ACE = ARB, but ACE + ARB worsens renal outcomes (ONTARGET)
Does the combination of an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin receptor blocker (ARB) improve outcomes in patients at high risk for renal complications?
In patients with atherosclerosis or diabetes with end-organ damage, ACEIs and ARBs are equally effective in preventing renal complications. However, the combination of an ACEI and ARB increases the rate of patients requiring acute dialysis. (LOE = 1b)
Mann JF, Schmieder RE, McQueen M, et al., for the ONTARGET investigators. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 2008;372(9638):547-553. [PMID:18707986]
Randomized controlled trial (double-blinded)
In spite of the data being limited to patients with advanced renal disease, it is common practice to treat patients at high risk for renal complications with both ACEIs and ARBs. After a 3-week single-blind run-in period, these investigators randomized patients older than 55 years with known atherosclerosis or with diabetes and end-organ damage to receive either an ACEI (ramipril 10 mg daily; n = 8576), an ARB (telmisartan 80 mg daily; n = 8542), or both (n = 8502). Keep in mind that although run-in periods are similar to the real world (patients who don't like the treatment stop taking it), they can stack the deck by removing patients who don't tolerate the treatment, making the medication look more tolerable. In this case, 11% of the patients who started the run-in period didn't proceed to the trial. The patients were evaluated every 6 months for approximately 56 months. The authors used intention to treat to analyze the data. At the end of the study, approximately 12% of the patients in each group died. No patients went on to renal transplant. Slightly less than 2% of the patients in each group had a doubled serum creatinine level and slightly less than 1% required dialysis (acute and chronic). However, patients taking an ACEI and an ARB were statistically more likely (0.33%) to require acute dialysis than those taking either the ACEI (0.15%) or the ARB (0.23%). Compared with the ACEI alone one would need to treat 565 patients (95% CI, 297 - 3450) with an ACEI plus an ARB for 56 months to cause one additional patient to require acute dialysis. Since there were no clinical benefits to using the combination, this practice should stop.
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