Concern has been raised that Asian-Americans may have a higher bleeding risk than Caucasian-Americans when treated with fibrinolytic and antithrombotic agents. To date there is limited evidence to support or refute this hypothesis or evaluate bleeding risk and its related outcomes in Caucasian-Americans versus Asian-Americans with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions (PPCI). We evaluated Asian-Americans and Caucasian-Americans with STEMI receiving reperfusion therapy in the National Registry of Myocardial Infarction (NRMI) 4 and 5 (n = 90,317). We studied risk-adjusted major bleeding and in-hospital mortality. Major bleeding rates after fibrinolysis were similar in Asian-Americans (n = 705) and Caucasian-Americans (n = 42,243, 11.1% vs 10.3%, adjusted odds ratio [OR] 0.97, 95% confidence interval [CI] 0.69 to 1.36, p = 0.5002). Although the observed major bleeding rate was higher in Asian-Americans (n = 1,037) compared to Caucasian-Americans (n = 46,332) treated with PPCI (10.3% vs 7.8%, p = 0.0036), these rates differed only marginally after adjusting for baseline clinical variables (OR 1.24, 95% CI 0.97 to 1.59). Overall adjusted mortality was similar in Asian-Americans and Caucasian-Americans when treated with fibrinolysis (OR 0.96, 95% CI 0.56 to 1.65) or with PPCI (OR 1.35, 95% CI 0.85 to 2.13). Major bleeding after PPCI or fibrinolysis was associated with similar increased risks for mortality in these ethic groups. In conclusion, despite suggestions to the contrary, Asian-Americans with STEMI treated with fibrinolysis or PPCI had similar bleeding and bleeding-related mortality risks compared to Caucasian-Americans. Given the genotypic and phenotypic differences between the 2 cohorts, similar studies in the rapidly growing Asian-American population are needed to confirm our findings and to understand the safety and effectiveness of newer potent antiplatelet and antithrombotic agents in patients with coronary syndromes.
There has been a long-held belief that Asians are more susceptible to bleeding and stroke events when treated with antiplatelets, anticoagulants, or in particular fibrinolytic agents, often resulting in underuse of these agents. To date, however, evidence supporting this contention is limited. One study did find that Asians with non–ST-segment elevation acute coronary syndrome had slightly higher risks of bleeding compared to Caucasians. However, there are no published data on bleeding risks in Asians treated with fibrinolytic therapy or primary percutaneous coronary interventions (PPCI) for acute ST-segment elevation myocardial infarction (STEMI). The purpose of this analysis was to examine bleeding risks and associated in-hospital mortality in Asian-American compared to Caucasian-American patients with STEMI receiving reperfusion therapy in the National Registry of Myocardial Infarction (NRMI) 4 and 5.
Methods
We studied patients enrolled in the NRMI 4 and 5. The methods and patient populations of this United States–based registry have been previously published. Patients with acute STEMI and non-STEMI were enrolled in this registry. For this analysis we included patients with a principal discharge diagnosis code of 410X1 who had STEMI or presumed new left bundle branch block and were treated with fibrinolysis or PPCI and had MI symptom onset within 12 hours of their first hospital arrival. Patients were excluded if they were of racial descent other than Caucasian or Asian, had presenting cardiogenic shock, a do-not-resuscitate order active at time of presentation, received facilitated PCI, or were transferred out. Remaining patients with STEMI were stratified based on their primary reperfusion strategy and further based on race into 4 groups: Caucasian-Americans treated with fibrinolysis, Asian-Americans treated with fibrinolysis, Caucasian-Americans treated with PPCI, and Asian-Americans treated with PPCI.
Baseline demographics, medical history, medications, procedures, complications, and clinical events were collected prospectively on the case-report form in the NRMI. Investigators were required to check a single box on the case-report form indicating whether patients were Caucasian, African-American, Hispanic, Asian, American Indian, or other based on their perception of a patient’s race. Clinical end-point definitions (including that for major bleeding) were provided to all sites. Major bleeding was defined as that requiring any interventions (inotropes for pressure support, transfusions of red blood cells, or surgical intervention to stop bleeding) or with hemodynamic instability or hemorrhagic stroke.
We compared differences in clinical features, angiographic characteristics, and outcomes between Caucasian-Americans and Asian-Americans treated with fibrinolysis and PPCI. Univariable comparisons were made using Pearson chi-square or Fisher’s exact test (when cells had expected counts ≤5) for categorical variables. For continuous variables a normality test was performed within each group and, if the normality condition was not satisfied, then a nonparametric p value was calculated based on Wilcoxon rank-sum test. Otherwise, p values were given based on the type III sums of squares from a general linear model procedure.
Multivariable logistic regression analysis was performed to evaluate factors independently associated with risk of bleeding in patients with STEMI receiving any reperfusion therapy. In addition to other variables previously shown to be associated with risk of bleeding, race (Asian-American vs Caucasian-American) was entered into the model as a covariate and the race-by-treatment (fibrinolysis vs PPCI) interaction was examined.
The following baseline factors (in addition to race) were included in the model: age, gender, medical history (MI, smoking, diabetes, coronary artery bypass grafting [CABG], stroke, hyperlipidemia, and hypertension), hospital type, insurance status, findings on physical examination (Killip class, systolic and diastolic blood pressures, heart rate, height, weight, infarct location, and serum creatinine), and time to treatment. To adjust for center-level differences, the unique hospital identifier was also included in the model as a random effect. To exclude the impact of invasive procedure in fibrinolytic-treated patients (cardiac catheterization, PCI, or CABG), we reran the bleeding model excluding those who had these procedure(s).
Similarly, in-hospital mortality among different categories was compared after adjustment for baseline confounders using multivariate logistic regression analysis. The interaction of race and bleeding was also examined in this model. For all analyses a 2-tailed p value <0.05 was considered statistically significant. All analyses were performed using SAS, version 9.2 (SAS Institute, Cary, North Carolina).
Results
The number of patients receiving reperfusion in each racial category is presented in Table 1 . Despite a similar age as that for Caucasian-Americans treated with fibrinolysis, Asian-Americans treated with these drugs were more likely to be men and have a history of diabetes, hypertension, and renal failure but were less likely to have a history of chronic obstructive pulmonary disease, family history of coronary artery disease, previous MI, or previous revascularization. Presentation with heart failure, higher Killip class, anteroseptal MI, and creatine kinase values >2 times the upper limit of normal were more frequent in Asian-Americans. Presenting systolic and diastolic blood pressures were lower in Asian-Americans. Medical treatments at discharge were similar between the 2 groups. Differences in baseline characteristics for the 2 ethnic groups undergoing PPCI were similar to those seen for fibrinolysis with the exception of marginally lower uses of heparin in the hospital and thienopyridine agents at discharge and lower left ventricular ejection fraction in Asian-Americans ( Table 2 ).
| Characteristics | Rx With Fibrinolysis | Rx with PPCI | p Value | |||
|---|---|---|---|---|---|---|
| Caucasian-Americans (n = 42,243) | Asian-Americans (n = 705) | Caucasian-Americans (n = 46,332) | Asian-Americans (n = 1,037) | Asian-Americans vs Caucasian-Americans Rx With Fibrinolysis | Asian-Americans vs Caucasian-Americans Rx With PPCI | |
| Age (years) | 61 (52–71) | 60 (51–70) | 60 (52–71) | 60 (52–72) | 0.0838 | 0.5795 |
| Age >70 years | 11,292 (27%) | 175 (25%) | 12,185 (26%) | 277 (27%) | 0.2541 | 0.7583 |
| Women | 11,933 (28%) | 150 (21%) | 12,887 (28%) | 223 (22%) | <0.0001 | <0.0001 |
| Height (inches) | 68.2 (65.0–71.0) | 65.0 (63.0–67.0) | 69.0 (65.4–71.0) | 66.0 (63.0–68.0) | <0.0001 | <0.0001 |
| Weight (kg) | 84.0 (73.0–97.0) | 70.0 (62.0–81.0) | 84.1 (73.0–97.7) | 70.0 (61.0–80.0) | <0.0001 | <0.0001 |
| Body mass index (kg/m 2 ) | 28.0 (25.0–31.7) | 25.8 (23.1–28.8) | 28.0 (25.1–31.6) | 25.6 (23.1–28.2) | <0.0001 | <0.0001 |
| Body mass index ≥30 kg/m 2 | 13,535 (35%) | 111 (17%) | 15,056 (35%) | 144 (15%) | <0.0001 | <0.0001 |
| Hypertension | 20,919 (50%) | 402 (57%) | 23,427 (51%) | 539 (52.0%) | <0.0001 | 0.3679 |
| Diabetes mellitus | 7,480 (18%) | 178 (25%) | 7,962 (17%) | 261 (25%) | <0.0001 | <0.0001 |
| Current smoker | 18,930 (45%) | 228 (32%) | 19,836 (43%) | 229 (29%) | <0.0001 | <0.0001 |
| Hypercholesterolemia | 17,278 (41%) | 279 (40%) | 19,861 (43%) | 432 (42%) | 0.4772 | 0.4369 |
| Angina pectoris | 3,438 (8.1%) | 45 (6.4%) | 4,126 (8.9%) | 57 (5.5%) | 0.0904 | 0.0001 |
| Previous myocardial infarction | 7,010 (17%) | 95 (14%) | 7,694 (17%) | 119 (12%) | 0.0271 | <0.0001 |
| Previous stroke | 1,307 (3.1%) | 20 (2.8%) | 1,892 (4.1%) | 41 (4.0%) | 0.6956 | 0.8344 |
| Heart failure | 1,500 (3.6%) | 23 (3.3%) | 1,349 (2.9%) | 24 (2.3%) | 0.6813 | 0.2569 |
| Chronic obstructive pulmonary disease | 4,322 (10%) | 41 (5.8%) | 3,983 (8.6%) | 29 (2.8%) | 0.0001 | <0.0001 |
| Cerebrovascular disease | 913 (2.2%) | 10 (1.4%) | 1,185 (2.6%) | 20 (1.9%) | 0.1774 | 0.2033 |
| Percutaneous coronary interventions | 5,210 (12%) | 58 (8.2%) | 7,376 (16%) | 111 (11%) | 0.0010 | <0.0001 |
| Coronary artery bypass surgery | 2,942 (7.0%) | 23 (3.3%) | 2,960 (6.4%) | 35 (3.4%) | 0.0001 | <0.0001 |
| Renal failure | 991 (2.3%) | 36 (5.1%) | 1,007 (2.2%) | 30 (2.9%) | <0.0001 | 0.1174 |
| Presenting features | ||||||
| Killip class II or III | 3,255 (7.7%) | 73 (10.4%) | 2,924 (6.3%) | 109 (10.5%) | 0.0091 | <0.0001 |
| Heart rate (beats/min) | 74 (63–88) | 74 (64–87) | 75 (63–88) | 73 (61–86) | 0.7757 | 0.0954 |
| Systolic blood pressure (mm Hg) | 139 (119–160) | 132 (115–154) | 140 (120–160) | 131 (111–153) | 0.0003 | <0.0001 |
| Diastolic blood pressure (mm Hg) | 81 (69–94) | 78 (67–90) | 82 (70–95) | 79 (66–92) | 0.0005 | <0.0001 |
| Anterior myocardial infarction | 12,069 (29%) | 271 (38%) | 14,242 (31%) | 391 (38%) | <0.0001 | <0.0001 |
| Inferior myocardial infarction | 27,551 (65%) | 406 (58%) | 28,517 (62%) | 580 (56%) | <0.0001 | 0.0002 |
| Creatine kinase-MB ≥2 upper limit of normal | 31,759 (84%) | 534 (81%) | 30,573 (74%) | 661 (71%) | 0.0352 | 0.0571 |
| Initial creatinine (mg/dl) | 1.1 (0.9–1.4) | 1.0 (0.9–1.3) | 1.1 (0.9–1.4) | 1.1 (0.9–1.3) | 0.3617 | 0.3704 |
| Insurance ⁎ | ||||||
| Private | 28.435 (68%) | 444 (64%) | 32,241 (70%) | 609 (59%) | 0.0305 | <0.0001 |
| Medicare/Medicaid | 17,381 (41%) | 245 (35%) | 18,022 (39%) | 393 (38%) | 0.0011 | 0.4566 |
| Self-pay/no insurance | 4,400 (10%) | 106 (15%) | 4,464 (9.7%) | 140 (14%) | <0.0001 | <0.0001 |
| Hospital characteristics | ||||||
| Hospital type | ||||||
| Urban | 36,425 (88%) | 669 (96%) | 42,227 (95%) | 1,022 (100%) | <0.0001 | <0.0001 |
| Teaching | 6,588 (16%) | 178 (26%) | 6,793 (15%) | 257 (25%) | <0.0001 | <0.0001 |
| Onsite cardiac surgical capabilities | 36,275 (86%) | 573 (81%) | 42,919 (93%) | 966 (93%) | <0.0001 | 0.9191 |
| Annual ST-segment elevation myocardial infarction volume in highest quartile | 31,340 (74%) | 429 (61%) | 34,787 (75%) | 640 (62%) | <0.0001 | <0.0001 |
| Drug Therapies | Rx With Fibrinolysis | Rx With PPCI | p Value | |||
|---|---|---|---|---|---|---|
| Caucasian-Americans (n = 42,243) | Asian-Americans (n = 705) | Caucasian-Americans (n = 46,332) | Asian-Americans (n = 1,037) | Asian-Americans vs Caucasian-Americans Rx With Fibrinolysis | Asian-Americans vs Caucasian-Americans Rx With PPCI | |
| In-hospital medications <24 hours | ||||||
| Time to reperfusion from hospital arrival (hours) | 0.6 (0.4–0.9) | 0.7 (0.4–1.2) | 1.7 (1.3–2.4) | 1.7 (1.3–2.4) | 0.0028 | 0.7006 |
| Aspirin | 39,220 (93%) | 644 (91%) | 43,509 (94%) | 980 (95%) | 0.1270 | 0.4267 |
| β Blockers | 34,370 (81%) | 542 (77%) | 38,581 (83%) | 819 (79%) | 0.0025 | 0.0003 |
| Heparin—any | 33,735 (80%) | 534 (76%) | 35,753 (77%) | 780 (75%) | 0.0070 | 0.1393 |
| Calcium channel blockers | 2,062 (4.9%) | 27 (3.8%) | 3,022 (6.5%) | 69 (6.7%) | 0.1980 | 0.8655 |
| Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers | 16,296 (39%) | 268 (38%) | 21,691 (47%) | 436 (42%) | 0.7608 | 0.0023 |
| Glycoprotein IIb/IIIa antagonist | 13,842 (33%) | 184 (26%) | 35,437 (77%) | 780 (75%) | 0.0002 | 0.3412 |
| At discharge | ||||||
| Aspirin | 36,729 (92%) | 599 (90%) | 42,615 (95%) | 944 (95%) | 0.0736 | 0.7634 |
| β Blockers | 33,781 (84%) | 599 (84%) | 40,121 (89%) | 879 (88%) | 0.6809 | 0.4341 |
| Calcium channel blockers | 2,437 (6.1%) | 44 (6.6%) | 2,143 (4.8%) | 46 (4.6%) | 0.5864 | 0.8408 |
| Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers | 22,705 (57%) | 385 (58%) | 29,546 (66%) | 637 (64%) | 0.6070 | 0.2900 |
| Clopidogrel/other antiplatelet ⁎ | 4,832 (75%) | 61 (60%) | 13,860 (86%) | 323 (83%) | 0.0004 | 0.0231 |
| Antiarrhythmic | 2,084 (5.2%) | 23 (3.4%) | 1,781 (4.0%) | 49 (4.9%) | 0.0421 | 0.1220 |
| Procedures | ||||||
| Cardiac catheterization | 35,924 (85%) | 557 (79%) | 46,332 (100%) | 1,037 (100%) | <0.0001 | — |
| Angioplasty | 27,104 (64%) | 400 (57%) | 46,332 (100%) | 1,037 (100%) | <0.0001 | — |
| Coronary artery bypass surgery | 5,129 (12.1%) | 91 (12.9%) | 1,669 (3.6%) | 45 (4.3%) | 0.5370 | 0.2087 |
| Intra-aortic balloon pump | 2,533 (6.0%) | 48 (6.8%) | 3,653 (7.9%) | 89 (8.6%) | 0.3681 | 0.4098 |
| Left ventricular ejection fraction <40% | 7,176 (20%) | 88 (16%) | 7,942 (20%) | 157 (18%) | 0.0093 | 0.1778 |
⁎ Data available only in National Registry of Myocardial Infarction 5.
In patients receiving fibrinolysis almost all clinical adverse events were similar in Asian-Americans compared to Caucasian-Americans ( Table 3 ). Only cardiogenic shock was higher in Asian-Americans. In patients undergoing PPCI recurrent MI, cardiogenic shock, and heart failure were higher in Asian-Americans.
| Events | Rx With Fibrinolysis | Rx With PPCI | p Value | |||
|---|---|---|---|---|---|---|
| Caucasian-Americans (n = 42,243) | Asian-Americans (n = 705) | Caucasian-Americans (n = 46,332) | Asian-Americans (n = 1,037) | Asian-Americans vs Caucasian-Americans Rx With Fibrinolysis | Asian-Americans vs Caucasian-Americans Rx With PPCI | |
| Recurrent angina/ischemia | 5,535 (13%) | 89 (13%) | 2,641 (5.7%) | 66 (6.4%) | 0.7087 | 0.3620 |
| Recurrent myocardial infarction | 977 (2.3%) | 16 (2.3%) | 509 (1.1%) | 22 (2.1%) | 0.9395 | 0.0020 |
| Congestive heart failure | 4,215 (10%) | 76 (11%) | 3,813 (8.2%) | 121 (12%) | 0.4812 | <0.0001 |
| Cardiogenic shock | 2,049 (4.9%) | 48 (6.8%) | 2,643 (5.7%) | 85 (8.2%) | 0.0167 | 0.0007 |
| Bleeding needing intervention | 4,345 (10%) | 78 (11%) | 3,637 (7.8%) | 107 (10%) | 0.5002 | 0.0036 |
| Bleeding needing intervention in patients receiving glycoprotein IIb/IIIa inhibitors | 1,330 (9.6%) | 24 (13%) | 2,743 (7.7%) | 82 (11%) | 0.1170 | 0.0043 |
| Bleeding needing intervention in patients not receiving glycoprotein IIb/IIIa inhibitors | 3,015 (11%) | 54 (10%) | 894 (8.2%) | 25 (9.7%) | 0.8357 | 0.3805 |
| Noncatheterization, noncoronary artery bypass surgery bleeding | 454 (7.7%) | 7 (5.1%) | — | — | 0.2569 | — |
| Transfusions ⁎ | 3,557 (82%) | 68 (87%) | 2,946 (81%) | 89 (83%) | 0.2263 | 0.5711 |
| Any stroke | 652 (1.6%) | 10 (1.4%) | 231 (0.5%) | 4 (0.4%) | 0.7865 | 0.6089 |
| Hemorrhagic stroke (%) | 373 (0.9%) | 3 (0.4%) | 27 (0.1%) | 1 (0.1%) | 0.1960 | 0.6171 |
| New-onset atrial fibrillation | 2,722 (6.4%) | 36 (5.1%) | 2,488 (5.4%) | 64 (6.2%) | 0.1509 | 0.2581 |
| Sustained ventricular tachycardia/fibrillation | 3,735 (8.8%) | 50 (7.1%) | 4,708 (10.2%) | 93 (9.0%) | 0.1041 | 0.2079 |
| Second-/third-degree atrioventricular block | 1,555 (3.7%) | 21 (3.0%) | 1,849 (4.0%) | 49 (4.7%) | 0.3253 | 0.2330 |
| Cardiac arrest/rupture | 2,185 (5.2%) | 33 (4.7%) | 2,178 (4.7%) | 56 (5.4%) | 0.5586 | 0.2934 |
| Death | 2,096 (5.0%) | 36 (5.1%) | 1,358 (2.9%) | 43 (4.1%) | 0.8608 | 0.0223 |
| Death in patients without bleeding | 1,459 (3.9%) | 25 (4.0%) | 943 (2.2%) | 26 (2.8%) | 0.8741 | 0.2302 |
| Death in patients with bleeding | 637 (13.8%) | 11 (13.8%) | 415 (11.4%) | 17 (15.9%) | 0.9843 | 0.1478 |
| Death or recurrent myocardial infarction | 2,902 (6.9%) | 49 (7.0%) | 1,785 (3.9%) | 58 (5.6%) | 0.9332 | 0.0042 |
| Length of stay (days) | 4.0 (2.9–6.0) | 4.5 (3.2–6.9) | 3.1 (2.4–4.4) | 3.3 (2.6–4.9) | <0.0001 | 0.0005 |
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