Blood pressure and homocysteine-lowering effects of the amlodipine/folic acid combination in patients with hypertension and serum homocysteine concentration ≥10 μmol/l (H-type hypertension): a multicenter, randomized, double-blind, parallel-controlled clinical trial

BACKGROUND: Elevated plasma homocysteine (Hcy ≥10 μmol/l) and hypertension, defined as H-type hypertension, can synergistically increase the risk of cardiovascular diseases, especially for stroke. We aimed to assess the efficacy and safety of amlodipine-folic acid in lowering both blood pressure (BP) and plasma Hcy, compared with amlodipine alone. METHODS: Eligible participants (299 males and 241 females) were randomly assigned in a 1:1:1 ratio to 5 mg amlodipine (control, group A), 5 mg amlodipine plus 0.4 mg folic acid (group B), or 5 mg amlodipine plus 0.8 mg folic acid (group C). All participants were followed at 2, 4, 6, and 8 weeks. The primary outcome was the efficacy of lowering both BP and Hcy. RESULTS: Among the 540 participants who were randomized, the efficacy of lowering both BP and Hcy was significantly better in groups B and C compared with group A at the end of 4 weeks, and sustained at the end of 8 weeks (group B vs. group A: 31.7% vs. 6.1%, P < 0.001; group C vs. group A: 32.8% vs. 6.1%, P < 0.001). Both groups B and C were more efficacious in lowering Hcy and raising folate levels than amlodipine alone at 8 weeks. There was no significant difference in BP lowering and adverse events among the three treatment groups. CONCLUSIONS: In H-type hypertension patients, amlodipine-folic acid (5 mg/0.4 mg or 5 mg/0.8 mg) had a significantly higher efficacy of lowering both BP and plasma Hcy compared with amlodipine alone. The efficacy of BP lowering and safety profile were comparable among the three treatment groups. This trial was registered in clinicaltrials.gov, identifier: NCT01848873.