Angiotensin II receptor blockers (ARBs): Uses, common brands, and safety info

High blood pressure is a common medical condition that affects hundreds of millions of Americans. Angiotensin II receptor blockers (ARBs) are a class of drugs used to lower blood pressure and are one of the first types of drugs that doctors will prescribe for this condition. They are highly effective and have been used to treat hypertension (high blood pressure) for decades. ARBs are used to treat other types of cardiovascular disease as well. This article will provide an overview of this class of medications. We will list the different brand and generic names, provide information on their cost, outline how the drugs work, and cover their uses and safety considerations.

Other ARBs

• Teveten (eprosartan)

ARBs are often combined with other antihypertensive drugs—such as a diuretic or calcium channel blocker—to reduce the number of pills patients take per day. Below are some examples:

• Exforge (valsartan and amlodipine)

• Avalide (irbesartan and hydrochlorothiazide)

• Azor (olmesartan and amlodipine)

• Twynsta (telmisartan and amlodipine)

• Hyzaar (losartan and hydrochlorothiazide)

• Diovan HCT (valsartan and hydrochlorothiazide)

• Benicar HCT (olmesartan and hydrochlorothiazide)

• Micardis HCT (telmisartan and hydrochlorothiazide)

What are angiotensin II receptor blockers (ARBs)?

Angiotensin II receptor blockers—or “ARBs” for short—are a class of medications used to treat high blood pressure. While all ARBs are FDA approved to treat high blood pressure, certain ARBs have FDA approval for use in other clinical situations such as heart failure, kidney disease related to diabetes, or prevention of cardiovascular events. ARBs are very commonly prescribed and have been used since the 1990s.

How do ARBs work?

The body regulates blood pressure and volume using a communication network called the renin-angiotensin-aldosterone system (RAAS). This system allows the kidneys to send signals to blood vessels and other organs. The kidneys produce a protein called renin. This protein is used to make angiotensin II, a hormone that tells the blood vessels, pituitary glands, and adrenal glands to increase blood pressure and blood volume.

This is where ARBs come in. These drugs block the effects of angiotensin II so that this hormone cannot communicate with other organs. Thus, ARBs prevent rise in blood pressure and blood volume.

ARBs are very similar to another class of blood pressure medication. Angiotensin-converting enzyme inhibitors, or “ACE inhibitors” for short, also interfere with the RAAS system. However, ACE inhibitors break down communication earlier in the signaling cascade, disrupting more lines of communication. ARBs interfere later in the cascade and block signals that are more specific to blood pressure control. For this reason, ARBs cause fewer adverse effects when compared to ACE inhibitors.

What are ARBs used for?

All ARBs are FDA approved for hypertension. Some ARBs such as losartan, candesartan, and valsartan are also FDA approved for a specific heart disease called congestive heart failure. Specific ARBs have other FDA-approved indications including:

• Prevention of CV events in patients with left ventricular dysfunction after a myocardial infarction (heart attack)

• Kidney disease caused by diabetes (proteinuria/microalbuminuria)

• Left ventricular hypertrophy

The following are FDA-approved indications for specific ARBs:

• Hypertension: All ARBs

• Heart failure: Candesartan, valsartan

• Left ventricular hypertrophy: Losartan, losartan-hydrochlorothiazide

• Myocardial infarction: Valsartan

• Kidney disease caused by diabetes: Losartan, irbesartan

ARBs are used “off-label” in other clinical situations such as:

• Atrial fibrillation

• Chronic kidney disease (CKD)

• Scleroderma

• Migraine prevention

Different ARBs exhibit slightly different properties. For this reason, certain ARBS are more useful for certain medical conditions. For example, candesartan has demonstrated effectiveness for preventing migraines due to its lipophilic properties.

While many ARBs can be used for a particular condition, specific ARBs may be necessary depending on patient characteristics. For example, losartan is the ARB of choice in patients who have hyperuricemia, while candesartan, olmesartan, and valsartan may worsen this condition. Some ARBs may be “preferred” over others for certain clinical scenarios. Losartan is the first-line option for hypertensive patients who are at high risk of stroke. Ultimately, it is up to the discretion of a physician to determine the best ARB for a particular patient.

Who can take ARBs?

Infants, children, and adolescents

Many ARBs are safe and effective for the treatment of hypertension in children. Losartan, valsartan, and olmesartan have FDA approval for use in children older than 6 years, while candesartan has approval for use in children older than 1 year. According to the National Kidney Foundation, these drugs may be preferred agents to slow the progression of CKD in children. Other ARBs have been prescribed “off-label” in children, despite limited data to support safety and efficacy in this population. Safe and effective use of ARBs in children requires dose adjustment based on age and weight.

Adults

ARBs are generally considered safe and effective for use in adults. The most common side effects are minor and may include dizziness, headache, cough, and drowsiness. Some patients may experience less tolerable side effects. It is important to consult a healthcare provider about troublesome side effects so that treatment can be adjusted accordingly. 

Seniors

ARBs are just as safe and effective in elderly patients as they are in younger patients. The elderly population constitutes most patients receiving renal replacement therapy, and ARBs may provide a significant benefit by slowing the progression of kidney disease. The most important adverse effect noted in elderly patients taking ARBs was increased serum potassium (hyperkalemia). Close monitoring of serum potassium is recommended for this patient population as the risk for hyperkalemia increases with age and the number of comorbidities.

Patient with liver impairment

Patients with liver disease who are taking ARBs may need to begin at a lower dose. The starting dose of losartan is 25 mg for patients with liver impairment; that is half the normal recommended starting dose. The package inserts for candesartan also recommends using half the normal starting dose for patients with liver disease. Because ARBs are primarily eliminated from the body by the liver, it is important to start at a low dose and carefully increase therapy in this patient population.

Are ARBs safe?

ARB recalls

Multiple distributors of valsartan, losartan, and irbesartan-containing products were recalled due to NMBA impurities. The recalls began in mid-2018 and continued through September 2019. An archive of updates and press announcements concerning these recalls is posted online by the FDA, as well as a comprehensive list of all products involved in the ongoing recalls of ARB medications. Distributors affected by the recalls include, but are not limited to, Teva, Macleods, Mylan, Torrent, Aurobindo, Solco Healthcare, Prinston, and Camber Pharmaceuticals. Your pharmacist can help with questions or concerns related to recalled medications.

ARB restrictions

Do not take any ARB medication if there is known hypersensitivity to any of its ingredients.

ARBs should be used with caution in patients with electrolyte imbalances including low sodium (hyponatremia) and high potassium levels (hyperkalemia). ARBs may worsen these imbalances by decreasing sodium retention at the proximal and distal tubules of the kidney, and by decreasing potassium secretion in the collecting duct.

Patients with a vascular disease, known as renal artery stenosis (RAS), in both kidneys, or patients with a single functional kidney and a diagnosis of RAS, should not take ARBs. ARBs affect blood circulation at the kidneys, which can lower the glomerular filtration rate in patients with severe renal disease. This can worsen kidney function and lead to kidney failure.

Similarly, volume depletion should be corrected in patients before starting therapy with an ARB. When a patient is volume depleted, the kidneys’ filtration rate is highly dependent on angiotensin II, thus ARBs may further compromise kidney function when taken in this state.

ARBs should not be taken by patients who are using ACE inhibitors or direct renin-inhibitors (DRI) such as Tekturna (aliskiren). All three types of medication work on the renin-angiotensin system and taking them together compounds the risk of renal impairment, hyperkalemia, and hypotension. Make sure your doctor is aware of all medications you are taking in order to avoid potentially dangerous drug interactions.

Can you take ARBs while pregnant or breastfeeding?

Stop taking an ARB as soon as you suspect you might be pregnant and contact your doctor immediately. ARBs should be avoided during pregnancy and breastfeeding if possible. All ARB medications carry a black box warning about potential harm or fatality to the fetus when ARBs are used in pregnancy.

Are ARBs controlled substances?

No, angiotensin II receptor antagonists are not controlled substances.

Common ARB side effects

The following are common side that may occur while taking ARBs. This is not an exhaustive list, as it only covers side effects common to all ARBs. Additional side effects may be common to individual drugs within this class. If you are experiencing worrisome or intolerable side effects, consult a doctor or pharmacist for further information and advice.

• Headache

• Diarrhea

• Cough

• Upper respiratory infection (URI)

• High potassium (hyperkalemia)

• Hypotension

• Dizziness

• Fatigue

• Asthenia (weakness or lack of energy)

• Musculoskeletal pain

ARBs have been known to cause a severe side effect called angioedema. However, this side effect is far less common in ARBs when compared to ACE inhibitors. This side effect is believed to be caused by bradykinin, a vasodilating peptide that can cause swelling and inflammation. ARBs do not increase bradykinin to the same level as ACE inhibitors.

How much do ARBs cost?

Many of the drugs in this class are available as generics at a lower cost than their brand-name counterpart. For example, Benicar can cost upward of $300 for a 30-day supply. The generic version, olmesartan, is available for less than $5 with a SingleCare coupon. While many brand-name ARBs cost more than $200, the generic versions typically cost less than $30 through SingleCare.

ARBs are covered by most Medicare and insurance plans, although some ARBs may be preferred over others. For example, losartan is typically listed as a tier 1 medication—or “preferred” drug-while some combination drugs like candesartan-hydrochlorothiazide may not be covered at all. Additionally, your insurance plan may determine coverage based on the diagnosis indicated on the patient’s prescription. Hypertension is the most likely diagnosis to warrant coverage.

Even if an insurance plan covers your medication, it may be less expensive to use a SingleCare coupon. 

Resources:

• An overview of generic angiotensin receptor blockers

• Other preventive anti-migraine treatments: ACE inhibitors, ARBs, calcium channel blockers, serotonin antagonists, and NMDA receptor antagonists

• More than 100 million Americans have high blood pressure

• The different therapeutic choices with ARBs. Which one to give? When? Why?

• KDIGO 2021 clinical practice guidelines for the management of blood pressure in chronic kidney disease

• Efficacy of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the preventative treatment of episodic migraine in adults

• Efficacy and safety of angiotensin II receptor blockade in elderly patients with diabetes,

• Angiotensin receptor blockers shift the circadian rhythm of blood pressure by suppressing tubular sodium reabsorption

• Hyperkalemia associated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers

• Angiotensin II Receptor Blockers (ARB)

• Angiotensin-converting enzyme inhibitors and receptor blockers in heart failure and chronic kidney disease – demystifying controversies