Underdosing of GDMT
The CHAMP-HF registry contained further disappointing news regarding the state of treatment of patients with HFrEF in ambulatory settings: Among those patients who were on GDMT, very few were receiving the recommended target doses of the medications as established in major clinical trials and specified in the guidelines. Only 14% of patients on an ARNI were on the target dose, as were 28% on a beta-blocker, and 17% of those on an ACE inhibitor or ARB. And among patients who were eligible for all classes of GDMT, just 1% were simultaneously on the target doses of an MRA, beta-blocker, and ARNI, ACE inhibitor, or ARB. This despite solid evidence that, although some benefit is derived from initiating these medications, incremental benefit comes from dose titration.
“Even for those of us who feel like we do this quite well, if we examine our practices systematically – and we’ve done this in our own practices at Brigham and Women’s – you see that a lot of eligible patients aren’t on optimal therapy. And you might argue that many of them have contraindications, but even when you do a deep dive into the literature or the electronic medical record and ask the question – Why is this patient with normal renal function and normal potassium with class II HFrEF not on an MRA? – sometimes it’s hard to establish why that’s the case,” said Dr. Desai.
Interrupting GDMT during hospitalizations
This is common practice. But in fact, continuation of GDMT is generally well tolerated in the setting of acute decompensated heart failure in the absence of severe hypotension and cardiogenic shock. Moreover, in-hospital discontinuation or dose reduction is associated with increased risks of readmission and mortality.
And in treatment-naive HFrEF patients, what better place to introduce a medication and assess its tolerability than the hospital? Plus, medications prescribed at discharge are more likely to be continued in the outpatient setting, he noted.
Being seduced by the illusion of stability
The guidelines state that patients with NYHA class II or III HFrEF who tolerate an ACE inhibitor or ARB should be transitioned to an ARNI to further reduce their risk of morbidity and mortality. Yet many physicians wait to make the switch until clinical decompensation occurs. That’s a mistake, as was demonstrated in the landmark PARADIGM-HF trial. Twenty percent of study participants without a prior hospitalization for heart failure experienced cardiovascular death or heart failure hospitalization during the follow-up period. Patients who were clinically stable as defined by no prior heart failure hospitalization or none within 3 months prior to enrollment were as likely to benefit from ARNI therapy with sacubitril/valsartan (Entresto) as were those with a recent decompensation (). “A key message is that stability is an illusion in patients with symptomatic heart failure,”said Dr. Desai. “In PARADIGM-HF, the first event for about half of patients was not heralded by a worsening of symptoms or a heart failure hospitalization, it was an abrupt death at home. This may mean that a missed opportunity to optimize treatment may not come back to you down the road, so waiting until patients get worse in order to optimize their therapy may not be the best strategy.”