Preventing Stroke Among Blacks: Title and subTitle BreakThe Challenges Continue

Stroke continues to have a disproportionate public health impact on blacks compared with whites in the United States. Excess mortality from stroke has been reported among blacks and remained significant despite recent declines in stroke mortality.¹ Data from national samples, the Greater Cincinnati Stroke Study, the Baltimore Washington Cooperative Study, and the Northern Manhattan Study have consistently demonstrated 2-fold to 3-fold greater stroke incidence rates for blacks than whites in the same communities.^{2 - 4} Blacks not only have stroke more frequently but also have a greater risk of stroke due to small-vessel disease leading to ischemic lacunar infarction and intracerebral hemorrhage, as well as ischemic infarction from large-artery intracranial atherosclerosis.^{5 - 6} The aging and continuing growth of the black population will undoubtedly lead to future increases in the number of blacks with stroke. This major public health concern has led to a number of challenges to stroke research and health care.

The classification of race and ethnicity often leads to spirited debate; however, despite this controversy, the public health implications of racial and ethnic health disparities need to be confronted. The reasons for the racial/ethnic disparities in stroke are not entirely clear and represent an important challenge to ongoing stroke epidemiological research. Potential explanations include variations in risk factor potency, prevalence, and treatment arising from socioeconomic, environmental, and genetic factors. Prior epidemiological studies have not enrolled sufficient numbers of underrepresented minority groups to address these issues adequately, which represents a further research challenge to the study of stroke in this high-risk group. The lack of understanding of variations in risk factors and associated mechanisms that lead to disparities in stroke incidence, mortality, and morbidity among various racial, cultural, and sex population subgroups are major gaps in current knowledge. Some of these deficiencies have been noted by the Stroke Progress Review Group of the National Institute of Neurological Disorders and Stroke⁷ and are the ongoing priorities of future stroke research.

The vigorous efforts of the National Institutes of Health (NIH) to ensure the adequate enrollment of black patients in stroke studies are starting to pay off. The ability of stroke epidemiological studies to address risk factors and treatments among blacks is finally becoming a reality. Black populations have been found to have a greater prevalence of stroke risk factors, such as hypertension and diabetes, and the proportion of strokes attributed to these conditions among blacks is greater than among white populations.^{8 - 9} Community characteristics including indices of poverty and community stability independently contribute to elevations in stroke risk.¹⁰ Ongoing prospective cohort studies such as the Multi-ethnic Study of Atherosclerosis, the Jackson Heart Study, and the Northern Manhattan Study should provide new insights on conventional as well as novel risk factors for stroke among blacks.^{11 - 12}

In this issue of THE JOURNAL, Gorelick and colleagues¹³ report a clear example of a focused, hypothesis-driven, randomized treatment trial addressing an important problem among blacks with stroke. The investigators and patients involved with the African American Antiplatelet Stroke Prevention Study (AAASPS) are to be congratulated for accomplishing this important task. The extra effort of the coordinators to recruit minority patients, who are sometimes more difficult to enroll in studies, has established new standards. The authors identified barriers to enrollment of minority patients in clinical trials, such as mistrust of the health care system, socioeconomic disadvantages, inadequate awareness of the availability of clinical studies, and communication barriers.¹⁴ They described a "recruitment triangle" consisting of the patient, key family members and friends, and the primary care physician, all of whom need to be equally considered to enhance the entry of minority participants in trials. Their strategies included working with key black investigators in the trial, choosing centers that provided care to large numbers of black patients with stroke, and appealing to the black community through churches, social organizations, and community leaders to help support the trial. By virtue of these strategies and their persistence, the investigators recruited more blacks than any other stroke trial to date.

The AAASPS was designed to compare 1 antiplatelet agent, ticlopidine, to aspirin. Preliminary data led to the hypothesis that ticlopidine could provide a more effective means of reducing the burden of recurrent stroke in this high-risk population. This hypothesis was based on the increased risk of stroke and the lower risk of neutropenia with ticlopidine among black patients and the hint of increased efficacy in this subgroup from an earlier study.¹⁵ Rather than use this grade C evidence to recommend ticlopidine for stroke prevention among black patients, the investigators designed a trial to answer the question. The investigators hypothesized that aspirin would be inferior to ticlopidine in this high-risk group. Unexpectedly, no significant difference was noted between ticlopidine and aspirin in terms of prevention of recurrent stroke. The low likelihood of achieving any superiority of ticlopidine compared with aspirin led the trial's data and safety monitoring board to recommend early termination of the trial for futility, in what may have also been a precedent-setting move. Although decisions to terminate for futility are infrequent among NIH-sponsored trials, the combination of a clear lack of efficacy and potential concern for safety undoubtedly led to the decision.

The AAASPS has clinical implications for the prevention of recurrent stroke. It provides new data on an alternate antiplatelet agent that should no longer be recommended for prevention of recurrent stroke—certainly not in black patients. Although many clinicians had decreased their use of this antiplatelet agent because of the potential adverse effects, the authors note that this drug still captured third place in the prescription nonaspirin antiplatelet market. Current stroke prevention guidelines recommend aspirin, extended-release dipyridamole plus aspirin, and clopidogrel as acceptable agents for the prevention of recurrent stroke after transient ischemic attack and noncardioembolic stroke.^{16 - 17} However, the available data from trials involving these agents are insufficient to fully evaluate the efficacy of these agents among the high-risk black population. These antiplatelet agents are also more costly than aspirin. Among lower socioeconomic populations without prepaid prescription plans, the cost of any medication may be a barrier to adherence and compliance. The AAASPS provides supportive evidence for the use of aspirin, an inexpensive and widely available therapy, to reduce the risk of stroke recurrence among black patients. All stroke survivors should receive some form of antithrombotic therapy and clinicians need to consider cost when choosing the best medication, especially for certain high-risk groups.

Antithrombotic therapy is only one part of the current approach to stroke prevention. In recent years, great strides have been made in expanding the ability to prevent stroke through specific interventions for patients with hypertension, atrial fibrillation, elevated cholesterol levels, coronary artery disease, and carotid disease. Clinical trials have led to grade A evidence and level I recommendations in the approach to patients with high stroke risk.^{18 - 19} More effective preventive health strategies aimed at identification and control of vascular risk factors in stroke-prone patients could have a tremendous role in reducing the burden of stroke.

At present, control of stroke risk factors is still less than adequate, particularly in communities of lower socioeconomic status, who are less educated about the importance of these conditions and also have decreased access to health care for proper detection and management of these risk factors. In addition, data from the AAASPS cohort demonstrate the lack of awareness, treatment, and control of vascular risk factors among black stroke patients.²⁰ The number of blacks with uncontrolled hypertension, untreated diabetes, and elevated cholesterol levels as well as those who are stroke survivors and are not adequately protected from recurrent stroke is far too great. More innovative approaches are needed to translate the successes of clinical stroke research studies into the community. Effective stroke prevention continues to be elusive, and patients at highest risk present the biggest challenges.