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Carl J Pepine - One of the best experts on this subject based on the ideXlab platform.

  • ces1p1 variant 816a c is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of Trandolapril
    European Journal of Clinical Pharmacology, 2016
    Co-Authors: Taimour Y Langaee, Julie A Johnson, Xinwen Wang, Carl J Pepine, Rhonda M Cooperdehoff, Yan Gong, John S Markowitz
    Abstract:

    Purpose The majority of angiotensin-converting enzyme inhibitors (ACEIs) are synthesized as ester prodrugs that must be converted to their active forms in vivo in order to exert therapeutic effects. Hepatic carboxylesterase 1 (CES1) is the primary enzyme responsible for the bioactivation of ACEI prodrugs in humans. The genetic variant −816A>C (rs3785161) is a common variant located in the promoter region of the CES1P1 gene. Previous studies report conflicting results with regard to the association of this variant and therapeutic outcomes of CES1 substrate drugs. The purpose of this study was to determine the effect of the variant −816A>C on the activation of the ACEI prodrug Trandolapril in human livers and the blood pressure (BP)-lowering effect of Trandolapril in hypertensive patients.

  • long term mortality in hypertensive patients with coronary artery disease results from the us cohort of the international verapamil sr Trandolapril study
    Hypertension, 2016
    Co-Authors: Islam Y Elgendy, Eileen M Handberg, Rhonda M Cooperdehoff, Yan Gong, Anthony A Bavry, Carl J Pepine
    Abstract:

    The dyad of hypertension and coronary artery disease is prevalent; however, data on systolic blood pressure (SBP) control and long-term all-cause mortality are lacking. Using extended follow-up data from the US cohort of the International Verapamil (SR)/Trandolapril Study (mean 11.6 years), subjects were categorized by age at enrollment (50 to Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00133692.

  • invest revisited review of findings from the international verapamil sr Trandolapril study
    Expert Review of Cardiovascular Therapy, 2009
    Co-Authors: Rhonda M Cooperdehoff, Eileen M Handberg, Giuseppe Mancia, Qian Zhou, Annette Champion, Udo F Legler, Carl J Pepine
    Abstract:

    The International Verapamil SR–Trandolapril Study (INVEST), a randomized trial of 22,576 predominantly elderly patients with an average 2.7-year follow-up, compared a calcium antagonist-led strategy (verapamil SR plus Trandolapril) with a β-blocker-led strategy (atenolol plus hydrochlorothiazide) for hypertension treatment and prevention of cardiovascular outcomes in coronary artery disease patients. Patients received individualized dose and drug titration following a flexible, multi-drug, guideline-based treatment algorithm, with the objective of achieving optimal blood pressure (BP) control individualized for comorbidities (e.g., diabetes). The primary outcome (PO) was first occurrence of death (all-cause), nonfatal myocardial infarction or nonfatal stroke. The strategies resulted in significant and very similar BP reduction, with approximately 70% of patients in both strategies achieving BP control (<140/90 mmHg). Increasing number of office visits with BP in control was associated with reduced risk of...

  • factors influencing blood pressure response to Trandolapril add on therapy in patients taking verapamil sr from the international verapamil sr Trandolapril invest study
    American Journal of Cardiology, 2007
    Co-Authors: Carl J Pepine, Rhonda M Cooperdehoff, Martin Brunner, Yan Gong, Jason H Karnes, Taimour Y Langaee, Julie A Johnson
    Abstract:

    Factors such as age and race/ethnicity might influence blood pressure (BP) response to drugs. Therapeutic response to the angiotensin-converting enzyme inhibitor Trandolapril used as add-on therapy to stable calcium channel blocker therapy with verapamil sustained release 240 mg was addressed in a racially/ethnically diverse group of 1,832 hypertensive patients with coronary artery disease. Furthermore, the association with a polymorphism (1166A→C) in the angiotensin II type 1 receptor gene ( AGTR1 ) was tested. BP response was compared between groups using analysis of covariance after adjustment for covariates associated with BP response. Genotyping was performed using polymerase chain reaction and pyrosequencing. Trandolapril decreased mean unadjusted systolic and diastolic BPs by −9.1 ± 17.3 (SD) and −4.1 ± 10.1 mm Hg, respectively. The percentage of patients with BP under control ( AGTR1 1166A→C genotype and BP response. In conclusion, Trandolapril add-on therapy was effective in increasing BP control, with age and baseline BP associated with both systolic and diastolic BP response. Race was associated with diastolic BP response, although the difference is likely not to be clinically significant and AGTR1 genotype was not associated with BP response.

  • antihypertensive properties of a high dose combination of Trandolapril and verapamil sr
    Blood Pressure, 2007
    Co-Authors: Franz H Messerli, William H Frishman, William J Elliott, Peter H Bacher, Carl J Pepine
    Abstract:

    The superior diastolic blood pressure reduction (BP) of high‐dose combination therapy with Trandolapril (Tr) and verapamil‐SR (Ve) compared with monotherapy has previously been reported. Guideline changes, placing greater emphasis on systolic BP, prompted a re‐evaluation of TV‐51 and an assessment of a subset of patients from the INternational VErapamil‐SR Trandolapril STudy (INVEST). The objective of this analysis was to determine if the short‐term antihypertensive effects of high‐dose Tr+Ve (Tr/Ve study) could be confirmed in a sample of higher‐risk INVEST patients with longer follow‐up. The Tr/Ve study was a double‐blind, randomized, parallel‐group, placebo‐controlled trial to evaluate the antihypertensive effects of Trandolapril and verapamil‐SR alone or in combination in 631 patients randomized to placebo, 4 mg Trandolapril, 240 mg verapamil‐SR or 4mg/240mg Tr+Ve combination for 6 weeks; 581 INVEST patients were selected for comparison with 24‐month BP data, 90% use of Trandolapril and verapamil‐SR c...

Rhonda M Cooperdehoff - One of the best experts on this subject based on the ideXlab platform.

  • ces1p1 variant 816a c is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of Trandolapril
    European Journal of Clinical Pharmacology, 2016
    Co-Authors: Taimour Y Langaee, Julie A Johnson, Xinwen Wang, Carl J Pepine, Rhonda M Cooperdehoff, Yan Gong, John S Markowitz
    Abstract:

    Purpose The majority of angiotensin-converting enzyme inhibitors (ACEIs) are synthesized as ester prodrugs that must be converted to their active forms in vivo in order to exert therapeutic effects. Hepatic carboxylesterase 1 (CES1) is the primary enzyme responsible for the bioactivation of ACEI prodrugs in humans. The genetic variant −816A>C (rs3785161) is a common variant located in the promoter region of the CES1P1 gene. Previous studies report conflicting results with regard to the association of this variant and therapeutic outcomes of CES1 substrate drugs. The purpose of this study was to determine the effect of the variant −816A>C on the activation of the ACEI prodrug Trandolapril in human livers and the blood pressure (BP)-lowering effect of Trandolapril in hypertensive patients.

  • long term mortality in hypertensive patients with coronary artery disease results from the us cohort of the international verapamil sr Trandolapril study
    Hypertension, 2016
    Co-Authors: Islam Y Elgendy, Eileen M Handberg, Rhonda M Cooperdehoff, Yan Gong, Anthony A Bavry, Carl J Pepine
    Abstract:

    The dyad of hypertension and coronary artery disease is prevalent; however, data on systolic blood pressure (SBP) control and long-term all-cause mortality are lacking. Using extended follow-up data from the US cohort of the International Verapamil (SR)/Trandolapril Study (mean 11.6 years), subjects were categorized by age at enrollment (50 to Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00133692.

  • invest revisited review of findings from the international verapamil sr Trandolapril study
    Expert Review of Cardiovascular Therapy, 2009
    Co-Authors: Rhonda M Cooperdehoff, Eileen M Handberg, Giuseppe Mancia, Qian Zhou, Annette Champion, Udo F Legler, Carl J Pepine
    Abstract:

    The International Verapamil SR–Trandolapril Study (INVEST), a randomized trial of 22,576 predominantly elderly patients with an average 2.7-year follow-up, compared a calcium antagonist-led strategy (verapamil SR plus Trandolapril) with a β-blocker-led strategy (atenolol plus hydrochlorothiazide) for hypertension treatment and prevention of cardiovascular outcomes in coronary artery disease patients. Patients received individualized dose and drug titration following a flexible, multi-drug, guideline-based treatment algorithm, with the objective of achieving optimal blood pressure (BP) control individualized for comorbidities (e.g., diabetes). The primary outcome (PO) was first occurrence of death (all-cause), nonfatal myocardial infarction or nonfatal stroke. The strategies resulted in significant and very similar BP reduction, with approximately 70% of patients in both strategies achieving BP control (<140/90 mmHg). Increasing number of office visits with BP in control was associated with reduced risk of...

  • factors influencing blood pressure response to Trandolapril add on therapy in patients taking verapamil sr from the international verapamil sr Trandolapril invest study
    American Journal of Cardiology, 2007
    Co-Authors: Carl J Pepine, Rhonda M Cooperdehoff, Martin Brunner, Yan Gong, Jason H Karnes, Taimour Y Langaee, Julie A Johnson
    Abstract:

    Factors such as age and race/ethnicity might influence blood pressure (BP) response to drugs. Therapeutic response to the angiotensin-converting enzyme inhibitor Trandolapril used as add-on therapy to stable calcium channel blocker therapy with verapamil sustained release 240 mg was addressed in a racially/ethnically diverse group of 1,832 hypertensive patients with coronary artery disease. Furthermore, the association with a polymorphism (1166A→C) in the angiotensin II type 1 receptor gene ( AGTR1 ) was tested. BP response was compared between groups using analysis of covariance after adjustment for covariates associated with BP response. Genotyping was performed using polymerase chain reaction and pyrosequencing. Trandolapril decreased mean unadjusted systolic and diastolic BPs by −9.1 ± 17.3 (SD) and −4.1 ± 10.1 mm Hg, respectively. The percentage of patients with BP under control ( AGTR1 1166A→C genotype and BP response. In conclusion, Trandolapril add-on therapy was effective in increasing BP control, with age and baseline BP associated with both systolic and diastolic BP response. Race was associated with diastolic BP response, although the difference is likely not to be clinically significant and AGTR1 genotype was not associated with BP response.

  • predictors of development of diabetes mellitus in patients with coronary artery disease taking antihypertensive medications findings from the international verapamil sr Trandolapril study invest
    American Journal of Cardiology, 2006
    Co-Authors: Rhonda M Cooperdehoff, Franz H Messerli, Jerome D Cohen, George L Bakris, Serap Erdine, Ann C Hewkin, Stuart Kupfer, Carl J Pepine
    Abstract:

    Knowledge of predictors of diabetes mellitus (DM) development in patients with coronary artery disease (CAD) who use antihypertensive therapy could contribute to decreasing this adverse metabolic consequence. This is particularly relevant because the standard of care, β blockers combined with diuretics, may contribute to adverse metabolic risk. The INternational VErapamil SR-Trandolapril STudy compared a calcium antagonist-based (verapamil SR) and a β-blocker–based (atenolol) strategy with Trandolapril and/or hydrochlorothiazide added to control blood pressure (BP) in patients with CAD. The 16,176 patients without DM at entry were investigated with regard to newly diagnosed DM during follow-up. Newly diagnosed DM was less frequent in the verapamil SR versus atenolol strategy (7.0% vs 8.2%, hazard ratio 0.85, 95% confidence interval 0.76 to 0.95, p

Christian Torppedersen - One of the best experts on this subject based on the ideXlab platform.

  • the long term impact of the angiotensin converting enzyme inhibitor Trandolapril on mortality and hospital admissions in patients with left ventricular dysfunction after a myocardial infarction follow up to 12 years
    Acc Current Journal Review, 2005
    Co-Authors: Pernille Buch, Lars Kober, J E Carlsen, Steen Z Abildstrom, Soren Rasmussen, Christian Torppedersen
    Abstract:

    Aims To investigate the long-term benefits of treatment with angiotensin-converting enzyme (ACE)-inhibitors in patients with myocardial infarction (MI) and left ventricular dysfunction (LVD). Methods and results In the Trandolapril cardiac evaluation (TRACE) study, 1749 patients with LVD (ejection fraction � 35%) were randomized to Trandolapril (n ¼ 876) or placebo (n ¼ 873) 3–7 days post-MI. Enrolment lasted from 1990 to 1994; on-treatment follow-up ranged from 2 to 4 years. At study closure, all patients were recommended continued ACE-inhibitor use. National registries were used to track deaths and hospitalizations until 2002. Mortality was analysed with Cox proportional hazard models and hospitalization with Poisson regression models (models adjusted for observation time). Over 10–12 years of follow-up, a total of 1283 deaths and 9220 hospitalizations were registered. Compared with the placebo group, the Trandolapril group had a significantly reduced risk of all-cause mortality (relative risk 0.89, 95% CI 0.80–0.99, P ¼ 0.03), all-cause hospitalizations (rate ratio 0.92, 95% CI 0.88–0.96, P , 0.001), and cardiovascular hospitalizations (rate ratio 0.95, 95% CI 0.91–1.00, P ¼ 0.047), including congestive heart failure hospitalizations (rate ratio 0.85, 95% CI 0.77–0.93, P , 0.001). Conclusion In patients with LVD, use of Trandolapril shortly after an MI for 2–4 years has long-term benefits. The beneficial effect on mortality and hospitalization rates is maintained for at least 10–12 years.

  • the angiotensin converting enzyme inhibitor Trandolapril has neutral effect on exercise tolerance or functional class in patients with myocardial infarction and reduced left ventricular systolic function
    European Heart Journal, 2003
    Co-Authors: Jawdat Abdulla, Lars Kober, Hans Burchardt, Steen Z Abildstrom, Christian Torppedersen
    Abstract:

    Aims To study the effect of angiotensin-converting enzyme (ACE) inhibitor Trandolapril on exercise tolerance time (ETT) and New York Heart Association (NYHA) classification in patients with reduced left ventricular systolic dysfunction (LVSD) after acute myocardial infarction (AMI). Methods and results The Trandolapril Cardiac Evaluation (TRACE) was a randomized controlled study designed to evaluate the effect of Trandolapril on mortality in 1749 consecutive Danish patients with LVSD after AMI. NYHA class was recorded every 3 months in all patients. In a prospective sub-study, 254 patients underwent exercise tolerance tests at 1, 3 and 12 months. The two treatment arms showed equal improvement in NYHA class both in the entire and exclusively symptomatic population over 4 years of follow-up ( P =ns). ETT increased equally in both treatment arms at 1, 3, 12 months ( P =ns). A mean of 12mg/day of furosemide was spared in Trandolapril arm ( P =0.001). Conclusions Trandolapril had a mild diuretic-sparing effect. These results emphasis the importance of explaining to patients that ACE inhibitors provide protection against death and hospitalisation for heart failure but do not have any significant effect upon symptoms.

  • Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction
    Circulation, 1999
    Co-Authors: Ole Pedersen, Henning Bagger, Lars Kober, Christian Torppedersen
    Abstract:

    Background—Studies have suggested that ACE inhibitors have an antiarrhythmic effect on ventricular arrhythmias. Whether they have an effect on atrial fibrillation is unknown. Methods and Results—We investigated the effect of ACE inhibition with Trandolapril on the incidence of atrial fibrillation in patients with reduced left ventricular function secondary to acute myocardial infarction. The patients in this study were those who qualified for inclusion into the Trandolapril Cardiac Evaluation (TRACE) study, a randomized double-blind placebo-controlled study and who had sinus rhythm on the ECG obtained at randomization. Patients who fulfilled the criteria for inclusion were randomized to treatment with the ACE inhibitor Trandolapril or placebo and were followed up for 2 to 4 years. Development and time to occurrence of atrial fibrillation in one 12-lead ECG recorded at the outpatient visits was the primary end point of this investigation. Of the 1749 patients included in the TRACE study, 1577 had sinus rhy...

  • effect of ace inhibitor Trandolapril on life expectancy of patients with reduced left ventricular function after acute m yocardial infarction
    The Lancet, 1999
    Co-Authors: Christian Torppedersen, Lars Kober
    Abstract:

    Summary Background The survival benefit from the use of inhibitors of angiotensin-converting enzyme (ACE) in patients with acute myocardial infarction is usually presented in terms of risk ratios and lives saved per 1000 people treated. A more relevant way to present the extent of benefit would be in terms of an increase in life expectancy, but this approach has not previously been possible because of limited data on long-term outcome. We aimed to calculate the effect of Trandolapril on life expectancy with follow-up data from the Trandolapril Cardiac Evaluation (TRACE) Study. Methods The TRACE study previously showed a significant survival benefit with Trandolapril in patients with reduced left-ventricular function after an acute myocardial infarction who were treated for at least 2 years. We ascertained the survival status of all patients in the TRACE study in June, 1998, at which time they had been followed up for a minimum of 6 years. We estimated life expectancy as median lifetime, which was the time for 50% of the patients to have died. Change in life expectancy is expressed as change in median lifetime. Analysis was by intention to treat. Findings The life expectancy of patients was 4·6 years for those given placebo versus 6·2 years for those on Trandolapril. Thus, for patients on Trandolapril, median lifetime was increased by 15·3 months or 27% (95% Cl 7 to 51). Analysis of follow-up after the end of the study indicated no decrease of this benefit during the course of double-blind treatment; continued use of Trandolapril was recommended at study closure. Interpretation In patients with severely reduced left-ventricular function, long-term treatment with an ACE inhibitor during the critical period after myocardial infarction is associated with a substantial increase in life expectancy.

  • effect of the angiotensin converting enzyme inhibitor Trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction
    Journal of the American College of Cardiology, 1999
    Co-Authors: Ida Gustafsson, Christian Torppedersen, Lars Kober, Finn Gustafsson, Per Hildebrandt
    Abstract:

    Abstract OBJECTIVES This study evaluated the efficacy of long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor Trandolapril in diabetic patients with left ventricular dysfunction after acute myocardial infarction (AMI). BACKGROUND Patients with diabetes mellitus have a high mortality following AMI, probably due to a high risk of congestive heart failure and reinfarction. Because ACE inhibition effectively reduces progression of heart failure, it could be particularly beneficial in diabetic patients after AMI. METHODS The study is a retrospective analysis using data from the Trandolapril Cardiac Evaluation (TRACE) study, which was a randomized, double-blind, placebo-controlled trial of Trandolapril in 1,749 patients with AMI and ejection fraction ≤35%. The mean follow-up time was 26 months. RESULTS A history of diabetes was found in 237 (14%) of the 1,749 patients. Treatment with Trandolapril resulted in a relative risk (RR) of death from any cause for the diabetic group of 0.64 (95% confidence interval 0.45 to 0.91) versus 0.82 (0.69 to 0.97) for the nondiabetic group. In the diabetic group, Trandolapril reduced the risk of progression to severe heart failure markedly (RR, 0.38 [0.21 to 0.67]), and no significant reduction of this end point was found in the nondiabetic group. CONCLUSIONS The ACE inhibition after myocardial infarction complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives and substantially reducing the risk of progression to severe heart failure.

Belen M Cid - One of the best experts on this subject based on the ideXlab platform.

Piero Ruggenenti - One of the best experts on this subject based on the ideXlab platform.

  • THE BENEDICT STUDY GROUP
    2015
    Co-Authors: Complications Trial, Piero Ruggenenti, Grazia Maria Costa, Aneliya Parvanova, Giovanni Antonio Giuliano, Dipl Stat, Nicola Motterlini, Stat Sci D
    Abstract:

    OBJECTIVE — In patients with type 2 diabetes, left ventricular hypertrophy (LVH) predicts cardiovascular events, and the prevention of LVH is cardioprotective. We sought to compare the effect of ACE versus non-ACE inhibitor therapy on incident electrocardiographic (ECG) evi-dence of LVH (ECG-LVH). RESEARCH DESIGN ANDMETHODS — This prespecified study compared the inci-dence of ECG-LVH by Sokolow-Lyon and Cornell voltage criteria in 816 hypertensive type 2 diabetic patients of the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT), who had no ECG-LVH at baseline and were randomly assigned to at least 3 years of blinded ACE inhibition with Trandolapril (2 mg/day) or to non-ACE inhibitor therapy. Treatment was titrated to systolic/diastolic blood pressure130/80mmHg. ECG readings were centralized and blinded to treatment. RESULTS — Baseline characteristics of the two groups were similar. Over a median (inter-quartile range) follow-up of 36 (24–48) months, 13 of the 423 patients (3.1%) receiving Trandolapril compared with 31 of the 376 patients (8.2%) receiving non-ACE inhibitor therapy developed ECG-LVH (hazard ratio [HR] 0.34 [95%CI 0.18–0.65], P 0.0012 unadjusted, an

  • effects of verapamil added on Trandolapril therapy in hypertensive type 2 diabetes patients with microalbuminuria the benedict b randomized trial
    Journal of Hypertension, 2011
    Co-Authors: Piero Ruggenenti, Anna Fassi, Ilian Iliev, Nadia Rubis, Giulia Gherardi, Aneliya Parvanova Ilieva, Carlos Chiurchiu, Bogdan Eneiordache, Flavio Gaspari, Annalisa Perna
    Abstract:

    OBJECTIVES To address whether nondihydropyridine calcium-channel blocker added-on angiotensin-converting-enzyme inhibitor therapy ameliorates albuminuria and cardiovascular outcomes in type 2 diabetes patients. DESIGN The Bergamo Nephrologic Diabetes Complications Trial-B was a multicentre, prospective, double-blind, parallel-group trial comparing renal and cardiovascular outcomes in 281 hypertensive type 2 diabetes patients with microalbuminuria randomized to at least 2-year VeraTran (verapamil/Trandolapril 180 mg/2 mg daily) or Trandolapril (2 mg daily, identical image) treatment. Main outcome was persistent macroalbuminuria (albuminuria >200 µg/min in two consecutive visits). Treatment targets were SBP/DBP less than 120/80 mmHg and HbA1C less than 7%. RESULTS Over a median follow-up of 4.5 years, 18 patients (13%) on VeraTran vs. 15 (10.5%) on Trandolapril [unadjusted hazard ratio (95% confidence interval [CI]) 1.07 (0.54-2.12), P = 0.852] progressed to macroalbuminuria, respectively; 62 (44.9%) vs. 71 (49.7%) [0.80 (0.57-1.12), P = 0.198] regressed to normoalbuminuria (urinary albumin excretion <20 µg/min), and 20 (14.5%) vs. 21 (14.7%) [hazard ratio 0.93 (0.50-1.72), P = 0.816] had major cardiovascular events. BP and metabolic control were similar between groups. Patients with cardiovascular events were significantly less [13 (9.8%) vs. 28 (18.9%), hazard ratio: 0.37 (0.19-0.71), P = 0.003] among those regressing to normoalbuminuria than those without regression. Difference was independent of treatment allocation and was significant also after adjusting for baseline characteristics [0.40 (0.20-0.79), P = 0.009], follow-up SBP [0.40 (0.20-0.80), P = 0.010] or DBP [0.36 (0.18-0.73), P = 0.004] BP or HbA1C [0.43 (0.21-0.88), P = 0.021]. CONCLUSION In hypertensive type 2 diabetes patients with microalbuminuria, verapamil added-on Trandolapril did not improve renal or cardiovascular outcomes. Independent of verapamil, Trandolapril normalized albuminuria in half of patients and this translated into significant cardioprotection.

  • Managing hypertension in diabetic patients – focus on Trandolapril/verapamil combination
    Dove Medical Press, 2007
    Co-Authors: Sanjib Kumar Sharma, Piero Ruggenenti, Giuseppe Remuzzi
    Abstract:

    Sanjib Kumar Sharma1,3, Piero Ruggenenti1,2, Giuseppe Remuzzi1,2, 1Clinical Research Centre for Rare Diseases “Aldo e Cele Daccò”, Mario Negri Institute for Pharmacological Research, Villa Camozzi, Ranica, Italy; 2Unit of Nephrology, Azienda Ospedaliera, Ospedali Riuniti, Bergamo, Italy; 3Department of Medicine, BP Koirala Institute of Health Sciences, Dharan, NepalAbstract: Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease. Several well conducted clinical trials indicate that aggressive treatment of hypertension in individual with diabetes reduces these complications. Combinations of two or more antihypertensive drugs are frequently required to reach the target blood pressure and to improve the cardiovascular and renal outcomes in these patients. There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics. Trandolapril/verapamil sustained released (SR) is a fixed-dose combination of Trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure. The antihypertensive efficacy of Trandolapril/verapamil SR has been evaluated extensively in large trials. In the INVEST trial, a verapamil SR-based treatment strategy that included Trandolapril in most patients was effective in reducing the primary outcome in hypertensive patients with coronary artery disease. The new onset of diabetes was also significantly lower in the verapamil SR/Trandolapril treatment group in comparison with those on the atenolol/hydroclorothiazide treatment group. The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT) documented that in hypertensive diabetes and normoalbuminuria, Trandolapril plus verapamil or Trandolapril alone delayed the onset of microalbuminuria independent of their blood pressurereducing effect. Thus, Trandolapril/verapamil is an effective option for treatment of hypertensive diabetes patients requiring more than one agent to achieve target blood pressure.Keywords: diabetes mellitus, hypertension, Trandolapril, verapamil S

  • managing hypertension in diabetic patients focus on Trandolapril verapamil combination
    Vascular Health and Risk Management, 2007
    Co-Authors: Sanjib Kumar Sharma, Piero Ruggenenti, Giuseppe Remuzzi
    Abstract:

    Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease. Several well conducted clinical trials indicate that aggressive treatment of hypertension in individual with diabetes reduces these complications. Combinations of two or more antihypertensive drugs are frequently required to reach the target blood pressure and to improve the cardiovascular and renal outcomes in these patients. There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics. Trandolapril/verapamil sustained released (SR) is a fixed-dose combination of Trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure. The antihypertensive efficacy of Trandolapril/verapamil SR has been evaluated extensively in large trials. In the INVEST trial, a verapamil SR-based treatment strategy that included Trandolapril in most patients was effective in reducing the primary outcome in hypertensive patients with coronary artery disease. The new onset of diabetes was also significantly lower in the verapamil SR/Trandolapril treatment group in comparison with those on the atenolol/hydroclorothiazide treatment group. The BErgamo NEphrologic Diabetes Complications Trial (BENEDICT) documented that in hypertensive diabetes and normoalbuminuria, Trandolapril plus verapamil or Trandolapril alone delayed the onset of microalbuminuria independent of their blood pressure-reducing effect. Thus, Trandolapril/verapamil is an effective option for treatment of hypertensive diabetes patients requiring more than one agent to achieve target blood pressure.

  • Preventing microalbuminuria in type 2 diabetes.
    The New England journal of medicine, 2004
    Co-Authors: Piero Ruggenenti, Anna Fassi, Anelja Parvanova Ilieva, Simona Bruno, Ilian Iliev, Varusca Brusegan, Nadia Rubis, Giulia Gherardi, Federica Arnoldi, Maria Ganeva
    Abstract:

    Background The multicenter double-blind, randomized Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) was designed to assess whether angiotensin-converting–enzyme inhibitors and non-dihydropyridine calcium-channel blockers, alone or in combination, prevent microalbuminuria in subjects with hypertension, type 2 diabetes mellitus, and normal urinary albumin excretion. Methods We studied 1204 subjects, who were randomly assigned to receive at least three years of treatment with Trandolapril (at a dose of 2 mg per day) plus verapamil (sustained-release formulation, 180 mg per day), Trandolapril alone (2 mg per day), verapamil alone (sustained-release formulation, 240 mg per day), or placebo. The target blood pressure was 120/80 mm Hg. The primary end point was the development of persistent microalbuminuria (overnight albumin excretion, ≥20 μg per minute at two consecutive visits). Results The primary outcome was reached in 5.7 percent of the subjects receiving Trandolapril plus verapamil, 6.0 percen...