A consortium of ten international academic organisations within the Global Cardiovascular Research Funders Forum (GCRFF) is launching a new international study. For the first time, the study will investigate the optimal antiplatelet therapy for spontaneous coronary artery dissection (SCAD), a distinct form of heart attack that primarily affects women. The initiative is led by the German Centre for Cardiovascular Research (DZHK) and is coordinated by the University Medical Center Hamburg-Eppendorf (UKE).
Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome in which blood flow to the heart muscle is reduced or interrupted. It predominantly affects women between 30 and 55 years of age and typically occurs in the absence of atherosclerosis.
For many years, SCAD remained underdiagnosed and has only recently been more systematically recognised. An international research consortium led by the DZHK is now launching the SCAD-ALIGN trial, the first randomised study to systematically compare two antiplatelet treatment strategies in patients with SCAD.
Heart attack without atherosclerosis
SCAD is usually not associated with significant atherosclerosis or the classic vessel occlusion caused by a blood clot. Instead, bleeding occurs within the wall of a coronary artery, causing the vessel layers to separate and thereby impairing or completely obstructing blood flow. Patients develop symptoms of acute myocardial infarction, such as chest pain, shortness of breath, or nausea. A characteristic feature is that these symptoms often occur in individuals without a prior history or risk of heart disease.
Platelets play a crucial role in blood clotting but can also accumulate inside blood vessels and further impair flow. Antiplatelet medications are used to prevent this. In current clinical practice, SCAD patients are often treated according to general guidelines for acute coronary syndrome, which typically include two different antiplatelet therapies, a strategy developed and tested in older patients with proven atherosclerosis
How intensive should antiplatelet therapy be?
The SCAD-ALIGN trial is based on a fundamental difference between SCAD and classic heart attacks. In typical heart attacks, a blood clot usually blocks a vessel, and after the implantation of a vascular support device (“stent”), intensive antiplatelet therapy is used to prevent further clot formation. In SCAD, however, the underlying problem is a tear or bleeding within the vessel wall. In this situation, intensive antiplatelet therapy could delay the resolution of the bleeding or even worsen it, thereby adversely affecting the course of the disease. The study will therefore investigate whether a less intensive treatment strategy may be more beneficial in these patients.
The SCAD-ALIGN trial compares two treatment strategies: moderate antiplatelet therapy with a single medication for three months versus more intensive therapy with two agents for three months, followed by nine months of treatment with a single medication. The primary endpoint is a composite of recurrent myocardial ischemia, recurrent SCAD, myocardial infarction, the need for revascularization, and death.
“Until now, we have treated SCAD patients according to standards developed for other cardiovascular conditions,” says Professor Peter Clemmensen, national principal investigator for Germany. “With the SCAD-ALIGN trial, we aim to determine which form of antiplatelet therapy truly benefits patients and which may instead cause harm. Our goal is to establish a robust foundation for future treatment recommendations.”
International collaboration for women’s cardiovascular health
The SCAD-ALIGN trial is part of the Multinational Clinical Trials Initiative of the Global Cardiovascular Research Funders Forum (GCRFF). “This study addresses a clinical question that primarily affects women and for which robust evidence remains very limited, with little commercial incentive for industry-led development,” emphasises Professor Christina Magnussen, national co-principal investigator for Germany and member of the global Executive Board.
For the first time, multiple international funding organisations are collaborating based on a shared study protocol. The scientific concept for the trial originated from members of the DZHK.
“Reaching beyond the medical question, this study shows how an alliance of international funding organisations and researchers can create sustainable structures to address major clinical challenges,” says Professor Stefan Blankenberg from the University Heart and Vascular Center Hamburg, scientific lead and initiator of the study.
He adds: “A coordinated effort by funding organisations from democratic countries, including Germany, the United Kingdom, the Netherlands, Denmark, Sweden, Spain, Australia, New Zealand, and Canada, complemented by support from the Kühne Foundation and followed by participation of Brazil, Argentina, and Chile, is creating a global academic framework. Particularly in times global challenges this jointly legitimised approach demonstrates its unique strength.”
The study is designed as an international, multicentre, randomised, open-label clinical trial. Because SCAD is a rare condition, close collaboration across national borders is essential. The results are expected to make an important contribution to the development of evidence-based treatment recommendations for SCAD, improve care and quality of life for patients worldwide.
Participating GCRFF Funding Organisations:
Participating National and Institutional Funding Organisations:
- Danish Heart Foundation (Hjerteforeningen), Denmark
- Swedish Heart-Lung Foundation, Sweden
- Swiss Heart Foundation, Switzerland – Application process not yet finalised
- Institutional funding from the Victor Chang Cardiac Research Institute, Sydney, Australia
- Institutional funding from the Westmead Applied Research Centre, University of Sydney and NSW Health Cardiovascular Research Grant, Australia
- Institutional funding from the University Medical Center Hamburg-Eppendorf, Germany
- Institutional funding from participating Spanish centres (including Hospital Universitario de La Princesa, Madrid, Spain)
Participating Private Foundation:
Scientific contact: Professor Stefan Blankenberg, University Heart & Vascular Center, University Medical Center Hamburg-Eppendorf (UKE), s.blankenberg@uke.de
