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

Abstract

Objective: To evaluate the impact of olmesartan alone or combined with one to three antihypertensive drugs on 24-h blood pressure variability (BPV) and on distribution of BP reduction in a pooled individual data analysis of 10 double-blind, randomized, ambulatory BP monitoring (ABPM) studies.

Methods: ABPMs were performed before and after 6-12 weeks of treatment with placebo (n = 119), active control monotherapy [n = 1195, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), dihydropyridine calcium channel blockers (DCCBs)] olmesartan monotherapy (n = 1410), active control dual combination [n = 79, DCCB + thiazide diuretic (TD)], olmesartan dual combination (n = 637, DCCB or TD), and triple combination therapy (n = 102, DCCB+TD). 24-h BPV was calculated as unweighted or weighted SD of the mean BP, and average real variability. BP control was assessed by smoothness index and treatment-on-variability index.

Results: The greatest effect on 24-h systolic BPV/diastolic BPV was observed under olmesartan triple [-2.6/-1.9; -1.9/-1.3; -1.4/-1.3 mmHg] and active control dual combination [-1.8/-1.4; -1.9/-1.5; -1.2/-1.1 mmHg]. Smoothness indexes and treatment-on-variability indexes were significantly (P = 0.0001) higher under olmesartan dual (1.53/1.22, 1.67/1.29, 2.05/1.59), olmesartan triple (2.47/1.85, 2.80/2.06, 3.64/2.67), or active control dual 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, 1.01/0.82; olmesartan: 1.02/0.86, 0.95/0.78, 1.23/1.00). They were also greater in patients receiving high-dose olmesartan monotherapy or high-dose olmesartan dual combination than in the corresponding low-dose group.

Conclusion: Olmesartan plus a DCCB and/or a TD produces a larger, more sustained, and smoother BP reduction than placebo and monotherapies, a desirable feature for a more effective prevention of the cardiovascular consequences of uncontrolled hypertension.

FIGURE 1

Adjusted 24 h, day and night SBP and DBP mean changes (95% confidence interval) from baseline after double blind treatment with placebo (n = 119), active control monotherapy (n = 1195), olmesartan monotherapy (n = 1410), active control dual combination therapy (n = 79), olmesartan dual combination therapy (n = 637), and olmesartan triple combination therapy (n = 102). The statistical significance of differences between individual pairs of treatments is indicated by the P value. Changes are adjusted for baseline value, age, sex, BMI, and region. BP, blood pressure.

FIGURE 2

Average hourly SBP and DBP values at baseline (dashed lines) and at the end of the double-blind treatment (continuous lines) in patients treated with placebo (n = 119), active control monotherapy (n = 1195), olmesartan monotherapy (n = 1410), active control dual combination therapy (n = 79), olmesartan dual combination therapy (n = 637), and olmesartan triple combination therapy (n = 102). BP, blood pressure.

FIGURE 3

Adjusted average changes (95% confidence interval) in 24-h SBP and DBP variability from baseline after double blind treatment with placebo (n = 119), active control monotherapy (n = 1195), olmesartan monotherapy (n = 1410), active control dual combination therapy (n = 79), olmesartan dual combination therapy (n = 637), and olmesartan triple combination therapy (n = 102). BPV is shown as uSD, wSD, or ARV, and as uVC, wVC, or variation coefficient of average real variability. The statistical significance of differences between individual pairs of treatments is indicated by the P value. Changes are adjusted for baseline value, age, sex, BMI, and region. ARV VC, variation coefficient of average real variability; uVC, unweighted variation coefficient; uSD, unweighted SD; wVC, weighted variation coefficient; wSD, weighted SD.

FIGURE 4

Correlation between 24-h average SBP or DBP changes with treatment and changes in 24-h SBP or DBP variability with treatment. BP variability is shown as uSD, wSD, or ARV. The correlation coefficient (r) and its statistical significance (P) are shown inside each panel. The continuous line refers to the identity line, the dashed line to the line of best fit (or trend line). ARV, average real variability; uSD, unweighted SD; wSD, weighted SD.

FIGURE 5

Adjusted average (95% confidence interval) SI and TOVI, and boxplots of TPR after double blind treatment with placebo (n = 119), active control monotherapy (n = 1195), olmesartan monotherapy (n = 1410), active control dual combination therapy (n = 79), olmesartan dual combination therapy (n = 637), and olmesartan triple combination therapy (n = 102). Data are shown for SBP and DBP. The statistical significance of differences between individual pairs of treatments is indicated by the P value. SI and TOVI data are adjusted for age, sex, BMI and region. ARV, average real variability; SI, smoothness index; TOVI, treatment on variability index; TPR, trough-to-peak ratio; wSD, weighted SD.