Angiotensin II receptor antagonist

In pharmacology, Angiotensin II receptor antagonists, also called Angiotensin II Type 1 receptor blockers ('ARBs) are "agents that antagonize angiotensin II type 1 receptor. Included are angiotensin II analogs such as saralasin and biphenylimidazoles such as losartan. Some are used as antihypertensive agents."

Inhibition of the renin-angiotensin system is used to treat hypertension, heart failure, and chronic kidney disease.

Mechanism of action

Angiotensin II receptor antagonists block angiotensin II AT₁ receptors, in contrast to angiotensin-converting enzyme inhibitors, which block the conversion of angiotensin I to the hypertensive angiotensin II. Along with Angiotensin-converting enzyme inhibitors. Randomized controlled trials have investigated the use of the two classes together for a synergistic effect, but have found increased adverse effects with no added benefit from their combination.

Applications

Hypertension

A meta-analysis by the Cochrane Collaboration concluded:

• The blood pressure "lowering effect of ARBs is modest and similar to ACE inhibitors as a class; the magnitude of average trough BP lowering for ARBs at maximum recommended doses and above is -8/-5 mmHg. Furthermore, 60 to 70% of this trough BP lowering effect occurs with recommended starting doses."
• "There are no clinically meaningful BP lowering differences between available ARBs."

Heart failure

Two meta-analyses have review the role of adding ARBs to ACE inhibitors:

• "ARBs should not routinely be added to ACEI therapy for left ventricular dysfunction."
• "Combination ARB plus ACE inhibitor therapy in subjects with symptomatic left ventricular dysfunction was accompanied by marked increases in adverse effects."

Clinical practice guidelines state:

• 2011 The National Institute for Health and Clinical Excellence
  • Consider adding an ARB, but the guideline lists the option of adding an aldosterone antagonist first
• 2008 European Society of Cardiology:
  • "Unless contraindicated or not tolerated, an ARB is recommended in patients with HF and an LVEF ≤40% who remain symptomatic despite optimal treatment with an ACEI and β-blocker, unless also taking an aldosterone antagonist."
• 2009 update of ACC/AHA guidelines:
  • "Addition of an aldosterone antagonist is recommended in selected patients with moderately severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal function and normal potassium concentration. Creatinine should be 2.5 mg per dL or less in men or 2.0 mg per dL or less in women and potassium should be less than 5.0 mEq per liter."
  • "potassium should be reassessed within 1 to 2 weeks after initiation and followed closely after changes in dose"

Chronic kidney disease

ARBs may also be used to protect the kidneys.

Adverse effects

Hyperkalemia

Angiotensin II receptor antagonists can cause hyperkalemia. The rise in potassium has been reported to be both similar to and less that occurs with angiotensin-converting enzyme inhibitors. A newer factorial randomized controlled trial has compared these drugs.

Angioedema

Patients who previously had angioedema (a hypersensitivity reaction) with angiotensin-converting enzyme inhibitors may be at increased risk of angioedema with angiotensin II receptor antagonists.

Cancer

ARBs may increase the rate of cancer.