The funding will support a one-year feasibility phase of the United States portion of a major international clinical trial designed to answer a deceptively simple question: is aspirin alone sufficient, or is a more intensive combination of blood-thinning medications the better approach for patients with SCAD? The study will be led by the Clinical Trial Center of Mount Sinai Fuster Heart Hospital and the Institute for Transformative Clinical Trials. If the feasibility phase succeeds, Mount Sinai will receive approximately $14 million over seven years from the NIH to launch the larger United States portion of the same trial, an investment that signals how seriously federal funders view the gap in evidence surrounding this disease.

The biological distinction at the heart of the trial is critical to understanding why it matters. In the typical heart attacks that dominate cardiology textbooks and clinical guidelines, the culprit is atherosclerosis — the gradual buildup of cholesterol-laden plaque inside the artery. When that plaque ruptures, platelets in the blood rush to the site and form clots that can completely block the vessel. Standard treatment after such an event relies heavily on antiplatelet medications, which make platelets less likely to stick together and form the clots that could cause a second attack. Decades of randomized trials in this patient population have established how aggressively such therapy should be applied.

SCAD, by contrast, is caused by a problem within the artery wall itself rather than by cholesterol buildup. A tear develops spontaneously in the layers of the vessel, and blood can accumulate within the wall, compressing the channel through which blood flows to the heart. Because the underlying pathology is fundamentally different, the rationale for applying the same intensive antiplatelet regimens is far less clear. Yet doctors have had no large, randomized trial conducted specifically in SCAD patients to guide them, and many of the treatments these patients receive today were developed and validated in entirely different populations. The result is a persistent uncertainty that affects treatment decisions made every day in emergency rooms and cardiac catheterization laboratories around the world.

The stakes are heightened by who SCAD affects. Roughly 80 to 95 percent of cases occur in women, most of whom are between 42 and 52 years old. Many have no traditional cardiovascular risk factors such as high cholesterol or diabetes, which means the condition often arrives without warning and can be mistaken for other causes of chest pain. Because SCAD disproportionately affects women at a relatively young age and without the traditional warning signs of heart disease, the researchers argue that identifying the optimal treatment is particularly important — the goal, as the trial’s leadership describes it, is to determine which treatment provides the best protection while exposing patients to the least unnecessary risk.

Roxana Mehran, MD, Mount Sinai Professor in Cardiovascular Clinical Research and Outcomes at the Icahn School of Medicine, is a Principal Investigator for the trial’s clinical coordinating center. Deepak L. Bhatt, MD, MPH, Director of Mount Sinai Fuster Heart Hospital and also a Principal Investigator of the clinical coordinating center, has emphasized that SCAD is a very different disease from the type of heart attack encountered most often, yet many treatments in use today were adopted from studies conducted in other patient populations. In his view, the trial offers an opportunity to generate the rigorous evidence that patients with SCAD and their physicians have long been waiting for — evidence that could finally place treatment of the condition on the same evidentiary footing as the care of more common heart attacks.

The trial itself, known as SCAD-ALIGN, has been designed to settle the antiplatelet question directly. It will compare a moderate antiplatelet strategy — aspirin alone for three months — against a more intensive strategy consisting of dual antiplatelet therapy for three months followed by nine months of single antiplatelet therapy. Researchers plan to enroll roughly 3,500 patients internationally, with approximately 500 of those in the United States across 60 sites. Participants will be evaluated for major cardiovascular outcomes, including cardiovascular death, myocardial infarction, recurrent SCAD, unplanned coronary revascularization, stroke, transient ischemic attack, and bleeding. That last outcome is especially important, because more aggressive blood thinning always carries an increased risk of hemorrhage, and the trial is structured to capture whether the intensive strategy’s potential benefits outweigh that hazard.

The scale of the effort reflects a fundamental challenge in studying rare diseases. SCAD is relatively uncommon, which means no single center or country can easily enroll enough patients to answer the question reliably. Alan Moskowitz, MD, Professor of Population Health Science and Policy at the Icahn School of Medicine and a Principal Investigator for the trial’s data coordinating center, has noted that the project brings together research networks and national funding organizations across multiple countries under one common study protocol. Annetine Gelijns, PhD, Chair of the Department of Population Health Science and Policy and a Principal Investigator for the data coordinating center, has added that the trial is expected to represent a novel model of international academic collaboration and to provide the first large-scale randomized evidence to help guide antiplatelet therapy in this patient population.

The collaborative architecture extends well beyond the United States. SCAD-ALIGN was endorsed by the Multinational Clinical Trials Initiative of the Global Cardiovascular Research Funders Forum, and the global collaboration includes investigators and funding organizations from the United States, Germany, the United Kingdom, Canada, the Netherlands, Denmark, Sweden, Spain, Australia, New Zealand, and other participating countries, with additional participation from centers in South America. Emilia Bagiella, PhD, Director of the Center for Biostatistics in the Department of Population Health Science and Policy and a Principal Investigator for the data coordinating center, has described this coordinated approach as intended to generate robust evidence for an important clinical question that affects women disproportionately and for which large-scale industry-sponsored research has been limited — a candid acknowledgment that commercial incentives have historically underserved conditions like SCAD.

For the patients and physicians who have navigated SCAD without the benefit of dedicated trial evidence, the launch of this feasibility phase marks a turning point. The condition’s rarity, its predilection for young and otherwise healthy women, and its fundamentally distinct mechanism have long combined to leave clinicians extrapolating from data that were never meant to apply to these patients. If the feasibility phase demonstrates that the international network can recruit and follow participants at the required scale, the full trial will proceed with the backing of approximately $14 million in NIH support over seven years, and the results could ultimately reshape treatment recommendations for SCAD patients worldwide — replacing inherited convention with evidence earned from the very population the disease affects most.

Subject of Research: An international randomized clinical trial comparing antiplatelet treatment strategies for spontaneous coronary artery dissection, a heart attack cause that predominantly affects young women.

Article Title: Mount Sinai awarded $2 million to launch international clinical trial on spontaneous coronary artery dissection

Article References: Mount Sinai awarded $2 million to launch international clinical trial on spontaneous coronary artery dissection. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: SCAD, spontaneous coronary artery dissection, Mount Sinai, NIH, clinical trial, antiplatelet therapy, aspirin, women's heart health, cardiology, SCAD-ALIGN, heart attack, dual antiplatelet therapy