Press Release: Preclinical safety studies must include equally balanced male/female animal models to shed light on sex-dependent vascular responses in humans

“Sex Differences in the Outcomes of Stent Implantation in Mini-Swine Model” published in PLOS ONE

“Retrospective analyses of pooled animal data can provide important insights into sex-dependent anatomic and pathophysiologic differences,” said Rami Tzafriri, PhD, Director of Research and Innovation, CBSET.

LEXINGTON, Mass., Feb. 12, 2018 – CBSET, a non-for-profit preclinical research institute dedicated to biomedical research, education and advancement of medical technologies, announced today that its scientists have published data and analyses (“Sex differences in the outcomes of stent implantation in mini-swine model”) that “illustrate differences in the dynamic healing responses of male and female pigs to stent implantation in single and overlapped configurations.” The study is published online by the multidisciplinary and Open Source journal PLOS ONE.

“Animals are ideal models for testing specific hypotheses that drive vascular disease. In fact, much of what we know of vascular biology is derived from animal work. Over the years we have used male and female animals to evaluate a large range of endovascular stents yet, in retrospect, none of these individual studies was sufficiently powered to capture sex-dependent effects,” said Peter Markham, MS, President and CEO of CBSET and co-senior author of the article. “It is only when we pooled years of data that we were able to find sex-related differences in vascular responses to stent implantation.”

“The accentuation of sex-dependent differences in vascular responses at six months and one year are intriguing given the consideration of erodible scaffolds, and even non-implantable endovascular therapies such as drug-coated balloons. Time will tell if our findings in juvenile pigs extend to the clinical setting, yet already they provide context for preclinical safety studies and illustrate how more-refined animal models might shed light on sex dependent vascular responses in humans,” said Elazer Edelman, MD, PhD, chairman and co-founder of CBSET, and co-senior author of the paper.

“Already more than a decade ago, the Institute of Medicine declared that research should concentrate on sex-differences in diagnosis and treatment, and on the mechanisms and therapies related to sex differences, and that obstacles to advance sex-related research in health and illness must be eliminated. This prompted the NIH to consider sex as a biological variable and a criterion in evaluation of research funding proposals and yet sex has rarely been evaluated in animal model systems,” said Mie Kunio, PhD, Institute of Medical Engineering and Science (IMES) and first author.

While the influence of sex on clinical outcomes is widely studied, many challenges remain.

“For example, a large amount of research has identified sex differences that may affect the symptoms and therapeutic outcomes of cardiovascular disease (CVD), such as anatomic and physiologic differences. However, the percentage of women in stent implantation and drug therapies for atherosclerosis and CVD clinical studies is only 20-30%. Moreover, as onset of CVD is about 10 years later in women than in men, the women considered in clinical studies tended to be older and presented more risk than the men. The recent PLATINUM Diversity study showed the difference in one-year outcomes of everolimus-eluting stent implantation between men and women after adjusting the baseline clinical and angiographic risk factors differences, but it also pointed out the socioeconomic influence on the outcomes. All the studies suggest that it would be difficult to tease out purely sex-related differences in the outcomes of stent implantation if we focus only on clinical data,” added Dr. Kunio.


CBSET Inc. — 500 Shire Way, Lexington, MA 02421 — is an established translational research leader in endovascular and interventional cardiology, renal disease models, chronic drug-resistant hypertension, women’s health, minimally invasive surgery, orthopedics, biological and synthetic tissue repair, drug delivery, bioresorbable devices, and combination medical device and drug-eluting products. CBSET occupies a 35,000-square-foot, state-of-the-art GLP-compliant facility near Boston that includes an AAALAC-accredited vivarium, catheterization/imaging suites, dedicated labs for SEM, histopathology/pathology, and provides drug metabolism and pharmacokinetics services. CBSET is a registered 501c3 nonprofit with a mission to provide technical, scientific, and regulatory support for novel biomedical therapies.