The Vascular Effects of Carvedilol Controlled Release (CR) in Abdominally Obese Hypertensive Patients

St. Paul Heart Clinic

Status and phase: Completed; Phase 3

Conditions: Hypertension; Abdominal Obesity

Treatments: Drug: Lisinopril + HCTZ; Drug: Carvedilol CR + Lisinopril

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00459056

SPHC 2007-01

Details and patient eligibility

About

The purpose of this study is to compare the effects of two different combination therapies for high blood pressure on vascular health.

Full description

Hydrochlorothiazide (HCTZ) has been a popular choice for the treatment of hypertension mainly due to its efficacy in lowering blood pressure, safety, and cost-effectiveness. Similarly, angiotensin converting enzyme inhibitors (ACE-I), because of their neutral to positive impact on glycemic control, have been a popular choice for addressing hypertension in abdominally obese patients. Furthermore, the ACE-I drug class has been shown to improve vascular endothelial function and inflammation in addition to its blood pressure lowering effects.

Conversely, beta-adrenergic receptor blockers (b-blockers) have generally been avoided as first line anti-hypertensive therapy in pre-diabetic patients due to concerns about worsening glycemic control and potential hastening of progression to type 2 diabetes mellitus (T2DM). However, recent data have shown that the 3rd generation b-blocker carvedilol does not negatively affect glucose metabolism and therefore may be a safe and effective choice for blood pressure control in these patients. This neutral glycemic effect is likely due to the fact that carvedilol is a non-selective b-receptor antagonist (blocks both b1 and b2 receptors) with alpha1-receptor blocking properties. In addition, carvedilol possesses anti-oxidant properties and improves endothelial function, potentially making it an attractive anti-hypertensive treatment strategy in patients with abdominal obesity.

The combination of carvedilol and lisinopril may be especially effective in reducing blood pressure and may act synergistically to address the impaired vascular function and increased inflammation and oxidative stress present in patients with the metabolic syndrome phenotype. Therefore the primary objective of the current study will be to evaluate the effects of carvedilol CR + lisinopril compared to lisinopril + HCTZ on vascular function in a head to head trial in abdominally obese, hypertensive patients. The secondary objective will be to compare the effects of these two anti-hypertensive therapies on plasma biomarkers of endothelial activation, inflammation, and oxidative stress in these patients.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• >18 years old
• Systolic blood pressure (SBP) >130 and/or diastolic blood pressure (DBP) >85 (or currently taking anti-hypertensive medication)
• Waist circumference >102 cm (men) and >88 cm (women)
• Stable cardiovascular medication regimen (or other medications known to affect endothelial function) at least 1 month prior to enrollment and throughout the study

Exclusion criteria

• Use of anti-hypertensive medications within one month of randomization (patients may be washed-out from anti-hypertensive medications)
• Unstable angina
• History of angina symptoms within 3 months of screening
• Decompensated heart failure
• History of myocardial infarction
• Stroke or coronary artery bypass graft within 3 months of screening
• Standard clinical contraindications to beta-blocker therapy
• Standard clinical contraindications to ACE-I therapy
• Women who are currently pregnant or planning to become pregnant (pregnancy testing will occur at specific intervals throughout study and women will be informed of potential risks during the consenting process; information specific to this risk will be detailed in the consent form)
• Breastfeeding women
• Clinically significant liver disease
• Creatinine > 2.5 mg/dL
• Hepatic function greater than 3 times upper limit of normal

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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25 participants in 2 patient groups

Carvediolol CR + Lisinopril, then Lisinopril + HCTZ

Experimental group

Description:

Subjects were randomly assigned to Carvedilol CR + Lisinopril for three months, then had a washout period of one month, and then were given Lisinopril + HCTZ for the final three months.

Treatment:

Drug: Carvedilol CR + Lisinopril

Drug: Lisinopril + HCTZ

Lisinopril + HCTZ, then Carvedilol CR + Lisinopril

Active Comparator group

Description:

Subjects were randomally assigned to Lisinopril + HCTZ for three months, then had a washout period for one month, and then were given Carvedilol CR + Lisinopril for the final three months.

Treatment:

Drug: Carvedilol CR + Lisinopril

Drug: Lisinopril + HCTZ