Women With Chest Pain and no Significant Coronary Artery Stenosis; A Study on Microvascular Resistance

Microvascular Resistance in Women With Chest Pain and no or Minimal Coronary Artery Disease

Female patients presenting with persistent chest pain despite no obstructive coronary artery disease have impaired prognosis. Stress tests are often positive or inconclusive. As much as 20% of women with chest pain and minimal angiographic CAD have evidence of myocardial ischemia, suggesting impaired coronary microcirculation. The index of microvascular resistance (IMR) is a method for indirectly investigating microvascular function in the cardiac catheterization laboratory.

66 female patients, age 30-70 years, with chest pain and "normal" or near normal coronary angiograms will be included. After coronary physiologic evaluation, patients will be randomized in a double blind study to rosuvastatin 20 mg/day or matching placebo tablets for altogether 6 months.

The investigators hypothesize that:

1. A substantial number of women with chest pain and normal or minimal pathology on angiograms have microvascular dysfunction defined by a raised IMR.
2. Statins, based on its pleiotropic action will improve endothelial function and thereby IMR.

Study Overview

• Status: Completed
• Conditions: Angina Pectoris
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Placebo.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0380
    • Oslo University Hospital, Dep of Cardiology, Rikshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female gender
2. Age 30 - 70 years
3. Chest pain suggestive of symptomatic coronary artery disease
4. A coronary angiogram with no or minimal coronary artery disease
5. Fractional flow reserve value over 0,80

Exclusion Criteria:

1. Male gender
2. Age under 30 years or over 70
3. Coronary artery stenosis ≥ 33 % in any epicardial vessel
4. Fractional flow reserve value ≤ 0,80
5. Pregnant or nursing women
6. Women of childbearing potential not using contraception
7. Short life expectancy
8. Uncontrolled endocrinological disease
9. Arterial hypertension
10. Structural heart disease
11. Significant mental disorder, including dementia
12. Inability to comply with the protocol -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Angina. IMR. Statin.	Drug: Rosuvastatin; Rosuvastatin 20 mg once daily vs placebo for 6 months
Placebo Comparator: Angina. IMR. Placebo.	Drug: Placebo.; Placebo once daily vs rosuvastatin for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temporal changes in microvascular perfusion indices (Index of Microvascular Function (IMR) and Coronary Flow Reserve (CFR)).	During a left heart catheterization IMR and CFR are measured at baseline and at 6 months. Patients are randomized to rosuvastatin vs placebo. The objectives are to determine whether women with chest pain with no or minimal angiographic coronary artery disease, have a raised index of microvascular resistance and to determine whether high-dose statin treatment will modify microvascular perfusion indices in these patients.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Angina pectoris classification (CCS).	Women with chest pain are randomized to rosuvastatin vs placebo. Angina pectoris (CCS classification) will be compared in the two arms.	6 months

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Lars Aaberge, MD, PhD, Oslo University Hospital Rikshospitalet, Oslo, Norway

Publications and helpful links

General Publications

• Solberg OG, Stavem K, Ragnarsson A, Beitnes JO, Skardal R, Seljeflot I, Ueland T, Aukrust P, Gullestad L, Aaberge L. Index of microvascular resistance to assess the effect of rosuvastatin on microvascular function in women with chest pain and no obstructive coronary artery disease: A double-blind randomized study. Catheter Cardiovasc Interv. 2019 Nov 1;94(5):660-668. doi: 10.1002/ccd.28157. Epub 2019 Feb 21.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: April 16, 2012
• First Submitted That Met QC Criteria: April 19, 2012
• First Posted (Estimate): April 20, 2012

Study Record Updates

• Last Update Posted (Estimate): September 27, 2016
• Last Update Submitted That Met QC Criteria: September 26, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: 3tcAZ; 2011-002630-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Analyses of the study will start within a few weeks or months. Publication planned in 2017