Effects of manidipine vs. amlodipine on intrarenal haemodynamics in patients with arterial hypertension.

AIMS: Intraglomerular pressure is one of the main drivers of progression of renal failure. Experimental data suggest that there are important differences between calcium channel blockers (CCBs) in their renal haemodynamic effects: manidipine reduces, whereas amlodipine increases intraglomerular pressure. The aim of this study was to investigate the effects of manidipine and amlodipine treatment on intragomerular pressure (P(glom)) in patients with mild to moderate essential hypertension. METHODS: In this randomized, double-blind, parallel group study, hypertensive patients were randomly assigned to receive manidipine 20 mg (n = 54) or amlodipine 10 mg (n = 50) for 4 weeks. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were determined by constant-infusion input-clearance technique with p-aminohippurate (PAH) and inulin. P(glom) and resistances of the afferent (R(A)) and efferent (R(E)) arterioles were calculated according to the model established by Gomez. RESULTS: P(glom) did not change in the manidipine group (P = 0.951), whereas a significant increase occurred in the amlodipine group (P = 0.009). There was a significant difference in the change of P(glom) by 1.2 mmHg between the manidipine and amlodipine group (P = 0.042). In both treatment arms, R(A) was reduced (manidipine P = 0.018; amlodipine P < 0.001). The reduction of R(A) was significantly more pronounced with amlodipine compared with manidipine treatment (P < 0.001). R(E) increased in both treatment arms (manidipine P = 0.012; amlodipine P = 0.002), with no difference between the treatment arms. Both CCBs significantly reduced systolic and diastolic blood pressure (BP) (both P < 0.001). However, amlodipine treatment resulted in a significantly greater decrease of BP compared with manidipine (P < 0.001). CONCLUSIONS: In accordance with experimental data after antihypertensive treatment of 4 weeks, intraglomerular pressure was significantly lower with the CCB manidipine than with amlodipine, resulting and explaining their disparate effects on albuminuria.

Antihypertensive efficacy and safety of manidipine versus amlodipine in elderly subjects with isolated systolic hypertension: MAISH study.

BACKGROUND AND OBJECTIVE: Isolated systolic hypertension (ISH) affects 10-20% of the elderly population and is strongly related to the risk of cardiovascular events. Elevated systolic BP values are primarily caused by reduced large vessel compliance with a consequent increase in total peripheral resistance. Vasodilating drugs, such as calcium channel antagonists, have proven to be effective in controlling ISH in elderly patients. This study set out to compare the antihypertensive efficacy and safety of two different calcium channel antagonists, manidipine and amlodipine, administered once daily in elderly subjects with ISH. METHODS: In a European, randomised, double-blind, multicentre, parallel-group study, after a 2-week placebo run-in period, 195 patients aged >or=60 years with ISH received manidipine 10-20 mg once daily or amlodipine 5-10 mg once daily. Chlortalidone 25mg once daily could be added to the high dose of test drug in the event of insufficient antihypertensive control. The primary efficacy parameter was the proportion of patients with a reduction in office sitting systolic BP (SBP) >or=15 mm Hg, measured at trough, at the final visit. Secondary efficacy parameters included: the proportion of patients with a normal sitting SBP value (<140 mm Hg) at the final visit; a change from baseline to the final visit in mean office trough sitting SBP; a change from baseline to the final visit in the cardiovascular risk score as measured by the INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) project score; the proportion of patients with at least a two-point reduction in the cardiovascular risk score; the percentage of patients requiring upward dose titration and diuretic add-on treatment and the investigator's final judgement. Safety and tolerability evaluations were based on adverse events, ECG and laboratory tests, and clinically relevant reports of abnormalities. RESULTS: In the intention-to-treat population (n = 189), 76% and 72% of patients in the manidipine and amlodipine groups, respectively, had a reduction in sitting SBP of >or=15 mm Hg (p-value not significant for between-group comparison). The percentage of patients with a normal sitting SBP value was 52% in the manidipine group and 51% in the amlodipine group (p-value not significant for between-group comparison). Sitting SBP reductions at the end of treatment were -19.5 +/- 11.8 mm Hg in patients receiving manidipine and -18.4 +/- 11.1 mm Hg in patients receiving amlodipine. Both treatments induced a small reduction in cardiovascular risk score, with 45% of patients in both treatment groups having a two-point reduction in the final score. At the final visit, approximately half of the patients in both treatment groups were still being treated with the low dose of one of the test drugs (manidipine 10mg or amlodipine 5mg). Chlortalidone was added to the high dose of test drugs in 7% and 11% of patients in the amlodipine and manidipine groups, respectively. Both drugs were well tolerated, with a higher incidence of oedema in the amlodipine group (9% vs 4%). No clinically relevant changes in heart rate were induced by either treatment. CONCLUSION: In elderly patients with ISH, treatment with manidipine for 12 weeks was well tolerated and effective and the antihypertensive effects obtained with manidipine were the same as those obtained with amlodipine.

Effects of the fixed combination of manidipine plus delapril in the treatment of hypertension inadequately controlled by monotherapy with either component: a phase III, multicenter, open-label, clinical trial.

BACKGROUND: Failure to achieve good blood pressure (BP) control is probably the most important reason for high rates of morbidity and mortality in patients with hypertension. Combination therapy has been shown to increase the percentage of patients in whom BP control is achieved. One combination is a calcium channel blocker (CCB) and an angiotensin-converting enzyme inhibitor (ACE-I). OBJECTIVE: The aim of this study was to assess the effects of the fixed combination of the CCB manidipine and the ACE-I delapril in the treatment of hypertensive patients already given monotherapy with either component but with poor results (ie, insufficient BP control or adverse events [AEs]). METHODS: In this Phase III, multicenter, open-label, clinical trial, patients with mild to moderate hypertension were assigned to 1 of 2 groups. Group 1 comprised patients whose diastolic BP (DBP) was >90 mm Hg or who experienced AEs with manidipine 20 mg once daily. Group 2 comprised patients who had a DBP >90 mm Hg or who experienced AEs with delapril 30 mg BID. In both groups, patients aged <65 years were to be treated with a fixed combination of manidipine 10 mg plus delapril 30 mg once daily for 12 weeks, whereas patients aged ≥65 years were to be treated with manidipine 5 mg plus delapril 15 mg once daily for 2 weeks and then manidipine 10 mg plus delapril 30 mg once daily for 10 weeks. Patients were assessed at baseline and at 2, 4, 8, and 12 weeks of treatment. At each visit, systolic blood pressure (SBP), DBP, and heart rate were measured 24 hours after dosing, and AEs were recorded. RESULTS: Group 1 included 154 patients (80 men, 74 women; mean [SD] age, 55 [6] years); group 2 included 158 patients (79 men, 79 women; mean [SD] age, 56 [5] years). Mean BP decreased significantly in both groups (P<0.01). Compared with baseline values, mean SBP/DBP decreased 16.2 (3.8)/10.1 (1.9) mm Hg in group 1 and 15.8 (3.1)/11.0 (1.5) mm Hg in group 2 at the last visit. The success rate-rate of normalized DBP (≤90 mm Hg) and responder rate (DBP reduction ≥10 mm Hg)-was 79% in group 1 and 82% in group 2. The rates of treatment-related AEs were 11% in group 1 and 8% in group 2. In group 1, heart rate significantly increased from baseline only at 2 weeks (P<0.05); in group 2, at each visit (P<0.05) except at week 12. However, none of these differences were clinically significant. CONCLUSION: In this study population of patients whose BP was not adequately controlled by monotherapy, the fixed combination of manidipine 10 mg plus delapril 30 mg, once daily, was effective and well tolerated.