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Progress continues in CVD risk reduction through clinical trials
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CV risk is an evolving topic because of numerous clinical trials that are changing how health care professionals recommend therapy to affected patients, according to a webinar hosted by Amarin Corp.
“It’s really about the changing nature of cardiovascular risk, and a large part of that is driven by the convergence between a number of different fields, which heretofore been very separate, particularly the area of diabetes care and cardiovascular care and cardiovascular risk reduction,” Craig Granowitz, MD, PhD, chief medical officer at Amarin, said during the webinar.
Health care professionals have started to better understand the major risk factors for heart disease and stroke in the past few years, which include family history, high cholesterol, smoking, diabetes and high BP.
“The idea of preventive cardiology is, No. 1, to identify men and women in the community who may have a family history of heart disease, may have risk factors of heart disease, and the ultimate goal is to prevent them from having one of these major debilitating events,” Michael Miller, MD, FACC, FAHA, professor of medicine, epidemiology and public health at the University of Maryland School of Medicine in Baltimore, director of the Center for Preventive Cardiology at University of Maryland Medical Center and staff physician at Veterans Affairs Medical Center in Baltimore, said in the webinar.
National CVD trends
One population that has many risk factors for heart disease is veterans, which may be contributed to their stressful lifestyle during their combat years. Other factors include diabetes, high BP, history of smoking, high cholesterol and high triglycerides.
The number of people who are dying from CVD is increasing in the United States and globally. Lifestyle, diet, smoking and constant stress continue to affect these populations. One factor that continues to contribute to CVD risk in the United States is portion control, which can lead to increases in BP, hypertension, metabolic syndrome and diabetes.
“That has now been displaced to different parts of the world, but because of this 24/7 environment that we live in and all the added stresses, that I think is contributing to the increases in some of these overall risk factors in development of cardiovascular disease.”
Although the rate of CVD has decreased in the past 5 to 10 years, the number of patients dying from strokes and MIs continue to increase because heart disease has a cumulative effect that has progressed in the past 30 to 40 years, according to the webinar.
“Consequently, individuals that may have had … some of the earmarks for the development of cardiovascular disease back in the 1960s and 1970s are now having the events,” Miller said. “The events are occurring in our middle to older age population while rates may have to some extent been reduced due to a reduction in smoking in some sectors.”
Access to care for patients having a CV event is predicated upon where they live. Those who live in an urban community have better access to care, Miller said. The development of units for patients having an acute MI who live in other areas can quickly transport them to a center for timely care.
“That’s really where some of the major advances have occurred over the last couple of decades, initiating early treatment during the throes of an acute cardiovascular event in order to reduce permanent damage to heart muscle and brain,” Miller said. “Having that ability to intervene within a relatively small window — 90 minutes, for example — is where we’d like to help our patients if they’ve experienced an acute event and may need critical intervention such as stent placement following MI.”
Five to 10 years ago, demographics and LDL levels largely determined a patient’s residual risk, but even with widespread use of statins, events have only been reduced by a magnitude of approximately 20% to 30%, Miller said.
The number of smokers in the United States has decreased, but patients have not changed other lifestyle patterns such as poor eating habits and stress management. Those factors can lead to elevated triglycerides, blood glucose levels and visceral adiposity, all of which promote systemic inflammation.
“Inflammation is literally a hot topic in part because of its promotion of heart disease,” Miller said. “As a consequence, other factors beyond statin therapy and LDL lowering contribute to heightened vascular risk.”
Clinical trials
Numerous outcomes trials have been completed throughout this year, including REVEAL, CANTOS and FOURIER. Evolocumab (Repatha, Amgen) in addition to statin therapy lowered LDL and reduced risk in the FOURIER trial.
“There are obviously issues related to cost and so forth, but the point is, is that we’ve built a solid portfolio of additional therapeutic measures beyond standard of care that will hopefully translate into improved overall CVD risk,” Miller said.
In the REVEAL trial, anacetrapib (Merck) with statin therapy did not have a substantial benefit even with an increase in HDL.
“The question as to whether artificially raising levels of HDL independently contributes to CVD risk reduction appears to have now been settled following the negative results of niacin and CETP inhibitor studies,” Miller said. “Although CVD risk reduction in REVEAL was modest, the LDL lowering effect likely accounted for the benefit rather than the HDL raising effect of the drug.”
Canakinumab (Novartis) reduced the risk for CV events in patients with a history of MI and an elevated high-sensitivity C-reactive protein level independent of cholesterol and other variables in the CANTOS trial.
Randomized controlled trials (RCTs) are arguably the best tools for advancing new therapies, but sometimes the cohort enrolled does not necessarily reflect real-world patients that clinicians treat on a day-to-day basis. For one, patients with multiple comorbidities, “the bread and butter patients,” that clinicians treat commonly are excluded from RCTs, Miller said.
“It’s well over the majority of the time,” Miller said. “In our practice, many of our patients whom we would like to enroll into the trial are excluded from the trial.”
Poor compliance to lifestyle and medication is another commonly encountered “real world” phenomenon that tends to be lower in RCTs where study subjects tend to be more highly motivated and have access to highly-trained support staff who closely monitor the study patient throughout the trial.
“We really need the broad-based landscape provided by real-world experiences and clinical trial evidence to support best care practices for our patients,” Miller said.
Other studies are anticipated to be completed in 2018. The ODYSSEY OUTCOMES trial is evaluating the PSCK9 inhibitor alirocumab (Praluent, Sanofi/Regeneron) added to statin therapy for the reduction of CV events in high-risk patients. Vitamin D and omega-3 will be analyzed in the VITAL trial, while researchers of the ASCEND trial will review the effects of 1 g of omega-3 in patients with diabetes. The REDUCE-IT study includes more than 8,000 patients treated with 4 g of an icosapent ethyl compound (Vascepa, Amarin) to see if it reduces CVD risk with close follow-up.
“It’s a very exciting time,” Miller said. – by Darlene Dobkowski
Reference:
Miller M, et al. Cardiovascular Risk: Navigating a Rapidly-Changing Therapeutic Landscape. Webinar presented Oct. 4, 2017.
Disclosure: Granowitz is an employee of Amarin. Miller reports he serves on the steering committee for REDUCE-IT and receives modest compensation from Amarin and is the author of Heal Your Heart.