Antihypertensive Effect of Irbesartan and Predictors of Response
Antihypertensive Effect of Irbesartan and Predictors of Response
Background: Obesity-associated hypertension is difficult to treat and puts patients at a substantially increased risk of cardiovascular events. Irbesartan has previously been shown to effectively lower blood pressure (BP) in high-risk groups including patients with type 2 diabetes mellitus or nephropathy, and may therefore also be suitable for the treatment of obesity-associated hypertension. In this study we aimed to: (a) assess the efficacy and tolerability of irbesartan alone and in combination with hydrochlorothiazide in patients with obesity-associated mild-to-moderate hypertension; and (b) investigate patient-associated determinants of poor BP control in this patient group.
Patients and Methods: This was a 3-month, prospective, open-label, multicentre, phase IV study in 72 479 hypertensive patients in 6989 general practices across Germany. Main outcome measures were BP reduction (primaryparameter of effectiveness) and BP response rates after 3 months, as well as adverse events (AEs). Independent predictors of poor control were identified in a multivariate proportional odds model.
Results: All of the patients were Caucasian, 50.5% were females, mean age was 62.1 ± 11.1 years, mean bodyweight was 88.6 ± 15.4kg, and mean body mass index (BMI) was 30.7 ± 4.8 kg/m. Almost all the patients were overweight or obese (92.3%). From a baseline value of 162/94mm Hg, systolic and diastolic BP were reduced by a mean of -23/-12mm Hg after 3 months.66.1% of the patients were responders (reduction of diastolic BP ≥10mm Hg), and 48.0% achieved BP normalisation (i.e. < 140/90mm Hg). 79% of patients met their individual treatment goals as defined by the treating physician (mean 135/80mm Hg). AEs were reported in only 322 patients (0.4%). Factors requiring special attention in patients not achieving BP control were age (> 55 years), high BMI category (> 25 kg/m), and increased waist circumference.
Conclusion: Treatment with irbesartan (± hydrochlorothiazide) appeared to be effective and well toleratedin the study population of patients with obesity-associated hypertension. Easily recognisable characteristics allow physicians to identify patients whose BP is likely to be difficult to control.
Obesity has become an epidemic that threatens global wellbeing. The prevalence of the disease, comprising body mass index (BMI) categories between 25 and 29.9 kg/m (overweight) and ≥ 30 kg/m (obesity), is constantly increasing, affecting about 30 million people in Germany. Obesity is now considered to be the second leading cause of preventable death after cigarette smoking.
Obesity is associated with a significantly increased risk of hypertension, type 2 diabetes mellitus, dyslipidaemia, certain forms of cancer, sleep apnoea and osteoarthritis. Consequently, obese patients often present with co-morbidities that pose a particular challenge to the treating physician. Data from representative multipurpose observational studies such as NHANES (National Health and Nutrition Examination Survey) in the US, HYDRA (Hypertension and Diabetes Screening and Awareness Study) in Germany or INTERSALT (International Study of Salt and Blood Pressure) worldwide have clearly shown the strong and clear association between BMI and hypertension. Roughly 30% of cases of hypertension may be attributed to obesity, and in men < 45 years of age, this figure may be as high as 60%. Because high blood pressure (BP) is a major determinant of cardiovascular events in the obese, tight BP control is essential in these patients.
From a pathophysiological perspective, sodium retention, volume expansion and high cardiac output are common findings in obese individuals. These changes are attributable to activation of the sympathetic nervous system and insufficient suppression of the renin-angiotensin system. Increased expression of angiotensin II-forming enzymes in adipose tissue and high activity of the renin-angiotensin system have recently been implicated in the development of insulin resistance and type 2 diabetes. Accordingly, antihypertensive agents that block the renin-angiotensin system may be a beneficial strategy for treatment of obesity-associated hypertension. Angiotensin II-receptor blockers may have advantages over ACE inhibitors, because they also block the effects of ACE-independent (e.g. chymase-dependent) angiotensin II production.
Against this background, irbesartan may be of particular efficacy in the treatment of obesity-associated hypertension. It selectively blocks the angiotensin II subtype 1 receptor, which is responsible for the pressor-related effects of angiotensin II. In comparative trials, irbesartan was significantly more effective than losartan and valsartan as treatment for mild-to-moderate essential hypertension. Irbesartan-based treatment appears effective for high-risk patients, such as those with diabetes, renal disease and cardiac hypertrophy. In patients with type 2 diabetes, irbesartan delays the development of nephropathy as well as the progression of renal failure. Irbesartan may have anti-athero-sclerotic properties beyond those expected from blood-pressure lowering per se: it decreases the vascular oxidative stress and prevents the procoagulant as well as the pro-inflammatory effects of angiotensin II.
The aims of the present investigation were to determine: (a) the BP-lowering effect and achievement of individual treatment targets, as well as tolerability, of 3 months' treatment with irbesartan, alone or in combination with the diuretic hydrochlorothiazide, in obese patients; and (b) the associations between various patient characteristics and co-morbidities and BP control.
Background: Obesity-associated hypertension is difficult to treat and puts patients at a substantially increased risk of cardiovascular events. Irbesartan has previously been shown to effectively lower blood pressure (BP) in high-risk groups including patients with type 2 diabetes mellitus or nephropathy, and may therefore also be suitable for the treatment of obesity-associated hypertension. In this study we aimed to: (a) assess the efficacy and tolerability of irbesartan alone and in combination with hydrochlorothiazide in patients with obesity-associated mild-to-moderate hypertension; and (b) investigate patient-associated determinants of poor BP control in this patient group.
Patients and Methods: This was a 3-month, prospective, open-label, multicentre, phase IV study in 72 479 hypertensive patients in 6989 general practices across Germany. Main outcome measures were BP reduction (primaryparameter of effectiveness) and BP response rates after 3 months, as well as adverse events (AEs). Independent predictors of poor control were identified in a multivariate proportional odds model.
Results: All of the patients were Caucasian, 50.5% were females, mean age was 62.1 ± 11.1 years, mean bodyweight was 88.6 ± 15.4kg, and mean body mass index (BMI) was 30.7 ± 4.8 kg/m. Almost all the patients were overweight or obese (92.3%). From a baseline value of 162/94mm Hg, systolic and diastolic BP were reduced by a mean of -23/-12mm Hg after 3 months.66.1% of the patients were responders (reduction of diastolic BP ≥10mm Hg), and 48.0% achieved BP normalisation (i.e. < 140/90mm Hg). 79% of patients met their individual treatment goals as defined by the treating physician (mean 135/80mm Hg). AEs were reported in only 322 patients (0.4%). Factors requiring special attention in patients not achieving BP control were age (> 55 years), high BMI category (> 25 kg/m), and increased waist circumference.
Conclusion: Treatment with irbesartan (± hydrochlorothiazide) appeared to be effective and well toleratedin the study population of patients with obesity-associated hypertension. Easily recognisable characteristics allow physicians to identify patients whose BP is likely to be difficult to control.
Obesity has become an epidemic that threatens global wellbeing. The prevalence of the disease, comprising body mass index (BMI) categories between 25 and 29.9 kg/m (overweight) and ≥ 30 kg/m (obesity), is constantly increasing, affecting about 30 million people in Germany. Obesity is now considered to be the second leading cause of preventable death after cigarette smoking.
Obesity is associated with a significantly increased risk of hypertension, type 2 diabetes mellitus, dyslipidaemia, certain forms of cancer, sleep apnoea and osteoarthritis. Consequently, obese patients often present with co-morbidities that pose a particular challenge to the treating physician. Data from representative multipurpose observational studies such as NHANES (National Health and Nutrition Examination Survey) in the US, HYDRA (Hypertension and Diabetes Screening and Awareness Study) in Germany or INTERSALT (International Study of Salt and Blood Pressure) worldwide have clearly shown the strong and clear association between BMI and hypertension. Roughly 30% of cases of hypertension may be attributed to obesity, and in men < 45 years of age, this figure may be as high as 60%. Because high blood pressure (BP) is a major determinant of cardiovascular events in the obese, tight BP control is essential in these patients.
From a pathophysiological perspective, sodium retention, volume expansion and high cardiac output are common findings in obese individuals. These changes are attributable to activation of the sympathetic nervous system and insufficient suppression of the renin-angiotensin system. Increased expression of angiotensin II-forming enzymes in adipose tissue and high activity of the renin-angiotensin system have recently been implicated in the development of insulin resistance and type 2 diabetes. Accordingly, antihypertensive agents that block the renin-angiotensin system may be a beneficial strategy for treatment of obesity-associated hypertension. Angiotensin II-receptor blockers may have advantages over ACE inhibitors, because they also block the effects of ACE-independent (e.g. chymase-dependent) angiotensin II production.
Against this background, irbesartan may be of particular efficacy in the treatment of obesity-associated hypertension. It selectively blocks the angiotensin II subtype 1 receptor, which is responsible for the pressor-related effects of angiotensin II. In comparative trials, irbesartan was significantly more effective than losartan and valsartan as treatment for mild-to-moderate essential hypertension. Irbesartan-based treatment appears effective for high-risk patients, such as those with diabetes, renal disease and cardiac hypertrophy. In patients with type 2 diabetes, irbesartan delays the development of nephropathy as well as the progression of renal failure. Irbesartan may have anti-athero-sclerotic properties beyond those expected from blood-pressure lowering per se: it decreases the vascular oxidative stress and prevents the procoagulant as well as the pro-inflammatory effects of angiotensin II.
The aims of the present investigation were to determine: (a) the BP-lowering effect and achievement of individual treatment targets, as well as tolerability, of 3 months' treatment with irbesartan, alone or in combination with the diuretic hydrochlorothiazide, in obese patients; and (b) the associations between various patient characteristics and co-morbidities and BP control.
