Significance of initial blood pressure and comorbidity for the efficacy of a fixed combination of an angiotensin receptor blocker and hydrochlorothiazide in clinical practice

Abstract

Background: Two-thirds of all patients with arterial hypertension need drug combinations to achieve blood pressure (BP) goals. Fixed combinations have high efficacy and result in high patient compliance. 300 mg irbesartan plus 25 mg hydrochlorothiazide (HCTZ) has been investigated only in clinical trials but not in daily practice.

Methods: A multicenter, noninterventional, noncontrolled observational study with 8123 patients seen by 1604 physicians in daily practice. BP reduction (office measurements), co-morbid disease and tolerability were documented over a 6-month observational period.

Results: At mean baseline BP of 161 +/- 15/94 +/- 10 mmHg, administering of fixed combination resulted in a substantial BP reduction averaging 28 +/- 15/14 +/- 10 mmHg (P < 0.001). Decrease of systolic BP ran parallel with increasing systolic baseline BP (Spearman's Rho -0.731; P < 0.0001; diastolic BP vs diastolic baseline BP Rho 0.740; P < 0.0001), independent from patient characteristics (age, obesity, diabetes or nephropathy) but enhanced with short history of hypertension (P < 0.0001 vs long history), prior beta blockers (P = 0.001 vs prior angiotensin receptor blockers [ARBs]), prior calcium channel blockers (P = 0.046 vs prior ARBs) and no prior medication (P = 0.012 vs prior ARBs). High compliance (>98%) and low incidence of adverse events (0.66%) were documented.

Conclusions: The fixed combination of 300 mg irbesartan with 25 mg HCTZ was efficacious and tolerable in an unselected patient population in primary care.

Keywords: combination therapy; diuretics; hypertension; irbesartan; noninterventional study; obesity.

Figure 1

Reduction in blood pressure (BP) after 6 months as a function of the systolic A) and diastolic B) initial blood pressure value.

Figure 2

Normalization of blood pressure (BP) after 6 months in total and as a function of the systolic A) and diastolic B) initial blood pressure value.

Figure 3

Reduction in systolic blood pressure (BP) (mmHg) as a function of defined patient characteristics/previous medication. Use of the Kruskal Wallis Test for differences within groups. Significant P-values for pairwise comparisons are indicated; other comparisons are not significant. Age: Lower tercile (LT) up to 58 years, middle tercile (MT) > 58 to 69 years, upper tercile (UT) > 69 years; body mass index (BMI): LT up to 25 kg/m², MT > 25 to 30 kg/m², UT > 30 kg/m²; duration of hypertension: LT up to 5 years, MT > 5 to 10 years, UT > 10 years. Abbreviations: ACE, angiotensin-converting enzyme; CCBs, calcium channel blockers.

Figure 4

Systolic normalization (<140 mmHg) according to systolic initial blood pressure value in the studies RAPiHD severe and RAPiHD moderate (after Franklin). RAPiHD severe was a 7-week trial in patients with severe hypertension (seated DBP [SeDBP] ≥ 110 mmHg). Eligible patients entered a 7-day single-blind placebo lead-in period. Patients with SeDBP ≥ 110 mmHg at 2 consecutive visits during the lead-in period were randomized in a 2:1 ratio to irbesartan/HCTZ 150/12.5 mg fixed-dose combination therapy force-titrated to 300/25 mg after week 1 or irbesartan 150 mg monotherapy force-titrated to 300 mg after week 1. RAPiHD moderate was a 12-week trial in patients with moderate hypertension (seated SBP [SeSBP] 160 180 mmHg or SeDBP 100 110 mmHg). Eligible patients entered a 21-day single-blind placebo wash-out period before randomization in a 3:1:1 ratio to irbesartan/HCTZ 150/12.5 mg fixed-dose combination therapy force-titrated to 300/25 mg after week 2, irbesartan 150 mg monotherapy force-titrated to 300 mg after week 2, or HCTZ 12.5 mg monotherapy force-titrated to 25 mg after week 2. Abbreviation: HCTZ, hydrochlorothiazide.