P1652Antihypertensive treatment effect on 24h blood pressure variability: pooled individual data analysis of ambulatory blood pressure monitoring studies based on olmesartan mono or combination treatment

Abstract

Background: A smooth and consistent 24h blood pressure (BP) control with antihypertensive therapy is important for an effective cardiovascular (CV) prevention. Purpose: To evaluate the impact of treatment with olmesartan (OLM) alone or combined with 1-2 antihypertensive drugs on 24h BP variability (V) and on distribution of BP reduction in a pooled individual data analysis of 10 double-blind, randomised, ambulatory blood pressure monitoring (ABPM) studies. Methods: ABPMs were performed before and after 6-12 weeks of treatment with placebo (n=119), active control monotherapy (n=1195, ACEIs, ARBs, dihydropyridine calcium channel blockers or DCCBs), OLM monotherapy (n=1410), active control dual combination therapy (n=79, DCCB + thiazide diuretic or TD), OLM dual (n=637, DCCB or TD) and OLM triple combination therapy (n=102, DCCB + TD). 24h BPV was calculated as unweighted (uSD) or weighted standard devia- tion (wSD) of the mean BP, or as average real variability (ARV). BP control was assessed by smoothness index (SI, 24h average hourly BP reduction divided by its SD) and treatment-on-variability index (TOVI, 24h avearge hourly BP reduction divided by 24h wSD or ARV under treatment). Results: Placebo had no effect on 24h BPV, small effects were observed under monotherapies, whereas the greatest effect was observed with the OLM triple combination [uSD: -2.5/-1.8; wSD: -1.6/-1.2; ARV: -1.1/-1.1 mmHg] and with the active control dual combination [SBP/DBP uSD: -1.6/-1.2; wSD: -1.7/-1.3; ARV: -0.9/-0.9 mmHg]. A multivariate regression analysis indicated BP changes as the main determinants of changes in BPV with treatment. SIs and TOVIs were significantly (p=0.0001) higher under OLM dual combination (1.53/1.22, 1.67/1.29, 2.05/1.59), OLM triple combination (2.47/1.85, 2.80/2.06, 3.64/2.67), or dual control combination (1.70/1.26, 1.85/1.33, 2.29/1.65) than under monotherapies (control: 0.86/0.73, 0.80/0.65, 1.00/0.82; OLM: 1.02/0.86, 0.95/0.77, 1.22/1.00), and greater in patients receiving high dose (40 or 80 mg daily) OLM monotherapy (1.11/0.95, 1.00/0.81, 1.31/1.04) than in those treated with low dose OLM monotherapy (2.5 to 20 mg daily: 1.00/0.85, 0.95/0.77, 1.22/0.99), and in patients treated with the high (1.71/1.35, 1.86/1.42, 2.30/1.76) than with the low dose (1.17/0.96, 1.29/1.03, 1.55/1.27) OLM dual combination. Conclusion(s): OLM plus a DCCB and/or a TD is effective in producing a large, more sustained and smoother BP reduction than placebo and monotherapies. It also has a buffering effect on BPV, a desirable feature for a more effective prevention of the CV consequences of uncontrolled hypertension.