Blood pressure control in Italy: results of recent surveys on hypertension

BACKGROUND: Blood pressure (BP) control is reported to be poor in hypertensive patients worldwide. OBJECTIVE: BP levels, the rate of BP control, prevalence of risk factors and total cardiovascular risk were assessed in a large cohort of hypertensive patients, derived from recent surveys performed in Italy. METHODS: Fifteen studies on hypertension, performed in different clinical settings (general population, general clinical practice, specialist outpatient clinics and hypertension centres) over the past decade were considered. RESULTS: The overall sample included 52 715 hypertensive patients (26 315 men and 26 410 women, mean age 57.3 +/- 6.9 years). Despite the high percentage of patients on stable antihypertensive treatment (n = 36 556, 69%), mean systolic and diastolic BP levels were 147.8 +/- 8.5 and 89.5 +/- 5.2 mmHg, respectively. On the basis of the nature of the study (population surveys or clinical referrals), systolic BP levels were consistently higher than the normality threshold in both settings (142.6 +/- 12.4/84.8 +/- 3.7 mmHg and 150.4 +/- 4.6/91.9 +/- 4.1 mmHg, respectively). The BP stratification could be assessed in 40 829 individuals: 4.5% had optimal, 9.2% normal and 8.3% high-normal BP levels, however, the large majority were in grade 1 (39%) or grades 2-3 (32.6%) hypertension. In the overall sample, 55.9% of hypertensive patients had hypercholesterolemia, 28.7% were smokers, 36.4% were overweight or obese and 15.0% had diabetes mellitus. Cardiovascular risk stratification was assessed in 37 813 hypertensives: 23.2% had low, 33.9% moderate, 30.2% high and 12.7% very high added risk. CONCLUSION: Our analysis demonstrates the persistence of poor BP control and high prevalence of risk factors, supporting the need for more effective, comprehensive and urgent actions to improve the clinical management of hypertension

Pharmacoeconomics of Hypertension Management: The Place of Combination Therapy

Pharmacological treatment of hypertension has been shown to reduce the risk of stroke, coronary events, heart failure and progression of renal disease. However, rates of successful blood pressure control remain low among treated patients while antihypertensive medication represents a large and increasing proportion of healthcare expenditure in many countries. Several influential pharmacoeconomic analyses have confirmed the cost effectiveness of conventional antihypertensive treatments, usually involving monotherapy with diuretics or beta-blockers, compared with alternative strategies. Recent research has shown that a considerable proportion of the total cost of antihypertensive treatment in general practice is due to factors such as inadequate blood pressure control, poor compliance with therapy, discontinuation and switching between therapies. These factors operate to a much lesser extent in well-conducted clinical trials, and have not been fully incorporated into most economic studies. Some novel strategies, particularly low dose combinations of antihypertensive agents, may offer advantages in terms of efficacy, reduced adverse effects and improved compliance with treatment. There is therefore a need for comprehensive pharmacoeconomic analyses of novel strategies, taking these additional factors into account. Until such studies are available, the wider use of low dose combination therapy and other novel strategies should not be held back on the basis of earlier economic studies that have not included all relevant considerations.Antihypertensives, Cost analysis, Cost benefit, Cost effectiveness, Cost utility, Hypertension, Pharmacoeconomics

Tolerability of nebivolol in head-to head clinical trials vs. other cardioselective beta-blockers in the treatment of hypertension. A meta-analysis.

Objective: To assess the comparative tolerability of nebivolol and other cardioselective -blockers (CSBs) in the treatment of mild-to-moderate hypertension.Data source: Database searches of MEDLINE, EMBASE, and the Cochrane Controlled Trials Register up to August 2004 identified randomised clinical trials comparing nebivolol and other CSBs in patients with mild-to-moderate hypertension, with a treatment duration of at least 4 weeks and reporting any tolerability data.Design and methods: Baseline and post-intervention data on tolerability and efficacy were extracted from the studies. Tolerability was assessed by the rate of patients with adverse events (AEs), the total number of AEs and the number of drug-related AEs. Efficacy endpoints were the changes from baseline in diastolic and systolic blood pressure and the rate of treatment responders. For meta-analysis of data presenting relative frequency or means and standard deviations, the random effects model for proportions and means was applied. Absolute frequency data were normalised to the expected frequencies in 1000 patients and analysed by methods for comparison of Poisson distributed data. The quality of each trial was evaluated using a pre-defined checklist reflecting the basic potency of a selected study to detect the relative tolerability of the drugs investigated. The final analysis was performed in the high-quality studies; the low-quality studies were included, where appropriate, in robustness analysis.Results: Ten trials comparing nebivolol with the CSBs atenolol, metoprolol or bisoprolol were selected. According to the pre-defined criteria, three studies were assessed as high-quality studies and seven as low-quality studies. The ratio of the rates of patients with AEs treated with nebivolol compared with those treated with the CSBs was 0.63 (95% CI 0.44, 0.91). The difference of the rates of patients with AEs reached -12.8% (95% CI -23.3%, -2.3%). The ratio of normalised total AEs was 0.71 (95% CI 0.62, 0.82), and the ratio of normalised drug-related AEs was 0.38 (95% CI 0.29, 0.50). In the expected frequencies of AEs in 1000 patients, the differences in number of normalised total AEs and drug-related AEs with nebivolol compared with the other CSBs were -147 (95% CI -205, -89) and -126 (95% CI -159, -93), respectively. In the efficacy meta-analysis, nebivolol was at least as effective as the other CSBs.Conclusions: This meta-analysis revealed that the tolerability of nebivolol is superior to that of atenolol, metoprolol and bisoprolol, and confirmed that nebivolol is at least as effective as these CSBs in the treatment of mild-to-moderate hypertension. The treatment of mild-to-moderate essential hypertension with antihypertensive drugs that have a relatively favourable tolerability profile, such as nebivolol, may be a way to improve persistence with antihypertensive treatment and overcome the consequences of poor compliance

Effects of early treatment with zofenopril in patients with myocardial infarction and metabolic syndrome: the SMILE Study

Claudio Borghi, Arrigo FG Cicero, Ettore AmbrosioniDepartment of Clinical Medicine, University of Bologna, Bologna, Italy. On behalf of the Survival of Myocardial Infarction Long-term Evaluation (SMILE) StudyObjective: To evaluate the clinical efficacy of the early administration of zofenopril in a group of patients with and without metabolic syndrome (MS+ and MS–) and anterior myocardial infarction enrolled in the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study.Methods: Patients were randomized double-blind to zofenopril (n = 719) or placebo (n = 699) for 6 weeks. The primary end point was the effect of treatment on the 6-week combined occurrence of death and severe congestive heart failure. The secondary end point was the 1-year mortality rate.Results: Of the 1418 patients included in this post-hoc analysis, 686 (48.3%) had MS. After 6 weeks of treatment zofenopril significantly reduced the incidence of all-cause death and severe congestive failure (risk reduction: 69%, 95% CI: 7–78; 2p = 0.002) in MS+ patients. This was the case for 1-year mortality, too (29%, 95% CI: 4–41; 2p = 0.048). Zofenopril was effective also in MS− patients but the amount of relative risk reduction was less than in MS+ for both the primary (–11%; 2p = 0.61) and secondary endpoint (–19%; 2p = 0.025).Conclusions: Results of this post-hoc analysis of the SMILE Study demonstrate the striking benefit of early administration of zofenopril in MS+ patients with acute anterior myocardial infarction.Keywords: SMILE Study, angiotensin converting enzyme inhibitor, zofenopril, myocardial infarction, metabolic syndrom

Effects of early treatment with zofenopril in patients with myocardial infarction and metabolic syndrome: the SMILE Study

To evaluate the clinical efficacy of the early administration of zofenopril in a group of patients with and without metabolic syndrome (MS+ and MS-) and anterior myocardial infarction enrolled in the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study

Efficacy and Safety of Zofenopril Versus Ramipril in the Treatment of Myocardial Infarction and Heart Failure: A Review of the Published and Unpublished Data of the Randomized Double-Blind SMILE-4 Study

Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on endothelial dysfunction. Its clinical efficacy and safety have been described in the four randomized controlled trials of the SMILE program, which globally enrolled more than 3600 patients in post-acute myocardial infarction (AMI) setting. The SMILE-4 study specifically selected patients with left ventricular dysfunction at admission, and compared the effects of zofenopril or ramipril in combination with acetylsalicylic acid (ASA). Zofenopril demonstrated its superiority over ramipril in reducing the combined occurrence of death or hospitalization for cardiovascular causes both in the overall population included in the original study and in subgroups of patients at highest risk, namely hypertensive and diabetic subjects. The effects of the early treatment with zofenopril were sustained over time, and, after 5\ua0years of follow-up, zofenopril increased the survival likelihood and reduced the hospitalization rate. Compared to ramipril, zofenopril was cost-effective with a number to treat of 13 and an incremental cost-effectiveness ratio (ICER) of 2125.45 euros for any additional event prevented. Furthermore, in real-world settings, zofenopril decreased the risk of death in patients with heart failure, particularly in men, and in subjects older than 76\ua0years or with ejection fraction lower than 54%. These results support the early use of zofenopril immediately after AMI, even in the presence of comorbidities, and its maintenance over time to reduce the risk of heart failure. Funding: Menarini International Operations Luxembourg S.A

Cardioprotective role of zofenopril in hypertensive patients with acute myocardial infarction: a pooled individual data analysis of the SMILE studies

Purpose: The four SMILE studies demonstrated that early administration of zofenopril following acute myocardial infarction is prognostically beneficial compared to placebo or other angiotensin-converting enzyme (ACE) inhibitors. In the present retrospective pooled analysis of individual SMILE studies, we evaluated the efficacy of zofenopril on cardiovascular (CV) outcomes in 1880 hypertensive and 1662 normotensive patients. Materials and methods: Four hundred and forty-nine hypertensives and 486 normotensives were treated with placebo, 980 and 786 with zofenopril 30–60 mg daily, 252 and 259 with lisinopril 5–10 mg daily, 199 and 131 with ramipril 10 mg daily, for 6 to 48 weeks. Results: The 1-year risk of death or hospitalization for CV causes was significantly reduced with zofenopril and lisinopril vs. placebo in both hypertensive (HR: 0.65; 95%CI: 0.48–0.86; p = .003 and .60, .36–.99; p = .049, respectively) and normotensive patients (0.56, 0.42–0.75; p = .0001 and .51, .28–.90; p = .020), whereas this was not the case for ramipril (hypertensives: 1.02, 0.69–1.52; p = .918; normotensives: 0.91, 0.59–1.41; p = .670). Zofenopril significantly reduced the risk of CV outcomes vs. the other two ACE-inhibitors pooled together in hypertensive (0.76; 0.58–0.99; p = .045), but not in normotensive patients (0.77; 0.55–1.10; p = .150). Conclusions: In cardiac patients of the SMILE studies with arterial hypertension treatment with the ACE-inhibitor zofenopril was beneficial in reducing the 1-year risk of CV events as compared to placebo and ramipril. An efficacy similar to that of zofenopril was observed with lisinopril