The SHIFT Study: Results and Implications

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The HCPLive Peer Exchange “Advances in Heart Failure Management” features expert opinion and analysis from leading physician specialists on the latest developments in heart failure research, diagnosis, and management.

This Peer Exchange is moderated by Peter Salgo, MD, professor of medicine and anesthesiology at Columbia University and an associate director of surgical intensive care at the New York-Presbyterian Hospital in New York City.

The panelists are:

• Michael Felker, MD, MHS, Professor of Medicine, Chief of the Heart Failure Section, Director of the Heart Center Clinical Research Unit, and Director of the Advanced Heart Failure Fellowship at Duke University School of Medicine
• Jim Januzzi, MD, Roman W. DeSanctis Endowed Distinguished Clinical Scholar in Medicine at Massachusetts General Hospital and Hutter Professor of Medicine at Harvard Medical School
• Christian Schulze, MD, PhD, Associate Professor of Medicine, Division of Cardiology at Columbia University Medical Center, and Director of Research for the Center of Advanced Cardiac Care at Columbia University Medical Center

In this segment of the Peer Exchange, the panelists discuss the mechanism of action of ivabradine, as well as the results of the phase 3 SHIFT trial and its interpretations.

Ivabradine is a novel agent that slows the heart rate by inhibiting the l(f) channels. Schulze explains, “this drug specifically slows down heart rate by inhibiting the pacemaker function of the sinus node.”This mechanism enables heart rate to be slowed down without much of the decrease in blood pressure that is typically seen with many other bradycardiac agents, says Salgo.

Ivabradine was studied in Europe in the large phase 3 SHIFT trial, which led to priority review designation by the US Food and Drug Administration. In order to participate, patients with chronic heart failure were required to have a heart rate >70 beats per minute. SHIFT showed about a 20% risk reduction in the primary composite endpoint of cardiovascular death plus heart failure hospitalization, with more of the effect coming from the hospitalizations, says Felker.

The SHIFT investigators had to uptitrate beta blockers to the highest possible dose or document why the dose could not be uptitrated any higher, according to Felker. It is still under debate whether the beta blockers were truly maximized in the trial, says Januzzi. Beta blockers “are probably the most likely to be under-dosed and have the most propensity for a dose-related benefit,” he says, “and that’s the real challenge in terms of interpreting the results with SHIFT.”