Efficacy and safety of a combination of fluvastatin and bezafibrate in patients with mixed hyperlipidaemia (FACT study).

Preliminary data suggest that fluvastatin may be safely combined with fibrates. The Fluvastatin Alone and in Combination Treatment Study examined the effects on plasma lipids and safety of a combination of fluvastatin and bezafibrate in patients with coronary artery disease and mixed hyperlipidaemia. A total of 333 patients were randomly allocated in this multicentre double-blind trial to receive 40 mg fluvastatin alone (n=80), 400 mg bezafibrate (n=86), 20 mg fluvastatin+400 mg bezafibrate (n=85) or 40 mg fluvastatin+400 mg bezafibrate (n=82) for 24 weeks. Low-density lipoprotein (LDL)-cholesterol decreased >20% in all fluvastatin-containing regimens, with significantly greater decreases compared with bezafibrate alone (P<0.001). Bezafibrate alone and fluvastatin+bezafibrate combinations resulted in greater increases in high-density lipoprotein (HDL)-cholesterol and decreases in triglycerides compared with fluvastatin alone (P<0.001). Fluvastatin (40 mg)+bezafibrate was the most effective for all lipid parameters with a decrease from baseline at endpoint in LDL-cholesterol of 24%, a decrease in triglycerides of 38% and an increase in HDL-cholesterol of 22%. All treatments were well tolerated with no increase in adverse events for combination therapy versus monotherapy, or between combination regimens. No clinically relevant liver (aspartate aminotransferase [ASAT] or alanine aminotransferase [ALAT]) greater than three times the upper limit of normal) or muscular (creatine phosphokinase (CPK) greater than four times the upper limit of normal) laboratory abnormalities were reported. This large study shows 40 mg fluvastatin in combination with 400 mg bezafibrate to be highly effective and superior to either drug given as monotherapy in mixed hyperlipidaemia, and to be safe and well tolerated.

Long-term treatment of essential arterial hypertension with nitrendipine.

The efficacy and safety of long-term treatment with oral nitrendipine were evaluated in 34 patients with essential arterial hypertension. Nitrendipine alone significantly lowered systolic and diastolic blood pressure levels in 28 patients who completed the preliminary four-week dose-setting phase. Twenty-one patients completed the one-year treatment. Blood pressure control was maintained by nitrendipine alone in 11 patients. Ten patients not adequately controlled at the end of the dose-setting phase were successfully treated with nitrendipine combined with acebutolol or muzolimine. It is concluded that nitrendipine is a promising calcium antagonist for the treatment of arterial hypertension.

[Antihypertensive effect and tolerability of slow-release nicardipine]. / Effetto antipertensivo e tollerabilità di nicardipina a rilascio graduale.

In order to evaluate the antihypertensive efficacy and tolerability of a new nicardipine formulation, 26 mild-to-moderate essential hypertensive patients were given slow-release nicardipine, 40 mg, twice daily for 6 weeks. Systolic (SBP) and diastolic (DBP) blood pressure were measured after a 1 week single-blind placebo run-in period and after 1, 2, 4 and 6 weeks of active treatment, just before the morning administration. After 1 week, nicardipine induced a significant blood pressure reduction (p less than 0.01), with a decrease in mean SBP/DBP values of -15/-11 mmHg (from baseline values of 165/104 to 150/93 mmHg) in supine and of -16/-12 mmHg (from 158/110 to 142/98 mmHg) in standing position. After 6 weeks the decrease was of -15/-12 mmHg in supine and of -15/-14 mmHg in standing position. The responder rate (DBP decrease of at least 10 mmHg) was 62% (16/26). Normalization rate (DBP less than 95 mmHg with a concomitant decrease of at least 10 mmHg) was 54% (14/26). Eleven patients reported adverse events (headache, peripheral oedema, palpitations, nausea, constipation, flush, dizziness and asthenia). Due to an improved pharmacokinetic profile, the slow-release formulation prolongs to 12 hours the antihypertensive effect of nicardipine, thus facilitating patient's compliance.

Nitrendipine 20 mg once daily versus nicardipine slow release 40 mg twice daily in mild essential hypertension: evaluation by 24-hour ambulatory blood pressure monitoring.

The extent and duration of the blood pressure (BP) lowering effect of 20 mg nitrendipine (NIT) once daily and 40 mg nicardipine slow release (NIC) twice daily were compared in 12 men (aged 39-55 years) with mild essential hypertension according to a randomized, cross over study. Twenty-four-hour non invasive ambulatory BP monitoring (Spacelabs 5200) was performed at the end of a 2-week placebo run-in and after 4 weeks of each active treatment; automatic BP measurements were programmed at 15-min intervals. Both treatments significantly (p less than .01) reduced mean 24-hour and daytime systolic (SBP) and diastolic (DBP) BP, but had different effects on daytime BP profiles. NIT decreased SBP and DBP (p less than .05) in 5 out of 8 two-hour subperiods (from 8 a.m. to 6 p.m.), followed by a loss of effect; NIC reduced SBP and DBP (p less than .05) in 7 out of 8 two-hour subperiods (from 8 a.m. to 10 p.m.). During the night-time, NIT reduced mean SBP (p less than .05) and NIC both mean SBP and DBP values (p less than .05; p less than .05 vs NIT for SBP). Heart rate was not affected by either treatment. Thus, after short-term treatment in mild essential hypertensives nitrendipine once daily was not as effective as nicardipine slow release twice daily in reducing blood pressure throughout the 24 hours.

Antihypertensive and hemodynamic effects of slow-release nicardipine.

The antihypertensive efficacy, the hemodynamic effects and the tolerability of a new slow-release nicardipine (SR-Nic) formulation, capsules containing 40 mg of active drug, have been tested in a randomized, double-blind placebo (P)-controlled study. Thirty mild-to-moderate essential hypertensives were enrolled and after a one-week single-blind placebo run-in period randomly allocated to SR-Nic or P twice-day for six weeks. Blood pressure (BP) was measured after 1, 2, 4 and 6 weeks of treatment. Hemodynamic parameters were evaluated non-invasively by the impedance cardiography technique, using the Noninvasive Continuous Cardiac Output Monitor (NNCOM 3, BoMed Medical Manufacturing Ltd), after 2 and 4 weeks of treatment. All the determinations were made before the morning administration, i.e., 12-14 h after evening intake of SR-Nic or P. The blood pressure (p less than .01) and hemodynamic response (p less than .01 for the systemic vascular resistances) in the SR-Nic group significantly differed from those in the P group. At the end of the study, there were decreases in mean systolic/diastolic BP values of 17/12 in the sitting and of 18/12 mmHg in the standing position in the SR-Nic group; in the P group, the changes were +2/-2 in the sitting and +2/-1 mmHg in the standing position. Systemic vascular resistances were reduced by 17.3% in the SR-Nic and by 1.9% in the P group after 4 weeks of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive effect of once daily sustained release isradipine: a placebo controlled cross-over study.

To evaluate the magnitude and duration of the antihypertensive effect of sustained release (SRO) isradipine, 37 uncomplicated essential hypertensive patients (diastolic blood pressure 100-115 mm Hg after a one month run-in on placebo) were randomised to receive, according to a double-blind cross-over design, isradipine SRO 5 mg once daily and the corresponding placebo for 1 month. At the end of each treatment period, sitting blood pressure and heart rate were measured immediately before and every hour for 6 h after the last dose. Thirty-four patients [16 m, age 54 (7) y] completed the study. As compared to randomised placebo, isradipine SRO significantly reduced the systolic (SBP) and diastolic (DBP) blood pressure. Absolute DBP decrements versus placebo peaked 6 h after dosing (-8.8 mm Hg) and were not significantly lower (-8.2 mm Hg) at the end of the dose interval. At the same times, the absolute decrements in SBP were -9.8 mm Hg and -9.7 mm Hg, respectively. DBP was normalised in 19 patients (56%) at peak and in 17 (50%) at trough time. The trough to peak efficacy ratio in patients with peak DBP < or = 90 mm Hg was 70%. Heart rate was slightly increased by isradipine SRO. Adverse effects monitored with a check-list occurred in 8/36 patients (22%) on isradipine SRO and in 4/35 (11%) on randomized placebo. The data suggest that isradipine SRO is an effective antihypertensive drug, with a trough to peak efficacy ratio supporting once daily administration in most mild to moderate essential hypertensives.