Effects of angiotensin-converting enzyme inhibitors and digoxin on health outcomes of very old patients with heart failure. SAGE Study Group. Systematic Assessment of Geriatric drug use via Epidemiology.
BACKGROUND
Randomized trials have shown that angiotensin-converting enzyme (ACE) inhibitors reduce mortality and morbidity, and improve symptoms and exercise tolerance in selected patients with congestive heart failure (CHF). There is, however, no evidence on the effectiveness of ACE inhibitors in the typical, very old and frail patients with CHF.


OBJECTIVE
To compare the effects of ACE inhibitors and digoxin on 1-year mortality, morbidity, and physical function among patients aged 85 years.


METHODS
We conducted a retrospective cohort study using the SAGE database, a long-term care database linking patient information with drug utilization data. Among 64637 patients with CHF admitted to all nursing homes in 5 states between 1992 and 1995, we identified 19492 patients taking either an ACE inhibitor (n = 4911) or digoxin (n = 14890). Record of date of death was derived from Medicare enrollment files, and we used the part A Medicare files to identify hospital admissions and discharge diagnoses. As a measure of physical function, we used a scale for activities of daily living performance. The effect of ACE inhibitors was estimated using Cox proportional hazards models with digoxin users as the reference group.


RESULTS
The overall mortality rate among ACE inhibitor recipients was more than 10% less than that of digoxin users (relative rate, 0.89; 95% confidence interval, 0.83-0.95). Mortality was equally reduced regardless of concomitant cardiovascular conditions and baseline physical function. Treatment with ACE inhibitors was associated with a tendency toward reduced hospital admissions that was more evident among patients with greater functional impairment. The adjusted relative rate for hospitalization for any reason was 0.96 (95% confidence interval, 0.91-1.01). The rate of functional decline was greatly reduced among ACE inhibitor recipients (relative rate, 0.74; 95% confidence interval, 0.69-0.80), and this effect was consistent and independent of background comorbidity and baseline physical function.


CONCLUSIONS
These data suggest that survival and functional benefits of ACE inhibitor therapy extend to patients with CHF 85 years and older, and mostly women, both systematically underrepresented in randomized trials. Alternatively, digoxin has a detrimental effect in this population.
Gambassi
G
G
Istituto di Medicina Interna e Geriatria, Università Cattolica del Sacro Cuore, Rome, Italy.
Lapane
K L
KL
Sgadari
A
A
Carbonin
P
P
Gatsonis
C
C
Lipsitz
L A
LA
Mor
V
V
Bernabei
R
R
D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015986:Confounding Factors, Epidemiologic; D004077:Digoxin / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D004077:Digoxin