Beta-Blocker Use With vs Without Diabetes After MI
Beta-Blocker Use With vs Without Diabetes After MI
Between June 2005 and December 2008, patients from 24 US hospitals were enrolled into the Translational Research Investigating Underlying disparities in acute Myocardial infarction Patients' Health status (TRIUMPH) study. Patients were required to have biomarker evidence of myocardial necrosis and additional evidence supporting the clinical diagnosis of an MI (eg, ischemic signs/symptoms ≥20 minutes or electrocardiographic ST changes) during the initial 24 hours of admission. Baseline data were obtained through chart abstraction and a structured interview by trained research staff within 24 to 72 hours of admission. In addition, consenting patients had fasting blood specimens collected before discharge. Approximately 20 mL of fasting blood was drawn from each subject in 3 tubes, which were processed, refrigerated, and sent by overnight mail to the core laboratory (Clinical Reference Laboratory, Lenexa, KS) on a daily basis. Blood was analyzed for glucose and HbA1c. Chart data on laboratory values drawn for clinical purposes were also recorded. Each participating hospital obtained institutional research board approval, and all patients provided written informed consent. The TRIUMPH was sponsored by a grant from the National Institutes of Health (National Heart, Lung, and Blood Institute): SCCOR grant number P50HL077113–01. This study was sponsored by an investigator-initiated research grant from Gilead Sciences, Foster City, CA. The funding organizations did not play a role in the design and conduct of the study or in the collection, management, analysis, and interpretation of the data.
As this analysis was investigating practice patterns associated with patients with known DM, we defined DM as prevalent DM (ie, DM by chart abstraction or DM medications at admission [except metformin or thiazolidindiones, which can be used for DM prevention]) or newly diagnosed DM that was recognized during hospitalization. Newly diagnosed DM was defined as HbA1c ≥6.5% by core laboratory or chart assessment. If HbA1c level was missing, DM could be additionally diagnosed as (1) ≥2 fasting blood glucose levels >126 mg/dL or (2) ≥1 fasting blood glucose >126 mg/dL and random blood glucose (at presentation) ≥200 mg/dL. Patients with newly diagnosed DM were considered "recognized" if they were discharged on any DM medications or received DM education during MI hospitalization. β-Blockers prescribed at discharge were categorized by their impact on glucose control. Vasodilating β-blockers (acebutalol, betaxolol, carvedilol, labetalol, and nebivolol) were categorized as DM-friendly, and nonvasodilating β-blockers (all others: eg, metoprolol, atenolol, and propranolol) were categorized as non–DM-friendly. Patients with chart-documented contraindications to β-blockers at discharge (ie, systolic blood pressure <90 mm Hg, heart rate <50 beat/min, or allergy) were excluded from the analyses (n = 138).
Detailed follow-up interviews were attempted on all survivors at 1, 6, and 12 months after MI. In addition to a report of interval events and an assessment of health status, participants were asked to read the names and doses of their medications from their prescription bottles. Patients could opt for 6-month follow-up by telephone or in-home visit, which allowed for collection of additional laboratory data, which was analyzed for HbA1c at the core laboratory. Worsened glucose control at the 6-month follow-up was defined as either an increase in HbA1c from baseline of ≥0.1% or an intensification of DM meds. Intensification of DM medications was defined, per prior work, as any of the following: (1) increase in dose of a medication, (2) addition of a medication, (3) increase in daily basal insulin of 20%, or (4) addition of insulin. If a patient was missing 6-month follow-up medication data, 12-month data were used if available. In addition, we did a second analysis defining worsened glycemic control as an increase in HbA1c from baseline of ≥0.5% or intensification of DM medications.
The frequency of prescription of DM-friendly β-blockers among patients with and without DM was compared using the χ test. We then constructed a hierarchical logistic regression model among patients who were discharged on a β-blocker to examine the association of DM with use of a DM-friendly β-blocker, with site included as a random effect to account for clustering of patients within sites. The first model was unadjusted, and a second model included factors other than DM that might impact prescription with a DM-friendly (ie, vasodilating) β-blocker: age (vasodilating β-blockers may cause orthostasis in elderly patients), atrial fibrillation (nonvasodilating β-blockers may be superior for rate controlling atrial arrhythmias), chronic lung disease (vasodilating β-blockers may cause increased wheezing), left ventricular dysfunction and a history of heart failure (vasodilating β-blockers are considered by many to be better for patients with heart failure), self-reported avoidance of medications due to costs (vasodilating β-blockers were not available as a generic medication for the first 2 years of TRIUMPH), heart rate (nonvasodilating β-blockers lower heart rate more than vasodilating β-blockers), and systolic blood pressure at discharge (vasodilating β-blockers lower blood pressure more than nonvasodilating β-blockers). We also performed a sensitivity analysis excluding patients who might not be considered candidates for vasodilating β-blockers: patients with atrial fibrillation, chronic lung disease, or systolic blood pressure at discharge of <110 mm Hg.
As practice patterns may have changed due to changes in medication availability over time (eg, metoprolol succinate became generic in 2006, carvedilol became generic in 2007, and nebivolol was introduced in 2007), we examined the association of time with the prescription of DM-friendly β-blockers by adding time (as quarter of year) to the multivariable model. To examine if patients with DM were more likely to be treated with DM-friendly β-blockers over time, we also examined the interaction of DM × time. Spline terms were considered for all continuous variables, and all models were hierarchical, with hospital included as a random effect to adjust for patient clustering by site.
Among patients with DM discharged on a β-blocker, we examined the association of DM-friendly β-blocker at discharge with glycemic control over the following 6 months using hierarchical modified Poisson regression, adjusted for clinical and demographic factors (age, left ventricular dysfunction, history of heart failure, chronic lung disease, self-reported avoidance of medical care due to costs, and baseline HbA1c). All analyses were conducted using SAS version 9.2 (SAS Institute, Inc, Cary, NC), and statistical significance was determined by a 2-sided P < .05.
Methods
Study Population and Protocol
Between June 2005 and December 2008, patients from 24 US hospitals were enrolled into the Translational Research Investigating Underlying disparities in acute Myocardial infarction Patients' Health status (TRIUMPH) study. Patients were required to have biomarker evidence of myocardial necrosis and additional evidence supporting the clinical diagnosis of an MI (eg, ischemic signs/symptoms ≥20 minutes or electrocardiographic ST changes) during the initial 24 hours of admission. Baseline data were obtained through chart abstraction and a structured interview by trained research staff within 24 to 72 hours of admission. In addition, consenting patients had fasting blood specimens collected before discharge. Approximately 20 mL of fasting blood was drawn from each subject in 3 tubes, which were processed, refrigerated, and sent by overnight mail to the core laboratory (Clinical Reference Laboratory, Lenexa, KS) on a daily basis. Blood was analyzed for glucose and HbA1c. Chart data on laboratory values drawn for clinical purposes were also recorded. Each participating hospital obtained institutional research board approval, and all patients provided written informed consent. The TRIUMPH was sponsored by a grant from the National Institutes of Health (National Heart, Lung, and Blood Institute): SCCOR grant number P50HL077113–01. This study was sponsored by an investigator-initiated research grant from Gilead Sciences, Foster City, CA. The funding organizations did not play a role in the design and conduct of the study or in the collection, management, analysis, and interpretation of the data.
Definition of DM and DM-friendly β-blockers
As this analysis was investigating practice patterns associated with patients with known DM, we defined DM as prevalent DM (ie, DM by chart abstraction or DM medications at admission [except metformin or thiazolidindiones, which can be used for DM prevention]) or newly diagnosed DM that was recognized during hospitalization. Newly diagnosed DM was defined as HbA1c ≥6.5% by core laboratory or chart assessment. If HbA1c level was missing, DM could be additionally diagnosed as (1) ≥2 fasting blood glucose levels >126 mg/dL or (2) ≥1 fasting blood glucose >126 mg/dL and random blood glucose (at presentation) ≥200 mg/dL. Patients with newly diagnosed DM were considered "recognized" if they were discharged on any DM medications or received DM education during MI hospitalization. β-Blockers prescribed at discharge were categorized by their impact on glucose control. Vasodilating β-blockers (acebutalol, betaxolol, carvedilol, labetalol, and nebivolol) were categorized as DM-friendly, and nonvasodilating β-blockers (all others: eg, metoprolol, atenolol, and propranolol) were categorized as non–DM-friendly. Patients with chart-documented contraindications to β-blockers at discharge (ie, systolic blood pressure <90 mm Hg, heart rate <50 beat/min, or allergy) were excluded from the analyses (n = 138).
Outcome Assessment
Detailed follow-up interviews were attempted on all survivors at 1, 6, and 12 months after MI. In addition to a report of interval events and an assessment of health status, participants were asked to read the names and doses of their medications from their prescription bottles. Patients could opt for 6-month follow-up by telephone or in-home visit, which allowed for collection of additional laboratory data, which was analyzed for HbA1c at the core laboratory. Worsened glucose control at the 6-month follow-up was defined as either an increase in HbA1c from baseline of ≥0.1% or an intensification of DM meds. Intensification of DM medications was defined, per prior work, as any of the following: (1) increase in dose of a medication, (2) addition of a medication, (3) increase in daily basal insulin of 20%, or (4) addition of insulin. If a patient was missing 6-month follow-up medication data, 12-month data were used if available. In addition, we did a second analysis defining worsened glycemic control as an increase in HbA1c from baseline of ≥0.5% or intensification of DM medications.
Statistical Analysis
The frequency of prescription of DM-friendly β-blockers among patients with and without DM was compared using the χ test. We then constructed a hierarchical logistic regression model among patients who were discharged on a β-blocker to examine the association of DM with use of a DM-friendly β-blocker, with site included as a random effect to account for clustering of patients within sites. The first model was unadjusted, and a second model included factors other than DM that might impact prescription with a DM-friendly (ie, vasodilating) β-blocker: age (vasodilating β-blockers may cause orthostasis in elderly patients), atrial fibrillation (nonvasodilating β-blockers may be superior for rate controlling atrial arrhythmias), chronic lung disease (vasodilating β-blockers may cause increased wheezing), left ventricular dysfunction and a history of heart failure (vasodilating β-blockers are considered by many to be better for patients with heart failure), self-reported avoidance of medications due to costs (vasodilating β-blockers were not available as a generic medication for the first 2 years of TRIUMPH), heart rate (nonvasodilating β-blockers lower heart rate more than vasodilating β-blockers), and systolic blood pressure at discharge (vasodilating β-blockers lower blood pressure more than nonvasodilating β-blockers). We also performed a sensitivity analysis excluding patients who might not be considered candidates for vasodilating β-blockers: patients with atrial fibrillation, chronic lung disease, or systolic blood pressure at discharge of <110 mm Hg.
As practice patterns may have changed due to changes in medication availability over time (eg, metoprolol succinate became generic in 2006, carvedilol became generic in 2007, and nebivolol was introduced in 2007), we examined the association of time with the prescription of DM-friendly β-blockers by adding time (as quarter of year) to the multivariable model. To examine if patients with DM were more likely to be treated with DM-friendly β-blockers over time, we also examined the interaction of DM × time. Spline terms were considered for all continuous variables, and all models were hierarchical, with hospital included as a random effect to adjust for patient clustering by site.
Among patients with DM discharged on a β-blocker, we examined the association of DM-friendly β-blocker at discharge with glycemic control over the following 6 months using hierarchical modified Poisson regression, adjusted for clinical and demographic factors (age, left ventricular dysfunction, history of heart failure, chronic lung disease, self-reported avoidance of medical care due to costs, and baseline HbA1c). All analyses were conducted using SAS version 9.2 (SAS Institute, Inc, Cary, NC), and statistical significance was determined by a 2-sided P < .05.
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