Follow-up of Antihypertensive Therapy Improves Blood Pressure Control: Results of HYT (HYperTension survey) Follow-up.

INTRODUCTION: Although improved during the past few years, blood pressure control remains sub optimal. AIM: The impact of follow-up assessment on blood pressure control was evaluated in a group of patients of the HYT (HYperTension survey), treated with a combination of different dihydropyridine calcium-channel blockers (CCBs regimen) and inhibitors of renin-angiotensin-aldosterone system (RAAS) and with uncontrolled blood pressure. This was obtained assessing (a) the rate of blood pressure control at 3 and 6 months of follow-up in the whole group of patients, (b) the rate of blood pressure control and the average blood pressure values in subjects treated with different DHP-CCBs regimen. METHODS: From the 4993 patients with uncontrolled blood pressure, (BP ≥ 140/90 or ≥140/85 in patients with diabetes), 3729 (mean age 61.2 ± 11.5 years), maintained CCBs regimen combined wih RAAS blockers and were evaluated at 3 and 6 months follow-up. At each visit BP (semiautomatic device, Omron-M6, 3 measurements), heart rate, adverse events and treatment persistence were collected. RESULTS: At 1st and 2nd follow-up the rate of controlled BP was 63.5 and 72.8% respectively (p < 0.05 vs 35.3% at baseline), whereas in diabetes was 32.5 and 37.9% respectively (p < 0.05 vs 20% at baseline). No differences in heart rate were observed. No differences in control rate were observed between the different CCBs regimen. The incidence of drugs related adverse events was 3.6%. CONCLUSIONS: These findings provide evidence that: (a) the follow-up of hypertensive patients under therapy increase the rate of blood pressure control; (b) there is no significant difference in the antihypertensive effect between different CCBs regimen;

NEbivolol inhibition of coronary artery smooth muscle cell proliferation after percutaneous coronary artery intervention. Results of the NESCIO Study, a randomized, double blind trial.

OBJECTIVES: This study compared the efficacy of metoprolol and nebivolol in reducing the frequency of in-stent restenosis (ISR) after a percutaneous coronary intervention (PCI). BACKGROUND: ISR results from excessive neointimal proliferation. Nebivolol inhibits proliferation of human coronary endothelial and smooth muscle cells in vitro. Its efficacy has not been studied in clinical trials. MATERIAL AND METHODS: In a single-centre double-blind study, 79 subjects with de novo lesions were randomly assigned to receive either nebivolol (n=37) or metoprolol (n=42) 3 to 7 days before elective PCI with bare metal stents. The study medication was continued for 6 months. Nebivolol was administered at 5 mg/day for 3 weeks, then at 10 mg/day. Metoprolol was administered at 100 mg/day. The endpoints were the difference in fractional flow reserve (deltaFFR) between values immediately after PCI and those at 6 months and ISR during the 6 months following PCI The study was powered to detect a deltaFFR of 6% with 30 subjects per treatment group. RESULTS: Among subjects who underwent angiography at 6 months, mean deltaFFR was--0.08 for the nebivolol group (n=25) and -0.12 in the metoprolol group (n=26; p = 0.367). ISR occurred in 11 subjects (26.2%) on metoprolol and in 3 (8.1%) on nebivolol during treatment, and in 7 subjects on metoprolol and in 3 on nebivolol at 6 months (p = 0.014) CONCLUSION: There was a non-significant trend toward less decline in detaFFR at 6 months with nebivolol. Nebivolol should be investigated further in larger trials. Nebivolol significantly reduced the frequency of ISR as compared to metoprolol.

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.

PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial.

BACKGROUND: Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. AIMS: To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. PATIENTS: One hundred patients (aged 6 months-15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. METHODS: After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children > or =6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency > or =3/week and encopresis < or =1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. RESULTS: A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. CONCLUSIONS: PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation.

Paradoxical pressor effects of beta-blockers in standing elderly patients with mild hypertension: a beneficial side effect.

BACKGROUND: Baroreflex sensitivity declines with age, creating a fall in systolic blood pressure and pulse pressure when standing. If, in addition, blood pressure is reduced as a result of antihypertensive medication, compensatory mechanisms may be inadequate and orthostatic problems may occur. This may be less true in patients on beta-blockers. beta-blockers cause pressor effects in standing patients with autonomic neuropathy, but their effects on standing pulse pressures in elderly subjects with mild hypertension have not been systematically studied. METHODS AND RESULTS: We studied 3741 patients with mild hypertension for 6 months who were being treated with the beta-blocker nebivolol 5 mg daily. Blood pressures were measured after 10 minutes in the supine position and after 1 minute in the standing position. Overall, systolic and diastolic blood pressures rose slightly while standing, whereas pulse pressures remained unchanged. When previously untreated patients (n=2085) >60 and <60 years of age were assessed separately, supine pulse pressures were consistently higher in the elderly group compared with those of the younger subjects by 6 to 11 mm Hg (P<0.001 to 0.0001). However, while standing, pulse pressures rose in the younger subjects, whereas they tended to fall in the elderly group. After 6 months of beta-blockade, this pattern was unchanged in the younger subjects but reversed into significant rise of pulse pressures in the elderly group by 4 (SD 1) mm Hg (P<0.001). In the patients previously treated with other classes of antihypertensive drugs (n=712), the effects were essentially the same. CONCLUSIONS: In elderly patients with mild hypertension, a depressor trend of pulse pressure while standing can be turned into a significant pressor response by treatment with a beta-blocker.