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New Hypertension Treatment: Aliskiren


New Hypertension Treatment: Aliskiren

For patients with mild-to-moderate uncomplicated essential high blood pressure, aliskiren has shown to be effective as a single treatment according to data emerging from early studies of the drug. This new medication has been suggested to be well tolerated and that patients exhibit good adherence to the once-a-day oral medication, according to results of initial randomized controlled clinical trials.

Worldwide, 1 billion people are affected by hypertension, and the WHO (World Health Organization) has estimated that about 7.1 million people die from complications of hypertension, which is 13% of all mortality.

A significant portion of treated hypertensive patients remain uncontrolled and face serious morbidity and mortality as a consequence, despite the availability of many effective and well-tolerated drugs. Adherence to therapy and the need for most patients to take more than one drug to control their hypertension are the current challenges in the drug treatment of hypertension.

Current drug treatments for hypertension include the ones mentioned below, used alone and/or in combinations:

  • Beta blockers
  • Diuretics
  • ARBs (aldosterone receptor blockers)
  • Alpha-1 blockers
  • Calcium channel blockers
  • ACE (angiotensin-converting enzyme) inhibitors


The first drug in a new class of antihypertensive drugs called renin inhibitors is aliskiren. The formation of a substance called angiotensin II, which is the key mediator in the regulation of body fluid volume and blood pressure, is controlled by the enzyme called renin.

The renin-angiotensin-aldosterone system plays a role in controlling blood pressure, and renin is the first enzyme is this system. Renin cleaves angiotensinogen to angiotensin I, which is in turn converted to angiotensin II by ACE. Blood pressure is affected both directly and indirectly by angiotensin II. Angiotensin II directly causes the contraction of the arterial smooth muscle, leading to vasoconstriction and increased blood pressure. The production of aldosterone from the adrenal cortex is also stimulated by angiotensin II, causing the tubules of the kidneys to increase reabsorption of sodium, with water following thereby increasing blood pressure and plasma volume. Aliskiren binds to the S3bp binding pocket of renin, which is essential for its activity. The conversion of angiotensinogen to angiotensin is prevented by the binding to this pocket. Some of the adverse effects of aliskiren include:
 

  • Rash, gout, elevated uric acid, and renal stones
  • Angioedema
  • Diarrhea and other gastrointestinal symptoms
  • Hypotension, especially in volume-depleted patients
  • Hyperkalmia, especially when used with ACE inhibitors with diabetic patients
  • In some rare cases, difficulty breathing and allergic swelling of the face, lips or tongue.


CONTRAINDICATIONS:

Breast feeding:

The drug has been found present in milk during animal studies.
 

Pregnancy:

Neonatal death and fetal malformations have been associated with other drugs that also act on the renin-angiotensin system, such as ACE inhibitors.

In patients with significantly impaired renal function, aliskiren hasn’t been evaluated yet.

 

DRUG INTERACTIONS:

Aliskiren is a minor substrate of CYP3A4, and more importantly, P-glycoprotein:
 

  • Possible interaction with ciclosporin. The simultaneous use of ciclosporin and aliskiren is contraindicated.
  • Reduces furosemide blood concentration
  • Blood concentration may be increased with atorvastatin, but no dose adjustment is needed.
  • You should be cautious when administering aliskiren with ketoconazole or other moderate P-gp inhibitors, such as amiodarone, clarithromycin, itraconazole, erythromycin, telithromycin.


The recommendations state that for patients under the age of 55, ACE inhibitors should be offered as first-line treatment and in the case of patients over the age of 55 and black patients of any age should be given calcium channel blockers or thiazide diuretics as first-line treatment.

 

WHEN SHOULD ALISKIREN BE USED??

There isn't any convincing evidence currently to support the choice of aliskiren above other more established agents. The efficacy of aliskiren in severe hypertension isn't known yet, and it hasn't been studied in combination with a number of these established agents.

If there are any benefits of inhibiting the renin angiotensin pathway at an earlier stage than with ACE inhibitors and angiotensin receptor blockers, they're still not clear. Compared with other available antihypertensive drugs, this drug is expensive, and there aren't any long-term clinical outcome data with this agent. To control BP, many people who have hypertension require more than one agent. In people with uncontrolled hypertension using traditional treatment algorithms, aliskiren may have a role as an add-on therapy.

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Prepared By: Dr. Mehyar Al-Khashroum
Edited By: Miss Araz Kahvedjian




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