Reversal of cardiac and large artery structural abnormalities induced by long-term antihypertensive treatment with trandolapril

Luca, Nicola De; Rosiello, G.; Lamenza, F; Ricciardelli, Bruno; Marchegiano, R.; Volpe, Massimo; Marelli, Claudio; Trimarco, Bruno

doi:10.1016/0002-9149(92)90272-z

Cited by 34 publications

(13 citation statements)

References 28 publications

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“…Ejection fractions of both treatment groups, determined by echocardiography, increased significantly, thus also refuting any negative influence of verapamil. These findings correspond with those obtained by other authors who, however, registered even higher ejection fraction results [8,12]. The comparably slight increase of ejection fraction observed in our study group could be attributed to the shorter treatment period of only 2 weeks.…”

Section: Discussionsupporting

confidence: 93%

Effects of Verapamil on Top of Trandolapril on Exercise Tolerance and Cardiac Performance in Patients with Hypertension and Reduced Left Ventricular Function

Mitrović

Djuric

et al. 2001

Heart Drug

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Calcium antagonists and angiotensin-converting enzyme (ACE) inhibitors act synergistically in reducing blood pressure through additive hemodynamic and vasculoprotective effects. Objectives: The aim of this study was to investigate the hemodynamic and neurohumoral effects of combined verapamil SR plus trandolapril treatment (verapamil SR/trandolapril) versus trandolapril monotherapy at rest and during exercise in patients with essential hypertension (WHO I–II) and mild left ventricular dysfunction. Methodology: The investigation was performed in patients with a diastolic blood pressure ≧90 mm Hg and impaired left ventricular ejection fraction of 35–50%. A total of 84 patients (18–75 years) were randomized to double-blind treatment (42 in the verapamil SR/trandolapril and 42 in the trandolapril group) to whom verapamil SR (180 mg) plus trandolapril (2 mg) or trandolapril alone (2 mg) were administered orally once daily for 2 weeks. Hemodynamic and neurohumoral variables were estimated after a screening phase (baseline) and after 2 weeks of therapy at rest and during supine exercise by using right heart catheterization. Results: The heart rate was slightly reduced in the verapamil SR/trandolapril group compared to the trandolapril group both at rest (–9.4 ± 9.8 vs. 7.8 ± 11.3 bpm, nonsignificant) and at maximal comparable workload (–2.4 ± 10.8 vs. –1.9 ± 8.6 bpm, p > 0.05). Mean reduction of systolic blood pressure at rest was insignificantly higher in the verapamil SR/trandolapril group than in the trandolapril group both at rest (–20.6 ± 19.3 vs. –18.1 ± 14.4 mm Hg, p > 0.05) and at maximal comparable workload (–17.2 ± 23.7 vs. –13.1 ± 15.1 mm Hg, p > 0.05). Furthermore, mean reduction of diastolic blood pressure from baseline was slightly higher in the verapamil SR/trandolapril group than in the trandolapril group, both at rest (–13.8 ± 12.1 vs. –9.2 ± 7.8 mm Hg) and at maximal comparable workload (–12.0 ± 13.3 vs. –4.5 ± 11.0 mm Hg). Cardiac output showed a decrease in both groups at rest (–0.45 ± 1.44 vs. –0.57 ± 1.03 liter/min) and during exercise (–0.43 ± 2.88 vs. –0.21 ± 2.89 liter/min). Mean reduction of pulmonary capillary wedge pressure was significantly higher in the trandolapril group compared to the verapamil SR/trandolapril group both at rest (–1.6 ± 5.3 vs. –0.8 ± 4.6 mm Hg, p < 0.05) and during exercise (–2.9 ± 8.7 vs. –1.7 ± 8.5 mm Hg, p < 0.05). A decrease of norepinephrine between baseline and endpoint was registered when measured at rest both in the verapamil SR/trandolapril and the trandolapril group (–23 vs. –10%, p < 0.05, baseline median values 324 vs. 283 pg/ml). Renin increased under verapamil SR/trandolapril and trandolapril treatment, both at rest (+4.20 vs. +62%, p < 0.05, initial values 1.1 vs. 0.6 ng/ml/h). Angiotensin II experienced a decrease under verapamil SR/trandolapril and trandolapril administration, both at rest (–52 vs. –21%, p < 0.05, initial values 4.6 vs. 2.7 pg/ml). Atrial natriuretic peptide decreased significantly more under trandolapril than under verapamil SR/trandol...

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Section: Discussionsupporting

confidence: 93%

Effects of Verapamil on Top of Trandolapril on Exercise Tolerance and Cardiac Performance in Patients with Hypertension and Reduced Left Ventricular Function

Mitrović

Djuric

et al. 2001

Heart Drug

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“…21 Such effects are sustained with longer-term therapy. [22][23][24][25][26][27][28][29][30][31][32][33] In particular, the Complior Study, involving Ϸ2000 hypertensive patients and 6 months of treatment with perindopril, reported Ϸ1 m/s reduction in carotid to femoral PWV. 34 The current study demonstrates that similar PWV reductions are possible after 6 months ramipril therapy in PAD patients, a group with established atherosclerosis.…”

Section: R E T R a C T E D A R T I C L Ementioning

confidence: 99%

“…The persistence of these effects even after withdrawal of therapy, however, 22 suggests that ACE inhibitors promote structural remodeling of the arterial wall. ACE inhibitors are known to decrease the development of atherosclerotic lesions through antiproliferative and antimigratory effects.…”

Section: Mechanismsmentioning

confidence: 99%

Ramipril Reduces Large-Artery Stiffness in Peripheral Arterial Disease and Promotes Elastogenic Remodeling in Cell Culture

et al. 2005

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Abstract-Ramipril improves cardiovascular outcome in patients with peripheral arterial disease; however, the precise mechanisms of benefit remain to be elucidated. The effect of ramipril on large-artery stiffness in patients with peripheral arterial disease was examined. In addition, we determined the effect of ramiprilat on extracellular matrix from human aortic smooth muscle cell culture. Forty patients with peripheral arterial disease were randomized to receive ramipril, 10 mg once daily or placebo for 24 weeks. Arterial stiffness was assessed globally via systemic arterial compliance and augmentation index (carotid tonometry and Doppler velocimetry), and regionally via carotid-femoral pulse wave velocity. Angiotensin-converting enzyme inhibition increased arterial compliance by 0.10Ϯ0.02 mL/mm Hg, (PϽ0.001, all probability values relative to placebo) and reduced pulse wave velocity by 1.7Ϯ0.2 m/s (PϽ0.001), augmentation index by 4.1Ϯ0.3% (PϽ0.001), and systolic blood pressure by 5Ϯ1 mm Hg (PϽ0.001). Ramipril did not reduce mean arterial pressure significantly compared with placebo (Pϭ0.59). In cell culture, ramiprilat decreased collagen deposition by Ͼ50% and increased elastin and fibrillin-1 deposition by Ͼ3-and 4-fold respectively (histochemistry and immunohistochemistry). Fibrillin-1 gene expression was increased 5-fold (real-time reverse-transcriptase polymerase chain reaction). Ramiprilat also reduced gene and protein (Western) expression of both matrix metalloproteinase (MMP)-2 and MMP-3. In conclusion, ramipril promoted an elastogenic matrix profile that may contribute to the observed clinical reduction in large-artery stiffness and carotid pressure augmentation, which occurred independently of mean arterial blood pressure reduction in patients with peripheral arterial disease.

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“…Cardiac performance indices (LV stroke work and volume) were also signifi cantly increased (van der Ent et al 1998). In other small studies, signifi cant reductions were observed in total peripheral resistance (13%-23%), LV hypertrophy and remodeling (LV mass index 24%), end-systolic stress (8%-12%), pulmonary capillary wedge pressure (43%-45%), and pulmonary artery pressure (29%) (De Luca et al 1992;Guller et al 1993;van der Ent et al 1998).…”

Section: Pharmacodynamic and Pharmacokinetic Propertiesmentioning

confidence: 89%

Update on the use of Trandolapril in the management of cardiovascular disorders

Díaz

Ducharme²

2008

VHRM

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Abstract:Trandolapril is a well known angiotensin converting enzyme (ACE) inhibitor with many cardiovascular (CV) indications. The objectives of this article are to review the pharmacokinetics and pharmacodynamics properties of trandolapril and to focus on its clinical relevance in cardiovascular medicine. Various populations have been studied in large clinical trials including patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), diabetics, patients with hypertension (HTN), stable coronary artery disease (CAD) and prevention of proteinuria. Long-term treatment with trandolapril in patients with reduced left ventricular function soon after AMI signifi cantly reduced the risk of overall mortality, mortality from CV causes, sudden death, and the development of severe CHF. Treatment with trandolapril after AMI 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 CHF as well. Moreover, trandolapril reduces progression to proteinuria in high-risk patients. Some of the advantages of trandolapril over other ACE inhibitors are the wide spectrum of patient populations studied, the well established dosage and its proven trough-to-peak effect ratios permitting a safe once-a-day administration.

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Reversal of cardiac and large artery structural abnormalities induced by long-term antihypertensive treatment with trandolapril

Cited by 34 publications

References 28 publications

Effects of Verapamil on Top of Trandolapril on Exercise Tolerance and Cardiac Performance in Patients with Hypertension and Reduced Left Ventricular Function

Effects of Verapamil on Top of Trandolapril on Exercise Tolerance and Cardiac Performance in Patients with Hypertension and Reduced Left Ventricular Function

Ramipril Reduces Large-Artery Stiffness in Peripheral Arterial Disease and Promotes Elastogenic Remodeling in Cell Culture

Update on the use of Trandolapril in the management of cardiovascular disorders

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