Management of arterial hypertension with angiotensin receptor blockers: Current evidence and the role of olmesartan

Abstract

Elevated blood pressure (BP) is a major determinant of morbidity and mortality burden related to cardio-metabolic risk. Current guidelines indicate that controlling and lowering BP promotes cardiovascular (CV) risk reduction. Among antihypertensive agents, angiotensin receptor blockers (ARBs) are characterized by an efficacy profile equivalent to other antihypertensive agents and are provided with excellent tolerability and low discontinuation rates during chronic treatments. Moreover, CV outcomes are reduced by ARBs. Olmesartan is a long-lasting ARB which proved to achieve a comparable or more effective action in lowering BP when compared to other ARBs. Olmesartan, in fact, displayed a larger and more sustained antihypertensive effect over the 24 hours, with a buffering effect on short-term BP variability. These are important features which differentiate olmesartan from the other principles of the same class and that may help to control the increased CV risk in the presence of high BP variability. Olmesartan shows similar benefits as other ARBs in terms of all-cause and CV mortality, and a favorable tolerability profile. Combination of olmesartan with long-lasting calcium-channel blockers and thiazide diuretics represents a rational and effective therapy. Thus, ARBs, including olmesartan, represent one of the most effective and safe treatments for patients with arterial hypertension.

Keywords: ambulatory blood pressure; angiotensin receptor blockers; arterial hypertension; blood pressure; blood pressure variability; olmesartan.

Figure 1

Relative and absolute risk reduction of various outcomes in trials of blood pressure (BP) lowering. A, Intentional BP‐lowering trials. B, Intentional BP‐lowering trials exclusively in hypertensive (HT) patients. C, Intentional and nonintentional BP‐lowering trials together. Standardized Mantel–Haenszel risk ratio (RR) is to a systolic BP (SBP)/diastolic BP (DBP) difference of 10/5 mm Hg. The column absolute risk reduction reports the number and 95% confidence interval (CI) of events prevented for every 1000 patients treated for 5 years with a standardized RR. CHD indicates coronary heart disease [Redrawn from 10 with permission]

Figure 2

Relative risk reduction of various outcomes in trials of blood pressure (BP) lowering by different classes of drugs. A, Diuretics. B, Centrally acting drugs. C, Beta‐blockers. D, Calcium antagonists. E, Angiotensin‐converting enzyme (ACE) inhibitors. F, Angiotensin receptor blockers. CI indicates confidence intervals; DBP, diastolic blood pressure; pts, patients; RR, Mantel–Haenszel risk ratios; and SBP, systolic blood pressure [Redrawn from 10 with permission]

Figure 3

A, Relative treatment effects of Angiotensin Receptor Blockers at 24 weeks in terms of the absolute change (weighted mean difference and 95% credible interval or CI) in systolic blood pressure (SBP) and diastolic blood pressure (DBP). To interpret: weighted mean difference <0 favors the column‐defining treatment (eg, eprosartan, compared to irbesartan, is associated with increase in blood pressure by +3.14/+2.06 mm Hg). B, Relative treatment effects (odds ratio, OR, and 95% credible interval or CI) of Angiotensin Receptor Blockers on all‐cause and cardiovascular (CV)‐related mortality. To interpret: odds ratio >1 favors the column‐defining treatment [Redrawn from 41 with permission]

Figure 4

Reduction in the values of systolic and diastolic blood pressure (BP) over the 24 hours, the daytime, the nighttime and the last 4 hours of the dosing interval for different angiotensin receptor blockers and placebo. Values are adjusted by the baseline BP values, dose, age, and number of participants included in every cohort and are expressed as average and standard error. P value for the difference across treatments [Redrawn from 47 with permission]

Figure 5

Adjusted 24 hour, day and night systolic (SBP) and diastolic blood pressure (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, body mass index, and region [Redrawn from 52 with permission]

Figure 6

Adjusted average (95% confidence interval) smoothness index (SI) and treatment on variability index (TOVI), and boxplots of trough‐to‐peak ratio (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 systolic (SBP) and diastolic blood pressure (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, mass index, and region [Redrawn from 52 with permission]

Figure 7

Comparisons of the effects of blood pressure‐lowering treatments based on diuretics, beta‐blockers, calcium antagonists, and angiotensin‐converting enzyme inhibitors vs all other classes of drugs excluding angiotensin receptor blockers. The type of cardiovascular events considered was the composite of stroke and coronary heart disease or the composite of stroke, coronary heart disease, and heart failure, as indicated. ACEI, angiotensin‐converting enzyme inhibitors; All, all other classes together; ARB, angiotensin receptor blockers; BB, beta‐blockers; CA, calcium antagonists; CHD, coronary heart disease; CI, confidence interval; D, diuretics; HF, heart failure; RR, risk ratio [Redrawn from 56 with permission]