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Effect of telmisartan on histological activity and fibrosis of non-alcoholic steatohepatitis: A 1-year randomized control trial.
Alam, S, Kabir, J, Mustafa, G, Gupta, U, Hasan, SK, Alam, AK
Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association. 2016;(1):69-76
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Abstract
BACKGROUND/AIM: Telmisartan can attenuate two hit pathogenesis of non-alcoholic steatohepatitis (NASH). This study aimed to observe the effect of Telmisartan on non-alcoholic fatty liver disease (NAFLD) activity score (NAS) and fibrosis score in NASH patients. PATIENTS AND METHODS A total of 50 NASH patients were randomized; 35 of group 1 were treated with Telmisartan 40/80 mg once daily with life style modification (TL) and 15 of group 2 underwent only life style modification (L) for 1 year. At the end, 20 of TL group and 10 of L group were analyzed. Those who showed NAS improvement ≥ 2 or NAS improvement ≥ 1 with fibrosis improvement ≥ 1 were considered as responders. RESULTS Baseline alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin resistance index, components of metabolic syndrome, age, and sex were similar in both groups. At the end of study, NAS improvement in TL and L groups was 2.15 ± 1.66 and 1.10 ± 0.57 (P = 0.017) and fibrosis improvement was 0.65 ± 0.93 and -0.30 ± 0.48 (P = 0.001), respectively. NAS improved by ≥ 2 in 13 (65%) and 2 (20%) patients and fibrosis score improved by ≥ 1 in 8 (40%) patients and none of the patients in TL group and L group, respectively. Telmisartan and life style modification could improve steatosis, ballooning, lobular inflammation, and fibrosis. Life style modification could improve ballooning only, but fibrosis deteriorated. TL group showed improvement in NAS and fibrosis score [P value: 0.035; odds ratio (OR) =92.07, confidence interval (CI) =1.39-6106] to the level of response by regression analysis. Weight reduction and improvement of metabolic syndrome did not influence the response. There were similar minor adverse events in both groups. CONCLUSION Telmisartan improved NAS and fibrosis score in NASH with insignificant adverse events.
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Effect of Lactotripeptides (Isoleucine-Proline-Proline/Valine-Proline-Proline) on Blood Pressure and Arterial Stiffness Changes in Subjects with Suboptimal Blood Pressure Control and Metabolic Syndrome: A Double-Blind, Randomized, Crossover Clinical Trial.
Cicero, AF, Colletti, A, Rosticci, M, Cagnati, M, Urso, R, Giovannini, M, Borghi, C, D'Addato, S
Metabolic syndrome and related disorders. 2016;(3):161-6
Abstract
BACKGROUND Lactotripeptides (LTPs) have a mild antihypertensive effect in hypertensive subjects. The main aim of our clinical trial was to test if LTPs could have some influence on blood pressure (BP) and related hemodynamic parameters in a sample of outpatients affected by metabolic syndrome. METHODS A randomized, double-blind, placebo-controlled, crossover clinical trial was conducted in a group of 40 nonsmoking volunteers with metabolic syndrome. The treatment periods were 4 weeks long and were separated by a 4-week washout period. The dietary supplementation was made by daily administration of LTPs from casein, 10.2 mg/day, and compared with placebo. RESULTS During the LTP treatment, patients experienced a significant mean decrease in systolic BP (SBP; -3.4 ± 4.4 mmHg, P = 0.041), diastolic BP (DBP; -3.1 ± 3.2 mmHg, P = 0.049), and pulse wave velocity (PWV; -0.7 ± 0.3 m/sec, P = 0.001). After LTP treatment, delta SBP, DBP, and PP were all significantly improved (P < 0.01 for all) compared with placebo. PWV also improved significantly after LTP treatment with respect to the end of the treatment with placebo (-0.8 ± 0.4 vs. -0.1 ± 0.3 m/sec, P = 0.009). The square root of the ratio of peak:baseline pulse volume during hyperemia (√V2/V1) improved after LTP treatment only (1.2 ± 0.4 vs. 1.4 ± 0.5, P = 0.04). Through the evaluation of the hemodynamic parameters that were measured by the 24-hr ambulatory monitoring, we observed that SBP, MBP, and the percentage of time with SBP over the normal were significantly reduced only after the LTP treatment (P < 0.05). These parameters were also significantly improved when compared with the ones measured after the placebo treatment (P < 0.05). CONCLUSION In our trial, during LTP treatment, patients affected by metabolic syndrome experienced a mild but significant improvement in office and 24-hr BP, PWV, and endothelial function compared with placebo treatment.
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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.
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Effectiveness of using long-acting angiotensin II type 1 receptor blocker in Japanese obese patients with metabolic syndrome on morning hypertension monitoring by using telemedicine system (FUJIYAMA study).
Kinoshita, S, Ryuzaki, M, Sone, M, Nishida, E, Nakamoto, H, ,
Clinical and experimental hypertension (New York, N.Y. : 1993). 2014;(7):508-16
Abstract
AIM: Recently, obesity patients have been diagnosed as metabolic syndrome. The aim of this study was to evaluate which angiotensin type 1 receptor blockers (ARBs), telmisartan or candesartan, is superior for the control of home blood pressure (BP) in the morning when the outpatient clinic BP was well controlled in the patients with metabolic syndrome. METHODS The patients with metabolic syndrome were enrolled. Home BP was monitored by using a telemedicine system. After a 2- to 4-week control period to establish baseline home BP values, these patients were randomly divided into telmisartan (20-80 mg) and candesartan (4-12 mg) groups. These end points were evaluated by using the telemedicine system during steady-state active therapy. A total of 356 patients attending 60 outpatient Japanese centers were recruited. RESULTS On a day of active therapy, telmisartan significantly lowered both systolic and diastolic home BP in the morning to a greater extent compared to candesartan. At the end of the study, reductions in systolic and diastolic home BP in the morning, in telmisartan group were significantly larger compared to the changes in the candesartan group (systolic; Tel: 12.0 ± 8.9 versus Can: 8.1 ± 17.1 mmHg, p = 0.0292, diastolic; Tel: 7.4 ± 6.1 versus Can: 3.7 ± 6.8 mmHg, p = 0.0053). Additionally in the telmisartan treated group, LDL-cholesterol showed significant reduction (p = 0.037), but candesartan did not. CONCLUSION The present study by using the telemedicine system clearly demonstrated that telmisartan has a strong effect on reducing morning home BP, and a good effect on lipid metabolism in patients with metabolic syndrome.
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A randomized, double-blind, placebo-controlled crossover study of coenzyme Q10 therapy in hypertensive patients with the metabolic syndrome.
Young, JM, Florkowski, CM, Molyneux, SL, McEwan, RG, Frampton, CM, Nicholls, MG, Scott, RS, George, PM
American journal of hypertension. 2012;(2):261-70
Abstract
BACKGROUND Our aim was to examine the effects of adjunctive coenzyme Q(10) therapy on 24-h ambulatory blood pressure (BP) in subjects with the metabolic syndrome and inadequate BP control. METHODS In a randomized, double-blind, placebo-controlled 12-week crossover trial, coenzyme Q(10) (100 mg twice daily) or placebo was administrated to 30 subjects with the metabolic syndrome, and inadequate BP control (an average clinic BP of ≥140 systolic mm Hg or ≥130 mm Hg for patients with type 2 diabetes) while taking an unchanged, conventional antihypertensive regimen. Clinic and 24-h ambulatory BP were assessed pre- and post-treatment phases. The primary outcomes were the changes in 24-h systolic and diastolic BP during adjunctive therapy with coenzyme Q(10) vs. placebo and prespecified secondary outcomes included changes in BP loads. RESULTS Compared with placebo, treatment with coenzyme Q(10) was not associated with statistically significant reductions in systolic (P = 0.60) or diastolic 24-h ambulatory BP (P = 0.12) or heart rate (P = 0.10), although daytime diastolic BP loads, were significantly lower during coenzyme Q(10) administration with thresholds set at >90 mm Hg (P = 0.007) and ≥85 mm Hg (P = 0.03). Coenzyme Q(10) was well tolerated and was not associated with any clinically relevant changes in safety parameters. CONCLUSIONS Although it is possible that coenzyme Q(10) may improve BP control under some circumstances, any effects are likely to be smaller than reported in previous meta-analyses. Furthermore, our data suggest that coenzyme Q(10) is not currently indicated as adjunctive antihypertensive treatment for patients with the metabolic syndrome whose BP control is inadequate, despite regular antihypertensive therapy.
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Comparative efficacy and safety of aliskiren and irbesartan in patients with hypertension and metabolic syndrome.
Krone, W, Hanefeld, M, Meyer, HF, Jung, T, Bartlett, M, Yeh, CM, Rajman, I, Prescott, MF, Dole, WP
Journal of human hypertension. 2011;(3):186-95
Abstract
Metabolic syndrome, a cluster of risk factors that increase the risk of cardiovascular morbidity and mortality, is common in patients with hypertension. Chronic renin-angiotensin-aldosterone system (RAAS) activation, shown by elevated plasma renin activity (PRA), is implicated in many of the features of metabolic syndrome. The direct renin inhibitor aliskiren may be of benefit in this patient group as aliskiren targets the RAAS at the rate-limiting step. In this double-blind study, 141 patients with hypertension (mean baseline BP 155/93 mm Hg) and metabolic syndrome (modified National Cholesterol Education Program ATP III criteria) were randomized to aliskiren 300 mg or irbesartan 300 mg once daily. Patients treated with aliskiren 300 mg had their mean sitting blood pressure (BP) lowered by 13.8/7.1 mm Hg after 12 weeks, significantly greater (P≤0.001) than the 5.8/2.8 mm Hg reduction observed in patients treated with irbesartan 300 mg. A significantly greater proportion of patients treated with aliskiren achieved BP control to <135/85 mm Hg (29.2 vs 16.7% with irbesartan; P=0.019). Aliskiren treatment led to a 60% decrease in PRA from baseline, whereas irbesartan increased PRA by 99% (both P<0.001). Aliskiren and irbesartan had similar effects on glucose and lipid profiles and on a panel of biomarkers of inflammation and cardiovascular risk. Both aliskiren and irbesartan were well tolerated. Collectively, these results suggest that aliskiren 300 mg may offer treatment benefits compared with irbesartan 300 mg for BP reduction in patients with hypertension and metabolic syndrome.
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Blood pressure control by the nifedipine GITS-telmisartan combination in patients at high cardiovascular risk: the TALENT study.
Mancia, G, Parati, G, Bilo, G, Choi, J, Kilama, MO, Ruilope, LM, ,
Journal of hypertension. 2011;(3):600-9
Abstract
BACKGROUND Guidelines on hypertension regard combinations between two antihypertensive drugs to be the most important treatment strategy. Because of the complementary mechanism of action and the evidence of cardiovascular protective effects they include the combination of a calcium antagonist and an angiotensin receptor antagonist among the priorital ones to employ. AIMS To determine in hypertensive patients at high cardiovascular risk whether combining Nifedipine GITS at low dose and telmisartan reduced ambulatory and clinic blood pressure (BP) more than the combination components, controlled BP early after treatment initiation and allowed to also obtain a better long-term BP control compared to initiating treatment with the combination components and moving to the combination later. METHODS Four hundred and five patients with a clinic SBP ≥ 135 mmHg and with diabetes, a metabolic syndrome or organ damage were randomized to once-a-day telmisartan 80 mg, nifedipine GITS 20 mg or the combination of the two drugs in a 1: 1: 2 ratio for 8 weeks in the context of a multicenter double-blind study design. Patients on monotherapy were then moved to combination treatment and all three groups were followed for an additional 16-week period. Both 24-h and clinic BP were measured before treatment and at various times during treatment. RESULTS In the per-protocol patients (n = 327), baseline demographic and clinical characteristics were similar between the three groups. Baseline 24-h SBP values were 136.2 ± 11.6 mmHg (mean ± SD), 137.2 ± 12.5 mmHg and 136.8 ± 11.7 mmHg in the telmisartan monotherapy, nifedipine GITS monotherapy and combination therapy, respectively. The corresponding clinic values were 151.7 ± 11.8, 151.3 ± 11.9 and 151.1 ± 11.8 mmHg, respectively. All treatments lowered 24-h SBP significantly (P < 0.0001) but combination treatment (8 weeks) reduced it significantly more than monotherapies (10.8 ± 0.8 vs. 6.6 ± 1.1 mmHg and 8.0 ± 1.2 mmHg; P = 0.001 and 0.037). Similar data were obtained for clinic SBP for which the combination showed a significantly greater BP reduction (12.6 ± 0.6 vs. 8.6 ± 0.7 mmHg and 9.3 ± 0.8 mmHg; P = 0.003 and 0.024) also after 2 weeks of treatment. Moving from monotherapy to combination therapy increased the antihypertensive effect and made both ambulatory and clinic SBP superimposable in the three groups after 16 and 24 weeks of treatment. Similar findings were obtained for DBP. CONCLUSION Combination treatment with nifedipine GITS low dose and telmisartan provides a greater and earlier clinic and ambulatory BP reduction than the combination components in monotherapy. Initiating treatment with the combination did not result in any better longer term BP control compared to starting treatment with monotherapy and moving to the combination later.
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ALLHAT findings revisited in the context of subsequent analyses, other trials, and meta-analyses.
Wright, JT, Probstfield, JL, Cushman, WC, Pressel, SL, Cutler, JA, Davis, BR, Einhorn, PT, Rahman, M, Whelton, PK, Ford, CE, et al
Archives of internal medicine. 2009;(9):832-42
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The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is reevaluated considering information from new clinical trials, meta-analyses, and recent subgroup and explanatory analyses from ALLHAT, especially those regarding heart failure (HF) and the association of drug treatment with new-onset diabetes mellitus (DM) and its cardiovascular disease (CVD) consequences. Chlorthalidone was superior to (1) doxazosin mesylate in preventing combined CVD (CCVD) (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.13-1.27), especially HF (RR, 1.80; 95% CI, 1.40-2.22) and stroke (RR, 1.26; 95% CI, 1.10-1.46); (2) lisinopril in preventing CCVD (RR, 1.10; 95% CI, 1.05-1.16), including stroke (in black persons only) and HF (RR, 1.20; 95% CI, 1.09-1.34); and (3) amlodipine besylate in preventing HF, overall (by 28%) and in hospitalized or fatal cases (by 26%). Central independent blinded reassessment of HF hospitalizations confirmed each comparison. Results were consistent by age, sex, race (except for stroke and CCVD), DM status, metabolic syndrome status, and renal function level. Neither amlodipine nor lisinopril was superior to chlorthalidone in preventing end-stage renal disease overall, by DM status, or by renal function level. In the chlorthalidone arm, new-onset DM was not significantly associated with CCVD (RR, 0.96; 95% CI, 0.88-2.42). Evidence from subsequent analyses of ALLHAT and other clinical outcome trials confirm that neither alpha-blockers, angiotensin-converting enzyme inhibitors, nor calcium channel blockers surpass thiazide-type diuretics (at appropriate dosage) as initial therapy for reduction of cardiovascular or renal risk. Thiazides are superior in preventing HF, and new-onset DM associated with thiazides does not increase CVD outcomes.
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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.
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Clinical outcomes by race in hypertensive patients with and without the metabolic syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
Wright, JT, Harris-Haywood, S, Pressel, S, Barzilay, J, Baimbridge, C, Bareis, CJ, Basile, JN, Black, HR, Dart, R, Gupta, AK, et al
Archives of internal medicine. 2008;(2):207-17
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BACKGROUND Antihypertensive drugs with favorable metabolic effects are advocated for first-line therapy in hypertensive patients with metabolic/cardiometabolic syndrome (MetS). We compared outcomes by race in hypertensive individuals with and without MetS treated with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), an alpha-blocker (doxazosin mesylate), or an angiotensin-converting enzyme inhibitor (lisinopril). METHODS A subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind hypertension treatment trial of 42 418 participants. We defined MetS as hypertension plus at least 2 of the following: fasting serum glucose level of at least 100 mg/dL, body mass index (calculated as weight in kilograms divided by height in meters squared) of at least 30, fasting triglyceride levels of at least 150 mg/dL, and high-density lipoprotein cholesterol levels of less than 40 mg/dL in men or less than 50 mg/dL in women. RESULTS Significantly higher rates of heart failure were consistent across all treatment comparisons in those with MetS. Relative risks (RRs) were 1.50 (95% confidence interval, 1.18-1.90), 1.49 (1.17-1.90), and 1.88 (1.42-2.47) in black participants and 1.25 (1.06-1.47), 1.20 (1.01-1.41), and 1.82 (1.51-2.19) in nonblack participants for amlodipine, lisinopril, and doxazosin comparisons with chlorthalidone, respectively. Higher rates for combined cardiovascular disease were observed with lisinopril-chlorthalidone (RRs, 1.24 [1.09-1.40] and 1.10 [1.02-1.19], respectively) and doxazosin-chlorthalidone comparisons (RRs, 1.37 [1.19-1.58] and 1.18 [1.08-1.30], respectively) in black and nonblack participants with MetS. Higher rates of stroke were seen in black participants only (RR, 1.37 [1.07-1.76] for the lisinopril-chlorthalidone comparison, and RR, 1.49 [1.09-2.03] for the doxazosin-chlorthalidone comparison). Black patients with MetS also had higher rates of end-stage renal disease (RR, 1.70 [1.13-2.55]) with lisinopril compared with chlorthalidone. CONCLUSIONS The ALLHAT findings fail to support the preference for calcium channel blockers, alpha-blockers, or angiotensin-converting enzyme inhibitors compared with thiazide-type diuretics in patients with the MetS, despite their more favorable metabolic profiles. This was particularly true for black participants.