In another secondary analysis from the PARADIGM-HF investigators, the use of the angiotensin receptor/neprilysin inhibitor was shown to prevent clinical progression of surviving patients with heart failure much more effectively than enalapril. The sacubitril/valsartan group was 34% less likely to have an emergency department visit for worsening heart failure, 18% less likely to require intensive care, and 22% less likely to receive an implantable heart failure device or undergo cardiac transplantation. The reduction in the rate of heart failure hospitalization became significant within the first 30 days (Circulation. 2015 Jan 6;131[1]:54-61).
Moreover, the absolute benefit of sacubitril/valsartan in PARADIGM-HF was consistent across the full spectrum of patient risk (J Am Coll Cardiol. 2015 Nov 10;66[19]:2059-71).
To put this into perspective, Dr. Desai continued, for every 1,000 HFrEF patients switched from an ACE inhibitor or ARB to sacubitril/valsartan, the absolute benefit over the course of 27 months includes 31 fewer cardiovascular deaths, 28 fewer hospitalizations for heart failure, and 37 fewer hospitalizations for any reason.
“This is potent therapy for patients with HFrEF who have the right phenotype,” he observed.
While substitution of sacubitril/valsartan for an ACE inhibitor or ARB may be appropriate in many patients with chronic HFrEF who continue to have NYHA Class II-IV symptoms on guideline-directed medical therapy, several caveats apply, according to Dr. Desai.
It’s important to be aware of the PARADIGM-HF eligibility criteria, because it’s only in patients who fit that profile that sacubitril/valsartan provides evidence-based therapy. There are as yet no data to support the drug’s use in patients with new-onset HFrEF, acute decompensated HFrEF, in patients who are immediately post-MI, or in those with advanced chronic kidney disease, he emphasized.
“I think you have to be mindful of eligibility because the label that’s applied to this drug is basically ‘patients with HFrEF who are treated with guideline-directed medical therapy.’ There’s no specific requirement that you follow the detailed eligibility criteria of the PARADIGM-HF trial, but you should realize that the drug is known to be effective only in patients who fit the PARADIGM-HF eligibility profile,” he said.
Dr. Desai gave a few clinical pearls for prescribing sacubitril/valsartan. For most patients, the initial recommended dose is 49/51 mg twice daily. In those with low baseline blood pressure and tenuous hemodynamics, it’s appropriate to initiate therapy at 24/26 mg BID. It’s important to halt ACE inhibitor therapy 36 hours prior to starting sacubitril/valsartan so as to avoid overlap and consequent increased risk of angioedema. And while serum n-terminal prohormone brain natriuretic peptide (NT-proBNP) remains a useful biomarker to monitor heart rate severity and response to treatment while a patient is on sacubitril/valsartan, BNP is not because serum levels of that biomarker rise with neprilysin inhibition.
Dr. Desai reported receiving research support from Novartis and St. Jude Medical and serving as a consultant to those companies as well as Merck and Relypsa.