Effects of Intensive Long-Term Vasodilation in Hypertensive Patients With Microvascular Angina Pectoris

NCT ID: NCT00424801

Last Updated: 2009-05-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2008-12-31

Brief Summary

The purpose of this study is to determine if long-term vasodilatory treatment is more effective than the standard treatment in hypertensive patients with microvascular angina pectoris

Detailed Description

Patients with hypertension frequently develop angina pectoris. This can be caused by either epicardial stenotic disease or, equally frequent, by increased resistance in small resistance vessels - microvascular dysfunction. This increased resistance is caused by a process called remodelling, where the existing material in the vessel wall is rearranged around a smaller lumen, whereas the sensitivity of the smooth muscle cells to agonist stimuli is unchanged. Under resting conditions the resistance is determined by both the tone in the smooth muscle cells in the vessel walls and the structure of the vessels themselves (RREST). Under hyperemic conditions the muscles relax and the resistance is determined only by vessel structure (RMIN).

A literature survey of the various studies on this subject has shown that structural changes relates to tone rather than blood pressure. This suggests that resistance vessel structure will be normalized only by an antihypertensive treatment which normalizes RREST i.e. rely on vasodilatation as a cause of the antihypertensive effect more than reduction of cardiac output.

The main hypothesis is, that it is possible to reverse the structural changes in the resistance vessels by vasodilatory treatment for eight months, thereby achieving lower coronary and peripheral minimal resistance (as determined by MRI and plethysmography, respectively), higher work capacity on exercise-ECG and less tendency to angina in these patients.

We will include 80 patients with essential hypertension, angina pectoris CCS class II-III and signs of ischemia on exercise-ECG or myocardial SPECT, but without significant stenosis in angiography. The patients are randomised, in a parallel, open-label design, to either vasodilatory (lercanidipine, valsartan, doxazosin and nicorandil) or standard treatment (metoprolol, diltiazem and isosorbide mononitrate). The aim of treatment in both arms is BP below 120/80 and the protocol allows further add-on therapy to reach this goal. The patients will be followed for eight months with a titration period of two months. MRI, plethysmography, exercise-ECG and echocardiography will be performed before and after the study period. The primary endpoint is minimal coronary resistance as determined by MRI; secondary endpoints are peripheral vascular resistance as determined by plethysmography, work capacity and ischemia threshold on exercise-ECG or myocardial SPECT.

Conditions

Microvascular Angina; Hypertension

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vasodilatory

Patients in this arm will receive intensive vasodilatory treatment to lower blood pressure

Group Type: EXPERIMENTAL

Lercanidipine

Intervention Type: DRUG

Individual titration, max. dose 20 mg OD for 8 months

Valsartan

Intervention Type: DRUG

Individual titration, max. dose 160 mg OD for 8 months

Nicorandil

Intervention Type: DRUG

Individual titration, max. dose 20 mg BD for 8 months

Doxazosin

Intervention Type: DRUG

Individual titration, max. dose 4 mg OD for 8 months

Moxonidin

Intervention Type: DRUG

Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 0,2 mg OD for 8 months

Pindolol

Intervention Type: DRUG

Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 10 mg OD for 8 months

Amiloride, hydrochlorothiazide

Intervention Type: DRUG

Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 1 tbl. OD for 8 months

Interventions

Lercanidipine

Individual titration, max. dose 20 mg OD for 8 months

Intervention Type: DRUG

Valsartan

Individual titration, max. dose 160 mg OD for 8 months

Intervention Type: DRUG

Nicorandil

Individual titration, max. dose 20 mg BD for 8 months

Intervention Type: DRUG

Doxazosin

Individual titration, max. dose 4 mg OD for 8 months

Intervention Type: DRUG

Moxonidin

Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 0,2 mg OD for 8 months

Intervention Type: DRUG

Pindolol

Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 10 mg OD for 8 months

Intervention Type: DRUG

Amiloride, hydrochlorothiazide

Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 1 tbl. OD for 8 months

Intervention Type: DRUG

Other Intervention Names

Zanidip; Diovan; Angicor; Doxazosin "Stada"; Moxonidin "Alpharma"; Visken; Sparkal

Eligibility Criteria

Inclusion Criteria

• hypertension
• angina pectoris CCS class II-IV
• objective signs of ischemia on exercise-ECG or myocardial SPECT
• no significant stenosis on angiography (minimal lumen diameter >50% of relevant reference segment)

Exclusion Criteria

• known allergy to any study medication
• abnormal lab tests of clinical significance
• valvular disease of haemodynamic significance
• known secondary hypertension
• atrial fibrillation or other significant arrythmias
• myocardial infarction < 30 days before inclusion
• resting angina < one week before inclusion
• known endocrine disease, nephropathy or hepatic disease
• present malignant disease
• pregnancy
• fertile women not using safe contraceptives > 6 months before inclusion. Use of contraceptives must continue 1 month after completion or retraction from the study
• body mass index > 30
• significant chronic obstructive lung disease (FEV1 < 1.5 l)
• participant in another study including test medicine
• present treatment with dipyridamole
• present treatment with phosphodiesterase-5-inhibitors that the patient does not want to discontinue during the study period
• heart transplanted patients
• patients with magnetizable metallic implants

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Danish Cardiovascular Research Academy

UNKNOWN

Sponsor Role: collaborator

Danish Heart Foundation

OTHER

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Aarhus Hospital

Principal Investigators

Michael N Præstholm, MD

Role: PRINCIPAL_INVESTIGATOR

University of Aarhus

Kent L Christensen, MD, DrMSc

Role: STUDY_DIRECTOR

Aarhus Hospital, medical-cardiologic dept. A

Won Yong Kim, MD, DrMSc

Role: STUDY_DIRECTOR

Skejby Hospital, cardiologic dept. B

Hans Erik Bøtker, MD, DrMSc

Role: STUDY_DIRECTOR

Skejby Hospital, cardiologic dept. B

Locations

Aarhus Hospital

Aarhus, , Denmark

Countries

Denmark

Other Identifiers

Vasointense

Identifier Type: -

Identifier Source: org_study_id