trandolapril

No abstract text is available yet for this article.

Trandolapril, an angiotensin-converting enzyme inhibitor prodrug, needs to be activated by carboxylesterase 1 (CES1) in the liver to exert its intended therapeutic effect. A previous in vitro study demonstrated that the CES1 genetic variant G143E (rs71647871) abolished CES1-mediated trandolapril activation in cells transfected with the variant. This study aimed to determine the effect of the G143E variant on trandolapril activation in human livers and the pharmacokinetics (PKs) and pharmacodynamics (PDs) in human subjects...

Maintaining regular blood pressure control usually requires multidrug regimens rather than monotherapy. The objective of this study was to describe the effectiveness and safety of an angiotensin-converting enzyme inhibitor and a nondihydropyridine calcium channel blocker in a single-tablet combination in patients with hypertension, a heart rate higher than 70 beats/min, and type 2 diabetes mellitus (T2DM). This study was conducted in Turkey as a prospective, noninterventional, observational study. At 22 clinical sites, the data of 200 patients with hypertension were used for efficacy analysis; however, 262 patients received at least one dose of trandolapril/verapamil fixed-dose combination at two dose strengths...

Simultaneous administration of certain antihypertensive (renin-angiotensin system inhibitors and diuretics) and nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a renal toxicity syndrome known as "triple whammy" acute kidney injury (TW-AKI), yet poorly characterized at the pathophysiological level, as no specific experimental model exists on which to conduct preclinical research. Herein, we generated and characterized a rat model of TW-AKI (0.7 mg/kg/day trandolapril +400 mg/kg/day ibuprofen +20 mg/kg/day furosemide)...

INTRODUCTION: Albuminuria is an early marker of kidney disease and reduction of albuminuria translates into a decreased occurrence of cardiovascular and renal outcomes. AIMS: To evaluate the changes in the prevalence of albuminuria in diabetic hypertensive patients treated with several combinations of renin-angiotensin aldosterone system with calcium channel blockers. METHODS: We analysed data from 668 unselected patients from the PAIT survey (mean age 60...

AIMS: Data regarding the optimal systolic blood pressure (SBP) and heart rate (HR) for coronary artery disease (CAD) patients with hypertension and a history of heart failure (HF) are limited. Accordingly, using data from a large clinical trial, we investigated the association between SBP and heart rate and subsequent adverse outcomes in CAD patients with a history of HF, and we aimed to better understand how pre-existing HF impacts outcomes among patients with CAD. METHODS AND RESULTS: Among 22 576 CAD patients enrolled in the INternational VErapamil SR-Trandolapril STudy (INVEST), 1256 were identified with a history of physician-diagnosed HF New York Heart Association (NYHA) Class 1-3 at entry...

Objective: Our previous study in heterozygous Ren-2 transgenic rats (TGR) demonstrated that long-term treatment with endothelin receptor A (ETA ) blocker atrasentan added to the renin-angiotensin system (RAS) blockade had renoprotective effects in a model of chronic kidney disease (CKD) induced by partial nephrectomy. Since ETA blockade is known to cause edema, we were interested whether diuretic treatment added to this therapy would be beneficial. Design and Methods: Partial nephrectomy (NX) was performed at the age of 3 months in TGR rats which were subjected to: (i) RAS blockade alone (angiotensin receptor blocker losartan and angiotensin converting enzyme inhibitor trandolapril), (ii) combined RAS (losartan and trandolapril) and ETA receptor blockade (atrasentan), or (iii) diuretic (hydrochlorothiazide) added to the combined RAS + ETA blockade for 50 weeks following NX...

Background: Hypertension is a major modifiable risk factor for coronary artery disease (CAD), the main cause of death in women. While association between the two is frequent, limited data exist regarding the feasibility of blood pressure (BP) management and outcomes in women across the spectrum of CAD. Accordingly, we analyzed patient characteristics, BP control rates, and outcomes among hypertensive women with CAD, enrolled in The INternational VErapamil SR-trandolapril STudy (INVEST). Methods: The 11,770 hypertensive women with CAD in INVEST were studied based on presence ( n  = 3,879) or absence ( n  = 7,891) of history of myocardial infarction (MI) or coronary revascularization, to evaluate outcomes across risk groups based on severity of CAD...

We found recently that in Ren-2 transgenic hypertensive rats (TGR) addition of soluble epoxide hydrolase inhibitor (sEHi) to treatment with angiotensin-converting enzyme inhibitor (ACEi), surprisingly, increased the mortality due to heart failure (HF) induced by creation of the aorto-caval fistula (ACF). Since TGR exhibit sex-related differences in mortality, we examined here if such differentiation exists also in the response to the treatment with ACEi (trandolapril), alone or combined with sEHi [cis-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid, (c-AUCB)]...

INTRODUCTION: The most recent European guidelines for the treatment of hypertension suggest the use of renin-angiotensin-aldosterone system antagonists (RAAS inhibitors) and calcium channel blockers (CCBs) or diuretics fixed-dose combinations (FDCs) as the first therapeutic option. In antihypertensive therapy, the patient's adherence is one of the most important factors in reducing unwanted cardiovascular events. AIM: Our aim was to assess the one-year persistence of angiotensin-converting enzyme inhibitor (ACEI) and CCB FDCs in hypertensive patients...

AIMS: Klotho, an essential co-receptor for fibroblast growth factor (FGF)-23, has potentially beneficial inhibitory effects on the renin-angiotensin system. Limited data exist on the prognostic value of Klotho and FGF-23 levels in combination or their ability to predict benefit from angiotensin-converting enzyme (ACE) inhibition. METHODS AND RESULTS: A total of 3555 patients with stable ischaemic heart disease and left ventricular ejection fraction > 40% enrolled in the PEACE trial of trandolapril vs...

BACKGROUND: There have been significant advances in the treatment of patients with cardiomyopathy with reduced ejection fraction (EF < 40%). However, there is a dearth of information in the treatment of patients with cardiomyopathy and midrange EF (40-50%). Current guidelines state to treat these patients similarly to patients with cardiomyopathy and preserved EF. Data from the Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) trial were used to elucidate whether angiotensin-converting enzyme (ACE) inhibitors improve clinical outcomes in patients with ischemic cardiomyopathy and midrange EF...

Resistant hypertension (RHTN), defined as uncontrolled blood pressure (BP) ≥ 140/90 using three or more drugs or controlled BP (<140/90) using four or more drugs, is associated with adverse outcomes, including decline in kidney function. We conducted a genome-wide association analysis in 1194 White and Hispanic participants with hypertension and coronary artery disease from the INternational VErapamil-SR Trandolapril STudy-GENEtic Substudy (INVEST-GENES). Top variants associated with RHTN at p < 10-4 were tested for replication in 585 White and Hispanic participants with hypertension and subcortical strokes from the Secondary Prevention of Subcortical Strokes GENEtic Substudy (SPS3-GENES)...

Trandolapril has no sharp peak in its zero-order spectrum and therefore, it is difficult to be measured by direct spectrophotometry. In this manuscript, several univariate and multivariate spectrophotometric methods were developed and validated for determination of Trandolapril (TR) and Verapamil (VR) combination. The first method for measuring Trandolapril is Constant Multiplication-Spectrum Subtraction (CM-SS), where Trandolapril was measured at 210 nm in its zero-order curve after elimination of Verapamil spectrum...

Introduction: Increasing clinical evidence supports the implementation of genotyping for anti-hypertensive drug dosing and selection. Despite robust evidence gleaned from clinical trials, the translation of genotype guided therapy into clinical practice faces significant challenges. Challenges to implementation include the small effect size of individual variants and the polygenetic nature of antihypertensive drug response, a lack of expert consensus on dosing guidelines even without genetic information, and proper definition of major antihypertensive drug toxicities...

The Systolic Blood Pressure Intervention Trial (SPRINT) suggested a favourable effect of lowering blood pressure to < 120/80 mmHg in high-risk hypertensive patients; however, new American guidelines in 2017 have not followed SPRINT but lowered its recommended treatment target to < 130/80 mmHg. We aimed to review the latest research from large randomised controlled trials and observational analyses in order to investigate the evidence for new treatment targets. We assessed recent data from the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD) study, the International Verapamil-Trandolapril Study (INVEST), the Telmisartan, Ramipril or Both in Patients at High Risk for Vascular Events trial (ONTARGET)/the Telmisartan Randomised AssessmenNt Study in aCE iNtolerant participants with cardiovascular Disease (TRANSCEND) study and The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study...

We showed recently that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, retarded the development of renal dysfunction and progression of aorto-caval fistula(ACF)-induced congestive heart failure (CHF) in Ren-2 transgenic hypertensive rats (TGR). In that study the final survival rate of untreated ACF TGR was only 14 % but increased to 41 % after sEH blockade. Here we examined if sEH inhibition added to renin-angiotensin system (RAS) blockade would further enhance protection against ACF-induced CHF in TGR...

Trandolapril and verapamil are commonly used antihypertensive drugs. However, there is a lack of available data on the change of their pharmacokinetics in patients with liver or kidney impairment and hence the need for dose adjustment. In this article, a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the monitoring of trandolapril, its active metabolite trandolaprilat, and verapamil in human plasma of patients with renal impairment and/or liver insufficiency...

BACKGROUND: The majority of hypertensive individuals require combination antihypertensive therapy to achieve adequate blood pressure (BP) control. This study aimed to identify genetic variants associated with uncontrolled BP on combination therapy with a thiazide diuretic and a β-blocker. METHODS AND RESULTS: A genome-wide association study of uncontrolled BP on combination therapy was conducted among 314 white participants of the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) trial...

OBJECTIVES: A goal SBP 120 mmHg or less reduced mortality in high-risk Systolic Blood Pressure Intervention Trial patients; however, mortality implications of concomitant DBP lowering in coronary artery disease (CAD) are uncertain. We examined the relationship between DBP lowering and all-cause mortality with lower achieved SBPs in a large cohort. METHODS: We categorized 17 131 hypertensive patients from the INternational VErapamil-trandolapril STudy US cohort, aged at least 50 years with CAD, by mean achieved SBP (<120, 120 to <130, 130 to <140, and ≥140 mmHg) and DBP tertiles (low, middle, and high per SBP category) during active follow-up...