Antihypertensive treatment of masked hypertension guided by ambulatory blood pressure monitoring: a double-blind, placebo-controlled trial

Objective: Masked hypertension, office normotension combined with out-of-office hypertension, is associated with target organ damage (TOD), but whether antihypertensive treatment guided by out-of-office blood pressure (BP) would reduce TOD is unproven. We aimed to assess TOD change on antihypertensive treatment guided by ambulatory BP monitoring. Design and method: Double-blind, placebo-controlled randomized trial at 15 Chinese hospitals. Enrolment started on February 14, 2017 and follow-up ended on October 31, 2021. Patients of either sex, aged 30-70 years, not on antihypertensive drugs were eligible, if at two screening visits 1-week apart office BP was <140/<90 mmHg and the 24-hour, daytime or nighttime ambulatory BP was >=130/>=80, >=135/>=85, or >=120/>=70 mmHg, respectively. Patients had >=1 sign of TOD: ECG left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (baPWV) >=1400 cm/s, or urinary albumin-to-creatinine ratio (ACR) >=3.5 mg/mmol in women and >=2.5 mg/mmol in men. Active antihypertensive treatment consisted of allisartan starting at 80 mg/day to be increased to 160 mg/day at month 2 and to be combined with amlodipine 2.5 mg/day at month 4, if the ambulatory BP remained uncontrolled. Matching placebos were used likewise in the control group. The primary endpoint included normalization of baPWV, ACR or LVH or >=20% reduction in baPWV or ACR. Results: Of 320 patients (43.1% women; mean age 54 years), 153 were randomized to active antihypertensive treatment and 167 to placebo. At baseline, office BP averaged 130/81 mm Hg and the 24-hour BP 136/84 mm Hg. The prevalence of elevated baPWV, ACR and LVH was 97.5%, 12.5%, and 7.8%. At 1 year, the 24-hour systolic/diastolic decreased by 9.0/5.6 mm Hg (95% CI: 7.5-10.5/4.8-6.5 mmHg) on active treatment and by 1.4/1.0 mm Hg (-0.1-2.8/0.2-1.8 mm Hg) on placebo. Regression of TOD occurred more frequently in patients randomized to active treatment than in those assigned to placebo with 1 year rate of 45.8% (95% CI: 37.9-53.7%) and 25.8% (19.1-32.4%), respectively (P<.001 for between-group differences in BP and TOD). Per-protocol and subgroup analyses were confirmatory. Conclusions: Masked hypertensive patients require antihypertensive treatment guided by out-of-office BP monitoring before subclinical TOD progresses to major cardiovascular complications.