In the past 3 decades, pharmacotherapy has had a major impact on mortality and morbidity in cardiovascular disease. Few areas of medicine have seen the deployment of preventative therapy on a scale that changes the clinical face of a disorder in the way that statins have transformed atherosclerosis. However, in part as a result of these successes, more recent trials have exhibited more modest effects, and the pharmaceutical industry has become wary of large trials in the cardiovascular arena. At the same time, advances in genetics and quality measurement have driven calls to match drugs with disease biology in an effort to improve efficacy and reduce toxicity—the personalization of therapy.
One direct inference of personalized medicine is a need for novel drugs addressing the molecular mechanisms of each patient's disorder. Rigorous target identification remains a major hurdle for the discovery of new drugs, and the validity of several cherished cardiovascular targets has recently been challenged by the results of expensive clinical trials. Engaging clinicians and scientists alike to address questions at this translational interface has never been more important. In this issue, the article by Michael Marber and colleagues on p38alpha mitogen-activated protein kinase inhibitors in ischemic heart disease is the first in an occasional miniseries examining emerging therapeutic targets in the cardiovascular space. These reviews will focus on the rationale for the individual molecules as targets, the preclinical data supporting their clinical positioning, and early clinical data.
Calum A. MacRae, MD, ChB, PhD
Associate Editor, Circulation
- © 2012 American Heart Association, Inc.