P-209: Which population to treat preferentially with AT1-receptor-blockers (ARB) than with ACEI after OPTIMAAL study?

OPTIMAAL study having shown that in patients with recent myocardial infarct (MI) and heart failure (HF), cardiovascular mortality is higher with losartan than with captopril, the first choice in these patients is still ACEI, unless intolerance. In patients with CHD but without HF, HOPE study has established ramipril as the reference treatment because it decreased the risk of MI, HF and stroke independently of BP and in patients with uncomplicated hypertension ANBP-2 trial has recently suggested an edge of ACEI over thiazide in global cardiovascular protection in spite of lower cerebral protection. Paradoxically no trial has yet been launched to compare ARB to ACEI in 3 populations in which the chance of ARB superiority over ACEI are the greatest thanks to a better cerebral protection mediated by non-AT1-receptors whereas comparable protection for CHD is expected since comparable MI recurrence risk between losartan and captopril was observed in OPTIMAAL. These populations are those in which MI risk is lower than that of stroke because of a low initial prevalence of CHD (≥ 16%) but in which stroke risk is high because of stroke history as in PROGRESS and PATS, of severe hypertension as in LIFE or of age as in SCOPE. Indeed the experimentally proven non-AT1-receptor-mediated brain-antiischemic mechanisms have been recently supported by following clinical evidences: (1) the contrast between the lack of stroke protective effect (SPE) with AII-inhibiting perindopril (PROGRESS) and the 29% SPE with AII-stimulating of indapamide (PATS) for the same BP decrease. (2) the 25% greater selective SPE with AII-stimulating losartan than with the AII-suppressing atenolol for the same BP decrease. (3) the contrast between the 10% BP-independent SPE of AII-stimulating candesartan comparatively to the AII-neutral association of β -blocker and DHP in SCOPE. Conclusion : To base the preferential recommendation of ARB over ACEI in populations without CHD on evidence, a large trial comparing these 2 drugs is urgently needed in these populations.