aliskiren and azilsartan

Early phase studies of novel interventions for hypertension, such as renal sympathetic denervation, are sometimes single-armed (uncontrolled). We explored the wisdom of this by quantifying the blood pressure fall in the placebo arms of contemporary trials of hypertension. We searched Medline up to June 2014 and identified blinded, randomized trials of hypertension therapy in which the control arm received placebo medication or a sham (placebo) procedure. For nonresistant hypertension, we have identified all such trials of drugs licensed by the US Food and Drug Administration since 2000 (5 drugs). This US Food and Drug Administration-related restriction was not applied to resistant hypertension trials. This produced 7451 patients, who were allocated to a blinded control from 52 trials of nonresistant hypertension and 694 patients from 8 trials of resistant hypertension (3 drugs and 2 interventions). Systolic blood pressure fell by 5.92 mm Hg (95% confidence interval, 5.14-6.71; P<0.0001) in the nonresistant cohort and by 8.76 mm Hg (95% confidence interval, 4.83-12.70; P<0.0001) in the resistant cohort. Using metaregression, the falls were larger in trials that did not use ambulatory blood pressure monitoring as an inclusion criterion (z=2.84; P=0.0045), in those with higher baseline blood pressures (z=-0.3; P=0.0001), and in those where the patients were prescribed a continuous background of antihypertensives (z=-2.72; P=0.0065). The nontrivial magnitude of these apparent blood pressure reductions with perfectly ineffective intervention (placebo) illustrates that efficacy explorations of novel therapies for hypertension, once safety is established, should be performed with a randomized, appropriately controlled, and blinded design.

Topics: Amides; Antihypertensive Agents; Benzimidazoles; Benzopyrans; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Control Groups; Double-Blind Method; Drug Resistance; Eplerenone; Ethanolamines; Fumarates; Humans; Hypertension; Imidazoles; Kidney; Nebivolol; Oxadiazoles; Placebo Effect; Placebos; Randomized Controlled Trials as Topic; Regression Analysis; Research Design; Spironolactone; Sympathectomy; Tetrazoles; Treatment Outcome

In the last few years, a number of important clinical trials have been completed that have investigated the inhibition of the renin-angiotensin system. New drugs, focusing on this system, have now emerged as a result.. The authors review the most relevant information available, reported from the last 5 years, pertaining to the most important clinical trials on renin-angiotensin system blockers (ARBs). The authors' data review includes the trials of aliskiren, telmisartan, olmesartan and azilsartan. The authors also review the possible risk of cancer with ARBs.. The results of ASPIRE and ALTITUDE trials strongly suggested that dual inhibition of aliskiren with either ARBS or angiotensin converting enzyme inhibitors (ACEi) should be avoided. Olmesartan is an effective and safe antihypertensive agent, but special attention should be paid to high-risk patients, such as those with coronary disease, to avoid an excessive reduction in blood pressure. The authors also note that while azilsartan is probably the most potent ARB, there is still a lack of data regarding potential organ damage and the incidence of cardiovascular events. Lastly, recent evidence has shown a lack of a relationship between ARB therapy and the occurrence of cancer.

Topics: Amides; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Blood Pressure; Clinical Trials as Topic; Drug Evaluation; Fumarates; Humans; Imidazoles; Meta-Analysis as Topic; Neoplasms; Oxadiazoles; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Risk Factors; Telmisartan; Tetrazoles

In addition to its role in regulation of blood pressure, fluid and electrolyte homeostasis, the renin-angiotensin system (RAS) components were expressed in many other tissues suggesting potential roles in their functions.. The present study aims to evaluate the protective effect aliskiren, when used alone or in combination with azilsartan against high fat diet-induced liver disease in rats.. Thirty-two Wistar male rats, weighing 150-200 gm were allocated evenly into four groups and treated as follow: group I, rats were fed a specially formulated high-fat diet for 8 weeks to induce non-alcoholic liver disease and considered as control group; groups II, III and IV, the rats were administered azilsartan (0.5 mg/kg), aliskiren (25 mg/kg) or their combination orally via gavage tube once daily, and maintained on high fat diet for 8 weeks. The possible treatment outcome was evaluated through measuring serum levels of glucose, insulin, lipid profile, TNF-α, IL-1β and liver enzymes. Additionally, the liver tissue contents of glycogen and lipids and histological changes were also evaluated.. The results showed that azilsartan significantly improves the studied markers greater than aliskiren, and their combination o has no additive or synergistic effects on the activity of each one of them.. Both azilsartan and aliskiren protects the rats against high-fat diet induced NAFLD with predominant effects for the former, and their combination showed no beneficial synergistic or additive effects.

Topics: Amides; Animals; Benzimidazoles; Diet, High-Fat; Disease Models, Animal; Drug Therapy, Combination; Fumarates; Liver; Male; Non-alcoholic Fatty Liver Disease; Oxadiazoles; Rats; Rats, Wistar