The American College of Cardiology, together with the American Heart Association and Heart Failure Society of America recently released a joint updated pharmacological guideline for heart failure to include recommendations on 2 new medications: valsartan/sacubitril and ivabradine.
The Cardiology Advisor interviewed James M. Tauras, MD and Snehal R. Patel, MD, both of Montefiore Medical Center in Bronx, New York, to learn their thoughts on the clinical implications of the new guidelines.
Dr Tauras is the CCU director at Montefiore Weiler Hospital and assistant professor of medicine at Albert Einstein College of Medicine. Dr Patel is also an assistant professor of medicine at Albert Einstein College of Medicine.
The Cardiology Advisor (TCA): The 2 new agents, valsartan/sacubitril and ivabradine, appear to be recommended as complementary rather than first-line therapies. Can you speak to some of the reasoning behind this recommendation?
Dr Tauras: With regards to valsartan/sacubitril, while the data from the PARADIGM trial is compelling, it is still only one trial with many deficiencies in terms of special populations (racial minorities and the elderly for instance). Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) still have an enormous body of evidence demonstrating effectiveness in heart failure with reduced ejection fraction (HFrEF).
It will require more than one randomized controlled trial for angiotensin receptor-neprilysin inhibitors (ARNIs) to become first-line therapy over ACE inhibitors and ARBs. There will be additional trials with ARNIs, as well as post-marketing surveillance data to definitively assess for safety. I suspect it will take several more years of data accumulation for ARNI to truly become first line, if indeed they ever become first line.
Dr Patel: I agree with that, and they’re [valsartan/sacubitril] not really complementary. We have limited data as to how patients who are naive to ACE inhibitors or ARBs will react to them, but the ARNIs are considered a level I recommendation.
Ivabradine, on the other hand, may be complementary for a patient who has been on an ACE inhibitor or ARB, but this is based on the one clinical trial that we have that showed a reduction in hospitalizations. However, we don’t want to use this agent necessarily in lieu of an ACE inhibitor or ARB.
TCA: How can clinicians best avoid hypotension and other possible side effects?
Dr Tauras: The best way to avoid hypotension in our experience is to start with a low dose of valsartan/sacubitril, and to only use it with patients whose blood pressure is not too low at baseline. Additionally, as patients may diurese more due to the neprilysn inhibition, we often decrease the patient’s diuretic dose when they initiate treatment with the ARNI. The ARNI shouldn’t be used in patients with prior history of angioedema, and there should be a 36-hour washout period between last ACE inhibitor use and starting an ARNI to reduce the risk of angioedema.
Dr Patel: You wouldn’t want to start a patient on ARNIs if their blood pressure is too low (eg, systolic blood pressure <110 Hg mm) because these agents have not been initiated in volume depleted (ie, evolemic) patients. You might need to reduce the diuretic. In contrast, ivabradine actually demonstrates an increase in blood pressure so that’s something else to watch out for.