Angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the treatment of hypertension: should they be used together?

The combined use of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) poses a dilemma to clinicians. On the one hand, indirect evidence from compelling, but still surrogate outcome measures such as blood pressure and proteinuria suggest some merits of this combination. On the other hand, the outcome benefits of the ACEIs+ARBs combination in morbidity/mortality trials remain confined to patients with severe congestive heart failure (CHF) and reduced ejection fraction. Incidentally, most of the benefit offered by the ACEIs+ARBs combination in these patients was not driven by mortality, but by fewer rehospitalizations for CHF. Even in patients with renal disease and proteinuria, the combined use of ACEIs and ARBs, although highly effective in reducing urinary protein excretion, has not yet been proven to significantly delay end-stage renal disease and the need for dialysis. In the Ongoing Telmisartan Alone and In Combination With Ramipril Global Endpoint Trial (ONTARGET), the dual blockade of the renin angiotensin system did not produce additional outcome benefit over that afforded by ACE inhibition alone. Notably, however, patients with BP >160/100 mmHg at entry were excluded from ONTARGET, thus limiting the applicability of these results to the treatment of hypertension. The European Society of Hypertension guidelines do not suggest large-scale use of the ACEIs+ARBs combination in patients with hypertension. However, patients with resistant hypertension, particularly if proteinuria coexists, could benefit from this combination, which however requires close monitoring for adverse events, including hyperkalemia and worsening renal function.