This study was funded by Servier. Dr. Fox reported receiving personal fees and/or nonfinancial support from Servier, AstraZeneca, TaurX, Armgo, Broadview Ventures, and CellAegis. She also is director of Heart Research Lt. and Vesalius Trials Ltd. Detailed disclosures for all study authors are available at NEJM.org.
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The increased incidence of the primary endpoint among patients with Canadian Cardiovascular Society Class II or higher levels of angina in the SIGNIFY trial was surprising and warrants further study to ascertain whether this angina subgroup is one in which caution should be exercised.
In the meantime, caution should indeed be exercised with respect to the use of ivabradine (by physicians who have access to the drug) in those with more severe forms of angina, and adjustment of beta-blocker doses to effective levels should be considered before initiating ivabradine.
The experience from the trial of ivabradine in heart failure suggests that nearly 60% of patients were receiving inadequate doses of beta-blockers and that the majority of benefit with ivabradine was among patients who could not take beta-blockers or who were taking a lower dose. Whether this holds true for patients with angina is unknown, but a cautious approach may be reasonable pending better understanding of the matter.
More therapies are needed for patients with chronic angina – particularly in the United States, both to improve symptoms and to improve quality of life.
What we may need to consider is the level at which an individual patient might be willing to trade some potential risk of major nonfatal cardiovascular events for less angina and a better quality of life.
Dr. E. Magnus Ohman and Dr. Karen P. Alexander of Duke University, Durham, N.C., made these remarks in an accompanying editorial (N. Engl. J. Med. 2014, Aug. 31[doi: 10.1056/NEJMe1409369]). Dr. Ohman reported receiving grant support and/or consulting fees from Abiomed, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, Janssen, Pozen, Sanofi Aventis, The Medicines Company, and WebMD. Dr. Alexander reported receiving grant support from Gilead.
FROM THE ESC CONGRESS 2014