Trends and Outcomes Associated with Angiotensin-Converting Enzyme Inhibitors

The American Journal of Medicine (2006) 119, 616.e9-616.e16

CLINICAL RESEARCH STUDY

AJM Theme Issue: Cardiology

Trends and Outcomes Associated with AngiotensinConverting Enzyme Inhibitors Chyke Doubeni, MD, MPH,a,b Carol Bigelow, PhD,c Darleen Lessard, MS,d Frederick Spencer, MD,d Jorge Yarzebski, MD,d Joel Gore, MD,d Jerry Gurwitz, MD,b,e Robert Goldberg, PhDd a

Department of Family Medicine and Community Health and bMeyers Primary Care Institute, University of Massachusetts Medical School, Worcester; cProgram in Biostatistics and Epidemiology, School of Public Health, University of Massachusetts, Amherst; d Division of Cardiovascular Medicine and eDivision of Geriatrics, Department of Medicine, University of Massachusetts Medical School, Worcester. ABSTRACT BACKGROUND: Limited recent data are available describing the patterns of use of angiotensin converting enzyme inhibitor (ACEI) therapy in patients with acute myocardial infarction (AMI), particularly from the more generalizable population-based setting. The purpose of this study was to examine trends in the receipt of ACEIs and associated short-term outcomes in patients hospitalized with AMI in a large Northeastern community. METHODS: We conducted a community-wide study of 7991 patients hospitalized with AMI in all metropolitan Worcester, Massachusetts, medical centers during 8 annual periods between 1990 and 2003. RESULTS: Among all patients, 44% received ACEI therapy during their acute hospitalization. There was a marked increase in the use of ACEIs between 1990 (23%) and 2003 (68%), particularly among those who were not on ACEIs before hospitalization. Patients who were previously on ACEIs were more likely to receive this therapy during hospitalization for AMI than were patients who were not previously on this therapy. Patients treated with ACEIs were significantly less likely to die (adjusted odds ratio [OR] 0.33; 95% confidence interval [CI] 0.27-0.41) during hospitalization than were patients who did not receive this therapy, with benefits observed across all subgroups examined. CONCLUSIONS: The results of this observational study demonstrate marked increases in the use of ACEIs in patients with AMI in the community setting and demonstrate the benefits to be gained from use of this therapy. Despite these encouraging trends, there remains room for more optimal use of this therapy. © 2006 Elsevier Inc. All rights reserved. KEYWORDS: Angiotensin-converting enzyme inhibitors; Acute myocardial infarction

Treatment advances, including the increasing use of effective medical and interventional therapies, have resulted in significant improvements in hospital prognosis after acute myocardial infarction (AMI) over the last several decades.1,2 Several large clinical trials have found that early initiation of angiotensin-converting enzyme inhibitor (ACEI) therapy improves short-term outcomes after AMI, Requests for reprints should be addressed to Robert Goldberg, PhD, Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655. E-mail address: [email protected]

0002-9343/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2005.11.027

with particularly marked benefits observed for patients at increased risk for dying.3– 6 The American College of Cardiology/American Heart Association (ACC/AHA) guidelines published in 1996 recommended the use of ACEIs in the early treatment of patients with AMI.7 Despite the acknowledged benefits of ACEIs, data suggest that this class of medications may be underutilized in the immediate postinfarction period.8 The Worcester Heart Attack Study is an ongoing observational study of residents of the Worcester, Massachusetts, metropolitan area hospitalized with independently validated AMI.9,10 This study offers a unique opportunity to examine more than decade-long trends in the use of ACEIs in the

616.e10 treatment of residents hospitalized with AMI in a large Northeastern community. The present study examines trends (1990-2003) in the use of ACEIs in patients hospitalized with AMI and subgroups of patients in which this therapy may be underutilized. We also examine the association between hospital death rates and the use of ACEI therapy.

The American Journal of Medicine, Vol 119, No 7, July 2006

Data Analysis

We examined differences between patients treated as compared with those not treated with ACEIs during hospitalization for AMI with respect to their demographic, medical history, and clinical characteristics. The significance of trends over time (1990-2003) in the use of ACEIs was examined using the Mantel Haenszel chiCLINICAL SIGNIFICANCE square test for trend. Our trend METHODS analyses also were carried out in 2 ● Use of ACE inhibitors increased over time The Worcester Heart Attack Study patient subgroups defined accord(1990-2003) in a population-based samis an ongoing population-based ining to the use of ACEI therapy ple of patients hospitalized with AMI. vestigation examining long-term before hospitalization for AMI. trends in the incidence, hospital, ● Patients treated with ACE inhibitors difBecause angiotensin-II receptor and postdischarge case-fatality fered from patients who were not treated blockers may be used in place of rates of AMI among residents of with this therapy with regards to several ACEIs in the adjunctive treatment the Worcester metropolitan area of AMI, we also examined the use demographic, medical history, and clinhospitalized at all 16 greater of this therapy during the period 9,10 ical characteristics. Worcester medical centers. In for which information was availmore recent study years, acute car● Patients receiving ACE inhibitors during able (2001 and 2003). diac care services for greater hospitalization from AMI experienced We examined clinical and deWorcester residents were prolower hospital death rates than patients mographic factors associated with vided by fewer hospitals (n ⫽ 11) who did not receive this therapy. the receipt of ACEI therapy durdue to closures, mergers, and coning hospitalization for AMI using versions to chronic care facilities. several logistic regression models. The details of this study have been Logistic regression model estima9 –12 In brief, the medical records of described previously. tion also was used to examine the association between residents of the Worcester metropolitan area (2000 census ACEI therapy and hospital death rates for all patients, and in estimate ⫽ 478,000) hospitalized for possible AMI at all several risk groups, while simultaneously controlling for the area medical centers were individually reviewed, and a effects of several potential confounding variables. A priori diagnosis of AMI was validated according to predefined control variables in our logistic regression models included criteria. age, sex, previous angina, hypertension, diabetes mellitus, stroke, heart failure, or renal disease (defined as a history of Data Collection kidney disease or a serum creatinine of ⱖ2 mg/dL), LVEF Sociodemographic, medical history, and clinical data categorized as abnormal (LVEF ⱕ0.40), normal (LVEF were abstracted from the hospital medical records of ⬎0.40) or unknown (LVEF not determined)), AMI order (prior vs initial), location (anterior vs others), and type (Q geographically eligible patients with confirmed AMI by wave vs non-Q wave; ST-elevation vs non-ST-elevation), trained study physicians and nurses. Information was development of heart failure or cardiogenic shock during collected about patient’s age, sex, comorbidities, AMI hospitalization, and year of hospitalization. The use of other order (prior vs. initial), type (Q-wave vs. non–Q-wave; cardiac medications and cardiac interventional procedures ST-segment elevation vs non-ST-segment elevation), and also were considered as covariates in our regression models. location (anterior vs. inferior or posterior), left ventricular ejection fraction (LVEF), and hospital discharge status. Information was collected about the occurrence of clinically significant hospital complications, including heart failure11 and cardiogenic shock.12 Nurse and physician notes and medication administration records were reviewed to ascertain the use of ACEIs, angiotensin-II receptor blockers, other cardiac medications, and coronary interventional procedures.13 Patients were considered to have received ACEIs or angiotensin-II receptor blockers if they were prescribed these medications at any time during hospitalization, irrespective of whether they were previously treated with these therapies. Information on the receipt of angiotensin-II receptor blockers was collected from 2001 to the present.

RESULTS A total of 7991 metropolitan Worcester residents (94% white) were hospitalized with validated AMI during the 8 study years of 1990 (n ⫽ 766), 1991 (n ⫽ 846), 1993 (n ⫽ 953), 1995 (n ⫽ 949), 1997 (n ⫽ 1057), 1999 (n ⫽ 1025), 2001 (n ⫽ 1239) and 2003 (n ⫽ 1156). Of these, 3547 (44.4%) received ACEI therapy at some time during hospitalization. Among 1734 (21.7%) patients who were on ACEI therapy before hospitalization for AMI, the majority (86.7%) continued to receive this therapy during hospitalization; ACEI therapy was initiated in approximately one third (32.7%) of patients who had not been previously on this therapy.

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ACE Inhibitor Therapy and AMI

616.e11

Table 1 Distribution of Selected Characteristics in Patients with Acute Myocardial Infarction (AMI) According to Receipt of ACE Inhibitor Therapy: Worcester Heart Attack Study Patients Hospitalized in 2001/2003

Total Sample

Characteristic Age (years) (%) ⬍55 55-64 65-74 75-84 ⱖ85 Male (%) Medical history (%) Angina Hypertension Diabetes Heart failure Stroke Renal disease* AMI characteristics (%) Prior AMI Q-wave Anterior ST-elevation* Therapies (%) Aspirin Beta-blockers Calcium antagonists Digoxin Diuretics Lipid-lowering agents Prior use of ACEIs Thrombolytics Left ventricular ejection fraction Normal Abnormal Unknown Procedures (%) Cardiac catheterization Percutaneous coronary intervention Coronary artery bypass grafting Clinical complications (%) Heart failure Cardiogenic shock Death

Received ACE Inhibitors (⫹) (n ⫽ 3547)

Did not Receive ACE Inhibitors (⫺) (n ⫽ 4444)

Received ACE Inhibitors (⫹) (n ⫽ 1517)

Did not Receive ACE Inhibitors (⫺) (n ⫽ 878)

14.4 16.3 24.8 30.4 14.1 56.3

15.9 18.0 25.5 26.3 14.3 58.2

.09

16.4 17.2 21.2 29.4 15.9 57.4

10.4 15.3 21.3 29.4 23.7 54.2

25.5 71.0 36.7 26.3 12.4 17.4

24.5 54.7 25.0 16.4 9.6 22.2

.29 ⬍.001 ⬍.001 ⬍.001 ⬍.001 ⬍.001

22.0 74.3 36.1 23.7 11.7 13.3

23.1 64.9 27.0 24.6 13.1 20.5

.53 ⬍.001 ⬍.001 .61 .30 ⬍.001

39.8 31.8 25.2 48.9

32.0 34.3 26.5 41.1

⬍.001 ⬍.001 .20 ⬍.001

35.3 23.6 17.0 27.8

35.1 15.4 11.5 37.4

.93 ⬍.001 ⬍.001 ⬍.001

91.7 82.1 31.8 37.2 67.2 44.5 42.4 14.5

85.4 73.0 36.4 20.6 48.1 20.5 5.2 21.0

⬍.001 ⬍.001 ⬍.001 ⬍.001 ⬍.001 ⬍.001 ⬍.001 ⬍.001

94.3 93.5 26.0 26.3 59.5 75.1 43.6 7.5

82.9 77.3 26.7 20.3 55.3 50.2 3.2 6.3

⬍.001 ⬍.001 .72 ⬍.01 .08 ⬍.001 ⬍.001 .24

38.1 35.0 26.9

39.7 13.0 47.3

⬍.001

45.8 31.0 23.1

40.0 16.8 43.2

⬍.001

48.2 26.6

32.5 13.9

⬍.001 ⬍.001

60.5 41.9

39.9 24.3

⬍.001 ⬍.001

5.8

4.4

⬍.005

6.6

7.6

.34

49.1 6.6 8.4

29.3 5.9 15.3

⬍.001 .23 ⬍.001

42.5 5.0 5.7

33.8 5.4 18.3

⬍.001 .71 ⬍.001

P Value

⬍.001

P Value

⬍.001 .14

*Information on these variables was available from 1997 to 2003 (n ⫽ 4477).

Among patients in the 2001/2003 study cohorts, 98 (4.1%) received angiotensin-II receptor blockers. Of these, 25 patients (25.5%) also received an ACEI during hospitalization.

Characteristics of Patients Receiving ACEI Therapy Overall, patients receiving ACEI therapy during hospitalization were older and more likely to have a history of

each of the comorbid conditions examined, with the exception of renal disease, compared with those not receiving this therapy (Table 1). Patients treated with ACEIs were more likely to have experienced a prior or STelevation AMI; more likely to have received aspirin, beta-blockers, and lipid lowering agents; more likely to have undergone cardiac interventional procedures, and more likely to have an abnormal LVEF. Patients who

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The American Journal of Medicine, Vol 119, No 7, July 2006

100

A

80

Percentage

60 40 20 0 1990

1991

1993

1995

1997

1999

2001

2003

New Users Prior ACE inhibitor users

B

100

Percentage

80 60 40 20 0 1990

1991

1993

1995

1997

1999

2001

2003

Figure (A) ACEI use in patients with acute myocardial infarction: The Worcester Heart Attack Study; (B) ACEI use in patients with acute myocardial infarction according to utilization prior to hospitalization: The Worcester Heart Attack Study

received ACEIs were less likely to have received thrombolytic therapy. Differences in selected characteristics between patients who received ACEI therapy, as compared with those who did not, were less substantial among patients hospitalized with AMI in our two most recent study years of 2001 and 2003 (Table 1). We also examined the characteristics of patients according to the use of ACEI therapy before their hospitalization for AMI. Patients who received ACEIs before hospitalization were older (mean age: 73.0 vs 69.2 years, respectively) and were more likely to have a history of each of the comorbid conditions examined, especially hypertension (87.7% vs 54.8%, respectively), diabetes mellitus (47.5% vs 25.4%, respectively), and heart failure (40.5% vs 15.3%, respectively) when compared with new treatment initiators.

Trends (1990-2003) in ACEI Use Use of ACEIs increased markedly over the period under study (Figure 1A). In 1990, 23.2% of patients with AMI were treated with ACEIs. This proportion increased steadily during subsequent years, particularly between 1995 (34.1%) and 1997 (50.0%). Reflective of these trends, slightly more than two thirds (68.4%) of greater Worcester residents hospitalized with AMI in 2003 were

treated with ACEIs during the index hospitalization. In 1990, 15.4% of patients who were not on ACEI therapy before hospitalization for AMI were newly started on this therapy; this proportion increased to 57.4% in 2003 (Figure 1B). In comparison, 80.4% of patients who used ACEIs before hospitalization received this therapy during hospitalization for AMI in 1990; this proportion increased to 92.5% in 2003. We examined the association between various patientassociated characteristics with the receipt of ACEIs using logistic regression estimation. Compared with patients who were not treated with ACEIs before hospitalization, those treated with ACEIs before the index hospitalization were significantly more likely to receive this therapy during hospitalization for AMI (Table 2). Patients with a history of diabetes; those with a Q-wave AMI; those receiving aspirin, beta-blockers, digoxin and diuretics; those with an abnormal LVEF; patients who underwent percutaneous coronary procedures; and those who developed heart failure during hospitalization were significantly more likely to receive ACEI therapy when compared with respective comparison groups. Patients treated with thrombolytics or calcium channel blockers during hospitalization and those who underwent coronary artery bypass graft surgery were less likely to receive ACEIs. In analyses restricted to patients with information on STelevation characteristics of AMI and renal disease, those with ST-elevation AMI were slightly more likely to receive ACEIs (adjusted OR 1.16; 95% CI, 0.98-1.38) compared with patients with non-ST-elevation AMI. Patients with a history of renal disease were significantly less likely to receive ACEI therapy (adjusted OR 0.52; 95% CI, 0.42-0.64) compared with those without renal disease.

Receipt of ACEI Therapy and Hospital Death Rates Patients receiving ACEIs during hospitalization for AMI experienced lower hospital death rates than patients who did not receive this therapy (8.4% vs 15.3%, respectively). Our multivariable adjusted logistic regression analyses corroborated the beneficial association between ACEI use and in-hospital case-fatality rates (Table 3). In analyses stratified according to study year, there was a trend toward greater benefit associated with the receipt of ACEIs in patients with AMI hospitalized during the most recent years, as compared with earlier study years. Adjusting for the effects of other cardiac medications, coronary interventional procedures, left ventricular function, ST-elevation characteristics of AMI, and renal disease did not alter our findings. We also examined whether the beneficial effects on in-hospital survival associated with the use of ACEIs varied according to patient demographic and clinical characteristics (data not shown). The benefits on hospital survival with the receipt of ACEI therapy were seen in all

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616.e13

Table 2 Relative Odds of Receipt of ACEI Therapy in Patients with Acute Myocardial Infarction (AMI): Worcester Heart Attack Study

Characteristic Age (years) ⬍55 55-64 65-74 75-84 ⱖ85 Male Medical history Angina Hypertension Diabetes Heart failure Stroke Renal disease† AMI characteristics Prior AMI Anterior Q-wave ST-elevation† Therapies Aspirin Beta-blockers Lipid lowering agents Thrombolytics Calcium channel antagonists Digoxin Diuretics Prior use of ACEIs Left ventricular ejection fraction Normal Abnormal Unknown Procedures Cardiac catheterization Percutaneous coronary intervention Coronary artery bypass graft surgery Clinical complications Heart failure Cardiogenic shock

Overall Crude

Adjusted Odds Ratios (OR)*

Odds Ratios (OR) (95% CI)

Overall OR (95% CI)

1990/1991 OR (95% CI)

2001/2003 OR (95% CI)

1.00 1.00 1.07 1.28 1.09 0.93

(referent) (0.86-1.17) (0.93-1.24) (1.11-1.47) (0.93-1.28) (0.85-1.01)

1.00 0.85 0.80 0.99 0.91 0.97

(referent) (0.70-1.03) (0.66-0.96) (0.81-1.21) (0.71-1.15) (0.86-1.10)

1.00 0.66 0.43 0.60 0.44 1.11

(referent) (0.36-1.19) (0.24-0.76) (0.33-1.10) (0.21-0.91) (0.79-1.55)

1.00 0.71 0.56 0.71 0.56 0.92

(referent) (0.48-1.03) (0.38-0.81) (0.49-1.04) (0.36-0.85) (0.74-1.15)

1.06 2.03 1.74 1.83 1.33 0.74

(0.95-1.17) (1.85-2.23) (1.58-1.91) (1.64-2.04) (1.16-1.53) (0.64-0.86)

0.88 1.13 1.13 0.93 1.05 0.52

(0.77-1.01) (1.00-1.28) (1.00-1.29) (0.79-1.10) (0.87-1.27) (0.42-0.64)

1.09 1.27 1.10 1.11 1.04

(0.76-1.56) (0.90-1.78) (0.78-1.56) (0.73-1.70) (0.64-1.70)

0.80 1.16 1.11 0.89 0.96 0.50

(0.62-1.04) (0.91-1.48) (0.87-1.41) (0.66-1.21) (0.69-1.34) (0.38-0.67)

1.41 0.94 0.89 1.37

(1.28-1.54) (0.85-1.04) (0.81-0.98) (1.22-1.54)

0.92 1.13 1.23 1.16

(0.81-1.05) (0.99-1.28) (1.08-1.41) (0.98-1.38)

1.20 (0.84-1.71) 1.77 (1.29-2.42) 1.23 (0.88-1.74)

0.69 1.27 1.43 1.22

(0.54-0.87) (0.93-1.73) (1.08-1.91) (0.96-1.55)

1.88 1.70 3.10 0.64 0.82 2.29 2.21 13.41

(1.62-2.17) (1.52-1.89) (2.81-3.43) (0.56-0.72) (0.74-0.90) (2.07-2.53) (2.01-2.42) (11.56-15.55)

1.58 1.39 2.78 0.80 0.71 2.06 1.33 19.15

(1.29-1.94) (1.19-1.63) (2.43-3.17) (0.68-0.94) (0.62-0.80) (1.78-2.38) (1.15-1.54) (16.00-22.92)

1.84 0.75 1.95 0.79 0.94 3.40 1.74 32.06

(1.24-2.73) (0.53-1.07) (0.92-4.13) (0.52-1.22) (0.67-1.32) (2.38-4.84) (1.12-2.71) (19.99-51.42)

2.06 3.08 2.20 1.24 0.90 1.34 1.11 19.83

(1.40-3.03) (2.16-4.38) (1.73-2.79) (0.82-1.87) (0.71-1.16) (1.02-1.78) (0.84-1.46) (14.11-27.86)

1.00 (referent) 2.80 (2.48-3.16) 0.59 (0.53-0.66)

1.00 (referent) 2.68 (2.29-3.13) 0.60 (0.52-0.69)

1.00 (referent) 2.48 (1.60-3.83) 0.65 (0.43-0.99)

1.00 (referent) 2.10 (1.57-2.81) 0.56 (0.43-0.73)

1.93 (1.76-2.11) 2.24 (2.00-2.50) 1.34 (1.10-1.64)

1.27 (1.08-1.50) 1.83 (1.53-2.20) 0.46 (0.34-0.61)

0.88 (0.55-1.44) 0.92 (0.37-2.29) 0.78 (0.28-2.18)

1.27 (0.92-1.76) 1.43 (1.04-1.96) 0.34 (0.21-0.55)

2.33 (2.13-2.56) 1.12 (0.93-1.34)

1.90 (1.65-2.20) 0.96 (0.73-1.25)

2.94 (2.00-4.33) 0.93 (0.49-1.76)

1.58 (1.21-2.08) 0.86 (0.50-1.47)

*Respective referent categories; age ⬍55 years, female sex, absence of selected medical history factors, initial, inferior/posterior and non-Q wave AMI, and NSTEMI, normal LVEF, failure to receive selected therapies or interventional procedures. Discharge status (dead vs alive) was included as a covariate in the multivariable model. †Information on these variables was available from 1997 to 2003 (n ⫽ 4477).

subgroups examined, even after further adjusting for the use of cardiac medications and interventional reperfusion strategies in our regression models.

DISCUSSION The results of this community-wide study demonstrate significant increases in the use of ACEI therapy in patients hospitalized with AMI, with increases being most marked from the mid-1990s to our most recent study year of 2003. Although increases in the use of ACEIs were observed for most of the patient groups examined, there

remains substantial room for improvement in several high-risk groups. Although direct conclusions about the efficacy of this therapy cannot be drawn from data collected in the context of our nonrandomized observational study, administration of ACEIs was associated with enhanced hospital survival.

Patterns in the Receipt of ACEIs after AMI Despite clear evidence for the benefits of ACEI therapy on mortality after AMI,6 and guidelines that advocate the early use of ACEIs in a broad spectrum of patients,7,14

616.e14 Table 3

The American Journal of Medicine, Vol 119, No 7, July 2006 Relative Odds of Dying during Hospitalization in Relation to the Receipt of ACEI Therapy: Worcester Heart Attack Study

All patients Study year 1990/91 1993/95 1997/99 2001/03

Crude Odds Ratio (95% CI)

Adjusted Odds Ratio* (95% CI)

Adusted Odds Ratio† (95% CI)

0.51 (0.44-0.59)

0.33 (0.27-0.41)

0.38 (0.31-0.47)

1.03 0.90 0.44 0.27

0.57 0.49 0.29 0.18

0.56 0.52 0.33 0.24

(0.75-1.42) (0.67-1.21) (0.33-0.59) (0.21-0.36)

(0.35-0.91) (0.32-0.76) (0.20-0.44) (0.13-0.27)

(0.34-0.91) (0.33-0.80) (0.22-0.50) (0.17-0.35)

*Adjusted for age, sex, AMI location, type and prior vs initial AMI, prior use of ACEIs, medical history (angina, hypertension, diabetes, heart failure and stroke), LVEF, and development of cardiogenic shock and heart failure during hospitalization. †Adjusted for age, sex, AMI location, type and prior vs initial of AMI, prior use of ACEIs, medical history (angina, hypertension, diabetes, heart failure and stroke), LVEF, development of cardiogenic shock and heart failure during hospitalization, and use of various cardiac medications and cardiac procedures.

findings from earlier studies suggest considerable underutilization of this effective therapy.8,15 Our study found that ACEI therapy was underused in patients hospitalized with AMI, particularly in the early study years. However, there were marked increases in the receipt of ACEIs during the past decade. These changes are similar to findings in previous studies examining the use of ACEIs in patients with AMI.8,16 However, our study found that increases in the receipt of ACEIs were particularly marked among younger patients, those with an initial AMI, those on other effective cardiac medications, those with a normal LVEF, and among patients who underwent percutaneous coronary interventions. There was a sharp increase in the prescribing of ACEIs between 1995 and 1997; an increase that was temporally related to the publication of the 1996 ACC/AHA guidelines highlighting the indications for ACEI use after AMI.7 These encouraging increases may reflect a variety of factors including participation in, or awareness of, clinical trials and quality improvement programs.15,17–20 Based on the results of recently published clinical trials,21 current ACC/AHA guidelines recommend angiotensin-II receptor blockers for use in patients unable to tolerate ACEIs.22 As expected, we found that only a small proportion of patients received only angiotensin-II receptor blockers during hospitalization for AMI.

Patient Factors Associated With Non-receipt of ACEIs Use of ACEI therapy before hospitalization was the strongest predictor of receipt of this therapy during hospitalization for AMI. These findings suggest that physicians were more likely to be prompted to continue this therapy for AMI for those already on ACEIs than initiate it de novo. Patients with an abnormal LVEF were more likely to receive ACEI during hospitalization for AMI than those with a normal LVEF. Although we found that elderly patients were less likely to receive ACEI therapy during the earlier study years, similar to findings in some previous reports,23 these differ-

ences were not observed during the most recent years under study. Patients with renal disease have an increased risk of adverse cardiovascular outcomes after AMI, and ACEI therapy has been found to significantly reduce this risk.24 We found that patients with renal disease were less likely to receive this therapy than patients without such a history. In the later study years, patients with a prior AMI were less likely to receive ACEI therapy, compared with those with an initial AMI. This was surprising because patients with a prior AMI have an increased risk for poorer outcomes, and these patients may derive a greater absolute risk reduction with ACEI use.3,4,6

ACEI Therapy and Improved Outcomes after AMI Since the publication of several large randomized trials in the 1990s, ACEIs have become standard adjunctive therapy in the treatment of patients with AMI.7,14 Evidence for the benefits of early inhibition of the renin-angiotensin system in the treatment of AMI began with studies demonstrating the ability of these agents to reduce left ventricular remodeling.25 Findings from three large trials published in 1994 and 1995, in patients with AMI without clear contraindications to ACEI therapy, demonstrated survival benefits in association with use of this therapy.6 The survival benefit associated with ACEI therapy was shown to be greatest for high-risk patients. The use of ACEIs in our study was associated with a marked reduction in the likelihood of dying after AMI, and this reduced risk was similar across each of the subgroups examined.

Study Strengths and Limitations The present investigation included a large population of residents from a representative Northeastern metropolitan area hospitalized at all area hospitals with documented AMI, enhancing the generalizability of the present findings. Our findings provide insights into the treatment practices and outcomes of more typical patients with AMI treated in the community. This is in contrast to

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the findings obtained from studying patients treated in the context of randomized controlled trials, with their more narrowly defined inclusion criteria. Appropriate caution must be exercised in examining associations between prescribing of a specific therapy and hospital death rates in an observational study. In our population, ACEI therapy was associated with a significantly lower hospital death rate. We were, however, unable to measure other factors that may be associated with ACEI use or hospital outcomes, such as contraindications to ACEI therapy and clinically significant hypotension at hospital presentation. These and potential residual confounding related to indications for treatment may have affected our results.

CONCLUSIONS The results of this community-wide study demonstrate significant increases in the use of ACEI therapy during hospitalization for AMI. However, we found underutilization of this therapy, particularly among patients in some high-risk groups. Clinicians should be particularly vigilant about appropriately considering the use of this therapy in all patients hospitalized with AMI, especially those who might derive significant benefits from the use of this effective cardiac therapy.

616.e15

7.

8.

9.

10.

11.

12.

13.

14.

ACKNOWLEDGMENTS This research was made possible by the cooperation of the medical records, administration, and cardiology departments of participating hospitals in the Worcester metropolitan area and through funding support provided by the National Institutes of Health (RO1 HL35434). Dr. Doubeni is supported by a supplemental grant from the National Cancer Institute to the Cancer Research Network (U19 CA079689-06).

15.

16.

17.

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