Toronto—Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used for the management of hypertension, chronic kidney disease, heart failure, and diabetes. The drugs lower blood pressure by modulating the renin-angiotensin aldosterone system in different ways.

Now, a new study in JAMA Network Open suggests that exposure to ARBs, compared with ACEIs, is associated with a higher risk of suicide.

A team led by researchers from St. Michael’s Hospital and the University of Toronto note that the renin-angiotensin system has been implicated in mood disorders. Yet the effects on mental-health outcomes, especially suicide, are poorly understood, according to the authors.

The study team sought to examine the association between suicide and exposure to ACEIs and ARBs. Because of differences in their mode of action, researchers posited that ARBs would be associated with a higher risk of suicide than ACEIs and their suspicions were born out.

This population-based nested case-control study involved patients aged 66 years and older whose information was derived from administrative claims databases in Ontario, Canada, from January 1, 1995, to December 31, 2015. Data analysis was performed from January to April 2019.

Researchers defined cases as 964 individuals who died by suicide within 100 days of receiving an ACEI or ARB, with the date of death serving as the index date. For each case, four controls, totaling 3,856, were identified and matched by age (within 1 year), sex, and presence of hypertension and diabetes. All participants, who had a median age of 76 years and were mostly male, received an ACEI or ARB within 100 days before the index date.

Among cases, 260 (26.0%) were exposed to ARBs, and 704 (18.4%) were exposed to ACEIs. Among controls, meanwhile, 741 (74.0%) were exposed to ARBs, and 3,115 (81.6%) were exposed to ACEIs.

Results indicate that, compared with ACEI exposure, ARB exposure was associated with higher risk of death by suicide (adjusted odds ratio, 1.63; 95% CI, 1.33-2.00). The findings were consistent in a sensitivity analysis excluding individuals with a history of self-harm (odds ratio, 1.60; 95% CI, 1.29-1.98), researchers emphasize.

“The use of ARBs may be associated with an increased risk of suicide compared with ACEIs,” the authors concluded. “Preferential use of ACEIs over ARBs should be considered whenever possible, particularly in patients with severe mental health illness.”

Background information in the article points out that the two drugs lower blood pressure by modulating the renin-angiotensin aldosterone system in distinct ways. While ACE inhibitors inhibit the conversion of angiotensin I to angiotensin II (AII), ARBs block the binding of AII to its AII type 1 receptor, resulting in upregulation of AII and unopposed stimulation of the AII type 2 receptor.

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