Switching to ARNI improves LVEF in heart failure
In patients with heart failure with reduced ejection fraction (HFrEF), switch of therapy from an angiotensin-converting enzyme inhibitor (ACEI) to the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan significantly improves left ventricular ejection fraction (LVEF) at 1 year. [Pandey AK, et al, AHA 2017, poster S3196]
The results, from 100 patients with HFrEF on optimal medical therapy, also showed greater improvements in LVEF in patients with dilated cardiomyopathy (n=32) compared with those with ischaemic cardiomyopathy (n=68). In patients with dilated cardiomyopathy, LVEF improved from 27.1 percent at baseline to 45 percent at 1 year after switching to sacubitril/valsartan (p<0.001). In patients with ischaemic cardiomyopathy, LVEF improved from 26 to 36.2 percent (p<0.001).
Numerical improvements in fractional shortening were also found at 1 year after switching to sacubitril/valsartan (from 17.3 percent to 23.4 percent for patients with dilated cardiomyopathy [p=0.16]; from 15 percent to 19 percent in patients with ischaemic cardiomyopathy [p=0.06]).
In the single-centre retrospective study conducted in Cambridge, Ontario, Canada, sacubitril/valsartan was up-titrated to the full dose (103/97 mg BID) in 70 percent of the patients. Twenty percent of the patients were on an intermediate dose (51/49 mg BID), while 10 percent were on a low dose (26/24 mg BID). The main deterrent to dosage up-titration was symptomatic hypotension.
Patients in the study were on maximally tolerated background therapy with ACEIs, beta-blockers and mineralocorticoid receptor antagonists for a minimum of 3 months before switching from ACEIs to sacubitril/valsartan. The ARNI was generally well tolerated over 1 year. Only two patients discontinued sacubitril/valsartan and resumed ACEIs within 1 month of switching, as a result of hypotension.
According to the researchers, these findings may explain the clinical benefits of sacubitril/valsartan observed in the PARADIGM-HF study, which did not report the ARNI’s effects on LVEF. They also noted that in previous studies, improvements in cardiac ejection fraction and fractional shortening were found to be correlated to reductions in morbidity and mortality.