Efficacy of a fixed combination of candesartan (32 mg) and hydrochlorothiazide(25 mg) in previously untreated patients with severe essential hypertension [Effektiv therapiert: Stellenwert der hochdosis-fixkombination Candesartan + HCT bei unvorbehandelter, schwerer essenzieller Hypertonie]
Baumgart P.,Clemenshospital GmbH |
Kiel G.,Takeda Pharma GmbH
Perfusion | Year: 2011
Aim: To investigate the efficacy of a fixed combination of candesartan (32 mg) and hydrochlorothiazide (HCTZ, 25 mg) in previously untreated patients with severe essential hypertension. Methods: Prospective, open-label study with 105 patients with systolic blood pressure (SBP) of 150-200 mmHg and diastolic blood pressure (DBP) of 110-120 mmHg. The fixed titration schema over 9 weeks started with 16 mg Candesartan (week 1), Candesartan + HCTZ (16 mg/12.5 mg) (week 2.3), Candesartan + HCTZ (32 mg/25 mg) (week 4.9). Results: Blood pressure was lowered by 44.4±16.8 mmHg (SBP), and 32.0±11.3 mmHg (DBP) (p<0.0001). 92.4 % of patients achieved the defined goal of blood lowering below 140/90 mmHg or reduction of .20 mmHg (SBP) and 10 mmHg (DBP), respectively. The disorders were in line with the known safety profile of the study drugs. Conclusion: The maximal allowed treatment with a fixed combination of candesartan/HCTZ in Europe is effective and safe to achieve a considerable and swift blood pressure reduction in newly diagnosed severe arterial hypertension. © Verlag PERFUSION GmbH.
Mengden T.,Kerckhoff Klinik GmbH |
Hubner R.,Takeda Pharma GmbH |
Bramlage P.,Institute For Kardiovaskulare Pharmakologie Und Epidemiologie
Vascular Health and Risk Management | Year: 2011
Background: Fixed-dose combinations of candesartan 32 mg and hydrochlorothiazide (HCTZ) have been shown to be effective in clinical trials. Upon market entry we conducted a noninterventional study to document the safety and effectiveness of this fixed-dose combination in an unselected population in primary care and to compare blood pressure (BP) values obtained during office measurement (OBPM) with ambulatory blood pressure measurement (ABPM). Methods: CHILI CU Soon was a prospective, noninterventional, noncontrolled, open-label, multicenter study with a follow-up of at least 10 weeks. High-risk patients aged $18 years with previously uncontrolled hypertension were started on candesartan 32 mg in a fixed-dose combination with either 12.5 mg or 25 mg HCTZ. OBPM and ABPM reduction and adverse events were documented. Results: A total of 4131 patients (52.8% male) with a mean age of 63.0 ± 11.0 years were included. BP was 162.1 ± 14.8/94.7 ± 9.2 mmHg during office visits at baseline. After 10 weeks of candesartan 32 mg/12.5 mg or 25 mg HCTZ, mean BP had lowered to 131.7 ± 10.5/80.0 ± 6.6 mmHg (P, 0.0001 for both comparisons). BP reduction was comparable irrespective of prior or concomitant medication. In patients for whom physicians regarded an ABPM to be necessary (because of suspected noncontrol over 24 hours), ABP at baseline was 158.2/93.7 mmHg during the day and 141.8/85.2 mmHg during the night. At the last visit, BP had significantly reduced to 133.6/80.0 mmHg and 121.0/72.3 mmHg, respectively, resulting in 20.8% being normotensive over 24 hours (,130/80 mmHg). The correlation between OBPM and ABPM was good (r = 0.589 for systolic BP and r = 0.389 for diastolic BP during the day). Of those who were normotensive upon OBPM, 35.1% had high ABPM during the day, 49.3% were nondippers, and 3.4% were inverted dippers. Forty-nine adverse events (1.19%) were reported, of which seven (0.17%) were regarded as serious. Conclusion: Candesartan 32 mg in a fixed-dose combination with either 12.5 mg or 25 mg HCTZ is safe and effective for further BP lowering irrespective of prior antihypertensive drug class not being able to control BP.© 2011 Mengden et al, publisher and licensee Dove Medical Press Ltd.
Gasanin E.,Kerckhoff Klinik GmbH |
Patyna W.,Kurpark Klinik |
Tajdivand M.,Kerckhoff Klinik GmbH |
Fuchs W.,Takeda Pharma GmbH |
Mitrovic V.,Kerckhoff Klinik GmbH
Perfusion | Year: 2011
Background: During long-term therapy angiotensin converting enzyme inhibitors do not completely block the formation of angiotensin-II. Combination with angiotensin-II type 1 receptor antagonists could provide a better blockade of the RAAS system compared with monotherapy. Objectives: The aim of this study was to evaluate the hemodynamic and neurohumoral effects at rest and during exercise of angiotensin-II type 1 receptor antagonist candesartan cilexetil as add-on therapy to ACE inhibitors in patients with moderate to severe symptomatic heart failure NYHA class III-IV. Furthermore, the safety of candesartan cilexetil add-on therapy was investigated. Methods: This was a prospective, randomised, double-blind, placebo-controlled, parallel group study. 35 patients received either candesartan 8 mg/16 mg (week 1 and 2/week 3-24) or placebo as add-on therapy to their previous ACE inhibitor during a 24-weeks treatment period. The hemodynamic evaluation was performed by using right heart catheterization and and exercise capacity by ergospirometry. The ITT population comprised 14 patients in the candesartan and 15 patients in the placebo group. Results: Peak aerobic capacity remained about constant in the candesartan group (0.06 ± 1.43 mL/min/kg) and slightly decreased in the placebo group (-1.10 ± 1.51 mL/min/kg). No superiority of candesartan could be concluded (p=0.13). Exercise time showed a relevant increase in the candesartan group (31.9 ± 58.5 s) and a significant decrease in the placebo group (-25.9 ± 85.9 s) compared to baseline value. The difference between treatment groups was significant (p=0.0018). Further relevant differences between treatment groups were observed in changes of right atrial pressure at rest (candesartan: -1.9 ± 1.7 mmHg, placebo: 1.0 ± 2.7 mmHg; p=0.0045), pulmonary capillary wedge pressure at rest (candesartan: -3.1 ± 3.8 mmHg, placebo: 0.2 ± 4.6 mmHg; p=0.0497) and systemic vascular resistance at maximum exercise (candesartan: -141.9 ± 253.3 dyn·s/cm -5, placebo: 47.3 ± 221.0 dyn·s/cm -5; p=0.0296). Plasma-renin-concentration was significantly increased with candesartan (279.5 ± 901.9 ng/L; p=0.0127), but in the placebo group it remained unchanged (-29.0 ± 211.9 ng/L; p=0.6267). Conclusion: The efficacy of CHF treatment was improved by candesartan as add-on therapy to ACE inhibitors. In our patients population co-administration of candesartan did not impose an additional risk on patients treated with ACE inhibitors. © Verlag PERFUSION GmbH.
Effect of pioglitazone and ramipril on biomarkers of low-grade inflammation and vascular function in nondiabetic patients with increased cardiovascular risk and an activated inflammation: Results from the PIOace study
Pfutzner A.,Institute for Clinical Research and Development |
Pfutzner A.,Bingen University of Applied Sciences |
Hanefeld M.,GWT |
Dekordi L.A.,Institute for Clinical Research and Development |
And 4 more authors.
Journal of Diabetes Science and Technology | Year: 2011
Aims: This study investigated the effects of pioglitazone (PIO), ramipril (RAM), or their combination (PIRA) on low-grade inflammation in nondiabetic hypertensive patients with increased cardiovascular risk. Methods and Results: Patients enrolled in this placebo-controlled, double-blind, randomized, parallel trial (72 male, 77 female, aged 60 ± 9 years, body mass index 30.4 ± 4.7 kg/m2, duration of hypertension 9 ± 8 years) were treated with either 30/45 mg PIO (dose titration), 2.5/5 mg RAM, or their combination for 12 weeks. A reduction in high-sensitivity C-reactive protein was observed with PIO (-0.89 ± 1.98 mg/liter; -25%) and PIRA (-0.49 ± 2.11 mg/liter; -16%), while an increase was seen with RAM (0.58 ± 2.13 mg/liter; +20%, p < .05 vs PIO and PIRA). The 24-hour blood pressure profile showed a small increase with both monotherapies but a decrease with PIRA (p < .05 vs PIO). Improvements in biomarkers of chronic systemic inflammation and insulin resistance (IR) were observed in the PIO and PIRA arms only [PIO/RAM/PIRA: homeostasis model of assessment of IR: -0.78 ± 1.39 (-29%)/0.15 ± 1.03 (+5%)/ -1.44 ± 2.83 (-40%); adiponectin: 8.51 ± 5.91 (+104%)/ 0.09 ± 2.63 (+1%)/ 8.86 ± 6.37 mg/liter (+107%); matrix metallo-proteinase- 9: -48 ± 127 (-12%)/-1 ± 224 (0%)/-60 ± 210 ng/ml (-13%), p < .05 for RAM vs PIO or PIRA in all cases]. Conclusions: Our 3-month study in nondiabetic hypertensive patients showed a decrease in biomarkers of IR and chronic systemic inflammation with the PIO monotherapy and the PIRA combination only, which may help to explain some findings in other cardiovascular outcome trials. © Diabetes Technology Society.
Double-blind, randomized, multicentre, and active comparator controlled investigation of the effect of Pioglitazone, Metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: The PIOCOMB study
Hanefeld M.,GWT TUD mbH |
Pfutzner A.,IKFE GmbH |
Forst T.,IKFE GmbH |
Kleine I.,Takeda Pharma GmbH |
Fuchs W.,Takeda Pharma GmbH
Cardiovascular Diabetology | Year: 2011
Background: We analyzed specific effects of an add-on therapy with pioglitazone compared to metformin and their combination in patients with basal insulin treatment on biomarkers of CV risk.Methods: In this double-blind, randomized, multicentre, active comparator controlled trial, 121 patients with type 2 diabetes were enrolled. Inclusions: treatment with basal insulin, HbA 1C6.5% - 8.5%, age 30 - 75 years. After glargine therapy over 2 weeks for titration towards FBG ≤ 7.8 mmol/L, patients received either (A) bid 850 mg metformin (n = 42), (B) bid 15 mg pioglitazone (n = 40), or (C) 30 mg pioglitazone plus 1.7 g metformin (n = 39) over 6 months. Matrix Metal Proteinase 9 (MMP-9) was primary objective, together with biomarkers of CV risk.Results: Pioglitazone (B) reduced MMP-9 versus baseline by 54.1 + 187.1 ng/mL, with metformin (A) it was increased by 49.6 + 336.2 ng/mL (p = 0.0345; B vs. A), and with the combination of both (C) it was decreased by 67.8 + 231.4 ng/mL (A vs. C: p = 0.0416; B vs. C: p = 0.8695). After logarithmic transformation due to high variances the exploratory results showed significance for A vs. B (p = 0.0043) and for A vs. C (p = 0.0289).Insulin dosage was reduced by 7.3 units in group B (p < 0.0001), by 6.0 units in C (p = 0.0004), but was increased by 2.5 units (p = 0.1539) in A at follow up. Reduction in hs-CRP was significant within treatment groups for B (p = 0.0098) and C (p < 0.0001), and between the groups for A vs. C (p = 0.0124). All three single regimens reduced PAI-1. Adiponectin was significantly elevated in B and C (p < 0.0001) and between-groups. HbA 1Cwas only significantly decreased in the combination group. No significant effects were observed for NFkB and PGFα. peripheral edema were seen in 11.9% vs. 40.0% vs. 20.5%, and weight change was -0.7 kg vs. +4.3 kg vs. +2.7 kg (A vs. B vs. C).Conclusions: Addition of pioglitazone but not of metformin reduces MMP-9, hs-CRP and increased insulin sensitivity and adiponectin in this study. The combination of both had no additional effect on inflammation. Pioglitazone is suggested to be a rational add-on therapy to basal insulin in patients with high CV risk. © 2011 Hanefeld et al; licensee BioMed Central Ltd.