The Risk of Combining ACE-Inhibitors with ARBs

Angiotensin II is the villain in high blood pressure, or hypertension, and there are several successful drugs that work by neutralizing it. The angiotensin-converter inhibitors (ACE-inhibitors) were the first class of these drugs to be introduced, in 1981.  The angiotensin receptor blockers (ARBs) followed in 1995.  Both classes of drugs are very effective and safe in the control of hypertension. 

Combination treatment with an ACE inhibitor and an ARB improves outcomes, compared with single use of either, in patients with diabetic kidney disease and a particular type of heart failure (advanced systolic left ventricular dysfunction). The possibility of risks in the use of such a combination exists.  A study by Canadian researchers has assessed this, and reported in the Canadian Medical Association Journal. 

The data analyzed came from 32,000 seniors aged 65 or older who were prescribed an ACE inhibitor and/or an ARB.  Their average age was 76; 1,750 (5.4%) of them received combination therapy. However, 1,512 (86%) of those on the combination did not have the accepted indications, namely diabetic nephropathy or advanced systolic dysfunction.

Kidney dysfunction was more common among patients given combination therapy (5.2 events per 1000 patients per month) than among patients given single drug therapy (2.4 events per 1000 patients per month), i.e. 2.36-times more frequent.  Raised serum potassium was also more common in patients given the combination – 2.42-times more frequent.

The researchers admit there are gaps in their data that may have influenced the results slightly.  But the main finding – that combination therapy was frequently prescribed for patients without established indications and was associated with an increased risk of kidney disease and death when compared with single drug therapy – stands firm.  Physicians should take note of this when planning to prescribe an ACE inhibitor together with an ARB, and patients should be aware of the problem.