caution against combining the 2 classes of RAS inhibitors

The updated recommendation is based on the results of the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), an international study supported by Boehringer Ingelheim, the Heart and Stroke Foundation of Ontario, and the Canadian Institutes of Health Research. The main results of ONTARGET, published in 2008,^[9] showed that in 25,620 patients with vascular disease or type 2 diabetes, the combination therapy had a greater blood pressure-lowering effect than either telmisartan or ramipril alone, but it did not produce any additional benefit in terms of patient outcomes, and it was associated with more side effects, such as hyperkalemia, hypotension, and renal impairment. The guidelines also note that in patients with stage 3 chronic kidney disease (glomerular filtration rate > 30 mL/min) the ACE inhibitor plus ARB combination reduced urine protein but did not reduce cardiovascular outcomes, and it worsened renal outcomes, including the need for acute dialysis compared with the ACE inhibitor alone.

The only data to support improved patient outcomes with the combination of an ACE inhibitor plus an ARB are in people with heart failure, where, the guidelines note, the combination reduces recurrent hospitalization. Hence, the guidelines advise that the use of combination of ACE inhibitor with an ARB therapy should only be considered in selected and closely monitored people with advanced heart failure or proteinuric nephropathy. They advise that for people already on the combination and stable, physicians should consider that prescribing 1 of the 2 drug classes alone will reduce cardiovascular events to the same extent and that other therapeutic regimens have the potential to reduce cardiovascular events and blood pressure to a greater degree. Trials are ongoing of a combination of an ACE inhibitor with an ARB in people with chronic kidney disease and diabetes.