Socio-economic status and the therapeutic effectiveness of antihypertensive treatment--the design of the LEO study.

OBJECTIVE: The risk of arterial hypertension and subsequent cardiovascular disease morbidity and mortality increases with low socio-economic status (SES). Even small differences in blood pressure, whether untreated or despite treatment, account for this substantial difference. Most of the increased risk in the low socio-economic group is due to traditional cardiovascular risk factors such as overweight and obesity, alcohol consumption and a sedentary life style. Intense treatment of arterial hypertension has been shown to overcome these prognostic inequalities. Therefore, drugs with high efficacy, optimal treatment adherence and a low potential for drug-related side effects are needed in order to reduce the cardiovascular risk burden of patients with a low SES. The angiotensin receptor blocker (ARB) olmesartan will be used to investigate the effectiveness of this drug in different socio-economic classes. RESEARCH DESIGN AND METHODS: The LEO (Long-term Effectiveness of Olmesartan in different Socioeconomic groups) study is a large observational long-term study which has been set up to test the effectiveness of olmesartan within this context. The study has a matched-pairs design (1403 patients in both the low and the high socio-economic classes). MAIN OUTCOME MEASURES: The LEO study will test whether this regimen can reduce the SES-related difference in long-term blood pressure control and compliance in the low SES population. CONCLUSIONS: The study may generate valuable information about the antihypertensive effectiveness of olmesartan alone or in combination with hydrochlorothiazide in different socio-economic classes. It will further test whether the drug helps to reduce the inherent inequalities in cardiovascular prognosis between different socio-economic groups. CURRENT STATUS: The study commenced in July 2007. Results are anticipated in December 2008.

Nitric oxide, erectile dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus metoprolol in hypertensive men.

1. Hypertensive men treated with beta-blockers frequently complain of erectile dysfunction. The present study investigated the effects of two beta(1)-adrenoceptor-selective antagonists, namely nebivolol and metoprolol, on erectile function in hypertensive men. 2. Male out-patients (age range 40-55 years) with newly diagnosed or existing stage 1 essential hypertension (mean seated systolic blood pressure 140-159 mmHg; diastolic blood pressure 90-99 mmHg) were enrolled in the study. All patients lived in a stable, heterosexual partnership and had no history of sexual dysfunction. After a 2-week placebo run-in period, patients were randomized double-blind to either Treatment group A (comprising nebivolol 5 mg once daily for 12 weeks, followed by placebo for 2 weeks and then metoprolol succinate 95 mg once daily for 12 weeks) or Treatment group B (comprising metoprolol succinate 95 mg for 12 weeks, placebo for 2 weeks and then nebivolol 5 mg for 12 weeks). An international index of erectile function (IIEF) questionnaire and a diary documented patients' sexual function and activity. 3. Nebivolol and metoprolol lowered blood pressure to a similar extent. Metoprolol, but not nebivolol, significantly decreased the IIEF erectile function subscore by 0.92 in the first 8 weeks after onset of beta-blocker treatment. In contrast with metoprolol, nebivolol improved secondary sexual activity scores and other IIEF subscores. 4. Despite similar antihypertensive efficacy of the cardioselective beta(1)-adrenoceptor antagonists nebivolol and metoprolol, nebivolol may offer additional benefits by avoiding erectile dysfunction in male hypertensive patients on long-term beta-adrenoceptor antagonist therapy.

Nationwide efficacy-safety study of nebivolol in mildly hypertensive patients.

Nebivolol has been adequately tested in clinical efficacy trials of patients with mild hypertension. Clinical efficacy trials or their meta-analyses did not accurately predict the outcome of subsequent large studies. The primary objective was to assess the efficacy/safety of nebivolol 5-10 mg daily in a nationwide study of patients with mild hypertension. Secondary objectives were (1) to compare efficacy/safety as monotherapy versus add-on therapy and (2) to assess the effect of nebivolol on ISH. This was an open-label, 6-week follow-up study of 6,356 patients with mild hypertension or ISH, as defined by the 1999 World Health Organization guidelines, recruited from 2,700 facilities. Previous monotherapies were continued except for beta-blockers. Results are reported as means+/-SDs. Intention-to-treat analysis is given. A total of 5,740 patients completed the study; of the withdrawals, 90% were lost for follow-up or were noncompliant, 38% were untreated before, 23% had beta-blockers. In the accumulated data, mean systolic and diastolic blood pressures fell by 24+/-14 and 13+/-9 mm Hg (both P<0.001). The differences between the blood pressure-reducing effects of nebivolol monotherapy and add-on therapy were not statistically significant: 28+/-16 and 22+/-14 mm Hg for systolic and 15+/-11 and 11+/-8 mm Hg for diastolic blood pressures. Adverse events were limited to 0.5% of the patients, no serious adverse events were observed. In the ISH patients, diastolic blood pressure fell by 4+/-6 mm Hg compared with 15+/-10 mm Hg in the no-ISH patients (P<0.01). Efficacy-safety effects of nebivolol in patients with mild hypertension can be generalized in a nationwide assessment. The efficacy of nebivolol as monotherapy and as the efficacy as add-on therapy are very similar. Nebivolol is highly efficacious in patients with ISH.