American College of Cardiology

American College of Cardiology

March 15, 2015
3 min read

Harrington reflects on past, future of NSTEACS research

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SAN DIEGO — Research on non ST-segment elevation ACS has come a long way in the past 25 years, but new paradigms must be embraced in order to make more progress, Robert A. Harrington, MD, FACC, FAHA, FESC, said during the 46th annual Louis F. Bishop Lecture at the American College of Cardiology Scientific Sessions.

The first set of guidelines for non ST-segment elevation ACS (NSTEACS), published in 1994, advanced the long-overdue “notion that this should not be a group of patients confined to the back of the [ED] and waiting for biomarkers so that you could rule out or rule in MI,” Harrington, professor of medicine and chairman of the department of medicine at Stanford University, said. “In fact, this was a group of patients who were at dynamic risk for having bad things happen to them. They were a group of patients who, based upon their baseline risk, might be at increased risk of death or might be at more intermediate risk for recurrent MI, but this was a group that we needed to understand their risk, and we needed to act based on that risk. … The guidelines turned our attention to understanding risk, and understanding that risk also occurs in a dynamic way.”

Robert A. Harrington, MD, FACC, FAHA, FESC

Robert A. Harrington

A number of breakthroughs occurred thereafter, including linking the amount of troponin elevation to the amount of thrombosis risk, development of the GRACE risk score to better quantify in-hospital and 6-month prognosis, and the research and development of antiplatelet therapies to help patients with NSTEACS live longer with fewer events, he said.

Despite the tremendous strides that have been made in NSTEACS research, “there is much more work that needs to be done,” Harrington said, noting that less than 25% of guideline recommendations are based on level of evidence A.

That research, he said, must take novel forms, because it is not sustainable to continue to rely on large, expensive studies, given reductions in NIH funding.

The IMPROVE-IT trial took 10 years and millions of dollars to answer the question of whether lowering LDL improved outcomes, but “is that appropriate today with the way the world works?,” he asked, noting that the results mirrored what had been predicted in an analysis by the Cholesterol Trialists. “We knew that this was going to happen. It just took us 10 years to show it. We can’t do trials like that anymore.”

New research techniques are being pioneered to conduct studies in less time and for less money, he said. Examples include the SWEDEHEART research group, which conducts randomized trials within established registries; a partnership between Google, Stanford and Duke University to create a novel research paradigm involving imaging and informatics; and the American Heart Association’s Cardiovascular Genome-Phenome Study, which aims to “reimagine CV health using the fabulous datasets” of the Jackson Heart Study and the Framingham Heart Study, which comprise decades of bloodwork, imaging and genetic data.

Encouragingly, Harrington said, Apple and Stanford developed an app allowing iPhone and iPad users to enroll themselves in observational studies. When it was recently launched, 11,000 people signed up for the first study on the first day.

“There is now the ability to think about trials in a different way,” he said. “This is the new way of doing research. Now we have to figure out how to do randomized clinical trials on top of this.” – by Erik Swain


Harrington RA. The 46th Annual Louis F. Bishop Lecture. Presented at: American College of Cardiology Scientific Sessions; March 14-16, 2015; San Diego.

Disclosure: Harrington reports receiving consultant fees/honoraria from Adverse Events, Amgen, Daiichi Sankyo-Eli Lilly, Gilead, Janssen Research and Development, Medtronic, Merck, Novartis, The Medicines Company, Vida Health, Vox Media and WebMD; serving on a data safety monitoring board for Regado; having an officer, director, trustee or other fiduciary role in Evidint and Scanadu; holding equity in Element Science and MyoKardia; and receiving research grants from AstraZeneca, Bristol-Myers Squibb, CSL Behring, GlaxoSmithKline, Merck, Portola, Sanofi-Aventis and The Medicines Company.