the management of CVD and consider key data from clinical trials and clinical practice evaluating the role of telmisartan in CVD.

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