Impact of angiotensin-converting enzyme inhibitor underdosing on rehospitalization rates in congestive heart failure.
In a retrospective, cohort design, clinical usage of digoxin, diuretic, and angiotensin-converting enzyme (ACE) inhibitor was assessed in all patients readmitted over a 36-month period for congestive heart failure (CHF) diagnostic-related group (DRG) 127. ACE inhibitor dose-response analysis used the discharge dose of ACE inhibitor, converted to enalapril-equivalent doses and adjusted for renal function. Principal end points were time-to-readmission and 90-day readmission rate. Of 314 total patients, digoxin was used in 72%, diuretic in 86%, and 67% received an ACE inhibitor. Only 22% of those on an ACE inhibitor received currently recommended doses of enalapril > or = 20 mg/day or equivalent, whereas 41% received enalapril < or = 5 mg/day. Time-to-readmission was increased by an ACE inhibitor (p = 0.002) but not digoxin or diuretic. An ACE inhibitor was the principal covariate of 90-day readmission rate (p <0.05). The readmission rate was not reduced with daily ACE inhibitor doses of < or = 5 mg enalapril, whereas daily doses of > or = 10 mg enalapril reduced 90-day readmission rates by 28% compared to those receiving diuretic or digoxin therapy (p <0.05). Using a dynamic model, the dose required to achieve 90% to 95% of the theoretical maximum ACE inhibitor effect exceeded 100 mg enalapril daily. Thus, CHF readmission rates are lower when daily ACE inhibitor doses exceed 5 mg enalapril or the equivalent daily, but are unaffected by digoxin or diuretic. Modeled maximum ACE inhibitor benefits require doses 8- to 10-fold higher than current usage patterns.
Luzier
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AB
School of Pharmacy, State University of New York at Buffalo, Millard Fillmore Health System, USA.
Forrest
A
A
Adelman
M
M
Hawari
F I
FI
Schentag
J J
JJ
Izzo
J L
JL
D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D002316:Cardiotonic Agents / Q000627:therapeutic use; D015331:Cohort Studies; D004077:Digoxin / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000008:administration & dosage*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010359:Patient Readmission; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D004232:Diuretics; D004656:Enalapril; D004077:Digoxin