Statin and Angiotensin-converting Enzyme Inhibitor on Symptoms in Patients With SCAD (SAFER-SCAD)

The Effects of Statin and Angiotensin-converting Enzyme Inhibitor on Coronary Flow Reserve, indEx of Microcirculatory Resistance, and Symptoms in Patients With Spontaneous Coronary Artery Dissection (SAFER-SCAD) Study

An emerging cause of heart attack in young women is a dissection (or tear) in the coronary arteries. Many of these young women continue to have chest pain long after the tear has healed and this is thought to be due to problems with their small blood vessels of the heart (or microcirculation). We want to determine whether commonly used medications for coronary artery disease including statins (for cholesterol) and angiotensin-converting enzyme inhibitors (for blood pressure) reduce chest pain and improve small vessel function in these patients.

Study Overview

• Status: Terminated
• Conditions: Coronary Artery Dissection, Spontaneous
• Intervention / Treatment: Drug: placebo; Drug: rosuvastatin; Drug: ramipril

Detailed Description

In patients with spontaneous coronary artery dissection (SCAD), many continue to have ongoing signs and symptoms of ischemia after the dissection has healed. Further, 1 in 5 women will experience recurrent SCAD in long-term follow-up. To date, no study has investigated the pathophysiologic mechanism behind ongoing symptoms or recurrence of SCAD, but microvascular coronary dysfunction (MCD) has been suggested. Coronary reactivity testing (CRT) is an invasive procedure currently being done in MCD patients as the gold standard technique. In particular, a coronary flow reserve (CFR) < 2.5 has been shown to be both diagnostic of the condition and prognostic of a 2 fold increased risk of cardiac events. Please see below for a detailed description of CRT. In brief, a dual temperature and pressure sensor tipped wire by Radi Medical Systems (St Jude Medical, St Paul, MN) will be placed into the dissected and non-dissected coronary arteries of the patient. This will measure CFR by thermodilution and will also allow the measurement of the index of microcirculatory resistance (IMR). IMR has been found to correlate well with true microvascular resistance.

In addition to a lack of diagnostic strategies, there is a paucity of research into therapeutic strategies. Most women are conservatively managed with medications, however, there is no consensus as to which pharmacologic therapies should be used. Case reports have suggested benefit with antiplatelet agents (e.g. aspirin) and beta-blockers (reduction of arterial wall shear stress). To date no study has investigated the effects of statins or Angiotensin Converting Enzyme Inhibitors (ACEIs) in SCAD patients. Both agents have been studied in the MCD population and been found to reduce angina frequency and improve CFR after 16 weeks.

Purpose:

To measuring the CFR and IMR in 40 SCAD patients with ongoing chest pain who are at least 3 months from their dissection to determine the proportion with microvascular dysfunction and to investigate prospectively whether the addition of an ACEI or a statin to usual care in patients with ongoing chest pain and a CFR <3.0 improves chest pain frequency by Seattle Angina Questionnaire (SAQ) at 16 weeks compared to placebo.

Hypothesis:

We hypothesize that the average CFR in patients at least 3 months out from their SCAD will be <2.5 and that their IMR will be abnormal. Further, we hypothesize that the addition of either an ACEI and/or statin will improve chest pain frequency by at least 20 points on the SAQ at 16 weeks compared to placebo.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Any woman with prior SCAD who is at least 3 months out from her SCAD and has ongoing symptoms of chest pain.
• Females of child-bearing age must have a negative pregnancy test at enrollment
• Coronary Flow Reserve(CFR) < 3.0

Exclusion Criteria:

• Renal dysfunction with Glomerular Filtration Rate <50 ml/min
• Patients not willing to undergo coronary angiography
• Patients with a prior intolerance or allergy to rosuvastatin or ramipril
• Inability to perform CRT or CFR >3.0
• Obstructive coronary artery disease (stenosis >50% in any artery) or residual dissection >50% with distal flow abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin, placebo; rosuvastatin 10-20mg daily or placebo (suggested dose of 10mg for Asians, and 20mg for others)	Drug: placebo; Placebo; Drug: rosuvastatin; 10-20mg (suggested dose 10mg for Asians, 20mg for everyone else); Other Names: crestor
Experimental: Ramipril, placebo; ramipril (starting dose of ramipril at 5mg daily titrating up to 10mg daily at 1 week if tolerated) versus placebo	Drug: placebo; Placebo; Drug: ramipril; 5-10mg (starting dose 5mg titrating up to 10mg if tolerated after 1 week); Other Names: Altace

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Angina frequency domain of the SAQ	Angina frequency domain of the SAQ, collected at baseline and after each intervention to assess angina frequency change over time. We hypothesize that mean SAQ will improve by at least 20 points in each treatment group compared to placebo.	16 weeks after each intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute coronary syndrome or hospitalization for angina	As a secondary objective, to evaluate whether ACEI or statin versus placebo reduces the combined endpoint of acute coronary syndrome (ACS) or hospitalization for angina at 52 weeks	1 year

Collaborators and Investigators

• Sponsor: Cardiology Research UBC
• Investigators: Principal Investigator: Tara Sedlak, MD, University of British Columbia

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): September 13, 2019
• Study Completion (Actual): September 13, 2019

Study Registration Dates

• First Submitted: December 7, 2013
• First Submitted That Met QC Criteria: December 10, 2013
• First Posted (Estimated): December 11, 2013

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Angina; Coronary Artery Dissection, Spontaneous
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Aneurysm; Aortic Diseases; Dissection, Blood Vessel; Acute Aortic Syndrome; Vascular Diseases; Coronary Vessel Anomalies; Aortic Dissection; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Rosuvastatin Calcium; Ramipril
• Other Study ID Numbers: SAFER-SCAD