Objectives: Masked hypertension is associated with target organ damage and adverse outcomes. However, up to now there is no interventional evidence that antihypertensive therapy will be beneficial to the patients.

Design and methods: The ANTIhypertensive treatment in MASKed hypertension for target organ protection (ANTI-MASK) trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial (NCT02893358). Eligible patients were 30 to 70 years old, had untreated masked hypertension and at least one sign of target organ damage (TOD). Masked hypertension was defined as a normal office blood pressure (BP, <140/90 mmHg) and an elevated 24-hour (≥130/80 mmHg), daytime (≥135/85 mmHg) or nighttime BP (≥120/70 mmHg) at both screening visits. TOD included electrocardiogram diagnosed left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (ba-PWV) ≥1400 cm/s, or a random urinary albumin-to-creatinine ratio (ACR) ≥2.5 mg/mmol in men and ≥3.5 mg/mmol in women. Randomized patients were treated with alisartan 80 mg per day or placebo. If ambulatory BP was uncontrolled, drug dosage was doubled at the 2-month visit, and amlodipine 2.5 mg or matching placebo was added at the 4-month visit. The primary endpoint was the improvement rate of TOD after 12 months treatment, defined as the reverse (yes to no) of TOD or a significant decrease of ba-PWV or ACR by ≥20% of the baseline level.

Results: From Feb 2017 to Oct 2020, 317 patients with masked hypertension (43.2% women, mean age 54 years) were randomized in 13 hospitals in China. Overall, baseline office, 24-h, daytime and nighttime BPs averaged 130/81,137/85, 141/87, and 126/77 mmHg, respectively. At baseline, 98% had an elevated ba-PWV, 12% microalbuminuria, and 8% LVH. 252 patients completed the 12-month treatment and 65 (20.5%) withdrew from the trial. In the intention-to-treat analyses, the improvement rate of TOD was significantly higher in the antihypertensive treatment group than the placebo group (46.1% vs 26.1%, P<0.0001), as well as the decrease of the 24-h systolic/diastolic BPs (-9.1/-5.7 vs -1.5/-1.0 mmHg, P<0.0001).

Conclusions: Antihypertensive treatment was beneficial for patients with masked hypertension in terms of TOD protection.