Differential Effect of BP-Lowering Agents on Microvascular Function

A multicenter, open-label, randomized crossover trial with blinded endpoint assessment in Europe revealed that 4 weeks of treatment with amlodipine, losartan, or atenolol resulted in differential effects on cerebrovascular reactivity (CVR) in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) but not in patients with symptomatic sporadic small vessel disease. The trial enrolled 75 patients with sporadic small vessel disease (mean age 64·9 years) and 26 with CADASIL (53·1 years) between Feb 22, 2018, and April 28, 2022. The primary efficacy analysis included 62 with sporadic small vessel disease and 17 with CADASIL. There was significant difference in CVR between study drugs in patients with CADASIL (15·7 × 10^–4%/mm Hg for amlodipine; 19·4 × 10^–4%/mm Hg for losartan; –23·9 × 10^–4%/mm Hg for atenolol), but not in patients with sporadic small vessel disease (mean change in CVR 1·8 × 10^–4%/mm Hg for amlodipine; 16·7 × 10^–4%/mm Hg for losartan; –7·1 × 10^–4%/mm Hg for atenolol). However, CVR improved with both amlodipine and losartan compared with atenolol in an exploratory subgroup analysis in young sporadic patients using the median split of the study population (age 60 years) as a cutoff. In patients with CADASIL, pairwise comparisons showed that CVR improved with amlodipine compared with atenolol (–39·6 × 10^–4%/mm Hg and with losartan compared with atenolol (–43·3 × 10^–4%/mm Hg). No deaths or study drug related serious adverse events occurred. CVR declines with ageing and is associated with an increased risk of stroke and death. Source: https://www.thelancet.com/