Aliskiren is FDA approved to treat hypertension in adults and children six years and older. It may be used as monotherapy or in combination with other antihypertensive agents. It is currently available as a combination product with hydrochlorothiazide as well as with amlodipine and hydrochlorothiazide.

Aliskiren first received approval in 2007 after demonstrating its antihypertensive effects in six randomized, double-blind, placebo-controlled trials. All patients included had mild to moderate hypertension. Most patients demonstrated a blood pressure-lowering effect within two weeks of treatment. These studies demonstrated a mean reduction in systolic blood pressure of 2.9 to 10 mmHg and a mean reduction in diastolic blood pressure of 3.3 to 8.6 mmHg.[1][2][3]

In November of 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) released updated treatment guidelines for patients with high blood pressure. According to the 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults, most patients will have a blood pressure goal of less than 130/80 mmHg. This guideline is a significant change from the 2014 JNC 8 Guidelines (Evidence-based guideline for the management of high blood pressure in adults: a report from panel members appointed to the Eighth Joint National Committee JNC8). The JNC 8 guidelines recommended a blood pressure goal of 140/90 mmHg for most patients and an even higher blood pressure goal for elderly patients. For patients over the age of 60, the JNC 8 guideline recommended a blood pressure goal of less than 150/90 mmHg.  

In addition to the new lower blood pressure goals, the ACC/AHA guidelines have a strong focus on decreasing the risk of cardiovascular disease. Their current recommendation is that patients with elevated blood pressure should receive treatment with medication to reduce cardiovascular risk by lowering blood pressure. However, aliskiren does not currently have outcome data available demonstrating cardiovascular disease (CVD) risk reduction with its use. The ACC/AHA guidelines emphasize the importance of blood pressure-lowering over drug selection, but initial recommendations for most patients currently include calcium channel blockers, thiazide diuretics, angiotensin-converting enzyme inhibitors (ACEI), and angiotensin-receptor blockers (ARB) because of their evidence of CVD risk reduction.

There is also no outcome data for using aliskiren in patients with diabetes mellitus and nephropathy, patients with coronary artery disease, or post-MI patients. The ATMOSPHERE study found aliskiren not to be inferior to enalapril in congestive heart failure patients in the primary composite endpoint of cardiovascular death or heart failure hospitalization. Aliskiren does not have an indication for these disease states and would probably not be a substitute for ACEIs or ARBs for these patients.

At this time, aliskiren remains a medication that would be most appropriate for use as an add-on therapy for patients already managed with one or more medications that have demonstrated the ability to decrease cardiovascular risk.[4][5]

Aliskiren is active in the renin-angiotensin-aldosterone system (RAAS). Renin secretion occurs by specialized cells found in the juxtaglomerular apparatus within the kidney based on changes in blood volume and renal perfusion as sensed by the macula densa in the distal tubule of the nephron. Renin is responsible for converting angiotensinogen to angiotensin I. Angiotensin I is then converted to angiotensin II by the angiotensin-converting enzyme (ACE), which is present in the capillaries of the lungs as well as endothelial cells present in the kidneys. Angiotensin II is believed to be the first active mediator in the RAAS system and exerts its effects by binding to the AT1 receptor and works as a vasoconstrictor, causing the release of catecholamines and promoting aldosterone secretion and sodium reabsorption. These effects together act to increase blood pressure. Angiotensin II also can inhibit renin release, causing negative feedback to the renin-angiotensin-aldosterone system. 

Aliskiren acts as a renin inhibitor, which blocks the conversion of angiotensinogen to angiotensin I. This effect subsequently decreases the formation of angiotensin II. Angiotensin II acts on the AT1 receptor, which is responsible for vasoconstriction, aldosterone secretion, and catecholamine release.

Hence blood pressure is decreased by decreasing the amount of angiotensin II to reach the AT1 receptor, thereby causing a decrease in vasoconstriction, aldosterone secretion, and catecholamine release. Any agent that works to inhibit the RAAS can suppress the negative feedback loop.

Aliskiren is available as 150 mg or 300 mg tablets. Patients usually initiate therapy on 150 mg daily and may be increased to 300 mg daily if necessary. Doses over 300 mg daily did not demonstrate any additional blood pressure lowering but did show an increased rate of diarrhea. Aliskiren is also available as oral pellets for patients who cannot swallow tablets. The pellets are available as a 37.5 mg capsule.

Aliskiren administration is via the oral route. It should be taken daily at the same time. Patients may take aliskiren with or without a meal, but the recommendation is for consistent administration with regard to meals. High-fat meals can decrease the absorption of aliskiren.

Aliskiren is also available in combination with hydrochlorothiazide in multiple strengths: 150-12.5 mg, 150-25 mg, 300-12.5 mg, and 300-25 mg, respectively.

It is also available in combination with amlodipine and hydrochlorothiazide: 150-5-12.5 mg, 300-5-12.5 mg, 300-5-25 mg, 300-10-12.5 mg, and 300-10-25 mg, respectively.

According to the package insert, the primary adverse effect of aliskiren is diarrhea, with 2.3% of patients experiencing it. Other common adverse effects include a cough, skin rash, headaches, and dizziness.

Clinical lab findings seen in clinical trials include: increased blood urea nitrogen or serum creatinine, small decreases in hemoglobin and hematocrit, increases in serum potassium, increased serum uric acid, and increased creatine kinase.

Serious adverse reactions reported in clinical trials include fetal toxicity, anaphylactic reactions, head and neck angioedema, and hypotension.  

According to the manufacturer, aliskiren is contraindicated in patients with a known hypersensitivity to any component, in pediatric patients less than two years, and in patients with diabetes mellitus who are taking an ACE inhibitor or an angiotensin receptor blocker.

Patients should not use aliskiren in pregnancy or if they are taking an ARB or ACEI. Caution is necessary for patients who have volume depletion.