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

Phase 3

Completed

Conditions: Abdominal Obesity
Hypertension

Interventions: Drug: Carvedilol CR + Lisinopril
Drug: Lisinopril + HCTZ

Registration Number: NCT00459056

Lead Sponsor: St. Paul Heart Clinic

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

Detailed 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Lisinopril + HCTZ, then Carvedilol CR + Lisinopril	Lisinopril + HCTZ	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.
Carvediolol CR + Lisinopril, then Lisinopril + HCTZ	Lisinopril + HCTZ	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.
Carvediolol CR + Lisinopril, then Lisinopril + HCTZ	Carvedilol CR + Lisinopril	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.
Lisinopril + HCTZ, then Carvedilol CR + Lisinopril	Carvedilol CR + Lisinopril	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.

Primary Outcome Measures

Name	Time	Method
Change in Reactive Hyperemic Index by Period (Carvedilol CR + Lisinopril vs. Lisinopril + HCTZ)	Change from three months to seven months	Reactive hyperemic index is a measure of endothelial function. This is measured by the ratio of post-occlusion blood volume flow versus the baseline blood volume flow. The outcome reported is the change in this ratio after the first intervention phase compared to after the second intervention phase.

Secondary Outcome Measures