The benefit of an invasive strategy in non–ST-segment elevation myocardial infarction (NSTEMI) was established from randomized trials that included few anemic patients. The aim of this study was to describe the characteristics, therapies, and mortality of patients with NSTEMIs who undergo an invasive strategy in relation to their admission hemoglobin levels. Data from 73,067 patients with NSTEMIs who underwent cardiac catheterization and who were captured by the Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines (ACTION-GWTG) were examined. Patients were divided into 3 hemoglobin groups on the basis of initial hemoglobin level: (1) <10 g/dl, (2) 10 to 12 g/dl, or (3) >12 g/dl. Patients with hemoglobin <10 g/dl had more co-morbidities and more 3-vessel coronary artery disease at catheterization compared with those with hemoglobin >12 g/dl (46.2% vs 33.9%, all p values <0.0001). They received fewer acute antithrombotic therapies, less often underwent revascularization (57.4% vs 74.1%), and had higher rates of red blood cell transfusion before catheterization (32.1% vs 0.3%, all p values <0.0001). After adjustment, in-hospital mortality was inversely associated with initial hemoglobin, with a 7% increase for each 1 g/dl decrease in hemoglobin lower than 15 g/dl (odds ratio 1.07, 95% confidence interval 1.02 to 1.11). In conclusion, in patients presenting with NSTEMIs and managed with an invasive strategy, a lower hemoglobin level is associated with more extensive coronary artery disease, less use of revascularization and evidence-based therapies, and increased mortality.
Invasive care is recommended for patients with non–ST-segment elevation myocardial infarction (NSTEMI), but large randomized trials that addressed the use of an invasive strategy in this setting included few patients with anemia. Data from trials of acute coronary syndromes suggest that 15% of patients have admission hemoglobin levels <12 g/dl ; the prevalence of hemoglobin <12 g/dl is higher in real-world registries. Despite this high prevalence, management of patients presenting with low baseline hemoglobin and the frequency of use of blood transfusion before the invasive management of these patients have not been addressed previously. The purpose of our analysis was to describe according to hemoglobin level (1) the baseline characteristics and acute therapy, (2) the angiographic findings and use of revascularization strategies, and (3) the frequency of red blood cell transfusion overall and before cardiac catheterization. In addition, the relation between continuous baseline hemoglobin and in-hospital mortality in patients with NSTEMI selected to undergo an invasive strategy is described.
Methods
The starting population for this study was from the 162,361 patients enrolled from January 1, 2007 to December 31, 2009 at 397 hospitals from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines (ACTION-GWTG), a nationally representative, quality improvement registry of ST-segment elevation myocardial infarction and NSTEMI. Participating hospitals were required to submit data to ACTION-GWTG for all patients who presented <24 hours after the onset of an ischemic syndrome and if the primary diagnosis was either NSTEMI or ST-segment elevation myocardial infarction. All participating centers were required to abide by local institutional review or ethical review standards. Patients in ACTION-GWTG were included in this study if they had NSTEMIs and underwent cardiac catheterization (regardless of whether it showed significant or nonsignificant coronary artery disease [CAD]). Patients were ineligible for this analysis if they presented with ST-segment elevation myocardial infarctions (n = 63,816), did not undergo cardiac catheterization or their catheterization status was missing (n = 24,899), or were missing admission hemoglobin values (n = 579). Thus, the final analysis cohort consisted of 73,067 patients with NSTEMIs from 354 United States centers.
Data definitions for the elements captured in the ACTION-GWTG database are available on-line ( https://www.ncdr.com/WebNCDR/ACTION/default_ssl.aspx ). Definitions relevant to this analysis are in-hospital mortality, defined as all-cause mortality during hospitalization, and initial hemoglobin, defined as the first value collected after first medical contact. For descriptive purposes, patients were divided into 3 groups: (1) hemoglobin <10 g/dl, (2) hemoglobin 10 to 12 g/dl, and (3) hemoglobin >12 g/dl. Patients whose hemoglobin levels changed from 1 category to another during hospitalization were still stratified according to their initial admission hemoglobin levels.
Baseline demographics, clinical characteristics, and in-hospital treatments were compared across the hemoglobin groups. Continuous variables are reported as medians with interquartile ranges and categorical variables as percentages. Patients with hemoglobin <10 and 10 to 12 g/dl were compared with those with hemoglobin >12 g/dl (the reference group). Glomerular filtration rate was defined using the Modification of Diet in Renal Disease (MDRD) equation. p values were generated using Wilcoxon’s rank-sum tests for continuous variables and chi-square tests for categorical variables.
To evaluate the relation between continuous hemoglobin and in-hospital mortality, initial hemoglobin was plotted against rates of in-hospital mortality, and the linearity of the relation was tested. From the scatterplot, continuous hemoglobin was analyzed by allowing for 2 slopes by fitting a linear spline with a knot at 15 g/dl.
The logistic generalized estimating equations method with an exchangeable working correlation matrix was used to account for within-hospital clustering because patients at the same hospital were more likely to have similar responses relative to patients at other hospitals (i.e., within-center correlation for responses). We adjusted for variables that were found to be independently associated with mortality in the validated ACTION in-hospital mortality model : age, gender, race, weight, medical history of diabetes, previous peripheral arterial disease, hypertension, current or recent smoking, previous percutaneous coronary intervention, previous coronary artery bypass grafting, previous myocardial infarction, previous heart failure, previous stroke, insurance status, home medications use (aspirin, clopidogrel, warfarin, β blockers, statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone receptor antagonists, and nonstatin lipid-lowering drugs), systolic blood pressure on presentation, heart rate on presentation, heart failure or shock on admission (heart failure only, shock only, or heart failure with shock, vs none), electrocardiographic findings (ST-segment depression or transient ST-segment elevation or no ST-segment changes), initial troponin ratio, and initial serum creatinine. In addition, we adjusted for the number of diseased coronary arteries (≥50% stenosis), which was a clinically relevant difference among various hemoglobin groups. Adjusted associations are displayed as odds ratios with 95% confidence intervals, and a global comparison p value is reported. All analyses were performed using SAS version 9.2 (SAS Institute Inc., Cary, North Carolina).
Results
Overall, 73,067 patients with NSTEMI who underwent an invasive strategy were included. The distribution of admission hemoglobin values is presented ( Figure 1 ). A total of 2,417 patients (3.3%) had hemoglobin <10 g/dl, 9,940 patients (13.6%) had hemoglobin 10 to 12 g/dl, and 60,710 patients (83.1%) had hemoglobin >12 g/dl on presentation. Compared with patients with hemoglobin >12 g/dl, patients with hemoglobin 10 to 12 g/dl and <10 g/dl were more likely to have histories of chronic kidney disease, diabetes mellitus, heart failure, coronary revascularization, and peripheral arterial disease and were more likely to have heart failure and shock on presentation ( Table 1 ).
| Variable | Hemoglobin (g/dl) | ||
|---|---|---|---|
| <10 ∗ (n = 2,417) | 10–12 ∗ (n = 9,940) | >12 ∗ (n = 60,710) | |
| Age (yrs) | 72 (62–79) | 72 (62–80) | 62 (53–72) |
| Men | 49.2% | 44.3% | 68.9% |
| White | 77.1% | 79.3% | 85.1% |
| Black | 15.4% | 13.4% | 8.1% |
| Hispanic | 3.4% | 3.6% | 3.6% |
| Other | 3.0% | 3.1% | 2.4% |
| Body mass index (kg/m 2 ) | 27.9 (24.2–32.7) | 27.9 (24.3–32.6) | 29.0 (25.6–33.2) |
| Hypertension | 84.4% | 84.7% | 70.8% |
| Diabetes mellitus | 54.8% | 49.9% | 28.9% |
| Previous myocardial infarction | 33.6% | 33.5% | 24.5% |
| Previous coronary artery bypass grafting | 23.3% | 25.4% | 15.8% |
| Previous percutaneous coronary intervention | 32.4% | 31.8% | 24.2% |
| Previous heart failure | 27.5% | 22.7% | 8.4% |
| Peripheral arterial disease | 22.1% | 18.0% | 8.7% |
| Previous stroke | 13.0% | 12.5% | 6.3% |
| Heart failure on presentation | 37.2% | 28.1% | 12.0% |
| Shock on presentation | 3.0% | 2.1% | 1.1% |
| Systolic blood pressure on presentation (mm Hg) | 135 (115–156) | 141 (120–161) | 148 (129–168) |
| Heart rate on presentation (beats/min) | 89 (76–103) | 84 (71–100) | 80 (69–95) |
| Glomerular filtration rate (ml/min/1.73 m 2 ) † | 49.0 (34.2–69.5) | 56.2 (41.0–75.3) | 73.7 (58.8–89.7) |
| Hemoglobin (g/dl) | 9.2 (8.5–9.63) | 11.3 (10.8–11.7) | 14.3 (13.3–15.3) |
| Initial troponin ratio | 3.6 (1.0–17.3) | 2.5 (0.7–13.2) | 1.9 (0.4–9.8) |
∗ The groups with hemoglobin <10 and 10 to 12 g/dl were each compared with the reference group (hemoglobin >12 g/dl). The p values for all comparisons were <0.0001.
† Calculated using the MDRD formula in patients not on dialysis.
The early (within 24 hours) use of antiplatelet therapies was lower in patients with hemoglobin 10 to 12 g/dl and hemoglobin <10 g/dl than in those with hemoglobin >12 g/dl. Although the overall use of anticoagulant therapies was also lower in patients with lower hemoglobin levels, bivalirudin was used more frequently in patients with hemoglobin <10 g/dl. In addition, the use of evidence-based therapies was lower in patients with hemoglobin <10 g/dl and hemoglobin 10 to 12 g/dl ( Table 2 ).
| Medication Within 24 h | Hemoglobin (g/dl) | ||
|---|---|---|---|
| <10 ∗ (n = 2,417) | 10–12 ∗ (n = 9,940) | >12 ∗ (n = 60,710) | |
| Aspirin | 95.4% | 96.6% | 97.9% |
| Clopidogrel | 51.8% | 60.5% | 65.3% |
| β blockers | 87.9% | 90.7% | 92.4% |
| Statins | 56.8% | 60.7% | 62.7% |
| Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers | 42.5% | 52.5% | 50.1% |
| Any anticoagulant | 89.5% | 93.6% | 94.7% |
| Bivalirudin | 19.4% | 17.8% | 17.5% |
| Glycoprotein IIb/IIIa inhibitors | 22.3% | 34.4% | 48.8% |
∗ The groups with hemoglobin <10 and 10 to 12 g/dl were each compared with the reference group (hemoglobin >12 g/dl). The p values for all comparisons were <0.0001, except for the comparison of bivalirudin use in patients with hemoglobin 10 to 12 and >12 g/dl (p = 0.375).
Patients with hemoglobin <10 and 10 to 12 g/dl had longer delays to catheterization than patients with hemoglobin >12 g/dl ( Table 3 ). Furthermore, patients with hemoglobin <10 and 10 to 12 g/dl were more frequently transfused than patients with hemoglobin >12 g/dl ( Figure 2 ). In fact, patients with hemoglobin <10 g/dl had an overall transfusion rate that was 6.5-fold higher compared with patients with hemoglobin >12 g/dl (64.2% vs 9.9%, p <0.0001). When requiring transfusion, patients with hemoglobin <10 g/dl were more frequently transfused before than after the time of cardiac catheterization, whereas patients with hemoglobin 10 to 12 g/dl and those with hemoglobin >12 g/dl who were transfused were often transfused after cardiac catheterization (overall rates of transfusion before catheterization for hemoglobin <10, 10 to 12, and >12 g/dl were 32.1%, 3.2%, and 0.3%, respectively, p <0.0001).
| Variable | Hemoglobin (g/dl) | ||
|---|---|---|---|
| <10 ∗ (n = 2,417) | 10–12 ∗ (n = 9,940) | >12 ∗ (n = 60,710) | |
| Time from hospital presentation until catheterization (h) | 43.2 (18.2–88.1) | 27.8 (14.1–58.0) | 20.0 (7.9–37.7) |
| Number of coronary arteries narrowed ≥50% | |||
| 0 | 6.4% | 8.1% | 7.8% |
| 1 | 19.6% | 21.9% | 29.1% |
| 2 | 27.0% | 26.5% | 28.4% |
| 3 | 46.2% | 42.6% | 33.9% |
| Left main CAD | 20.1% | 16.7% | 9.8% |
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