September 4th, 2013
Same Disease, Different Tools
Amanda Ruth Vest, MBBS
Several Cardiology Fellows who are attending ESC.13 in Amsterdam this week are blogging for CardioExchange. The Fellows include Paddy Barrett, Louis Handoko, and Amanda Vest. For more of our ESC.13 coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting, check out our Coverage Headquarters.
I sometimes feel frustrated that the available tools in my subspecialty of heart failure fall short of the therapeutic advances achieved in other subspecialties. The standard pharmacological heart-failure cocktail has been largely unchanged since I graduated medical school 8 years ago. Nesiritide held promise in acutely decompensated heart failure until definitive studies failed to demonstrate a mortality or rehospitalization benefit. Cardiac resynchronization therapy and ventricular assist devices have entered the arena for a subset of advanced heart failure patients, but where are the new drugs?
The joint ESC-AHA symposium on challenges in managing heart failure opened my eyes to the differing armamentarium available to European and American clinical cardiologists and to several evolving drug options.
Ivabradine is used by approximately 12% of patients in the European HF registry (as reported by Aldo P. Maggioni) but is not licensed for use in the U.S. It is a negative chronotrope that was approved for treatment of angina in Europe in 2005. The 2010 SHIFT trial demonstrated an ivabradine-associated reduction in heart failure mortality and readmissions for systolic heart failure patients in sinus rhythm with a heart rate above 70 bpm. It has proven particularly useful in patients whose beta-blocker tolerance is limited by hypotension. When session cochair Mariell Jessup asked the audience who routinely considers use of ivabradine for heart failure patients, I was one of only a few attendees who did not raise their hands. European practitioners again raised their hands en masse when asked whether they use levosimendan — a calcium sensitizer approved as inotropic therapy for acutely decompensated heart failure in many European countries. By contrast, far fewer hands were raised when the cochair asked whose home institutions offered percutaneous ventricular assist devices, destination ventricular assist devices, and cardiac transplantation – options that I am far more familiar with as a trainee at a large U.S. institution. I also learnt that the approval of tolvaptan for hyponatremia in the setting of decompensated heart failure is limited to the U.S.; in Europe, SIADH is the only approved indication. These geographic variations in options for heart failure management underscore the challenges faced by guideline writers who seek widely applicable clinical recommendations.
Useful additions to the heart failure toolbox may be on the horizon for cardiologists on both sides of the Atlantic. Serelaxin (recombinant human relaxin-2), which showed encouraging results for relief of dyspnea in in the RELAX-AHF study published earlier this year, was recently granted ‘breakthrough therapy’ designation by the FDA and is currently being considered for European approval. Other promising agents entering phase III evaluation include omecamtiv mecorbl (a cardiac-specific myosin activator) and ularitide (a natriuretic peptide).
This was an ideal session to gain appreciation of the differing strategies for managing heart failure in Europe and America. I left wishing that ivabradine were available to help U.S. cardiologists meet heart rate goals, but feeling encouraged by reports of potentially useful heart failure drugs in development. The international insights gained at my first ESC Congress have added to my clinical toolbox. I recommend this conference to U.S. cardiology fellows-in-training seeking a more global perspective to their clinical practice.
What do you see as the most salient differences in clinical cardiology practice between the U.S. and the rest of the world?
Did anyone mention perhexiline ?