Methods

All patients admitted to the University of Michigan Health System from January 1, 1999, to January 28, 2007, with diagnoses of ACS who survived to discharge were eligible for study inclusion. Those who died in the hospital before discharge or who were lost to follow-up at 2 years were excluded. A total of 4,147 ACS admissions occurred at the University of Michigan Medical Center from January 1, 1999, and January 28, 2007. We excluded 148 patients who died in the hospital before discharge and 556 patients who were lost to follow-up at 2 years. Patients lost to follow-up were more likely to have histories of angina, MI, and stroke. These patients were less likely to be admitted with ST-segment elevation MI but were more likely to undergo percutaneous coronary intervention or to receive thrombolytic therapy. Additional co-morbidities and clinical characteristics were similar between the 2 groups. A further 831 events were categorized as recurrent events and were counted as outcomes. Thus, a total of 2,684 patients discharged with diagnoses of ACS were included in the study population.

ACS were defined as unstable angina, ST-segment elevation MI, or non–ST-segment elevation MI using standard definitions. The diagnosis of ACS was documented by the presence of symptoms consistent with acute coronary insufficiency, increases in cardiac enzymes (creatine kinase-MB >2 times the upper limit of the hospital’s normal range and/or positive troponin I), and/or positive acute electrocardiographic changes, including (1) transient ST-segment elevations ≥1 mm in ≥2 contiguous leads, (2) ST-segment depressions ≥1 mm, (3) new T-wave inversions ≥1 mm, and (4) new left bundle branch block. Patients aged <18 years and those with noncardiovascular causes for the ACS events (including trauma and surgery) were excluded from the study. Full details of the University of Michigan Health System’s ACS registry have been published previously.

Information on demographics (age, gender, and race), co-morbidities, in-hospital management, and outcomes as documented in the patients’ medical records was collected on each participant. Smoking status, the presence of cardiovascular risk factors including diabetes, hyperlipidemia, hypertension, and history of heart disease (angina, heart failure, and MI), history of stroke and family history of CAD (defined as having any blood relative [parents, siblings, or children] with a history of angina, MI, and/or sudden cardiac death before the age of 55 years) was assessed for each patient. Data on in-hospital management included medications received and revascularization procedures completed (percutaneous coronary intervention and coronary artery bypass graft surgery). Receipt of medications at time of discharge was collected via chart review. Primary medications examined included aspirin, β blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers, and statins.

Using an algorithm based on evidence-based clinical practice guidelines that has been used in a previous study, an appropriateness level was determined for each subject. All patients were considered eligible for aspirin and β blockers unless a documented contraindication was present in the medical record. Patients were considered eligible for lipid-lowering therapy if they had histories of hyperlipidemia or had documented lipid profiles meeting any 1 of the following criteria: total cholesterol ≥200 mg/dl, low-density lipoprotein ≥100 mg/dl, or past or present use of lipid-lowering agents. Eligibility for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was determined by the presence of hypertension, heart failure (all classes), diabetes, or a documented left ventricular ejection fraction <40%. Patients with documented contraindications to any of these agents were considered ineligible to receive these medications. The appropriateness level score was then calculated for each patient on the basis of the number of these indicated EBMs received at the time of discharge. If the patient was discharged on none of these EBMs, he or she received a score of zero (level 0). An appropriateness level of 1 was defined as the receipt of 1 of 4 indicated EBMs at the time of discharge. Level 2 was defined as the receipt of 2 of 4 indicated EBMs at the time of discharge, level 3 was defined as the receipt of 3 of 4 indicated EBMs at the time of discharge, and level 4 was defined as the receipt of all indicated EBMs at the time of discharge. Information on thienopyridine (clopidogrel or ticlopidine) use was collected but was not included in the composite appropriateness level score, as the use and indications of these agents changed significantly over the study period. Use of thienopyridine was adjusted for in the multivariate models, in addition to other potential confounders. The primary outcome of interest was all-cause mortality at 2 years. The secondary outcome was the occurrence of CVD events at 2 years.

Information regarding ACS type, in-hospital treatment, and events in addition to demographic information was collected via chart review using standardized data collection methods by trained study personnel. Data not within the set limit ranges, inconsistencies, and/or unrecorded fields were flagged and reviewed for clarification and correction. Two-year follow-up data were obtained via telephone calls and review of the National Death Index. At least 3 phone call attempts were made to contact patients to query their health status. All aspects of this study were approved by the institutional review board at the University of Michigan Health System, and informed consent was obtained from all patients.

Baseline clinical and demographic characteristics, in-hospital management, and discharge medications were compared for men and women. Continuous variables are expressed as mean ± SD, and differences in these variables were determined using analysis of variance. Categorical variables are presented as frequencies and percentages. Chi-square and Fisher’s exact tests were used to determine the statistical significance in differences in the proportions of these variables between the 2 groups. Logistic regression models were used to examine the differences in outcomes between each appropriateness score level, by gender. Models were adjusted for thienopyridine use, year of discharge, and disease severity as defined by Global Registry of Acute Coronary Events (GRACE) risk score (age, history of congestive heart failure, history of MI, heart rate, systolic blood pressure, initial creatinine level, elevated cardiac biomarkers, and in-hospital percutaneous coronary intervention). Odds ratios (ORs) are presented as point estimates with 95% confidence intervals (CIs) and corresponding p values. A p value of <0.05 was considered to indicate statistical significance. All analyses were performed using SAS version 9.2 (SAS Institute Inc., Cary, North Carolina).

Results

A total of 2,684 patients who were discharged from January 1, 1999, to January 28, 2007, with diagnoses of ACS constituted the present study cohort for the primary and secondary outcomes. Men were younger than women at the time of presentation and had fewer co-morbidities, including stroke, congestive heart failure, diabetes, and hypertension ( Table 1 ). Men were more likely than women to have histories of smoking, both previous and current at the time of admission. Although there were no differences in the number of patients with previous MI, men had undergone more coronary artery bypass procedures and percutaneous coronary interventions than women. Men had lower in-hospital and 6-month GRACE risk for death. On presentation, men were more likely to present with ST-segment elevation MI than women, while women were more likely to present with unstable angina. In the hospital, men were more likely than women to receive thrombolytic agents or to undergo cardiac catheterization and subsequent percutaneous coronary intervention, although rates of coronary artery bypass graft surgery were similar between genders.

Most patients were eligible for aspirin, β blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and lipid-lowering agents ( Table 2 ). Among those eligible for lipid-lowering therapy, statins accounted for most of the lipid-lowering medications prescribed at discharge (97.3%), with similar rates between men (97.3%) and women (97.5%). With regard to the receipt of medications among eligible patients, men were more likely to be discharged on aspirin and lipid-lowering medications compared to women. Women and men were discharged on similar rates of β blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. A total of 169 men and women received angiotensin receptor blockers in our data sample. Overall, men were more likely to be discharged on all 4 EBMs compared to women ( Table 3 ).

Table 3

Distribution of patients with acute coronary syndromes by appropriateness levels

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