Dangers of Taking Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Together

A study published in the March 21, 2011, Canadian Medical Association Journal (CMAJ) found that people prescribed an angiotensin-converting enzyme inhibitor (ACEI) in combination with an angiotensin receptor blocker (ARB) had greater risks of kidney toxicity and higher blood levels of potassium compared to those using one of these two families of drugs alone.

ACEIs and ARBs are widely prescribed in the U.S. to treat heart failure, high blood pressure, kidney problems and other conditions in patients with type 2 diabetes. (Products containing either an ACEI or an ARB are listed in Tables 1 and 2.)

Previous gold-standard, randomized controlled trials had shown that the combination of an ACEI with an ARB increased the risk of kidney problems. This study was conducted, however, to test an optimistic belief by some doctors that the combination would not cause problems in everyday clinical practice, because doctors would individualize the dosing of both drugs and thereby cut the risk of kidney problems.

CMAJ study overview

The study’s researchers analyzed all residents of the province of Alberta aged 66 years and older who were prescribed an ACEI or an ARB for the first time (32,312 patients). Of those patients, whose average age was 76 years, 1,750 (5.4 percent) received combination treatment with an ACEI and an ARB. Unfortunately, of the 1,750 people who were prescribed a combination, 1,512 (86.4 percent) received the drugs to treat conditions, such as heart failure, for which the combination of ACEIs and ARBs has not proven to be beneficial in clinical trials compared to either drug alone.

Kidney toxicity

The study found that for every 1,000 patients taking a combination of an ACEI with an ARB for one month, an average of 5.2 people experienced kidney toxicity, about twice the rate as in those patients taking either an ACEI or an ARB alone. The researchers defined kidney toxicity as double the level of a blood chemical called creatinine, the development of renal disease requiring dialysis or death from any cause.

The results, therefore, show that the risks of kidney toxicity from the prescription of a combination of an ACEI and an ARB are not reduced in the everyday practice of medicine and actually are increased.

Abnormally high potassium levels

The researchers also checked for elevated blood levels of potassium, known as hyperkalemia. This condition often has no preliminary symptoms but can cause the heart to stop. Some people may have the following symptoms:

• Irregular heartbeat
• Nausea
• Slow, weak or absent pulse

The number of patients experiencing elevated blood levels of potassium was more than 2.5 times greater in patients receiving an ACEI with an ARB compared to those using either of these drugs alone.

What You Can Do

You should contact your health care provider as soon as possible if you have been prescribed a combination of an ACEI and an ARB.

If the above study is representative of the way the combination is prescribed, most people getting this combination do not have medical problems for which there is evidence the combination is beneficial. Thus, in view of these well-documented risks, the balance of benefit and risk tilts toward more harm than good for most people.

(The only indications for using both drugs at once that have been proven to work are protein in the urine or symptomatic heart failure that persist despite treatment with either an ACE inhibitor or an ARB drug alone).

Consumers should report serious adverse events or product quality problems to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online or by regular mail, fax or phone.

• Online: www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
• Regular mail: Use postage-paid, pre-addressed FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
• Fax: (800) FDA-0178
• Phone: (800) FDA-1088

* Do Not Use
** Limited Use (offers limited benefit or benefits certain people or conditions)

Table 2: ARBs Available in the U.S.

** Limited Use (offers limited benefit or benefits certain people or conditions)