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(Circulation. 2005;111:1217-1224.)
© 2005 American Heart Association, Inc.

Coronary Heart Disease

Influence of Race on Death and Ischemic Complications in Patients With Non–ST-Elevation Acute Coronary Syndromes Despite Modern, Protocol-Guided Treatment

Marc S. Sabatine, MD, MPH; Gavin J. Blake, MD, MPH; Mark H. Drazner, MD, MSc; David A. Morrow, MD, MPH; Benjamin M. Scirica, MD; Sabina A. Murphy, MPH; Carolyn H. McCabe, BS; William S. Weintraub, MD; C. Michael Gibson, MD, MS; Christopher P. Cannon, MD

From the TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass (M.S.S., D.A.M., B.M.S., S.A.M., C.H.M., C.M.G., C.P.C.); Department of Cardiology, Mater Misericordiae University Hospital, Dublin, Ireland (G.J.B.); University of Texas–Southwestern Medical Center, Dallas (M.H.D.); and Emory University, Atlanta, GA (W.S.W.).

Correspondence to Marc S. Sabatine, MD, MPH, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail msabatine{at}partners.org

Received October 1, 2004; revision received December 16, 2004; accepted December 27, 2004.

	Abstract

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Background— In the setting of acute coronary syndromes (ACS), nonwhite patients are less likely to undergo invasive cardiac procedures and may have worse clinical outcomes than white patients. Whether the disparate outcomes exist independently of potential biases in treatment patterns remains unclear.

Methods and Results— We examined the association between race and outcome in the Treat Angina with Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy–Thrombolysis in Myocardial Infarction 18 study (TACTICS-TIMI 18), a randomized trial of invasive versus conservative treatment strategy in patients with non–ST-elevation ACS. There were 1722 white and 461 nonwhite patients. After adjustment for differences in medical characteristics, nonwhite patients were at significantly increased risk for death, MI, or rehospitalization for ACS (hazard ratio [HR], 1.54; P=0.003). Rates of protocol-guided angiography and revascularization were similar in both groups. For non–protocol-guided care, however, we found significant disparities, with nonwhite patients less likely to be taking their cardiac medications at follow-up (odds ratio [OR], 0.59; P=0.0002), to undergo non–protocol-mandated angiography (OR, 0.40; P=0.03), to receive a stent if undergoing percutaneous coronary intervention (OR, 0.55; P=0.045), and to have less procedural success after percutaneous coronary intervention (acute gain, 1.40±0.83 versus 1.81±0.92 mm; P=0.004). Nonetheless, an invasive strategy was similarly efficacious in white (HR, 0.66; 95% CI, 0.50 to 0.88) and nonwhite (HR, 0.85; 95% CI, 0.52 to 1.39) patients (P_interaction=0.52), especially in those with troponin elevation or ST deviation.

Conclusions— After adjustment for baseline characteristics, nonwhite patients had a significantly worse prognosis than white patients, regardless of treatment approach. In the absence of protocol guidance, important disparities emerged between the care given the 2 groups. An early invasive strategy is beneficial in and should be considered for all patients, regardless of race.

Key Words: angiography • coronary disease • myocardial infarction • revascularization • stents

	Introduction

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The relationship between race and cardiovascular outcomes has been the focus of several studies that used administrative databases and registries. Nevertheless, it remains unclear whether race is independently associated with a worse prognosis after an acute coronary syndrome (ACS).^1–7 What has emerged from these analyses, however, is that nonwhite patients appear less likely to undergo invasive cardiac procedures.^5–11 Such variations in practice patterns could account for differences in outcomes and confound the association between race and outcome.

The Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS)–Thrombolysis in Myocardial Infarction (TIMI) 18 study is a recent randomized trial of an early invasive versus conservative strategy in the management of patients presenting with non–ST-elevation ACS (NSTEACS). TACTICS-TIMI 18 therefore offered an opportunity to examine the independent effects of race on cardiovascular outcomes in patients with NSTEACS receiving modern therapy in whom the use of invasive cardiac procedures was guided by a clinical trial protocol.

	Methods

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Patient Population
The study design and main results of TACTICS-TIMI 18 have been reported.¹² In brief, TACTICS-TIMI 18 enrolled 2220 patients with NSTEACS. Eighty-three percent of patients were enrolled in the United States. Patients were required to have ischemic discomfort within the prior 24 hours accompanied by objective evidence of ischemic heart disease. The latter consisted of ECG changes, elevated cardiac biomarkers of necrosis, or a documented history of coronary artery disease (CAD). Patients were randomized to either an early invasive or a conservative strategy, and there was no significant difference in the proportion assigned to the invasive strategy between whites and nonwhites (50% versus 53%; P=0.16). In the invasive arm, patients underwent angiography within 4 to 48 hours. In the conservative arm, patients were treated medically and underwent an exercise-tolerance test before being discharged. Patients who experienced spontaneous or significant, protocol-defined stress test–induced ischemia were considered to have failed medical therapy and were to undergo angiography. The decision for coronary revascularization was made at the discretion of the treating physician. Per protocol, all patients were to receive aspirin, unfractionated heparin, and upstream glycoprotein IIb/IIIa inhibition with tirofiban. Use of other medications was at the discretion of the treating physician. The relevant institutional review boards approved the protocol, and all patients provided written informed consent.

Clinical Data
Baseline data on demographics, cardiac risk factors, prior cardiovascular disease, medications, and ST deviation on the presenting ECG were prospectively gathered in the trial. Race was self-reported; the racial composition was as follows: 1722 white patients (77.6%), 257 black patients (11.6%), 204 Hispanic patients (9.2%), 14 Asian patients (0.6%), and 23 patients coded as "other" (1.0%). Given these proportions, black and Hispanic patients were grouped together as "nonwhite," and Asian and other patients were excluded. Cardiac biomarkers, including troponin T (Roche Diagnostics), C-reactive protein (CRP, Dade-Behring), and B-type natriuretic peptide (BNP, Biosite), were measured by the TIMI Biomarker Core Laboratory in 1846 patients. On the basis of prior work, we used clinical cut points of 0.01 ng/mL for troponin T, 15 mg/L for CRP, and 80 pg/mL for BNP.¹³

Local investigators recorded the extent and severity of CAD in all patients undergoing angiography. Patients who underwent angiography were eligible for enrollment in the angiographic substudy, for which angiographic data were sent to the TIMI Angiographic Core Laboratory for analysis (n=356). TIMI flow grade and TIMI myocardial perfusion grade were assessed as previously defined.¹⁴

Patients were followed up for the prespecified composite primary end point of death, myocardial infarction (MI), or rehospitalization for ACS through 6 months. Follow-up was complete in 99% of patients.

Statistical Analyses
Continuous variables were confirmed to be normally distributed and compared by use of t tests. Categorical variables were compared by use of ² tests. Unadjusted cumulative end-point incidence curves were plotted by inverting survival data from the Kaplan-Meier method and compared through the use of the log-rank test. To determine the independent effect of race on time to the composite end point, a multivariable Cox proportional-hazards model was constructed. A comprehensive search for potential confounders was conducted. Specifically, candidate variables for which we had data in >80% of subjects that either demonstrated an association with both race and outcome (at a significance threshold of P<0.25 for both) or were of known clinical importance were included in the final model.¹⁵ This approach yielded the following covariates that were included in the final model: age, gender, university hospital setting, hypertension, hypercholesterolemia, diabetes, smoking, prior MI, congestive heart failure, percutaneous coronary intervention (PCI), and CABG, prior ACE inhibitor and statin use, ST deviation, troponin elevation, CRP elevation, BNP elevation, and randomized treatment strategy. To test the validity of the proportional-hazards assumption in the Cox model, we created time-varying covariates for each covariate in the final model. For covariates that failed to meet the proportional-hazards assumption, separate baseline hazard functions were allowed in the Cox regression modeling using stratification.

Additional analyses were performed using variants of this main model. For patients assigned to the invasive arm in whom angiography was performed, treatment strategy was removed from the model, and extent of CAD and left ventricular ejection fraction were added. To explore the effect of cardiac medication discontinuation on the hazard associated with nonwhite race, regression analyses were performed in patients free of events through 30 days who were then stratified on the basis of whether any cardiac medications taken during the index hospitalization were discontinued by day 30. Multivariable logistic regression models were used to determine the independent effect of race on the likelihood of several categorical events, including discontinuation of cardiac medications by 30 days, non–protocol-mandated angiography in the conservative arm, and receipt of a stent if undergoing PCI. The same covariates as in the main Cox proportional-hazards models were used unless noted differently in the text.

	Results

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Baseline Characteristics
The baseline characteristics of the 1722 white patients and 461 nonwhite patients are shown in Table 1. Compared with white patients, nonwhite patients were younger, more likely to be female, and more likely to be enrolled at a university hospital (P<0.002 for each). Nonwhite patients were more likely to have hypertension (P<0.0001), diabetes (P=0.0006), and serum creatinine >1.5 mg/dL (P=0.04) but were less likely to have a history of tobacco use (P=0.04) or hypercholesterolemia (P<0.0001). Prior cardiac disease and procedures were similar except for a history of CABG, which was nearly twice as common in whites (P<0.0001). Baseline cardiac medications were similar in the 2 groups except for a trend toward higher use of ACE inhibitors (P=0.07) and lower use of statins (P=0.01) in nonwhite patients; however, when the analysis was restricted to patients with a history of hypercholesterolemia, use of statins was similar in whites and nonwhites (39% versus 36%; P=NS). ST deviation on the presenting ECG was seen more frequently in whites than in nonwhites (P=0.0002). There were trends toward greater proportions of white patients having an elevated troponin (P=0.11) and BNP (P=0.12). In contrast, CRP was elevated (15 mg/L) more frequently in nonwhite patients (P=0.0004). After adjustment for age, gender, weight, smoking, hypercholesterolemia, diabetes, renal dysfunction (serum creatinine >1.5 mg/dL), prior aspirin and statin use, and baseline troponin, nonwhite race remained significantly associated with an elevated CRP on presentation (adjusted odds ratio [OR], 1.50; P=0.004).

View this table: [in this window] [in a new window]   TABLE 1. Baseline Characteristics

Clinical Outcomes
Overall, 387 patients (17.7%) experienced the composite end point of death, MI, or repeated hospitalization for ACS by 180 days. Figure 1 shows the unadjusted cumulative end-point incidence curves for white versus nonwhite patients. This difference did not reach statistical significance (P=0.20). Given the significant differences in important baseline characteristics that were associated with the composite end point, a multivariable adjusted Cox proportional-hazards model was constructed to minimize confounding. After adjustment for age, sex, type of hospital, cardiac risk factors, prior cardiac history, baseline cardiac medications, presenting ST deviation, and cardiac biomarker levels, nonwhite race was associated with a highly statistically significant increased risk of the composite end point (adjusted hazard ratio [HR], 1.54; 95% CI, 1.16 to 2.05; P=0.003).

View larger version (15K): [in this window] [in a new window]   Figure 1. Cumulative incidence of primary end point of death, MI, or rehospitalization for ACS in white (solid line) and nonwhite (dashed line) patients.

To explore the robustness of our findings, we performed several additional exploratory analyses. Excess risk was directionally consistent across all components of the composite end point (Figure 2), including death (adjusted HR, 2.32; 95% CI, 1.19 to 4.53), MI (adjusted HR, 1.56; 95% CI, 0.92 to 2.62), and repeated hospitalization for ACS (adjusted HR, 1.34; 95% CI, 0.96 to 1.88). Excess risk of the composite end point was also apparent both during the index admission (adjusted HR, 1.99; 95% CI, 1.14 to 3.48) and after hospital discharge (adjusted HR, 1.43; 95% CI, 1.02 to 1.99). In terms of individual racial categories (Figure 3), compared with whites, excess risk was seen in both blacks (adjusted HR, 1.39; 95% CI, 0.95 to 2.03) and Hispanics (adjusted HR, 1.70; 95% CI, 1.18 to 2.44). In terms of gender, excess risk for nonwhites was seen in both men (adjusted HR, 1.64; 95% CI, 1.13 to 2.36) and women (adjusted HR, 1.41; 95% CI, 0.89 to 2.24). Of particular note, nonwhite patients were at increased risk of death and ischemic complications regardless of whether they were assigned to the conservative strategy (adjusted HR, 1.41; 95% CI, 0.94 to 2.11) or the early invasive strategy (adjusted HR, 1.88; 95% CI, 1.23 to 2.85). The point estimate for the excess risk of the composite end point in nonwhite patients was nearly twice as high among patients treated at a community hospital (adjusted HR, 2.31; 95% CI, 1.34 to 3.99) as among patients treated at a university hospital (adjusted HR, 1.38; 95% CI, 0.98 to 1.93), although the formal interaction term did not reach statistical significance (P=0.14).

View larger version (18K): [in this window] [in a new window]   Figure 2. Plot of adjusted HRs and 95% CIs for composite end point; for individual components of end point, including death, MI, and rehospitalization (rehosp) for ACS; and for end point during index hospitalization and after hospital discharge.

View larger version (24K): [in this window] [in a new window]   Figure 3. Plot of adjusted HRs and 95% CIs for composite end point in all nonwhite vs white patients, in black (n=257) vs white patients, in Hispanic (n=204) vs white patients, and in all nonwhite vs white patients in subgroups stratified by gender (for men, n=1432; for women, n=751), randomized treatment strategy (for conservative arm, n=1081; for invasive arm, n=1102), and hospital setting (for university, n=1592; for community, n=591).

Cardiac Medications
Rates of cardiac medication use during the index hospitalization and at the end of the study are shown in Figure 4. Aspirin use was mandated in the protocol, and 98% of patients received it during their initial hospitalization, with no difference between rates in whites and nonwhites. At both 30 days and 6 months, though, aspirin use was significantly lower in nonwhites than in whites (at 6 months, 70% versus 79%; P<0.001). Other cardiac medications were prescribed at the discretion of the treating physician. During the index hospitalization, ß-blocker use was slightly higher in nonwhites than in whites (85% versus 81%; P=0.053), but by 6 months, the relationship had reversed (50% versus 59%; P<0.001). ACE inhibitors or angiotensin receptor blockers were also used more frequently in nonwhites than in whites during the index hospitalization (50% versus 38%; P<0.001), but this gap narrowed by 6 months (37% versus 33%; P=0.051). Statin use was significantly less in nonwhites than in whites during the index hospitalization (46% versus 53%; P=0.022); this difference widened after 6 months (43% versus 56%; P<0.001). Restricting the analyses to patients with a history of hypercholesterolemia revealed identical rates of statin use in nonwhites and whites during the index hospitalization (71%) but a lower rate of use in nonwhites by 6 months (61% versus 68%; P=0.033). After adjustment for baseline characteristics, nonwhites were significantly less likely to still be on all their cardiac medications by 30 days (adjusted OR, 0.59; P=0.0002).

View larger version (22K): [in this window] [in a new window]   Figure 4. Cardiac medications taken during index hospitalization (Hosp), at discharge (D/C), at 30 days, and at end of study in white patients () and nonwhite patients (). For statin use, dashed lines indicate use in patients with history of hypercholesterolemia. Statistical significance for comparison between whites and nonwhites at specific time point is indicated by presence of 1 (P<0.05), 2 (P<0.01), or 3 (P<0.001) asterisks.

To explore the effect of discontinuation of cardiac medications on outcomes and its interaction with race, we examined the composite event rate from 30 to 180 days in patients free of events at 30 days. We stratified these analyses by whether a patient had discontinued any cardiac medication between hospital discharge and the day 30 visit and adjusted using our previously constructed Cox proportional-hazards model. We found that the excess risk of the composite end point in nonwhite patients was apparent among both patients who had discontinued any cardiac medications (adjusted HR, 1.52; 95% CI, 0.72 to 3.21) and those who had not (adjusted HR, 1.36; 95% CI, 0.82 to 2.25).

Conservative Strategy
The rates of angiography in the conservative arm were significantly higher in white patients than in nonwhite patients (55% versus 43%; P=0.0015), but this was almost entirely explained by a significantly higher rate of protocol-defined failure of medical therapy resulting from spontaneous or stress test–induced recurrent ischemia in white than in nonwhite patients (46% versus 35%; P=0.0041; Figure 5). In fact, the rates of protocol-mandated angiography in patients who failed medical therapy were equal in whites and nonwhites (96% in both; P=0.84), as were the rates of subsequent revascularization in patients undergoing angiography (74% versus 75%; P=0.84). Among patients who did not fail medical therapy, a lower proportion of nonwhite patients were taken to angiography than were white patients (10% versus 17%; P=0.039). After adjustment for baseline characteristics, this difference remained significant (adjusted OR, 0.40; 95% CI, 0.17 to 0.93; P=0.03); however, the number of patients proceeding to angiography in this manner was <10% of the entire conservative arm.

View larger version (14K): [in this window] [in a new window]   Figure 5. Rate of failure of medical therapy in conservative arm in white vs nonwhite patients stratified by spontaneous ischemia (closed segment of bar graph) and stress test–induced ischemia (open segment of bar graph).

Invasive Strategy
Among patients assigned to the early invasive strategy, 98% of both white and nonwhite patients had protocol-mandated angiography. The extent of CAD was more extensive in white patients than in nonwhite patients (P=0.0001; Figure 6). Left ventricular ejection fractions were not statistically significantly different between whites and nonwhites (0.53 versus 0.55; P=0.12). Incorporation of angiographic variables, including extent of CAD and left ventricular ejection fraction, made the excess hazard seen in nonwhites more pronounced (adjusted HR, 2.13; 95% CI, 1.28 to 3.56; P=0.004).

View larger version (25K): [in this window] [in a new window]   Figure 6. Extent of CAD categorized as 3-vessel or left main (3VD/LM), 2-vessel (2VD), single-vessel (1VD), or no significant (0VD) (70% stenosis) disease in patients randomized to invasive arm in white vs nonwhite patients.

The overall rate of revascularization in the invasive arm was higher in white than nonwhite patients (64% versus 53%; P=0.0018), but restricting the analyses to patients with at least 1 coronary artery stenosis 70% resulted in the difference no longer being statistically significant (76% versus 71%; P=0.20). Among patients undergoing revascularization, the proportion undergoing CABG was 32% in both white and nonwhite patients.

In patients undergoing PCI, nonwhites were significantly less likely to receive a stent (OR, 0.50; 95% CI, 0.28 to 0.89; P=0.018). This association remained significant after adjustment for sex, diabetes, university hospital setting, and number of vessels with significant stenoses (adjusted OR, 0.55; 95% CI, 0.30 to 0.99; P=0.045). This association also remained apparent after further adjustment for culprit vessel proximal normal reference segment diameter (adjusted OR, 0.51; 95% CI, 0.25 to 1.06) in the subgroup of patients in the angiographic substudy. Overall, in the invasive arm, after further adjustment for the type of revascularization (balloon angioplasty, stenting, or CABG), nonwhite patients were still at a significantly increased risk of death and ischemic complications (adjusted HR, 2.10; 95% CI, 1.25 to 3.52; P=0.005).

For patients in the angiographic substudy (n=356), pre-PCI and post-PCI variables are listed in Table 2. Before PCI, the culprit vessel proximal normal reference segment diameters were nearly identical in white and nonwhite patients, but there were trends toward white patients having more severe stenoses (70±18% versus 66±17%; P=0.052) and smaller minimum lumen diameters (0.98±0.57 versus 1.10±0.58 mm; P=0.10). After PCI, however, these trends were reversed, with nonwhite patients having significantly greater residual stenoses (20±22% versus 13±19%; P=0.018), smaller minimum lumen diameters (2.48±0.85 versus 2.76±0.85 mm; P=0.03), and less acute gain (1.40±0.83 versus 1.81±0.92 mm; P=0.004). This finding remained significant after the analyses were restricted to patients who received a stent (1.51±0.87 versus 1.95±0.87 mm; P=0.005).

View this table: [in this window] [in a new window]   TABLE 2. Angiographic Measurements

Benefit of an Early Invasive Strategy
Overall, in the study population, after adjustment for baseline characteristics, an invasive strategy was associated with a significant reduction in the odds of the composite end point (adjusted HR, 0.77; 95% CI, 0.55 to 0.89). An invasive strategy was similarly efficacious in white (adjusted HR, 0.66; 95% CI, 0.50 to 0.88) and nonwhite (adjusted HR, 0.85; 95% CI, 0.52 to 1.39) patients, (P_interaction=0.52). Restricting the analyses to patients with an elevated troponin (troponin T >0.01 ng/mL) demonstrated a significant and nearly identical benefit with an invasive strategy in white (adjusted HR, 0.45; 95% CI, 0.31 to 0.66; P<0.001) and nonwhite (adjusted HR, 0.48; 95% CI, 0.23 to 1.00; P=0.05) patients. Similar results were obtained when the analyses were restricted to patients with ST deviation (white patients: adjusted HR, 0.47; 95% CI, 0.30 to 0.73; P<0.001; nonwhite patients: adjusted HR, 0.42; 95% CI, 0.18 to 0.95; P=0.038).

	Discussion

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Despite participation in a modern clinical trial in NSTEACS, with all patients receiving early glycoprotein IIb/IIIa inhibition in addition to aspirin and heparin, nonwhite patients were at a significantly increased risk of death and ischemic complications. This hazard was seen both in those assigned to a conservative strategy and in those assigned to an invasive strategy. In terms of possible reasons, we did not find evidence for differences in the rate of angiography or revascularization after adjusting for indications for angiography and extent of CAD, respectively. We did, however, observe several important differences in non–protocol-guided therapies, including lower use of cardiac medications, lower likelihood of cardiac catheterization in the absence of clear-cut ischemia, less frequent use of stenting, and less procedural success with percutaneous coronary revascularization in nonwhite patients. Nevertheless, after adjustment for these differences, nonwhite patients still remained at significantly increased risk for death and ischemic complications. Importantly, though, despite the excess hazard in nonwhites, the benefit of an invasive strategy was seen regardless of race.

Studies of the association between race and outcomes in patients presenting with ACS have yielded conflicting results, with some studies showing higher rates of adverse cardiovascular events in nonwhites,^1,2,7 and other showing equivalent or lower rates.^3–6,16 What has emerged from these studies, however, is the observation that nonwhite patients appeared less likely to undergo invasive cardiac procedures.^5–11 Whether these differences in practice patterns explained the disparity in clinical outcomes remained unclear.

To that end, our findings offer several important new insights. First, after comprehensive adjustment for important differences in baseline medical characteristics, we found clear evidence that nonwhite patients were at a significantly increased risk of death and ischemic complications. Our findings were robust with directional consistency for all the individual components of the composite end point, for the composite end point during the index hospitalization and after hospital discharge, among blacks and Hispanics, and in men and women. Many prior studies used retrospective data analysis from administrative databases or registries and were forced to rely on discharge summaries or International Classification of Diseases, ninth edition, coding. Thus, when such studies showed no excess hazard in nonwhites, they were not able to fully adjust for the important potential confounders that we identified and likely significantly underestimated the true hazard.

Second, the randomized nature of the treatment strategy in TACTICS-TIMI 18 allowed us to examine the influence of race on outcomes without confounding from biases in treatment patterns. In our study, we found that nonwhite patients remained at excess risk for death and ischemic complications regardless of whether they were assigned a protocol-guided conservative or invasive treatment strategy. In the conservative arm, we found a lower rate of angiography in nonwhite patients, as has been noted in observational cohorts; however, this was due entirely to a lower rate of protocol-delineated failure of medical therapy. In fact, nonwhite patients were just as likely as white patients to undergo angiography if they failed medical therapy. Similarly, in the invasive arm, although nonwhite patients were less likely to undergo revascularization, they also had less extensive CAD. Among patients with at least 1 significant coronary artery stenosis, the rates of revascularization were similar in whites and nonwhites. Thus, the lower rates of angiography and revascularization in nonwhite patients reported in other studies may be explained, at least in part, by the lower likelihood of recurrent ischemia and the lesser extent of CAD. It remains possible that, in the absence of guidelines for angiography, additional biases are a factor.

Third, we did find significant disparities in several important, non–protocol-mandated elements of cardiac care. Nonwhite patients were less likely to be taking aspirin, ß-blockers, and statins by the end of the study. This may have been due to financial constraints, less access to medical care, or less rapport between the patient and their healthcare providers, all of which could negatively affect the use of accepted therapies and hence outcomes.^17,18 Still, the excess hazard for the composite end point in nonwhites was apparent even in patients who did not discontinue any cardiac medications, suggesting that it was not the sole cause of the discrepancy. We also found that nonwhite patients were less likely to be referred for coronary angiography in the absence of clear-cut ischemia, were less likely to receive a stent when undergoing percutaneous coronary revascularization, and had less successful procedural outcomes. These differences could reflect physician racial biases, care by physicians with fewer resources or less cardiovascular experience, or some combination.^19,20 Regardless, after adjustment for differences in rates and types of revascularization, nonwhite patients still had a worse prognosis.

Fourth, the randomized assignment to invasive and conservative treatment strategies allowed us to examine the efficacy of treatment without bias by indication (ie, selective referral for angiography on the basis of race and/or severity of illness). We found that an early invasive strategy was similarly beneficial regardless of race. Moreover, among patients with troponin elevation or ST deviation, the degree of benefit associated with an invasive strategy was large and nearly identical in white and nonwhite patients. These findings highlight that an early invasive strategy should be considered in all patients with clear evidence of NSTEACS, regardless of race.

As has been noted previously, "Race is a social construct, not a scientific classification."²¹ Still, because race is strongly correlated with socioeconomic status and because socioeconomic status influences the availability and delivery of health care, it is not surprising that race is associated with outcomes in medical care.²² Beyond the important issues of access to health care, cultural background and differences between patients and healthcare providers can affect the delivery of medical care. Specifically, patient expectations, physician recommendations, and patient acceptance of those recommendations may depend on race.^20,23,24 In addition, as a social construct, race reflects, albeit imperfectly, the geographic region of origin of a person’s ancestry.²⁵ Thus, race also serves as an imprecise proxy for genetic heritage. To that end, recent genetic studies have demonstrated not only potential associations between certain alleles and adverse cardiovascular outcomes but also clear differences in the distribution of these alleles in patients stratified by self-described race.^26,27 Thus, the association between race and outcomes that we observed is likely multifactorial, reflecting socioeconomic differences, physician and patient biases, and possibly genetic variation.

Our study has several potential limitations. Race was self-reported and coded as mutually exclusive categories. More recent guidelines recognize that individuals may consider themselves part of multiple races and differentiate race from ethnicity.²⁸ Blacks and Hispanics were pooled to maintain appropriately sized racial groups for multivariable modeling. Although we found similar excess hazards for death and ischemic events in blacks and Hispanics, important differences between these groups may exist and should be explored in larger studies. Although we did not find a statistically significant interaction between race and the benefit of an early invasive treatment strategy, this study may have been underpowered to do so. Nonetheless, when analyses were restricted to patients with troponin elevation or ST deviation, the HRs for the benefit of an early invasive strategy in white and nonwhite patients were virtually identical. The nonwhite patients enrolled in this clinical trial may not be representative of nonwhite patients treated in the general community. Socioeconomic data and insurance type were unavailable for this analysis and may represent part of the reason why nonwhites had a worse prognosis. Our study was designed to investigate whether nonwhite patients had a worse prognosis after careful adjustment for baseline medical differences but was not designed to dissect out the multiple socioeconomic and cultural factors that undoubtedly are at play.

In conclusion, we found that in the setting of modern therapy and a protocol-guided invasive treatment strategy in patients with NSTEACS, nonwhite patients had a significantly worse prognosis than white patients. Protocol-guided therapy was delivered without evidence for bias, whereas important differences in non–protocol-guided cardiac care were apparent between the 2 groups. An early invasive strategy was highly efficacious regardless of race. Our findings highlight that continued efforts are necessary to guarantee the availability of adequate resources, access to well-trained healthcare professionals, and adherence to accepted guidelines for care to ensure that the best possible care is delivered to all patients, regardless of race.^29,30

	Acknowledgments

 
TACTICS-TIMI 18 was supported by Merck & Co.

	References

Top Abstract Introduction Methods Results Discussion References

 

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