WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Dihydropyridine calcium channel blockers (CCBs) are widely used antihypertensive drugs. Evidence from animal studies indicates there are differences between CCBs in their renal haemodynamic effects suggesting that manidipine reduces, whereas amlodipine increases intraglomerular pressure but data from humans are scarce. WHAT THIS STUDY ADDS• In this study amlodipine was found to increase significantly intraglomerular pressure whereas manidipine decreased intraglomerular pressure in people with essential hypertension. This difference was attributed to significant vasodilation of the afferent arteriole with amlodipine compared with manidipine. This study for the first time has confirmed in humans data from experimental models on the different action of CCBs on dilatory capacity on efferent and afferent arterioles. AIMSIntraglomerular 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 (Pglom) in patients with mild to moderate essential hypertension. METHODSIn 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. Pglom and resistances of the afferent (RA) and efferent (RE) arterioles were calculated according to the model established by Gomez. RESULTSPglom 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 Pglom by 1.2 mmHg between the manidipine and amlodipine group (P = 0.042). In both treatment arms, RA was reduced (manidipine P = 0.018; amlodipine P < 0.001). The reduction of RA was significantly more pronounced with amlodipine compared with manidipine treatment (P < 0.001). RE 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). CONCLUSIONSIn 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.

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.

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Aim:The aim of this study was to assess the long-term tolerability and efficacy of a fixed combination of manidipine 10mg and delapril 30mg (M+D) as an antihypertensive treatment in patients with mild to moderate hypertension. Study design: This was a multicentre open study, with a two-week placebo run-in period, followed by a 50-week active treatment period. Three hundred and nine patients with a mean age of 56.4 years and a sitting (Si) diastolic blood pressure (DBP) of ≥95mm Hg and ≤110mm Hg were enrolled. During the treatment period systolic blood pressure (SBP) and DBP were assessed by conventional sphygmomanometry. Results: The decreases in SiSBP and SiDBP were clinically relevant after 4 weeks of treatment, with a mean reduction of 16.6mm Hg (95% confidence interval [CI] -18.2; -15) and 9.3mm Hg (95% CI -10.2; -8.4), respectively. At the end of treatment, SiSBP and SiDBP were significantly decreased by 21.8mm Hg [95% CI -23.4; -20.2) and 14.3mm Hg (95% CI -15.3; -13.4), respectively. Pulse pressure (PP) was 61.4 ± 9.8mm Hg at baseline and was reduced to 54.2 ± 10.8mm Hg after the first month of treatment (-7.3mm Hg, 95% CI -8.5; -6); at 50 weeks of treatment the PP was 54 ± 11mm Hg (-7.5mm Hg, 95% CI -8.8; -6.1). The success rate (reduction of SiDBP ≥10mm Hg from baseline or SiDBP ≤90mm Hg) was 86.4%, the normalisation rate (SiDBP ≤90mm Hg) was 80.6%. Forty-four patients (14.2%) reported adverse drug-related events. No clinically significant changes in heart rate, ECG or laboratory tests were found. Conclusion: The fixed combination M+D is effective in reducing blood pressure levels in patients with hypertension and in maintaining the reduction throughout the study period, with a good tolerability profile.

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