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.
Treatment of hypertension in metabolic syndrome subjects with amlodipine and olmesartan-effects on oxidized non-esterified free fatty acids and cytokine production.
Rosenson, RS
Cardiovascular drugs and therapy. 2009;(4):289-94
Abstract
PURPOSE Angiotensin II increases activation of oxidative signaling and vascular inflammatory gene expression, and interruption of the renin-angiotensin system has been considered more vasculoprotective than use of calcium channel antagonists and other anti-hypertensive therapies. Despite these putative mechanisms, amlodipine is equally efficacious as other therapies in reducing cardiovascular events. METHODS Double-blind, controlled trial, designed to investigate the effects of 2-months treatment with amlodipine and olmesartan on oxidized non-esterified fatty acids (ox-NEFA), and lipopolysaccharide-stimulated cytokine production in whole blood among 23 hypertensive subjects with the metabolic syndrome. RESULTS Treatment with olmesartan was no different than amlodipine in changing concentrations of total oxidized fatty acids (p = 0.37), total ox-NEFA (p = 0.43) and 9, 10, 11, 12, 13, 14, 15 and 16 ox-NEFA concentrations. In contrast, 8 ox-NEFA increased (median [interquartile ranges] by 45.2% [5.3 to 50.0] in olmesartan-treated subjects) compared with a decrease of 18.4% (-45.1-13.9) in amlodipine-treated subjects (p = 0.03). Lipopolysaccharide-stimulated cytokine production and levels of soluble cellular adhesion molecules did not change with either treatment. CONCLUSION Despite experimental data that demonstrates that angiotensin receptor antagonists reduce cellular oxidant stress and inflammation, olmesartan was not different than amlodipine in changing ox-NEFA and inflammatory markers in hypertensive subjects with the metabolic syndrome.
3.
Effects of doxazosin and amlodipine on mean platelet volume and serum serotonin level in patients with metabolic syndrome: a randomised, controlled study.
Demirtunc, R, Duman, D, Basar, M
Clinical drug investigation. 2007;(6):435-41
Abstract
BACKGROUND AND OBJECTIVE In addition to reducing blood pressure, antihypertensive drugs should modify other atherosclerotic risk factors. One such risk factor is the prothrombotic state, which is characterised mainly by increased fibrinogen and plasminogen activator inhibitor-1 levels and abnormalities in platelet function. Platelet activity and aggregation potential can be estimated by measuring mean platelet volume (MPV). Serotonin plays a role in vasospasm and increased platelet aggregation capacity, and has been shown to increase MPV in vitro. However, serotonin levels and MPV have not been studied in the metabolic syndrome. We evaluated mean platelet volume (MPV) in patients with the metabolic syndrome, and compared the effects of doxazosin and amlodipine on MPV and serum serotonin level in patients with this condition. METHODS Thirty-eight patients who met the Adult Treatment Panel III criteria for the metabolic syndrome and 20 healthy controls were included in the study. Patients were randomised into two groups to receive doxazosin 4 mg/day (n=20) or amlodipine 10 mg/day (n=18). Patients' MPV, serum serotonin, insulin, insulin sensitivity, fasting blood glucose and lipid profiles were measured at baseline and after 8 weeks. RESULTS Patients with the metabolic syndrome had a significantly higher MPV compared with the control group. MPV was significantly decreased in the doxazosin-treated group (from 6.9 +/- 1.0 fL at baseline to 6.1 +/- 1.1 fL after treatment; p=0.02) but not in the amlodipine-treated group (6.8 +/- 0.9 fL at baseline vs 6.9 +/- 1.0 fL after treatment; p=0.9). Fasting blood glucose and total cholesterol were also significantly decreased compared with baseline in the doxazosin group. In the amlodipine group, there was a significant increase in serum serotonin levels and a decrease in serum insulin and improved insulin sensitivity. CONCLUSION In patients with the metabolic syndrome, doxazosin treatment not only decreases platelet activity, as measured by a change in MPV, but also improves metabolic abnormalities. Amlodipine also has beneficial effects in patients with the metabolic syndrome but has no effect on MPV.