Adrenergic Polymorphisms and Survival in African Americans With Heart Failure: Results From A-HeFT.

BACKGROUND: Polymorphisms in adrenergic signaling affect the molecular function of adrenergic receptors and related proteins. The ß1 adrenergic receptor (ADRB1) Arg389Gly, G-protein receptor kinase type 5 (GRK5) Gln41Leu, G-protein ß-3 subunit (GNB3) 825 C/T, and α2c deletion affect adrenergic tone, impact heart failure outcomes and differ in prevalence by ethnicity. Their combined effect within black cohorts remains unknown. METHODS AND RESULTS: We analyzed subjects from the African American Heart Failure Trial (A-HeFT) by assessing event-free survival, quality of life, and gene coinheritance. Significant coinheritance effects on survival included GRK5 Leu41 among subjects co-inheriting GNB3 825 C alleles (n = 166, 90.4% vs 69.0%, P < 0.001). By contrast, the impact of ADRB1 Arg389Arg genotype was magnified among subjects with GNB3 825 TT genotype (n = 181, 66.3% vs 85.7%, P = .002). The lack of the α2c deletion (ie, insertion) led to a greater impact of the ARG389Arg genotype (n = 289, 76.4% vs 86.1%, P = .007). CONCLUSIONS: Polymorphisms in adrenergic signaling affects outcomes in black subjects with heart failure. Coinheritance patterns in genetic variation may help determine heart failure survival.

Heart Failure With Recovered Ejection Fraction in African Americans: Results From the African-American Heart Failure Trial.

BACKGROUND: Recent studies have described the entity of heart failure with recovered ejection fraction (HFrecEF), but population-specific studies remain lacking. The aim of this study was to characterize patients enrolled in the African-American Heart Failure Trial (A-HeFT) who had significant improvement in their ejection fraction (EF) during the 1st 6 months of follow-up. METHODS AND RESULTS: Subjects with HFrecEF (improvement in EF from <35% to >40% in 6 months; n = 59) were compared with 259 subjects with heart failure and persistently reduced EF (HFrEF), defined as EF ≤40% at 6-month follow-up. The effects of improvement in EF on all-cause mortality and 1st and all hospitalizations were analyzed. Compared with HFrEF, subjects with HFrecEF had a nonsignificant trend toward lower mortality (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.02-1.15; P = .068), fewer 1st HF hospitalizations (HR 0.22, 95% CI 0.07-0.71; P = .011), fewer recurrent HF hospitalizations (HR 0.13, 95% CI 0.05-0.37; P <.001), similar 1st all-cause hospitalizations (HR 0.67, 95% CI 0.39-1.15; P = .150), and fewer recurrent all-cause hospitalizations (HR 0.41, 95% CI 0.24-0.68; P <.001). CONCLUSIONS: These data confirm that, as in other populations, a small subgroup of black patients receiving standard care improve their EF with favorable outcomes. Further studies are required to determine whether myocardial recovery is permanent and the best management strategies in such patients.

Development and Evaluation of Two Abbreviated Questionnaires for Mentoring and Research Self-Efficacy.

OBJECTIVES: To reduce respondent burden for future evaluations of the National Heart, Lung, and Blood Institute-supported Programs to Increase Diversity Among Individuals Engaged in Health-Related Research (PRIDE), a mentored-research education program, we sought to shorten the 33-item Ragins and McFarlin Mentor Role Instrument (RMMRI), measuring mentor-role appraisals, and the 69-item Clinical Research Appraisal Inventory (CRAI), measuring research self-efficacy. METHODS: Three nationally recruited, junior-faculty cohorts attended two, annual 2-3 week Summer Institutes (SI-1/SI-2: 2011/2012, 2012/2013, 2013/2014) at one of six PRIDE sites. Mentees completed the RMMRI two months after mentor assignment and the CRAI at baseline (pre-SI-1) and 6-month (mid-year) and 12-month (post-SI-2) follow-up. Publications data obtained from Scopus in October 2015 were verified with mentees' curriculum vitae. The RMMRI and CRAI were shortened using an iterative process of principal-components analysis. The shortened measures were examined in association with each other (multiple linear regression) and with increase in publications (repeated-measures analysis of covariance). RESULTS: PRIDE enrolled 152 mentees (70% women; 60% Black, 35% Hispanic/Latino). Cronbach's alphas for the new 9-item RMMRI, 19-item CRAI, and four CRAI-19 subscales were excellent. Controlling for baseline self-efficacy and cohort, RMMRI-9 scores were independently, positively associated with post-SI-2 scores on the CRAI-19 and three subscales (writing, study design/data analysis, and collaboration/grant preparation). Controlling for cohort, higher RMMRI-9 and post-SI-2 CRAI-19 scores were each associated with greater increase in publications. CONCLUSIONS: The RMMRI-9 and CRAI-19 retained the excellent psychometric properties of the longer measures. Findings support use of the shortened measures in future evaluations of PRIDE.

Mentored Training to Increase Diversity among Faculty in the Biomedical Sciences: The NHLBI Summer Institute Programs to Increase Diversity (SIPID) and the Programs to Increase Diversity among Individuals Engaged in Health-related Research (PRIDE).

OBJECTIVE: To report baseline characteristics of junior-level faculty participants in the Summer Institute Programs to Increase Diversity (SIPID) and the Programs to Increase Diversity among individuals engaged in Health-Related Research (PRIDE), which aim to facilitate participants' career development as independent investigators in heart, lung, blood, and sleep research. DESIGN AND SETTING: Junior faculty from groups underrepresented in the biomedical-research workforce attended two, 2-3 week, annual summer research-education programs at one of six sites. Programs provided didactic and/or laboratory courses, workshops to develop research, writing and career-development skills, as well as a mentoring component, with regular contact maintained via phone, email and webinar conferences. Between summer institutes, trainees participated in a short mid-year meeting and an annual scientific meeting. Participants were surveyed during and after SIPID/PRIDE to evaluate program components. PARTICIPANTS: Junior faculty from underrepresented populations across the United States and Puerto Rico participated in one of three SIPID (2007-2010) or six PRIDE programs (2011-2014). RESULTS: Of 204 SIPID/PRIDE participants, 68% were female; 67% African American and 27% Hispanic/Latino; at enrollment, 75% were assistant professors and 15% instructors, with most (96%) on non-tenure track. Fifty-eight percent had research doctorates (PhD, ScD) and 42% had medical (MD, DO) degrees. Mentees' feedback about the program indicated skills development (eg, manuscript and grant writing), access to networking, and mentoring were the most beneficial elements of SIPID and PRIDE programs. Grant awards shifted from primarily mentored research mechanisms to primarily independent investigator awards after training. CONCLUSIONS: Mentees reported their career development benefited from SIPID and PRIDE participation.

Heart failure in women.

Heart failure (HF) is increasing in incidence globally, and approximately half of all HF patients are women. When women and men with HF are compared, there are significant differences in disease etiology, expression, outcomes, and perhaps, response to therapy. Hypertension rather than coronary artery disease is a more important etiology of HF in women, and HF with preserved left ventricular ejection fraction (HFPEF) is more common in women. Regardless of its etiology, women have better survival and less sudden cardiac death, but poorer quality of life with equivalent degrees of left ventricular dysfunction. Animal studies of myocardial response to stressors resulting in heart failure corroborate sex differences in ventricular remodeling, cellular morphology, and function. Despite the fact that women make up nearly 50 % of HF patients, their inclusion in randomized clinical trials has remained at about 20 %, with no trials including women as a prespecified subgroup for statistical analysis. Thus, the evidence base for treatment of HF in women is not robustly supported by sex-specific data.

Effect of fixed-dose combined isosorbide dinitrate/hydralazine in elderly patients in the African-American heart failure trial.

BACKGROUND: Fixed-dose combined isosorbide dinitrate/hydralazine (FDC I/H) significantly improved outcomes in patients with advanced heart failure (HF) receiving background neurohormonal therapy in the African-American Heart Failure Trial (A-HeFT). In this analysis, we investigated treatment effects by age <65 or ≥65 years. METHODS AND RESULTS: Time-to-event curves were produced by the Kaplan-Meier method. Hazard ratios were calculated with the Cox proportional hazards model. Baseline characteristics showed that patients ≥65 years old had less hypertensive and more ischemic HF, better quality of life (QoL) scores, higher plasma B-type natriuretic peptide and creatinine levels, and received less background neurohormonal therapy. Kaplan-Meier curves showed that FDC I/H improved mortality and event-free survival in elderly patients. The hazard ratios for mortality, first heart failure hospitalization, and event-free survival (both unadjusted and adjusted for baseline differences), were similar quantitatively and in direction of effect in both age groups. CONCLUSIONS: In A-HeFT, FDC I/H improved outcomes in HF patients aged <65 or ≥65 years, despite significant baseline differences between these age groups. Patients aged ≥65 years, a group at greater mortality risk, had the greatest survival benefit from FDC I/H.

Best practice in substance misuse.

While substance misuse by adolescents in the UK has declined over the last decade, the UK continues to have some of the highest rates of alcohol and drug use in Europe. Many young people will try smoking and drinking alcohol during their adolescence and a significant minority will misuse alcohol and illicit drugs. This behaviour remains a significant cause for concern owing to its associated risks to the health and wellbeing of adolescents. Guidance is emerging regarding good practice in the assessment and management of adolescent substance misuse. Paediatricians may encounter substance-misusing adolescents in a variety of clinical settings and can play a valuable role in the screening, management and support of this group of young people.

Nitric oxide modulation as a therapeutic strategy in heart failure.

Nitric oxide (NO) is recognized as one of the most important cardiovascular signaling molecules, with multiple regulatory effects on myocardial and vascular tissue as well as on other tissues and organ systems. With the growth in understanding of the range and mechanisms of NO effects on the cardiovascular system, it is now possible to consider pharmaceutical interventions that directly target NO or key steps in NO effector pathways. This article reviews aspects of the cardiovascular effects of NO, abnormalities in NO regulation in heart failure, and clinical trials of drugs that target specific aspects of NO signaling pathways.

Atrial fibrillation and mortality in African American patients with heart failure: results from the African American Heart Failure Trial (A-HeFT).

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF) and portends a worsened prognosis. Because of the low enrollment of African American subjects (AAs) in randomized HF trials, there are little data on AF in AAs with HF. This post hoc analysis reviews characteristics and outcomes of AA patients with AF in A-HeFT. METHODS AND RESULTS: A total of 1,050 AA patients with New York Heart Association class III/IV systolic HF, well treated with neurohormonal blockade (87% ß-blockers, 93% angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker), were randomized to an added fixed-dose combination of isosorbide dinitrate/hydralazine (FDC I/H) or placebo. Atrial fibrillation was confirmed in 174 (16.6%) patients at baseline and in an additional 9 patients who developed AF during the study, for a final cohort of 183 (17.4%). Comparison of patients with AF versus no AF revealed the following: mean age 61 ± 12 versus 56 ± 13 years (P < .001), systolic blood pressure (BP) 124 ± 18 versus 127 ± 18 mm Hg (P = .044), diastolic BP 74 ± 11 versus 77 ± 10 mm Hg (P = .002), creatinine level 1.4 ± 0.5 versus 1.2 ± 0.5 mg/dL (P < .001), and brain natriuretic peptide 431 ± 443 versus 283 ± 396 pg/mL (P < .001). No significant difference was observed in ejection fraction, left ventricular end-diastolic diameter, or quality-of-life scores. However, AF increased the risk of mortality significantly among AA patients (P = .018), and the use of FDC I/H reduced the risk of mortality in patients with AF (HR 0.21, P = .002). CONCLUSION: African Americans with HF and AF (vs no AF) were older, had lower BP, and had higher creatinine and brain natriuretic peptide levels. Mortality and morbidity were worse when AF was present, and these data suggest that there may be an enhanced survival benefit with the use of FDC I/H in AA patients with HF and AF.

Endothelial nitric oxide synthase (NOS3) polymorphisms in African Americans with heart failure: results from the A-HeFT trial.

BACKGROUND: Genetic heterogeneity at the endothelial nitric oxide synthase (NOS3) locus influences heart failure outcomes. The prevalence of NOS3 variants differs in black and white cohorts, but the impact of these differences is unknown. METHODS AND RESULTS: Subjects (n = 352) in the Genetic Risk Assessment of Heart Failure (GRAHF) substudy of the African-American Heart Failure Trial were genotyped for NOS3 polymorphisms: -786 T/C promoter, intron 4a/4b, and Glu298Asp and allele frequencies and compared with a white heart failure cohort. The effect of treatment with fixed-dose combination of isosorbide dinitrates and hydralazine (FDC I/H) on event-free survival and composite score (CS) of survival, hospitalization, and quality of life (QoL) was analyzed within genotype subsets. In GRAHF, NOS3 genotype frequencies differed from the white cohort (P < .001). The -786 T allele was associated with lower left ventricular ejection fraction (LVEF) (P = .01), whereas the intron 4a allele was linked to lower diastolic blood pressure and higher LVEF (P = .03). Only the Glu298Asp polymorphism influenced treatment outcome; therapy with FDC I/H improved CS (P = .046) and QoL (P = .03) in the Glu298Glu subset only. CONCLUSIONS: In black subjects with heart failure, NOS3 genotype influences blood pressure and left ventricular remodeling. The impact of genetic heterogeneity on treatment with FDC I/H requires further study.

Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine: consistency across subgroups in the African-American Heart Failure Trial.

BACKGROUND: We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality. METHODS AND RESULTS: Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P<0.001) and a 39% reduction in the risk for first hospitalization for HF (P<0.001). These benefits appeared to emerge early (at approximately 50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012). CONCLUSIONS: FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.

Exploring the potential synergistic action of spironolactone on nitric oxide-enhancing therapy: insights from the African-American Heart Failure Trial.

BACKGROUND: To investigate if treatment with an aldosterone antagonist affects the outcomes of treatment by fixed dose combination of isosorbide dinitrate/hydralazine (FDC I/H) or placebo in black heart failure (HF) patients treated with contemporary HF medications. In the African-American Heart Failure Trial (A-HeFT), FDC I/H was effective in reducing mortality and improving event-free survival. The beneficial effects of aldosterone antagonist (spironolactone [SP]), however have not been adequately assessed in black patients with or without the use of FDC I/H. METHODS AND RESULTS: A retrospective analysis was performed in A-HeFT data base (n = 1050) to determine the effect of using SP (39% of patients) on outcomes. Baseline comparisons were done by 2-sample t-test or Fisher's exact test. Kaplan-Meier survival analyses were used for comparing between and within groups for outcomes. SP had no effect on mortality, event-free survival, or first HF hospitalization in the overall A-HeFT population. However, SP decreased mortality risk in the FDC I/H group by 59% (P = .03), and a favorable trend was noted on event-free survival and first HF hospitalization. In contrast, the use of SP was not associated with a decrease in mortality or HF hospitalizations in the placebo group. CONCLUSIONS: This study suggests that in black patients with systolic heart failure on standard therapy of beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists, the beneficial effects of aldosterone antagonists require a background therapy of FDC I/H.

A common variant alters SCN5A-miR-24 interaction and associates with heart failure mortality.

SCN5A encodes the voltage-gated Na+ channel NaV1.5 that is responsible for depolarization of the cardiac action potential and rapid intercellular conduction. Mutations disrupting the SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and single-nucleotide polymorphisms (SNPs) linked to SCN5A splicing, localization, and function associate with heart failure-related sudden cardiac death. However, the clinical relevance of SNPs that modulate SCN5A expression levels remains understudied. We recently generated a transcriptome-wide map of microRNA (miR) binding sites in human heart, evaluated their overlap with common SNPs, and identified a synonymous SNP (rs1805126) adjacent to a miR-24 site within the SCN5A coding sequence. This SNP was previously shown to reproducibly associate with cardiac electrophysiological parameters, but was not considered to be causal. Here, we show that miR-24 potently suppresses SCN5A expression and that rs1805126 modulates this regulation. We found that the rs1805126 minor allele associates with decreased cardiac SCN5A expression and that heart failure subjects homozygous for the minor allele have decreased ejection fraction and increased mortality, but not increased ventricular tachyarrhythmias. In mice, we identified a potential basis for this in discovering that decreased Scn5a expression leads to accumulation of myocardial reactive oxygen species. Together, these data reiterate the importance of considering the mechanistic significance of synonymous SNPs as they relate to miRs and disease, and highlight a surprising link between SCN5A expression and nonarrhythmic death in heart failure.

Association of Variants in BAG3 With Cardiomyopathy Outcomes in African American Individuals.

Importance: The prevalence of nonischemic dilated cardiomyopathy (DCM) is greater in individuals of African ancestry than in individuals of European ancestry. However, little is known about whether the difference in prevalence or outcomes is associated with functional genetic variants. Objective: We hypothesized that Bcl2-associated anthanogene 3 (BAG3) genetic variants were associated with outcomes in individuals of African ancestry with DCM. Design: This multicohort study of the BAG3 genotype in patients of African ancestry with dilated cardiomyopathy uses DNA obtained from African American individuals enrolled in 3 clinical studies: the Genetic Risk Assessment of African Americans With Heart Failure (GRAHF) study; the Intervention in Myocarditis and Acute Cardiomyopathy Trial-2 (IMAC-2) study; and the Genetic Risk Assessment of Cardiac Events (GRACE) study. Samples of DNA were also acquired from the left ventricular myocardium of patients of African ancestry who underwent heart transplant at the University of Colorado and University of Pittsburgh. Main Outcomes and Measures: The primary end points were the prevalence of BAG3 mutations in African American individuals and event-free survival in participants harboring functional BAG3 mutations. Results: Four BAG3 genetic variants were identified; these were expressed in 42 of 402 African American individuals (10.4%) with nonischemic heart failure and 9 of 107 African American individuals (8.4%) with ischemic heart failure but were not present in a reference population of European ancestry (P < .001). The variants included 2 nonsynonymous single-nucleotide variants; 1 three-nucleotide in-frame insertion; and 2 single-nucleotide variants that were linked in cis. The presence of BAG3 variants was associated with a nearly 2-fold (hazard ratio, 1.97 [95% CI, 1.19-3.24]; P = .01) increase in cardiac events in carriers compared with noncarriers. Transfection of transformed adult human ventricular myocytes with plasmids expressing the 4 variants demonstrated that each variant caused an increase in apoptosis and a decrease in autophagy when samples were subjected to the stress of hypoxia-reoxygenation. Conclusions and Relevance: This study demonstrates that genetic variants in BAG3 found almost exclusively in individuals of African ancestry were not causative of disease but were associated with a negative outcome in patients with a dilated cardiomyopathy through modulation of the function of BAG3. The results emphasize the importance of biological differences in causing phenotypic variance across diverse patient populations, the need to include diverse populations in genetic cohorts, and the importance of determining the pathogenicity of genetic variants.

Combination of isosorbide dinitrate and hydralazine in blacks with heart failure.

BACKGROUND: We examined whether a fixed dose of both isosorbide dinitrate and hydralazine provides additional benefit in blacks with advanced heart failure, a subgroup previously noted to have a favorable response to this therapy. METHODS: A total of 1050 black patients who had New York Heart Association class III or IV heart failure with dilated ventricles were randomly assigned to receive a fixed dose of isosorbide dinitrate plus hydralazine or placebo in addition to standard therapy for heart failure. The primary end point was a composite score made up of weighted values for death from any cause, a first hospitalization for heart failure, and change in the quality of life. RESULTS: The study was terminated early owing to a significantly higher mortality rate in the placebo group than in the group given isosorbide dinitrate plus hydralazine (10.2 percent vs. 6.2 percent, P=0.02). The mean primary composite score was significantly better in the group given isosorbide dinitrate plus hydralazine than in the placebo group (-0.1+/-1.9 vs. -0.5+/-2.0, P=0.01; range of possible values, -6 to +2), as were its individual components (43 percent reduction in the rate of death from any cause [hazard ratio, 0.57; P=0.01] 33 percent relative reduction in the rate of first hospitalization for heart failure [16.4 percent vs. 22.4 percent, P=0.001], and an improvement in the quality of life [change in score, -5.6+/-20.6 vs. -2.7+/-21.2, with lower scores indicating better quality of life; P=0.02; range of possible values, 0 to 105]). CONCLUSIONS: The addition of a fixed dose of isosorbide dinitrate plus hydralazine to standard therapy for heart failure including neurohormonal blockers is efficacious and increases survival among black patients with advanced heart failure.

Isosorbide dinitrate and hydralazine in a fixed-dose combination produces further regression of left ventricular remodeling in a well-treated black population with heart failure: results from A-HeFT.

BACKGROUND: Isosorbide dinitrate combined with hydralazine therapy compared with placebo in patients with heart failure resulted in a sustained increase in left ventricular (LV) ejection fraction (EF) indicative of regression of LV remodeling in the first Vasodilator-Heart Failure Trial (V-HeFT-I) in patients receiving only digoxin and diuretic. In the African-American Heart Failure Trial (A-HeFT) a fixed-dose combination resulted in a 43% reduction in mortality in 1050 black patients with heart failure already treated with recommended neurohormonal inhibiting drugs. Whether the fixed-dose combination produces a further regression of LV remodeling when added to renin-angiotensin and sympathetic inhibitors has not been documented. METHODS AND RESULTS: Echocardiograms at baseline and 6 months after randomization to placebo or a fixed-dose combination of isosorbide dinitrate/hydralazine (FDC I/H) were analyzed in 678 A-HeFT participants in a core laboratory. LVEF rose by 2.8 EF units in the FDC I/H group versus 0.8% in the control group (P < .01), LV mass index fell by 7.4 g/m2 in the FDC I/H group versus an increase of 1.4 g/m2 in the placebo group (P < .05), LV diastolic transverse diameter fell by 2.2 mm in FDC I/H and was unchanged in placebo (P < .01), and the LV systolic and diastolic sphericity indices improved in the FDC I/H group but remained unchanged in the placebo group. The mean plasma B-type natriuretic peptide (BNP) also measured in a core laboratory fell in the FDC I/H group by 39 pg/mL compared with 8 pg/mL in the placebo group (P = .05). CONCLUSIONS: A fixed-dose combination of I/H produces regression of LV remodeling when added to background therapy with renin-angiotensin and sympathetic inhibitors in black patients with heart failure. This remodeling benefit may explain at least in part the mortality reduction in A-HeFT.

Race and ethnicity in trials of antihypertensive therapy to prevent cardiovascular outcomes: a systematic review.

PURPOSE: We wanted to systematically review (1) the participation of racial and ethnic minorities in clinical trials of antihypertensive drug therapy and (2) racial differences in the efficacy of these therapies for the prevention of cardiovascular outcomes. METHODS: MEDLINE, EMBASE, LILACS, African Index Medicus, and the Cochrane Library were searched from their inception to December 2005 for randomized controlled trials testing the efficacy of antihypertensive drug therapy in preventing myocardial infarction, stroke, revascularization, or cardiovascular death. MEDLINE was also searched from 2005 through 2006. The 2 authors independently assessed studies for inclusion and quality. RESULTS: Twenty-eight studies met inclusion criteria. Eight trials reported results by racial subgroup. Trials with black and Hispanic participants (ALLHAT, INVEST, VALUE) found similar primary outcomes, but ALLHAT found a greater magnitude of benefit for blacks on diuretic therapy compared with nonblacks. One trial (PROGRESS) compared Asians with non-Asians, reporting that angiotensin-converting enzyme inhibitors (vs placebo) were equally effective for preventing stroke in both groups. In the LIFE trial, post hoc analyses showed different outcomes for blacks and nonblacks, raising questions about the usefulness of angiotensin-receptor blockers as first-line antihypertensive agents in blacks. In 3 studies conducted exclusively in Asians (JMIC-B, FEVER, NICS-EH), calcium channel blockers were effective in preventing cardiovascular outcomes. No trials described cardiovascular outcomes in Native Americans. CONCLUSIONS: Five trials made interethnic group comparisons; 4 had similar primary outcomes for ethnic minorities and whites. Increased minority participation in future studies is needed to determine optimal prevention therapies, especially in outcome-driven trials comparing multidrug antihypertensive treatment regimens.