Response after single treatment with canakinumab predicts which patients will benefit mostNovember 13, 2017
A new analysis seeks to answer the question of which patients are likely to gain the greatest cardiovascular benefit when treated with the anti-inflammatory agent canakinumab. At the 2017 American Heart Association Scientific Sessions, Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital, presented a pre-specified analysis on CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) that identifies a simple, clinical method to define patient groups most likely to benefit from long-term canakinumab treatment. The results of this analysis, published simultaneously in The Lancet, could have a major impact not only on patient selection and cost-effectiveness of canakinumab, but also on the future development of anti-inflammatory agents for cardiovascular disease.
"We believe the clinical approach of targeting treatment to those who truly benefit on the basis of biologic response represents an elegant step toward personalized medicine and rational resource utilization," said Ridker. "Figuring out which patients with residual inflammatory risk benefit the most will allow us to get the right drug to the right patient, greatly reducing costs as well as hazards."
Major findings from the CANTOS trial were presented earlier this year. The trial was designed to test whether canakinumab, which lowers inflammation independent of lipid levels, could reduce risk of a future cardiovascular event by reducing inflammation among people who have had a prior heart attack and who have persistently elevated levels of the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) despite aggressive care. Overall, the trial found a significant fifteen percent reduction in risk of recurrent heart attacks, strokes and cardiovascular death among participants who received canakinumab at doses of either 150mg or 300mg, given once every three months. The critical question Ridker and colleagues have further investigated is whether reductions in the magnitude of inflammation achieved after a single treatment with canakinumab can predict greater or lesser clinical benefit for individual patients.
In the new analysis, the team found that baseline characteristics did not modify the effect of canakinumab on clinical outcomes. However, the magnitude of decrease in hsCRP with canakinumab related directly to the magnitude of clinical benefit associated with continued long-term therapy. For those treated with canakinumab who achieved hsCRP levels below 2mg/L after one dose, cardiovascular and all-cause mortality were both reduced by 31 percent with prolonged treatment. By contrast, no statistically significant reduction in these endpoints was observed among those treated with canakinumab who achieved hsCRP levels equal to or above 2mg/L. Similar large differences in all major cardiovascular outcomes were observed among those who did and did not have robust responses to initial therapy.
"The magnitude of hsCRP reduction following a single dose of canakinumab may provide a simple clinical method to identify individuals most likely to accrue the largest benefit from continued treatment. These data further suggest that 'lower is better' for inflammation reduction with canakinumab," said Brendan Everett, MD, an investigator in CANTOS and director of the General Cardiology Inpatient Service at BWH.
"While prior analyses have examined hsCRP as a predictive biomarker in the context of statin therapy, which both lowers cholesterol and lowers inflammation, our study is the first to analyze outcome data for an agent that only reduces inflammation without concomitant effects on cholesterol," Ridker said. "Our work suggests that patients with 'residual inflammatory risk' represent a separate and distinct group from patients with 'residual cholesterol risk' who likely require different personalized approaches to treatment."
The authors note that their findings could have implications for patient selection, cost-effectiveness and drug design and development going forward, with the potential to increase canakinumab's benefit to risk ratio. For example, the five-year number needed to treat (NNT) is 16 for among those treated with canakinumab who achieved hsCRP concentrations less than 2mg/L. By contrast, the five-year NNT was 57 for those who did not achieve this on-treatment hsCRP threshold. The occurrence of fatal infection observed in CANTOS among approximately one in every 1,000 patients treated was not related to the magnitude of inflammation reduction.
"The new analyses will be quite relevant to physicians, regulators, and payers who are all trying to understand how to achieve the greatest efficacy with the minimal hazard," said Peter Libby, MD, a CANTOS investigator with long-standing interests in inflammation biology.
"Reaching goals is critical for patients and physicians," said Roger Blumenthal, MD, the Kenneth J. Pollin Professor of Cardiology at Johns Hopkins University School of Medicine. "The new CANTOS analysis makes it clear that biologic response matters greatly. Reaching on-treatment hsCRP goals after taking canakinumab is a strong marker for long-term success."
More details about the cardiovascular findings from CANTOS can be found here. In CANTOS, cancer deaths were cut in half by canakinumab. Details about findings related to cancer death reductions can be found here. Ridker is also the principal investigator of the NHLBI-funded Cardiovascular Inflammation Reduction Trial that seeks to find out if low-dose methotrexate, an inexpensive generic anti-inflammatory agent, might have similar effects. That trial will complete in two to three years.
Brigham and Women's Hospital
Related Cardiovascular Articles:
A new analysis suggests that among older adults who take cardiovascular medications, those using non-selective beta-blockers may be at an increased of falling compared with those using selective beta-blockers.
Higher than normal body mass index (BMI) is known to lead to cardiovascular ill-health in mid-to-late life, but there has been limited investigation of its effect in young, apparently healthy, adults.
Cardiovascular diseases (CVD), including heart diseases and stroke, account for one-third of deaths throughout the world, according to a new scientific study that examined every country over the past 25 years.
In 2013, reduced kidney function was associated with 4 percent of deaths worldwide, or 2.2 million deaths.
The age of a person's immune cells may predict risk of cardiovascular disease, according to a preliminary study presented at the American Heart Association's Scientific Sessions 2016.
In a study published online by JAMA Cardiology, Stephen Sidney, M.D., M.P.H., of Kaiser Permanente Northern California, Oakland, and colleagues examined recent national trends in death rates due to all cardiovascular disease (CVD), heart disease (HD), stroke, and cancer, and also evaluated the gap between mortality rates from HD and cancer.
Pregnant women who experience even subtle blood pressure elevations in the upper ranges of what is considered 'normal' blood pressure appear more likely to develop metabolic syndrome after giving birth.
A widely recommended risk calculator for predicting a person's chance of experiencing a cardiovascular disease event -- such as heart attack, ischemic stroke or dying from coronary artery disease -- has been found to substantially overestimate the actual five-year risk in adults overall and across all sociodemographic subgroups.
Traditional Chinese exercises such as Tai Chi may lower blood pressure, improve cholesterol levels and quality of life and depression in patients living with heart disease and stroke.
This FASEB Science Research Conference will be of great interest to researchers and clinicians seeking the most up-to-date information on neural regulation of the cardiovascular system in healthy and diseased states.
Related Cardiovascular Reading:
Cardiovascular Care Made Incredibly Easy (Incredibly Easy! Series®)
by Lippincott Williams & Wilkins (Author)
Publisher’s Note: Products purchased from 3rd Party sellers are not guaranteed by the Publisher for quality, authenticity, or access to any online entitlements included with the product.
Does your heart skip a beat every time you think about the complexities of providing cardio care? Well, not anymore!
Written in the award-winning Incredibly Easy! style, this completely updated Third Edition of Cardiovascular Care Made Incredibly Easy is the ideal reference for those entering or needing a refresher in cardiovascular nursing care.
This... View Details
Cardiovascular Physiology 8/E (Lange Medical Books)
by David E. Mohrman (Author), Lois Jane Heller (Author)
The best cardiovascular physiology text for USMLE and exam review
A Doody's Core Title for 2017!
Cardiovascular Physiology is a concise and enjoyable way for you to gain a fundamental knowledge of the basic operating principles of the intact cardiovascular system and how those principles apply to clinical medicine. Succinct but thorough, it focuses on the facts and concepts you must know to get a solid "big picture" overview of how the cardiovascular systemoperates in normal and abnormal situations. No other text will prove more valuable in enhancing... View Details
Cardiovascular Physiology Concepts
by Richard E Klabunde PhD (Author)
Now in its second edition, this highly accessible monograph lays a foundation for understanding of the underlying concepts of normal cardiovascular function. Students of medicine and related disciplines welcome the book’s concise coverage as a practical partner or alternative to a more mechanistically oriented approach or an encyclopedic physiology text. A focus on well-established cardiovascular principles reflects recent, widely accepted research from the field.View Details
Advanced Cardiovascular Life Support (ACLS) Provider Manual 2015 Guidelines
by American Heart Association (Publisher)
NEW - INCLUDES PRECOURSE SELF-ASSESMENT CODE View Details
Cardiovascular Care Made Incredibly Visual! (Incredibly Easy! Series®)
by Lippincott (Author)
Take the innovative Made Incredibly Visual approach to the principles and practice of cardiovascular care!
Master essential cardiovascular anatomy and physiology - as well as assessment techniques, diagnostic tests, treatments, emergency procedures - through detailed visual aids and concise, clear information that brings complex concepts to life. Based on the well-known "Incredibly Easy" series, Cardiovascular Care Made Incredibly Visual, Second Edition, combines images and clear, concise text to make complex cardiovascular concepts easy to understand. A valuable reference or... View Details
Cardiovascular Physiology: Mosby Physiology Monograph Series (with Student Consult Online Access), 10e (Mosby's Physiology Monograph)
by Achilles J. Pappano PhD (Author), Withrow Gil Wier PhD (Author)
Cardiovascular Physiology gives you a solid understanding of how the cardiovascular system functions in both health and disease. Ideal for your systems-based curriculum, this title in the Mosby Physiology Monograph Series explains how the latest concepts apply to real-life clinical situations.Get clear, accurate, and up-to-the-minute coverage of the physiology of the cardiovascular system. Master the material easily with objectives at the start of each chapter; self-study questions, summaries, and key words and concepts; and a multiple-choice review... View Details
Cardiovascular Hemodynamics for the Clinician
by George A. Stouffer (Editor)
Cardiovascular Hemodynamics for the Clinician, 2nd Edition, provides a useful, succinct and understandable guide to the practical application of hemodynamics in clinical medicine for all trainees and clinicians in the field.
Concise handbook to help both practicing and prospective clinicians better understand and interpret the hemodynamic data used to make specific diagnoses and monitor ongoing therapy Numerous pressure tracings throughout the book reinforce the text by demonstrating what will be seen in daily practice Topics include coronary artery disease;... View Details
Manual of Cardiovascular Medicine
by Brian P. Griffin MD FACC (Author)
Inside the Fourth Edition of the Manual of Cardiovascular Medicine, you’ll find practical and effective approaches to common clinical syndromes—including clear guidance on administration of commonly prescribed medications and descriptions of proven therapeutic procedures. This best selling manual’s concise outline format and colorful design make essential facts easy to find. An ideal reference for the resident, fellow, practicing cardiologist, or nurse-practitioner treating patients with cardiovascular disease.
Skill-building features... View Details
Cardiac Vascular Nursing Certification Review 2018-2019: CVRN Review Book and Practice Test Questions for the CVRN Exam
by Cardiac Vascular Nursing Exam Prep Team (Author)
Think all Cardiac Vascular Nursing study guides are the same? Think again! With easy to understand lessons and practice test questions designed to maximize your score, you'll be ready. You don't want to waste time - and money! - retaking an exam. You want to accelerate your education, not miss opportunities for starting your future career! Every year, thousands of people think that they are ready for the CVN test but realize too late when they get their score back that they were not ready at all. They weren't incapable, and they certainly did their best, but they simply weren't studying the... View Details
Advanced Cardiovascular Exercise Physiology (Advanced Exercise Physiology)
by Denise L. Smith (Author), Bo Fernhall (Author)
Written for students and professionals working within exercise science and related health professions, Advanced Cardiovascular Exercise Physiology systematically details the effect of acute and chronic exercise training on each component of the cardiovascular system: the heart, the vasculature, and the blood (including blood clotting factors). Readers will gain a comprehensive understanding of the cardiovascular system and learn how to apply this knowledge to their work with athletes, other active individuals, and patients who have cardiovascular risk factors.
... View Details