Table 1.
Proposed framework for characterizing the adherence of individual patients to trial‐based strategies for the prescribing of neurohormonal antagonists for heart failure and a reduced ejection fraction
| Beta‐blocker | Mineralocorticoid receptor blocker | Neprilysin inhibitor | Inhibitor of renin–angiotensin system | |
|---|---|---|---|---|
|
Status I Receiving treatment consistent with strategy described in the landmark trial demonstrating a survival benefit |
In sinus rhythm and receiving a trial‐proven beta‐blocker at target doses (carvedilol 25 mg twice daily, metoprolol succinate 200 mg once daily, or bisoprolol 10 mg daily) | Receiving spironolactone or eplerenone at target doses, (spironolactone ≥25 mg daily or eplerenone 50 mg daily) | Receiving target doses of sacubitril/valsartan (97/103 mg twice daily) | Receiving sacubitril/valsartan |
|
In sinus rhythm and receiving subtarget doses of a trial‐proven beta‐blocker; was prescribed higher doses, but these could not be maintained because of documented clinically relevant bradycardia or intolerable drug‐related symptoms, which persisted despite adjustment of other medications or In atrial fibrillation or atrial flutter and is receiving carvedilol, metoprolol succinate, or bisoprolol |
Receiving spironolactone or eplerenone at subtarget doses; was prescribed higher doses, but these could not be maintained because of documented serum K+ ≥5.5 mmol/L or intolerable drug‐related adverse effects, which persisted despite adjustment of other medications | Receiving subtarget doses of sacubitril/valsartan; was prescribed higher doses, but these could not be maintained because of documented symptomatic hypotension, doubling of serum creatinine, serum K+ ≥5.5 mmol/L, or intolerable drug‐related adverse effects, which persisted despite adjustment of other medications |
Receiving enalapril ≥10 mg twice daily or equivalent or Receiving candesartan 32 mg daily or valsartan 160 mg twice daily or Receiving subtarget doses of ACE inhibitor, candesartan or valsartan; was prescribed higher doses, but these could not be maintained because of documented symptomatic hypotension, doubling of serum creatinine, serum K+ ≥5.5 mmol/L, or intolerable drug‐related symptoms, which persisted despite adjustment of other medications |
|
|
Status II Receiving treatment according to a strategy that differs from that described in the landmark trial demonstrating a survival benefit |
The patient is in sinus rhythm and receiving a trial‐proven beta‐blocker or In sinus rhythm and receiving subtarget doses of trial‐proven beta‐blocker and has not been prescribed higher doses or In sinus rhythm and receiving subtarget doses of trial‐proven beta‐blocker; was prescribed higher doses that were not maintained because of asymptomatic changes in heart rate or blood pressure or due to physician or patient preferences |
Receiving spironolactone or eplerenone at subtarget doses and was not prescribed higher doses or Receiving spironolactone or eplerenone at subtarget doses; was prescribed higher doses that were not maintained but there has been no documentation of serum K+ ≥5.5 mmol/L or intolerable drug‐related adverse effects, which persisted despite adjustment of other medications or Receiving spironolactone or eplerenone; was prescribed higher doses that were not maintained due to physician or patient preferences |
Receiving subtarget doses of sacubitril/valsartan and has not been prescribed higher doses or Receiving subtarget doses of sacubitril/valsartan and was prescribed higher doses that were not maintained due to asymptomatic changes in blood pressure or laboratory tests or Receiving subtarget doses of sacubitril/valsartan and was prescribed higher doses that were not maintained due to physician or patient preferences |
Receiving subtarget doses of an ACE inhibitor or ARB and has not been prescribed higher doses or Receiving subtarget doses of an ACE inhibitor or ARB; was prescribed higher doses that were not maintained due to asymptomatic changes in blood pressure or laboratory tests or Receiving subtarget doses of an ACE inhibitor or ARB; was prescribed higher doses that were not maintained due to physician or patient preferences |
|
Status III Not receiving the specified treatment |
Not receiving beta‐blocker | Not receiving spironolactone or eplerenone | Not receiving sacubitril/valsartan | Not receiving an ACE inhibitor or ARB |
ACE, angiotensin‐converting enzyme; ARB, angiotensin receptor blocker.