Sacubitril/Valsartan After a Stable ACE Inhibitor: A Patient Who Isn't Convinced
A single patient, clinically stable for eighteen months on a fully optimized ACE-inhibitor-based regimen, is offered a switch to sacubitril/valsartan on the strength of a real mortality benefit. He hears the actual numbers and says he'd rather stay on what he's already taking — the debate here is less about whether the drug works than about how many times a well-informed no should be revisited.
R.O., a 67-year-old man, spends most mornings walking his six-year-old grandson two blocks to school before the day's first coffee — a routine he picked up after moving in with his daughter's family the year his wife died, and one he has kept up carefully through the eighteen months heart failure has now been part of his life. That diagnosis followed a work-up for progressive shortness of breath and ankle swelling that had built up gradually over a couple of months rather than arriving all at once; it turned up a left ventricular ejection fraction of 30% and nonischemic dilated cardiomyopathy, with a normal coronary angiogram and no other clear precipitant found on further testing. He has since been titrated, over several follow-up visits, to near-target doses of four drug classes — an ACE inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor — manages a mild, well-controlled type 2 diabetes on metformin, and has not been hospitalized since the day he was diagnosed. His most recent echocardiogram, three months ago, put his ejection fraction at 38%, and he has told his cardiologist more than once that he feels better than he has in years.
At today's visit his cardiologist raises what has become a fairly standard next step for a patient doing this well: switching his lisinopril to sacubitril/valsartan, a combined angiotensin receptor–neprilysin inhibitor that adds inhibition of neprilysin — the enzyme that normally degrades natriuretic peptides and bradykinin — to the same angiotensin-receptor blockade already familiar from ACE-inhibitor therapy. The 2022 ACC/AHA/HFSA guideline lists this combination as the preferred agent in the class for HFrEF, a Class 1 recommendation, reserving ACE inhibitors and ARBs for patients in whom the switch genuinely isn't feasible. R.O. has none of the usual barriers — normal renal function, a potassium of 4.3, stable pressures — and is told so directly, along with the real trial numbers behind the recommendation. He listens to all of it, asks a few precise questions about what changing anything would actually involve, and says he'd rather stay on what he's already taking.
The conversation after he says no
He is doing well because the regimen he's on is working — that is not an argument for leaving it alone, it's the reason the next step is available to him at all. PARADIGM-HF's benefit accrued over a median of 27 months in patients who mostly felt about as stable as he does; "I feel fine" describes his symptoms, not his risk. Every month he stays on lisinopril instead of sacubitril/ valsartan is a month of exposure to a risk this switch measurably lowers, in a patient with no renal, potassium, or pressure barrier standing in the way.
If he had angioedema on any ACE inhibitor, or his eGFR were in the 30s, or his pressures wouldn't tolerate it, this would be a different conversation and I would not be pushing it. None of that applies here.
Let's actually put the numbers on the table, because "real mortality benefit" undersells the size of the ask he's declining and oversells the size of what he'd get. In PARADIGM-HF, the primary composite outcome occurred in 21.8% of the sacubitril/valsartan group versus 26.5% on enalapril — a number needed to treat of roughly 21 over that same 27-month follow-up to prevent one cardiovascular death or heart failure hospitalization. All-cause mortality alone was 17.0% versus 19.8%, NNT roughly 36. That's real, and it's also not the kind of number that makes "don't fix what isn't broken" an unreasonable thing for a patient to say out loud.
The other side of the ledger deserves the same precision. The 36-hour washout isn't administrative caution — concurrent ACE-inhibitor and neprilysin inhibition both slow bradykinin breakdown by separate mechanisms acting on the same pathway, and running them together measurably raises angioedema risk, which is why no same-day swap exists for this specific combination the way it does going the other direction from an ARB. And on cost: a generic sacubitril/valsartan has been been FDA-approved since 2024, though patent litigation kept it off pharmacy shelves until mid-2025, which has narrowed what used to be a much larger gap — but supply and insurance-formulary placement are still catching up unevenly this year, and for most patients it still isn't going to undercut a drug that's been at the four-dollar generic tier for over a decade. Neither of those facts should be waved off to make the guideline recommendation sound cleaner than it is.
I've seen R.O. every few months since before this diagnosis, and today he heard both of those framings — the strong case and the honest cost — and still said no. That's not a communication gap waiting on better numbers or a friendlier pitch. He takes every other pill on that list without being reminded, shows up to every appointment, and made a considered decision about this one. An informed refusal from a patient like that is a real clinical outcome, not a problem to keep solving until he gives the answer the guideline wants.
I don't think that means never raising it again — if he's hospitalized for heart failure, or his ejection fraction moves the wrong way, that's a genuinely new conversation and I'd expect it to happen. What I'd push back on is re-offering it as routine practice at every visit regardless of whether anything has changed. At some point that stops being shared decision-making and starts being attrition, and I don't think a patient this engaged in his own care needs to be worn down rather than heard.
Agreed: lisinopril continues unchanged today. No switch, no washout, no follow-up labs beyond his routine schedule.
Not agreed, and the reason the plan carries two live default expectations rather than one for what happens after today:
Re-raise the switch at every routine visit, the same way any guideline-preferred therapy a patient has declined is periodically revisited — one no today isn't evidence his calculus won't change on its own.
Only revisit if his clinical status actually changes — a heart failure hospitalization, a drop in ejection fraction, a new symptom. Otherwise honor the informed no he already gave rather than re-open it on a schedule he didn't ask for.
Both defaults keep him on the same regimen starting today; they diverge only in what triggers the next conversation. Nobody at the table treated that difference as small enough to paper over with a single shared plan, and it was left standing, unresolved, for whichever of them sees him next.