The impact of an ARB, with or without hydrochlorothiazide (HCTZ), on glycaemic factors and the risk for developing diabetes in hypertensive patients with the metabolic syndrome have not been fully assessed. This was a 52-week multicentre, prospective, phase-IV, open-label, cohort study of losartan or losartan/HCTZ in hypertensive patients with metabolic syndrome. All subjects were treated initially with losartan 50?mg?day(-1). Those not achieving target blood pressure (BP
: In experimental aortic stenosis (AS), blockade of the renin-angiotensin system attenuates AS-related left ventricular (LV) dysfunction and improves survival. We tested whether candesartan, an angiotensin II type 1 receptor blocker, favorably influences LV structure and function and improves exercise capacity in AS patients. Fifty-one patients with severe AS were randomized to receive candesartan (target dose 16 mg/d) or placebo. Eight patients discontinued treatment and the remaining 43 patients underwent echocardiography, walking test, and measurement of plasma N-terminal B-type natriuretic peptide (Nt-proBNP) before and after an average of 5-month treatment. No statistically significant changes in LV diameters, mass, or function were seen. The median 6-minute walking distance decreased from 390 to 368 m with candesartan (P = 0.003) and from 380 to 370 m with placebo (P = 0.523), reflecting natural progression of AS. Concomitantly, median Nt-proBNP increased from 319 to 414 ng/L with candesartan (P = 0.170) and from 413 to 561 ng/L with placebo (P = 0.035). No change with candesartan was statistically significantly different from the corresponding change with placebo. In conclusion, candesartan was well tolerated but had no favorable effects on the LV or effort tolerance. The benefits found in experimental AS of blocking the renin-angiotensin system could not be reproduced in patients with severe AS.
To examine the prevalence and the clinical characteristics associated with normoalbuminuric renal impairment (RI) in a general type 2 diabetes (T2D) population.
We included 94 446 patients with T2D (56% men, age 68.3±11.6 years, BMI 29.6±5.3 kg/m², diabetes duration 8.5±7.1 years; means±SD) with renal function (serum creatinine) reported to the Swedish National Diabetes Register (NDR) in 2009. RI was defined as estimated glomerular filtration (eGFR)20 µg/min. We linked the NDR to the Swedish Prescribed Drug Register, and the Swedish Cause of Death and the Hospital Discharge Register to evaluate ongoing medication and clinical outcomes.
17% of the patients had RI, and 62% of these patients were normoalbuminuric. This group of patients had better metabolic control, lower BMI, lower systolic blood pressure and were more often women, non-smokers and more seldom had a history of cardiovascular disease as compared with patients with albuminuric RI. 28% of the patients with normoalbuminuric RI had no ongoing treatment with any RAAS-blocking agent. Retinopathy was most common in patients with RI and albuminuria (31%).
The majority of patients with type 2 diabetes and RI were normoalbuminuric despite the fact that 25% of these patients had no ongoing treatment with RAAS-blocking agents. Thus, RI in many patients with type 2 diabetes is likely to be caused by other factors than diabetic microvascular disease and ongoing RAAS-blockade.
Only a minority of hypertensive individuals is adequately controlled for their hypertension, partially because reliable predictors for efficient antihypertensive drug therapy are lacking.
In a prospective, randomized, double-blind, cross-over, placebo-controlled study (The GENRES Study), 208 moderately hypertensive Finnish men (aged 35 to 60 years) were treated for 4 weeks with antihypertensive drugs from four different classes: amlodipine (5 mg), bisoprolol (5 mg), hydrochlorothiazide (25 mg), or losartan (50 mg) daily. Each individual received each of the four monotherapies in a randomized order. Four-week placebo periods were included before and between drug treatment periods. Antihypertensive responses were assessed with 24-h ambulatory and office measurements and analyzed according to age, body mass index, triceps skin fold thickness, waist-to-hip ratio, duration of hypertension, number of previous antihypertensive drugs, number of affected parents, and blood pressure (BP) levels, and profiles during placebo periods.
The median BP responses in 24-h ambulatory recordings (systolic/diastolic) were 11/8 mm Hg for bisoprolol, 9/6 mm Hg for losartan, 7/5 mm Hg for amlodipine, and 5/2 mm Hg for hydrochlorothiazide. The highest pairwise within-subject correlations in BP responses were seen for the combinations of bisoprolol-losartan and amlodipine-hydrochlorothiazide. The BP responses to bisoprolol and losartan did not vary according to the variables. Amlodipine and hydrochlorothiazide responses were positively correlated with age, placebo BP level, and lower night-time dipping on placebo.
Baseline clinical and BP parameters may be used to predict the efficacy of antihypertensive therapies. The GENRES Study material should provide an excellent platform for future pharmacogenetic analyses of antihypertensive drug responsiveness.
Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been shown to improve survival in patients with congestive heart failure (CHF). We wish to determine whether there are sex-related differences in the optimal treatment of congestive heart failure.
Using administrative databases, all patients >=65 years of age discharged with a diagnosis of CHF between January 1998 and March 2003 and who filled a prescription for an ARB or an ACE inhibitor within 90 days of discharge were identified. Time to all-cause death in women and men on ACE inhibitors or ARBs was compared.
There were 10,223 women (8627 ACE inhibitors and 1596 ARBs) and 9475 men (8484 ACE inhibitors and 991 ARBs). Hypertension was more common in women (50.1%) than men (33.1%). Women on ARBs had better survival than those on ACE inhibitors (adjusted hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.59, 0.80). There was no difference in survival in men prescribed ARBs compared to ACE inhibitors (HR 1.10, 95% CI 0.95, 1.30).
These sex differences in treatment-related outcome are important but should be confirmed in a randomized trial before ARBs are preferentially prescribed to women with CHF.
Modern diagnostics of chronic heart failure (CHF) is based on echocardiography. Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-II-antagonists (AIIAs) in case of ACEI intolerance, and beta-blockers are recommended as first-line drugs in patients with CHF and left ventricular systolic dysfunction. The aims of this study were to analyse the diagnostics and treatment of patients with CHF and to identify the optimal drug profile (target level) with regard to ACEI/AIIA- and beta-blocker treatment.
The medical records of all patients (n=635) from a part of a Swedish county who had a diagnosis of CHF in the year 2000 were analysed retrospectively.
The prevalence of CHF increased with age, from 0.9% and 1.6% in the age group 60-64 years in women and men, respectively, to 8.8% and 11.5%, respectively, in the age group 80-84 years. Only 17.6% of the patients had been examined by means of echocardiography. Of the patients without any contra-indication for the drugs, 45.9% received treatment with ACEI/AIIAs and 41.8% with beta-blockers. Treatment with ACEI/AIIAs and beta-blockers was given to 21.3%. The corresponding proportions for treatment of patients with CHF verified by echocardiography were 88.0% (ACEI/AIIA), 52.0% (beta-blocker) and 46.7% (the combination). The target level of the combination treatment was estimated to be about 70% in a group of unselected patients with CHF.
CHF was not optimally diagnosed in this cohort of patients. Correct diagnosing seems to be associated with more adequate treatment.