Is Dual RAAS Blockade Doomed?
The VA NEPHRON-D study is the third study to show that combining the agents, although it improves the surrogates and lowers blood pressure slightly more, does not reduce adverse outcomes -- especially acute renal injury, which is the main serious adverse event of using drugs from both classes.
Blood pressure was slightly lower, but the actual decline in renal function was virtually the same in this study, whether or not patients took both drugs. All patients had to be on losartan as a representative of the ARB class for at least 30 days, and also on increasing doses of an ACE inhibitor (in this case lisinopril), which was added in 10 mg, 20 mg, and eventually 40 mg doses to try to achieve a blood pressure of 110-130 mm Hg systolic.
That goal was achieved, and there was slight improvement in some of the outcomes analyzed, but not in the overall outcome and there was no improvement in renal function over the length of the study. They were not able to prove their primary endpoint, showing that this combination would in fact lessen the decline in renal function. Of greater importance, adverse events increased, especially hyperkalemia, which was about 3 times more common, and acute renal injury, which was even more common.
Right now, as the editorialist for the New England Journal of Medicine wrote, it might be time to put dual RAAS blockade therapy to rest. That will make life a little bit easier, in some ways, but we don't have enough data to be sure that we can't prevent the decline in renal function. It's not going to happen this way; maybe it will happen some other way.
3 Strikes Against Dual Blockade
The VA NEPHRON-D study is the third study to show that combining the agents, although it improves the surrogates and lowers blood pressure slightly more, does not reduce adverse outcomes -- especially acute renal injury, which is the main serious adverse event of using drugs from both classes.
Blood pressure was slightly lower, but the actual decline in renal function was virtually the same in this study, whether or not patients took both drugs. All patients had to be on losartan as a representative of the ARB class for at least 30 days, and also on increasing doses of an ACE inhibitor (in this case lisinopril), which was added in 10 mg, 20 mg, and eventually 40 mg doses to try to achieve a blood pressure of 110-130 mm Hg systolic.
That goal was achieved, and there was slight improvement in some of the outcomes analyzed, but not in the overall outcome and there was no improvement in renal function over the length of the study. They were not able to prove their primary endpoint, showing that this combination would in fact lessen the decline in renal function. Of greater importance, adverse events increased, especially hyperkalemia, which was about 3 times more common, and acute renal injury, which was even more common.
Right now, as the editorialist for the New England Journal of Medicine wrote, it might be time to put dual RAAS blockade therapy to rest. That will make life a little bit easier, in some ways, but we don't have enough data to be sure that we can't prevent the decline in renal function. It's not going to happen this way; maybe it will happen some other way.
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