1.
Anti-hypertensive strategies in patients with MEtabolic parameters, DIabetes mellitus and/or NephropAthy (the M E D I N A study).
Spinar, J, Vitovec, J, Soucek, M
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2014;(3):412-21
Abstract
AIMS: The primary questions asked by the MEDINA (MEtabolic parameters, DIabetes mellitus and NephropAthy) study are: 1) Do angiotensin converting enzyme inhibitors (ACE-I) have any advantages over angiotensin receptor blockers (ARB)? 2) Should the other drug for combination be a diuretic or a calcium-channel blocker (CCB)? 3) How are the risks reduced by the co administration of a statin? METHODS A total of 439 hypertensive patients with metabolic syndrome and/or diabetes mellitus were randomized to 2 groups: group 1--ramipril (ACE-I) or perindopril and group 2--losartan (ARB). Hydrochlorothiazide (diuretic) or amlodipine (CCB) were added to both groups. As a third step, a statin was added. RESULTS Blood pressure decreased 24.1/13.3 mmHg in the ACE inhibitor group and 25.9/13.5 in the losartan group. The difference was insignificant. Adding either hydrochlorothiazide or amlodipin was equally effective. There were no significant differences on metabolic parameters in the trial arms. Cholesterol level decreased by 0.95 mmol/L in the ACE-I group and 1.02 mmol/L in the ARB group (ns). CONCLUSION MEDINA has so far confirmed the equivalence of ACE-I and ARB in hypertension treatment. Adding either diuretic or CCB was equally effective. Our data support the current recommendations on adding a statin to reduce cardiovascular risk.
2.
Effect of tablets with a combination of telmisartan and amlodipine on patients with hypertension: the Cotalo study.
Ohishi, M, Kawai, T, Hayashi, N, Kitano, S, Katsuya, T, Nagano, M, Hirotani, A, Yamamoto, K, Kamide, K, Rakugi, H
Hypertension research : official journal of the Japanese Society of Hypertension. 2013;(7):620-6
Abstract
Fixed-dose combination (FDC) therapy with telmisartan 40 mg+amlodipine 5 mg (T40/A5) is expected to achieve tight blood pressure (BP) control because of the strong efficacy and long half-life of each drug. The aims of this study were to evaluate the 24-h antihypertensive efficacy of T40/A5 FDC therapy and to explore differences that may arise owing to different administration times in Japanese patients whose hypertension was not controlled by 5 mg of amlodipine per day. In this randomized clinical trial, 44 patients who had been taking amlodipine 5 mg per day and did not achieve their optimal BP target were enrolled (mean age: 67.8±10.2 years). The subjects were then randomly assigned to a T40/A5 morning or evening administration group (22 patients per group). At baseline and 8 weeks after randomization, we evaluated clinical BP and various laboratory values and performed ambulatory BP monitoring (ABPM). Clinical and mean BP evaluated with ABPM at 8 weeks (24 h, daytime, nighttime and early morning) were significantly decreased compared with BP at baseline. There were no significant differences in the diurnal BP profile change from baseline to 8 weeks between subjects in the morning and evening administration groups. There were also no significant differences in the diurnal BP profile change from baseline to 8 weeks between subjects with or without metabolic syndrome. We conclude that T40/A5 FDC therapy significantly decreased the 24-h mean and clinical BP, independent of administration time, in patients whose hypertension was not controlled by 5 mg of amlodipine.
3.
Dihydropyridine calcium channel blockers inhibit non-esterified-fatty-acid-induced endothelial and rheological dysfunction.
Yasu, T, Kobayashi, M, Mutoh, A, Yamakawa, K, Momomura, S, Ueda, S
Clinical science (London, England : 1979). 2013;(5):247-55
Abstract
Circulating NEFAs (non-esterified fatty acids) from adipose tissue lipolysis lead to endothelial dysfunction and insulin resistance in patients with the metabolic syndrome or Type 2 diabetes mellitus. The aim of the present study was to test the hypothesis that DHP (dihydropyridine) CCBs (calcium channel blockers) prevent NEFA-induced endothelial and haemorheological dysfunction independently of their antihypertensive properties. Using a double-blind cross-over study design, nifedipine, amlodipine, diltiazem or placebo were administered to eight healthy subjects for 2 days before each study day. On the study days, the following were assessed before and after the infusion of lipid and heparin to raise serum NEFAs: endothelial function, by measuring FBF (forearm blood flow) responses to ACh (acetylcholine); leucocyte activation, by ex vivo measurement of plasma MPO (myeloperoxidase) levels, adherent leucocyte numbers and whole blood transit time through microchannels; and oxidative stress, by determining plasma levels of d-ROMs (derivatives of reactive oxygen metabolites). Effects of the CCBs on NF-κB (nuclear factor κB) p65 phospholylation stimulated by NEFAs were assessed in cultured monocytic cells in vitro. Elevated NEFAs reduced the responses to ACh and significantly increased whole blood transit time, adherent leucocyte numbers and d-ROMs. Nifedipine and amlodipine, but not diltiazem, prevented NEFA-induced endothelial dysfunction, leucocyte activation and enhancement of oxidative stress without affecting BP (blood pressure), whereas all these drugs prevented NEFA-induced p65 activation in vitro. These results suggest that DHP CCBs, independent of their antihypertensive properties in humans, prevent NEFA-induced endothelial and haemorheological dysfunction through inhibition of NEFA-induced leucocyte activation, although the sensitivity to drugs of leucocyte Ca2+ channels may differ among cells.