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Jackson T Wright

Publications and source records attributed to Jackson T Wright.

At least 19 recordsLinked to original sources

Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial.

The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker-initiated therapy in older hypertensive individuals. Patients were randomized to amlodipine (n=9048) or lisinopril (n=9054). The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infarction, analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (CVD), end-stage renal disease (ESRD), cancer, and gastrointestinal bleeding. Mean follow-up was 4.9 years. Blood pressure control was similar in nonblacks, but not in blacks. No significant differences were found between treatment groups for the primary outcome, all-cause mortality, ESRD, or cancer. Stroke rates were higher on lisinopril in blacks (RR=1.51, 95% CI 1.22 to 1.86) but not in nonblacks (RR=1.07, 95% CI 0.89 to 1.28), and in women (RR=1.45, 95% CI 1.17 to 1.79), but not in men (RR=1.10, 95% CI 0.92 to 1.31). Rates of combined CVD were higher (RR=1.06, 95% CI 1.00 to 1.12) because of higher rates for strokes, peripheral arterial disease, and angina, which were partly offset by lower rates for heart failure (RR=0.87, 95% CI 0.78 to 0.96) on lisinopril compared with amlodipine. Gastrointestinal bleeds and angioedema were higher on lisinopril. Patients with and without baseline coronary heart disease showed similar outcome patterns. We conclude that in hypertensive patients, the risks for coronary events are similar, but for stroke, combined CVD, gastrointestinal bleeding, and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy. Some, but not all, of these differences may be explained by less effective blood pressure control in the lisinopril arm.

Amlodipine↗

Differing effects of antihypertensive drugs on the incidence of diabetes mellitus among patients with hypertensive kidney disease.

BACKGROUND: The African American Study of Kidney Disease and Hypertension was a multicenter trial of African Americans with hypertensive kidney disease randomized to an angiotensin-converting enzyme inhibitor (ramipril), a beta-blocker (metoprolol succinate), or a calcium channel blocker (amlodipine besylate). We compared the incidence of type 2 diabetes mellitus (DM) and the composite outcome of impaired fasting glucose or DM (IFG/DM) for the African American Study of Kidney Disease and Hypertension interventions. METHODS: Cox regression models were used to evaluate (post hoc) the association of the randomized interventions and the relative risk (RR) of DM and IFG/DM and to assess the RR of DM and IFG/DM by several prerandomization characteristics. RESULTS: Among 1017 participants, 147 (14.5%) developed DM; 333 (42.9%) of 776 participants developed IFG/DM. Respective DM event rates were 2.8%, 4.4%, and 4.5% per patient-year in the ramipril-, amlodipine-, and metoprolol-treated groups. The RRs of DM with ramipril treatment were 0.53 (P = .001) compared with metoprolol treatment and 0.49 (P = .003) compared with amlodipine treatment. Respective IFG/DM event rates were 11.3%, 13.3%, and 15.8% per patient-year in the ramipril-, amlodipine-, and metoprolol-treated groups. The RRs of IFG/DM with ramipril treatment were 0.64 (P<.001) compared with metoprolol treatment and 0.76 (P = .09) compared with amlodipine treatment. The RRs of DM and IFG/DM with amlodipine treatment compared with metoprolol treatment were 1.07 (P = .76) and 0.84 (P = .26), respectively. CONCLUSION: Ramipril treatment was associated with a significantly lower risk of DM in African Americans with hypertensive kidney disease than amlodipine or metoprolol treatment.

Adrenergic beta-Antagonists↗

Cardiovascular outcomes in high-risk hypertensive patients stratified by baseline glomerular filtration rate.

BACKGROUND: Chronic kidney disease is common in older patients with hypertension. OBJECTIVE: To compare rates of coronary heart disease (CHD) and end-stage renal disease (ESRD) events; to determine whether glomerular filtration rate (GFR) independently predicts risk for CHD; and to report the efficacy of first-step treatment with a calcium-channel blocker (amlodipine) or an angiotensin-converting enzyme inhibitor (lisinopril), each compared with a diuretic (chlorthalidone), in modifying cardiovascular disease (CVD) outcomes in high-risk patients with hypertension stratified by GFR. DESIGN: Post hoc subgroup analysis. SETTING: Multicenter randomized, double-blind, controlled trial. PARTICIPANTS: Persons with hypertension who were 55 years of age or older with 1 or more risk factors for CHD and who were stratified into 3 baseline GFR groups: normal or increased (> or = 90 mL/min per 1.73 m2; n = 8126 patients), mild reduction (60 to 89 mL/min per 1.73 m2; n = 18,109 patients), and moderate or severe reduction (< 60 mL/min per 1.73 m2; n = 5662 patients). INTERVENTIONS: Random assignment to chlorthalidone, amlodipine, or lisinopril. MEASUREMENTS: Rates of ESRD, CHD, stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease). RESULTS: In participants with a moderate to severe reduction in GFR, 6-year rates were higher for CHD than for ESRD (15.4% vs. 6.0%, respectively). A baseline GFR of less than 53 mL/min per 1.73 m2 (compared with >104 mL/min per 1.73 m2) was independently associated with a 32% higher risk for CHD. Amlodipine was similar to chlorthalidone in reducing CHD (16.0% vs. 15.2%, respectively; hazard ratio, 1.06 [95% CI, 0.89 to 1.27]), stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease), but less effective in preventing heart failure. Lisinopril was similar to chlorthalidone in preventing CHD (15.1% vs. 15.2%, respectively; hazard ratio, 1.00 [CI, 0.84 to 1.20]), but was less effective in reducing stroke, combined CVD events, and heart failure. LIMITATIONS: Proteinuria data were not available, and combination therapies were not tested. CONCLUSIONS: Older high-risk patients with hypertension and reduced GFR are more likely to develop CHD than to develop ESRD. A low GFR independently predicts increased risk for CHD. Neither amlodipine nor lisinopril is superior to chlorthalidone in preventing CHD, stroke, or combined CVD, and chlorthalidone is superior to both for preventing heart failure, independent of level of renal function.

Aged↗

Cardiovascular outcomes in the African American Study of Kidney Disease and Hypertension (AASK) Trial.

BACKGROUND: Patients with chronic kidney disease are at increased risk for cardiovascular (CV) events. METHODS: We randomly assigned 1,094 African Americans with hypertensive nephrosclerosis (glomerular filtration rate [GFR], 20 to 65 mL/min/1.73 m(2) [0.33 to 1.08 mL/s]) to initial antihypertensive treatment with either: (1) a beta-blocker, metoprolol; (2) an angiotensin-converting enzyme inhibitor, ramipril; or (3) a dihydropyridine calcium channel blocker, amlodipine, and either a usual-blood pressure (BP) or low-BP treatment goal. Using a design powered to detect renal outcome differences, we compared the effect of treatment on the CV event rate (cardiac death, myocardial infarction, stroke, and heart failure) during a mean follow-up period of 4.1 years and determined baseline factors that predict CV outcomes. RESULTS: Thirty-one patients died of CV disease (0.7%/patient-year), and 149 patients experienced at least 1 CV outcome (3.3%/patient-year). Overall, 202 CV events (4.5%/patient-year) occurred. The CV outcome rate was not related significantly to randomized interventions. In multivariable analyses, 7 baseline risk factors remained independently associated with increased risk for the CV composite outcome after controlling for age, sex, baseline GFR, and baseline proteinuria group: pulse pressure, duration of hypertension, abnormal electrocardiogram result, non-high-density lipoprotein cholesterol level, serum urea nitrogen level, urine protein-creatinine ratio, urine sodium-potassium ratio, and annual income less than 15,000 dollars. CONCLUSION: Neither randomized class of antihypertensive therapy nor BP level had a significant effect on the occurrence of CV events, possibly because of limited power. However, this analysis identifies unique and potentially modifiable CV risk factors in this high-risk cohort.

Adolescent↗

The metabolic syndrome: recognition and management.

The National Cholesterol Education Program defines the metabolic syndrome as three or more of five abnormalities: waist circumference of >40 in (102 cm) for men or >35 in (88 cm) for women, triglyceride level of > or =150 mg/dL, high-density lipoprotein cholesterol of <40 mg/dL in men or <50 mg/dL in women, blood pressure of > or =130 or > or =85 mm Hg, and fasting glucose of > or =110 mg/dL. It is related to insulin resistance, but the two terms are not synonymous. Both are associated strongly with obesity. The metabolic syndrome is important as an indicator of increased risk of cardiovascular disease (CVD) in patients with and without clinical CVD. The CVD risk of the metabolic syndrome is greater than that conferred by any single CVD risk factor. Since risk factors tend to cluster, if one component of the metabolic syndrome is present, one should assess for other risk factors. The metabolic syndrome is also predictive of new-onset type 2 diabetes. Early diagnosis provides justification for measures that can improve components of the syndrome and reduce CVD risk. The management strategy for metabolic syndrome focuses on overall CVD risk rather than single risk factors; effective therapy includes priority for weight reduction and increased physical activity. Pharmacotherapy is typically needed for control of high blood pressure, hypercoagulability, and increased levels of blood glucose and triglycerides.

Adult↗

Which drug should be used to treat patients with uncomplicated essential hypertension?

PURPOSE OF REVIEW: To review recent data and guidelines on selecting the initial antihypertensive drug. RECENT FINDINGS: The main driver of benefit from blood pressure-lowering therapy is blood pressure reduction, and there is little evidence supporting additional drug class-specific benefits in primary prevention of major cardiovascular outcomes. The results also confirm that in the patient with uncomplicated hypertension as well as in those patients with diabetes without nephropathy, initial therapy with 'newer therapies' (i.e. angiotensin-converting enzyme inhibitors, calcium channel blockers, and angiotensin receptor blockers) are effective, but not more effective than thiazide diuretics, at reducing stroke, coronary heart disease, morbidity or mortality, or all-cause mortality. SUMMARY: While compelling indications may exist for specific drug classes in those with specific target organ damage (i.e. heart failure, renal insufficiency, and coronary artery disease), thiazide diuretics remain unsurpassed in lowering blood pressure and in preventing hypertension-related clinical outcomes. Despite a more favorable metabolic profile, alpha-blockers are less effective in preventing cardiovascular disease, especially heart failure and stroke. Calcium channel blockers produce a similar reduction in blood pressure and cardiovascular disease outcomes compared with thiazide-type diuretics, although they are consistently less effective in preventing heart failure. In the absence of heart failure or renal disease, angiotensin-converting enzyme inhibitors have shown little advantage in clinical trials over diuretics in preventing cardiovascular disease and are not indicated as an initial therapy in Blacks.

Antihypertensive Agents↗

Differential effects of beta-blockers on albuminuria in patients with type 2 diabetes.

Increases in the cardiovascular risk marker microalbuminuria are attenuated by blood pressure reduction using blockers of the renin-angiotensin system. Such changes in microalbuminuria have not been observed when beta-blockers are used. A prespecified secondary end point of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial was to examine the effects of different beta-blockers on changes in albuminuria in the presence of renin-angiotensin system blockade. Participants with hypertension and type 2 diabetes were randomized to either metoprolol tartrate (n=737) or carvedilol (n=498) in blinded fashion after a washout period of all antihypertensive agents except for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Blinded medication was titrated to achieve target blood pressure, with a-5 month follow-up period. The current analysis examined microalbuminuria, using spot urine albumin:creatinine, in participants who had values at screening and trial end. A greater reduction in microalbuminuria was observed for those randomized to carvedilol (-16.2%Delta; 95% confidence interval, -25.3, -5.9; P=0.003). Of those with normoalbuminuria at baseline, fewer progressed to microalbuminuria on carvedilol versus metoprolol (20 of 302 [6.6%] versus 48 of 431 [11.1%], respectively; P=0.03). Microalbuminuria development was not related to differences in blood pressure or achievement of blood pressure goal (68% carvedilol versus 67%, metoprolol). Presence of metabolic syndrome at baseline was the only independent predictor of worsening albuminuria throughout the study (P=0.004). Beta-blockers have differential effects on microalbuminuria in the presence of renin-angiotensin system blockade. These differences cannot be explained by effects on blood pressure or alpha1-antagonism but may relate to antioxidant properties of carvedilol.

Adrenergic beta-Antagonists↗

Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs a diuretic: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

BACKGROUND: This study was performed to determine whether, in high-risk hypertensive patients with a reduced glomerular filtration rate (GFR), treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of renal disease outcomes compared with treatment with a diuretic. METHODS: We conducted post hoc analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertensive participants 55 years or older with at least 1 other coronary heart disease risk factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a mean of 4.9 years. Renal outcomes were incidence of end-stage renal disease (ESRD) and/or a decrement in GFR of 50% or more from baseline. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into normal or increased (> or =90 mL /min per 1.73 m(2), n = 8126), mild reduction (60-89 mL /min per 1.73 m(2), n = 18 109), or moderate-severe reduction (<60 mL /min per 1.73 m(2), n = 5662) in GFR. Each stratum was analyzed for effects of the treatments on outcomes. RESULTS: In 448 participants, ESRD developed. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking amlodipine in the mild (relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) or moderate-severe (RR, 0.92; 95% CI, 0.68-1.24) reduction in GFR groups. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking lisinopril in the mild (RR, 1.34; 95% CI, 0.87-2.06) or moderate-severe (RR, 0.98; 95% CI, 0.73-1.31) reduction in GFR groups. In patients with mild and moderate-severe reduction in GFR, the incidence of ESRD or 50% or greater decrement in GFR was not significantly different in patients treated with chlorthalidone compared with those treated with amlodipine (odds ratios, 0.96 [P = .74] and 0.85 [P = .23], respectively) and lisinopril (odds ratios, 1.13 [P = .31] and 1.00 [P = .98], respectively). No difference in treatment effects occurred for either end point for patients taking amlodipine or lisinopril compared with those taking chlorthalidone across the 3 GFR subgroups, either for the total group or for participants with diabetes at baseline. At 4 years of follow-up, estimated GFR was 3 to 6 mL /min per 1.73 m(2) higher in patients assigned to receive amlodipine compared with chlorthalidone, depending on baseline GFR stratum. CONCLUSIONS: In hypertensive patients with reduced GFR, neither amlodipine nor lisinopril was superior to chlorthalidone in reducing the rate of development of ESRD or a 50% or greater decrement in GFR. Participants assigned to receive amlodipine had a higher GFR than those assigned to receive chlorthalidone, but rates of development of ESRD were not different between the groups.

Aged↗

Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril.

CONTEXT: Few cardiovascular outcome data are available for blacks with hypertension treated with angiotensin-converting enzyme (ACE) inhibitors or calcium channel blockers (CCBs). OBJECTIVE: To determine whether an ACE inhibitor or CCB is superior to a thiazide-type diuretic in reducing cardiovascular disease (CVD) incidence in racial subgroups. DESIGN, SETTING, AND PARTICIPANTS: Prespecified subgroup analysis of ALLHAT, a randomized, double-blind, active-controlled, clinical outcome trial conducted between February 1994 and March 2002 in 33,357 hypertensive US and Canadian patients aged 55 years or older (35% black) with at least 1 other cardiovascular risk factor. INTERVENTIONS: Antihypertensive regimens initiated with a CCB (amlodipine) or an ACE inhibitor (lisinopril) vs a thiazide-type diuretic (chlorthalidone). Other medications were added to achieve goal blood pressures (BPs) less than 140/90 mm Hg. MAIN OUTCOME MEASURES: The primary outcome was combined fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI), analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined CVD (CHD death, nonfatal MI, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease. RESULTS: No significant difference was found between treatment groups for the primary CHD outcome in either racial subgroup. For amlodipine vs chlorthalidone only, HF was the only prespecified clinical outcome that differed significantly (overall: relative risk [RR], 1.37; 95% confidence interval [CI], 1.24-1.51; blacks: RR, 1.46; 95% CI, 1.24-1.73; nonblacks: RR, 1.32; 95% CI, 1.17-1.49; P<.001 for each comparison) with no difference in treatment effects by race (P = .38 for interaction). For lisinopril vs chlorthalidone, results differed by race for systolic BP (greater decrease in blacks with chlorthalidone), stroke, and combined CVD outcomes (P<.001, P = .01, and P = .04, respectively, for interactions). In blacks and nonblacks, respectively, the RRs for stroke were 1.40 (95% CI, 1.17-1.68) and 1.00 (95% CI, 0.85-1.17) and for combined CVD were 1.19 (95% CI, 1.09-1.30) and 1.06 (95% CI, 1.00-1.13). For HF, the RRs were 1.30 (95% CI, 1.10-1.54) and 1.13 (95% CI, 1.00-1.28), with no significant interaction by race. Time-dependent BP adjustment did not significantly alter differences in outcome for lisinopril vs chlorthalidone in blacks. CONCLUSIONS: In blacks and nonblack subgroups, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary CHD or any other prespecified clinical outcome, and diuretic-based treatment resulted in the lowest risk of heart failure. While the improved outcomes with chlorthalidone were more pronounced for some outcomes in blacks than in nonblacks, thiazide-type diuretics remain the drugs of choice for initial therapy of hypertension in both black and nonblack hypertensive patients.

Aged↗

Ethnicity and blood pressure.

The prevalence, impact, and control of hypertension differ across racial and ethnic subgroups in the United States population. Whether race/ethnicity should be a significant consideration in the choice of individual antihypertensive drugs continues to be a topic of intense interest and debate. This brief review will discuss recent findings that bear on the management of hypertension in these special patient groups.

Blood Pressure↗

Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial.

CONTEXT: Beta-blockers have been shown to decrease cardiovascular risk in patients with hypertension and type 2 diabetes mellitus (DM); however, some components of the metabolic syndrome are worsened by some beta-blockers. OBJECTIVE: To compare the effects of beta-blockers with different pharmacological profiles on glycemic and metabolic control in participants with DM and hypertension receiving renin-angiotensin system (RAS) blockade, in the context of cardiovascular risk factors. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, parallel-group trial (The Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives [GEMINI]) conducted between June 1, 2001, and April 6, 2004, at 205 US sites that compared the effects of carvedilol and metoprolol tartrate on glycemic control. The 1235 participants were aged 36 to 85 years with hypertension (>130/80 mm Hg) and type 2 DM (glycosylated hemoglobin [HbA1c], 6.5%-8.5%) and were receiving RAS blockers. Participants were followed up for 35 weeks. INTERVENTIONS: Participants were randomized to receive a 6.25- to 25-mg dose of carvedilol (n = 498) or 50- to 200-mg dose of metoprolol tartrate (n = 737), each twice daily. Open-label hydrochlorothiazide and a dihydropyridine calcium antagonist were added, if needed, to achieve blood pressure target. MAIN OUTCOME MEASURES: Difference between groups in mean change from baseline HbA1c following 5 months of maintenance therapy. Additional prespecified comparisons included change from baseline HbA1c in individual treatment groups, treatment effect on insulin sensitivity, and microalbuminuria. RESULTS: The 2 groups differed in mean change in HbA1c from baseline (0.13%; 95% confidence interval [CI], -0.22% to -0.04%; P = .004; modified intention-to-treat analysis). The mean (SD) HbA1c increased with metoprolol (0.15% [0.04%]; P<.001) but not carvedilol (0.02% [0.04%]; P = .65). Insulin sensitivity improved with carvedilol (-9.1%; P = .004) but not metoprolol (-2.0%; P = .48); the between-group difference was -7.2% (95% CI, -13.8% to -0.2%; P = .004). Blood pressure was similar between groups. Progression to microalbuminuria was less frequent with carvedilol than with metoprolol (6.4% vs 10.3%; odds ratio, 0.60; 95% CI, 0.36-0.97; P = .04). CONCLUSIONS: Both beta-blockers were well tolerated; use of carvedilol in the presence of RAS blockade did not affect glycemic control and improved some components of the metabolic syndrome relative to metoprolol in participants with DM and hypertension. The effects of the 2 beta-blockers on clinical outcomes need to be compared in long-term clinical trials.

Adrenergic beta-Antagonists↗

ALLHAT: setting the record straight.

The findings of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) have generated worldwide reaction from clinicians and researchers, including a recent commentary in this journal. Such response was expected for a trial of ALLHAT's size and scope, especially since its results challenged some widely held beliefs. This paper reviews key aspects of the ALLHAT design, analyses, findings, and conclusions to provide a perspective on the commentary about the trial's results and implications for clinical practice. Several of the most frequent comments regarding the study's results are addressed, particularly with respect to heart failure and diabetes outcomes. Responses to these comments reinforce the investigators' original conclusion that thiazide-type diuretics should remain the preferred first-step drug class for treating hypertension and should generally be a part of any multidrug regimen.

Antihypertensive Agents↗

Cardiovascular risk reduction in hypertensive black patients with left ventricular hypertrophy: the LIFE study.

OBJECTIVES: We report on a subanalysis of the effects of losartan and atenolol on cardiovascular events in black patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. BACKGROUND: The LIFE study compared losartan-based to atenolol-based therapy in 9,193 hypertensive patients with left ventricular hypertrophy (LVH). Overall, the risk of the primary composite end point (cardiovascular death, stroke, myocardial infarction) was reduced by 13% (p = 0.021) with losartan, with similar blood pressure (BP) reduction in both treatment groups. There was a suggestion of interaction between ethnic background and treatment (p = 0.057). METHODS: Exploratory analyses were performed that placed LIFE study patients into black (n = 533) and non-black (n = 8,660) categories, overall, and in the U.S. (African American [n = 523]; non-black [n = 1,184]). RESULTS: A significant interaction existed between the dichotomized groups (black/non-black) and treatment (p = 0.005); a test for qualitative interaction was also significant (p = 0.016). The hazard ratio (losartan relative to atenolol) for the primary end point favored atenolol in black patients (1.666 [95% confidence interval (CI) 1.043 to 2.661]; p = 0.033) and favored losartan in non-blacks (0.829 [95% CI 0.733 to 0.938]; p = 0.003). In black patients, BP reduction was similar in both groups, and regression of electrocardiographic-LVH was greater with losartan. CONCLUSIONS: Results of the subanalysis are sufficient to generate the hypothesis that black patients with hypertension and LVH might not respond as favorably to losartan-based treatment as non-black patients with respect to cardiovascular outcomes, and do not support a recommendation for losartan as a first-line treatment for this purpose. The subanalysis is limited by the relatively small number of events.

Aged↗

Antihypertensive efficacy of night-time graded-release diltiazem versus morning amlodipine in African Americans.

BACKGROUND: The effect of a once daily night-time (10 pm) graded-release diltiazem (GRD) on early morning blood pressure (BP), heart rate (HR), and rate-pressure product (RPP) were compared with the effect of morning (8 am) amlodipine in 262 African American individuals with hypertension. METHODS: The multicenter, randomized, double-blind, parallel-group, dose-to-effect trial evaluated changes from baseline in BP, HR, and RPP (HR x systolic BP) by ambulatory BP monitoring during the first 4 h after awakening (diastolic BP = primary), between 6 am and 12 noon, and over a 24-h period. Patients were randomized to night-time GRD 360 mg (n = 132) or morning amlodipine 5 mg (n = 130) for 6 weeks, and were titrated to GRD 540 mg or amlodipine 10 mg after 6 weeks if clinic systolic BP/diastolic BP (SBP/DBP) was > or = 130/85 mm Hg. RESULTS: Compared with amlodipine, GRD showed significantly greater DBP reductions of 3.5 mm Hg (P < .0049) and 3.2 mm Hg (P < .0019) during the first 4 h after awakening and between 6 am and 12 noon respectively, as well as comparable reduction for the 24-h mean DBP. The SBP reductions during the morning periods were comparable, but the reduction in the 24-h mean SBP was 3.4 mm Hg greater (P < .0022) for amlodipine. Mean reductions in HR and RPP were significantly greater (P < or = .0008) for GRD during all intervals; amlodipine increased whereas diltiazem reduced HR with mean differences of 6.7 to 9.3 beats/min. Both treatments were well tolerated. CONCLUSIONS: Night-time GRD was more effective than morning amlodipine in reducing early morning DBP, HR, and RPP, as well as 24-h HR and RPP in African American individuals with hypertension. Amlodipine was more effective in reducing SBP over the 24-h period.

Adolescent↗

A comparison of iothalamate-GFR and serum creatinine-based outcomes: acceleration in the rate of GFR decline in the African American Study of Kidney Disease and Hypertension.

In renal clinical trials, both slope-based and time-to-event renal outcomes have been used. These outcomes are typically based on estimates of GFR obtained using creatinine or iothalamate GFR (iGFR). The African American Study of Kidney Disease and Hypertension (AASK) was a trial in 1094 African Americans with hypertensive nephrosclerosis, which examined the effects of two levels of BP control and three antihypertensive regimens. This study compared the effects of the AASK interventions on outcomes based on serum creatinine with corresponding outcomes based on iGFR using 9742 matched pairs of iGFR and serum creatinine measurements. The iGFR-based outcomes included (1) a time-to-event composite outcome including a 50% GFR decline, ESRD, or death; (2) a composite outcome including a 50% GFR decline or ESRD; (3) mean decline in GFR in the first 3 mo after randomization (acute slope); (4) mean decline in GFR starting 3 mo after randomization (chronic slope); and (5) mean decline in GFR from baseline (total slope). The corresponding creatinine-based outcomes were (1) a composite of doubling of serum creatinine, ESRD, or death and (2) a composite of doubling of serum creatinine or ESRD and acute, chronic, and total slopes defined by the mean change in estimated GFR (eGFR), where eGFR was estimated from a regression equation for GFR depending primarily on serum creatinine and developed in AASK enrollees. Mean changes in iGFR and eGFR were also compared under extended models that allowed for the possibility that the rate of GFR decline may change over time during the chronic phase. an apparent acceleration in rate of decline of renal function over time was found. Subtle differences were observed between effects of the interventions on some of the creatinine and iGFR slope-based outcomes, but the main conclusions of the trial were similar for the serum creatinine and iothalamate-based measurements. This has important implications for the design of clinical trials with renal outcomes.

Adolescent↗