RESUMEN

We examined the association of orthostatic hypertension with all-cause mortality in the active treatment and placebo randomized groups of the Systolic Hypertension in the Elderly Program (SHEP). SHEP was a multicenter, randomized, double-blind, placebo-controlled clinical trial of the effect of chlorthalidone-based antihypertensive treatment on the rate of occurrence of stroke among older persons with isolated systolic hypertension (ISH). Men and women aged 60 years and above with ISH defined by a systolic blood pressure (SBP) of 160 mm Hg or higher and diastolic blood pressure lower than 90 mm Hg were randomized to chlorthalidone-based stepped care therapy or matching placebo. Among 4736 SHEP participants, 4073 had a normal orthostatic response, 203 had orthostatic hypertension, and 438 had orthostatic hypotension. Compared with normal response, orthostatic hypertension was associated with higher all-cause mortality at 4.5 and 17 years in analyses adjusted for age, gender, treatment, SBP, and pulse pressure (PP, HR 1.87, 95% CI 1.30-2.69, p = 0.0007; HR 1.40, 95% CI 1.17-1.68, p = 0.0003, respectively). These associations remained significant after additional adjustment for risk factors and comorbidities (HR 1.43, 95% CI 0.99-0.08, p = 0.0566 at 4.5 years, and HR 1.27, 95% CI 1.06-1.53, p = 0.0096 at 17 years). The increased risk of all-cause mortality associated with orthostatic hypertension was observed in both the active and placebo groups without significant interaction between randomization group and the effect on mortality. Orthostatic hypertension is associated with future mortality risk, is easily detected, and can be used in refining cardiovascular risk assessment.

Asunto(s)

Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Clortalidona/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/mortalidad , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Posición de Pie , Anciano , Anciano de 80 o más Años , Antihipertensivos/efectos adversos , Causas de Muerte , Clortalidona/efectos adversos , Método Doble Ciego , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Factores de Riesgo , Inhibidores de los Simportadores del Cloruro de Sodio/efectos adversos , Sístole , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología

RESUMEN

AIMS: Although group-level effectiveness of lipid, blood pressure, glucose, and aspirin treatment for prevention of cardiovascular disease (CVD) has been proven by trials, important differences in absolute effectiveness exist between individuals. We aim to develop and validate a prediction tool for individualizing lifelong CVD prevention in people with Type 2 diabetes mellitus (T2DM) predicting life-years gained without myocardial infarction or stroke. METHODS AND RESULTS: We developed and validated the Diabetes Lifetime-perspective prediction (DIAL) model, consisting of two complementary competing risk adjusted Cox proportional hazards functions using data from people with T2DM registered in the Swedish National Diabetes Registry (n = 389 366). Competing outcomes were (i) CVD events (vascular mortality, myocardial infarction, or stroke) and (ii) non-vascular mortality. Predictors were age, sex, smoking, systolic blood pressure, body mass index, haemoglobin A1c, estimated glomerular filtration rate, non- high-density lipoprotein cholesterol, albuminuria, T2DM duration, insulin treatment, and history of CVD. External validation was performed using data from the ADVANCE, ACCORD, ASCOT and ALLHAT-LLT-trials, the SMART and EPIC-NL cohorts, and the Scottish diabetes register (total n = 197 785). Predicted and observed CVD-free survival showed good agreement in all validation sets. C-statistics for prediction of CVD were 0.83 (95% confidence interval: 0.83-0.84) and 0.64-0.65 for internal and external validation, respectively. We provide an interactive calculator at www.U-Prevent.com that combines model predictions with relative treatment effects from trials to predict individual benefit from preventive treatment. CONCLUSION: Cardiovascular disease-free life expectancy and effects of lifelong prevention in terms of CVD-free life-years gained can be estimated for people with T2DM using readily available clinical characteristics. Predictions of individual-level treatment effects facilitate translation of trial results to individual patients.

Asunto(s)

Antihipertensivos/uso terapéutico , Aspirina/uso terapéutico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Hipoglucemiantes/uso terapéutico , Hipolipemiantes/uso terapéutico , Anciano , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Infarto del Miocardio/prevención & control , Pronóstico , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Factores de Tiempo

RESUMEN

BACKGROUND: Elevations of fasting glucose (FG) levels are frequently encountered in people treated with thiazide diuretics. The risk is lower in people treated with ACE inhibitors (ACEi). To determine if genetic factors play a role in FG elevation, we examined the interaction of a diabetes gene risk score (GRS) with the use of 3 different antihypertensive medications. METHODS: We examined 376 nondiabetic hypertensive individuals with baseline FG <100 mg/dl who were genotyped for 24 genes associated with risk of elevated glucose levels. All participants had ≥1 follow-up FG level over 6 years of follow-up. Participants were randomized to treatment with a thiazide-like diuretic (chlorthalidone), a calcium channel blocker (CCB; amlodipine), or an ACEi (lisinopril). Outcomes were an FG increase of ≥13 or ≥27 mg/dl, the upper 75% and 90% FG increase in the parent cohort from which the present cohort was obtained. Odds ratios were adjusted for factors that increase FG levels. RESULTS: For every 1 allele increase in GRS, the adjusted odds ratios (ORs) were 1.06 (95% confidence interval (CI): 0.99, 1.14; P = 0.06) and 1.09 (95% CI: 0.99, 1.20; P = 0.08). When results were examined by randomized medications, participants randomized to amlodipine had statistically significant odds for either outcome (OR: 1.23; 95% CI: 1.03, 1.48; P = 0.01 and OR: 1.31; 95% CI: 1.06, 1.62; P = 0.01). No such risk increase was found in participants randomized to the other 2 medications. CONCLUSIONS: A diabetes GRS predicts FG elevation in people treated with a CCB, but not with an ACEi or diuretic. These findings require confirmation. CLINICAL TRIALS REGISTRATION: Trial number NCT00000542.

Asunto(s)

Amlodipino/uso terapéutico , Glucemia/metabolismo , Clortalidona/uso terapéutico , Diabetes Mellitus/genética , Hipertensión/tratamiento farmacológico , Lisinopril/uso terapéutico , Polimorfismo de Nucleótido Simple , Alcadienos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Glucemia/efectos de los fármacos , Bloqueadores de los Canales de Calcio/uso terapéutico , Diabetes Mellitus/sangre , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Genotipo , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico

RESUMEN

A rapid decline in estimated glomerular filtration rate over 2 years in a large hypertensive cohort was associated with similar risks for overall cardiovascular disease in people with or without diabetes mellitus, but with higher all-cause mortality, heart failure, and end stage renal disease risk in people with diabetes.

Asunto(s)

Enfermedades Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Tasa de Filtración Glomerular/fisiología , Hipertensión/diagnóstico , Hipertensión/mortalidad , Fallo Renal Crónico/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/fisiopatología , Causas de Muerte , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/diagnóstico , Angiopatías Diabéticas/mortalidad , Angiopatías Diabéticas/fisiopatología , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/fisiopatología , Progresión de la Enfermedad , Femenino , Humanos , Hipertensión/complicaciones , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Mortalidad , Pronóstico , Factores de Riesgo

RESUMEN

BACKGROUND: Impaired renal function is a risk factor for cardiovascular disease, end-stage renal disease (ESRD), and mortality. The impact of short-term renal function decline on outcomes is less well studied. The association of antihypertensive medications with the impact of short-term estimated glomerular filtration rate (eGFR) decline is not known. METHODS: We examined 20,207 hypertensive participants with baseline and 2-year creatinine levels from which eGFR changes were estimated. The associations between eGFR change with incident coronary heart disease (CHD), stroke, heart failure (HF), all-cause mortality, and ESRD during 2.9 years of in-trial follow up, and with mortality during in-trial and post-trial follow-up (7.6 years), were studied. Results were assessed by primary hypertension (HTN) treatment (chlorthalidone, lisinopril, and amlodipine) and adjusted for baseline eGFR levels. RESULTS: In the short run, an eGFR decline below the cohort median (-1.28 ml/minute/1.73 m2/2 years) vs. above the median, or a 5 ml/min/1.73 m2/year decline vs. no decline, was associated with significant hazard risk for CHD (1.06-1.28), HF (1.24-1.91), ESRD (2.84-6.01), and mortality (1.08-1.19), but not with stroke risk. In the long term, there was a significant association with mortality (1.11-1.34). Interaction terms for outcomes by antihypertensive treatments were not statistically significant except for ESRD between amlodipine vs. chlorthalidone (hazard ratio: 3.17 [2.59, 3.88] vs. 2.41 [1.98, 2.97]; P interaction = 0.005) for a 5 ml/min/1.73 m2/year eGFR decline. CONCLUSION: Decline in eGFR over 2 years is associated with increased risk of clinical outcomes beyond the effects of baseline eGFR. These risks were the same irrespective of the primary medication used to treat HTN.

Asunto(s)

Antihipertensivos/uso terapéutico , Enfermedades Cardiovasculares/etiología , Tasa de Filtración Glomerular , Hipertensión/tratamiento farmacológico , Enfermedades Cardiovasculares/fisiopatología , Método Doble Ciego , Femenino , Humanos , Hipertensión/mortalidad , Hipertensión/fisiopatología , Fallo Renal Crónico/etiología , Masculino

RESUMEN

BACKGROUND AND PURPOSE: The visual analogue scale is a self-reported, validated tool to measure quality of life (QoL). Our purpose was to determine whether baseline QoL predicted strokes in the ALLHAT study (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) and evaluate determinants of poststroke change in QoL. In the ALLHAT study, among the 33 357 patients randomized to treatment arms, 1525 experienced strokes; 1202 (79%) strokes were nonfatal. This study cohort includes 32 318 (97%) subjects who completed the baseline visual analogue scale QoL estimate. METHODS: QoL was measured on a visual analogue scale and adjusted using a Torrance transformation (transformed QoL [TQoL]). Kaplan-Meier curves and adjusted proportional hazards analyses were used to estimate the effect of TQoL on the risk of stroke, on a continuous scale (0-1) and by quartiles (≤0.81, >0.81≤0.89, >0.89≤0.95, >0.95). We analyzed the change from baseline to first poststroke TQoL using adjusted linear regression. RESULTS: After adjusting for multiple stroke risk factors, the hazard ratio for stroke events for baseline TQoL was 0.93 (95% confidence interval, 0.89-0.98) per 0.1 U increase. The lowest baseline TQoL quartile had a 20% increased stroke risk (hazard ratio=1.20 [95% confidence interval, 1.00-1.44]) compared with the reference highest quartile TQoL. Poststroke TQoL change was significant within all treatment groups (P≤0.001). Multivariate regression analysis revealed that baseline TQoL was the strongest predictor of poststroke TQoL with similar results for the untransformed QoL. CONCLUSIONS: The lowest baseline TQoL quartile had a 20% higher stroke risk than the highest quartile. Baseline TQoL was the only factor that predicted poststroke change in TQoL. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

Asunto(s)

Antihipertensivos/administración & dosificación , Dislipidemias , Calidad de Vida , Accidente Cerebrovascular , Anciano , Antihipertensivos/efectos adversos , Supervivencia sin Enfermedad , Método Doble Ciego , Dislipidemias/sangre , Dislipidemias/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/inducido químicamente , Accidente Cerebrovascular/mortalidad , Tasa de Supervivencia

RESUMEN

PURPOSE OF REVIEW: This review summarizes the impact of thiazide diuretics on fracture risk in older hypertensive individuals. RECENT FINDINGS: We performed a post hoc evaluation of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a randomized, prospective, double blind hypertension study comparing a thiazide-like diuretic, a calcium channel blocker (CCB), and an angiotensin converting enzyme inhibitor (ACEi). We examined the risk of hip and pelvic fractures during the in-trial period (n = 22,180 participants; mean 4.9-year follow-up) and during the post-trial period using national data bases (n = 16,622 participants) (mean total follow-up 7.8 years). During the trial, participants randomized to the thiazide diuretic versus the CCB or the ACEi had a lower risk of fracture on adjusted analyses (HR 0.79 [95% CI, 0.63, 0.98], p = 0.04). Risk of fracture was significantly lower in participants randomized to the diuretic as compared to those randomized to the ACEi (HR 0.75 [95% CI, 0.58, 0.98]; p = 0.04), but not significantly different compared to the CCB (HR 0.87 [95% CI, 0.71, 1.09]; p = 0.17). Over the entire trial and post-trial period of follow-up, the cumulative incidence of fractures was non-significantly lower in participants assigned to the diuretic vs assignment to the ACEi or the CCB (HR 0.87 [0.74-1.03], p = 0.10) and versus each medication separately. These findings establish a benefit for thiazide diuretic treatment for the prevention of fractures versus other commonly used antihypertensive medications using prospective, randomized data. The effects of the thiazide diuretic on bone appear to be long lasting.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antihipertensivos/farmacología , Densidad Ósea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/farmacología , Diuréticos/farmacología , Fracturas Óseas/prevención & control , Fracturas de Cadera/prevención & control , Hipertensión/tratamiento farmacológico , Huesos Pélvicos/efectos de los fármacos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Diuréticos/efectos adversos , Método Doble Ciego , Femenino , Fracturas Óseas/inducido químicamente , Fracturas de Cadera/inducido químicamente , Humanos , Masculino , Huesos Pélvicos/lesiones , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento

RESUMEN

Randomized trials of hypertension have seldom examined heterogeneity in response to treatments over time and the implications for cardiovascular outcomes. Understanding this heterogeneity, however, is a necessary step toward personalizing antihypertensive therapy. We applied trajectory-based modeling to data on 39 763 study participants of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) to identify distinct patterns of systolic blood pressure (SBP) response to randomized medications during the first 6 months of the trial. Two trajectory patterns were identified: immediate responders (85.5%), on average, had a decreasing SBP, whereas nonimmediate responders (14.5%), on average, had an initially increasing SBP followed by a decrease. Compared with those randomized to chlorthalidone, participants randomized to amlodipine (odds ratio, 1.20; 95% confidence interval [CI], 1.10-1.31), lisinopril (odds ratio, 1.88; 95% CI, 1.73-2.03), and doxazosin (odds ratio, 1.65; 95% CI, 1.52-1.78) had higher adjusted odds ratios associated with being a nonimmediate responder (versus immediate responder). After multivariable adjustment, nonimmediate responders had a higher hazard ratio of stroke (hazard ratio, 1.49; 95% CI, 1.21-1.84), combined cardiovascular disease (hazard ratio, 1.21; 95% CI, 1.11-1.31), and heart failure (hazard ratio, 1.48; 95% CI, 1.24-1.78) during follow-up between 6 months and 2 years. The SBP response trajectories provided superior discrimination for predicting downstream adverse cardiovascular events than classification based on difference in SBP between the first 2 measurements, SBP at 6 months, and average SBP during the first 6 months. Our findings demonstrate heterogeneity in response to antihypertensive therapies and show that chlorthalidone is associated with more favorable initial response than the other medications.

Asunto(s)

Amlodipino , Enfermedades Cardiovasculares/prevención & control , Clortalidona , Doxazosina , Hiperlipidemias , Hipertensión , Lisinopril , Anciano , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Análisis de Varianza , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/etiología , Clortalidona/administración & dosificación , Clortalidona/efectos adversos , Doxazosina/administración & dosificación , Doxazosina/efectos adversos , Monitoreo de Drogas/métodos , Femenino , Humanos , Hiperlipidemias/complicaciones , Hiperlipidemias/diagnóstico , Hiperlipidemias/tratamiento farmacológico , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Lisinopril/administración & dosificación , Lisinopril/efectos adversos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento

RESUMEN

Importance: While statin therapy for primary cardiovascular prevention has been associated with reductions in cardiovascular morbidity, the effect on all-cause mortality has been variable. There is little evidence to guide the use of statins for primary prevention in adults 75 years and older. Objectives: To examine statin treatment among adults aged 65 to 74 years and 75 years and older when used for primary prevention in the Lipid-Lowering Trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). Design, Setting, and Participants: Post hoc secondary data analyses were conducted of participants 65 years and older without evidence of atherosclerotic cardiovascular disease; 2867 ambulatory adults with hypertension and without baseline atherosclerotic cardiovascular disease were included. The ALLHAT-LLT was conducted from February 1994 to March 2002 at 513 clinical sites. Interventions: Pravastatin sodium (40 mg/d) vs usual care (UC). Main Outcomes and Measures: The primary outcome in the ALLHAT-LLT was all-cause mortality. Secondary outcomes included cause-specific mortality and nonfatal myocardial infarction or fatal coronary heart disease combined (coronary heart disease events). Results: There were 1467 participants (mean [SD] age, 71.3 [5.2] years) in the pravastatin group (48.0% [n = 704] female) and 1400 participants (mean [SD] age, 71.2 [5.2] years) in the UC group (50.8% [n = 711] female). The baseline mean (SD) low-density lipoprotein cholesterol levels were 147.7 (19.8) mg/dL in the pravastatin group and 147.6 (19.4) mg/dL in the UC group; by year 6, the mean (SD) low-density lipoprotein cholesterol levels were 109.1 (35.4) mg/dL in the pravastatin group and 128.8 (27.5) mg/dL in the UC group. At year 6, of the participants assigned to pravastatin, 42 of 253 (16.6%) were not taking any statin; 71.0% in the UC group were not taking any statin. The hazard ratios for all-cause mortality in the pravastatin group vs the UC group were 1.18 (95% CI, 0.97-1.42; P = .09) for all adults 65 years and older, 1.08 (95% CI, 0.85-1.37; P = .55) for adults aged 65 to 74 years, and 1.34 (95% CI, 0.98-1.84; P = .07) for adults 75 years and older. Coronary heart disease event rates were not significantly different among the groups. In multivariable regression, the results remained nonsignificant, and there was no significant interaction between treatment group and age. Conclusions and Relevance: No benefit was found when pravastatin was given for primary prevention to older adults with moderate hyperlipidemia and hypertension, and a nonsignificant direction toward increased all-cause mortality with pravastatin was observed among adults 75 years and older. Trial Registration: clinicaltrials.gov Identifier: NCT00000542.

Asunto(s)

Enfermedades Cardiovasculares , Pravastatina/administración & dosificación , Anciano , Antihipertensivos/uso terapéutico , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol/análisis , Monitoreo de Drogas , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Masculino , Administración del Tratamiento Farmacológico , Evaluación de Procesos y Resultados en Atención de Salud , Prevención Primaria/métodos , Prevención Primaria/estadística & datos numéricos , Estados Unidos/epidemiología

RESUMEN

IMPORTANCE: On the basis of observational studies, the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. Data from randomized clinical trials are lacking. OBJECTIVE: To examine whether the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. DESIGN, SETTING, AND PARTICIPANTS: Using Veterans Affairs and Medicare claims data, this study examined hip and pelvic fracture hospitalizations in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to first-step therapy with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), or an angiotensin-converting enzyme inhibitor (lisinopril). Recruitment was from February 1994 to January 1998; in-trial follow-up ended in March 2002. The mean follow-up was 4.9 years. Posttrial follow-up was conducted through the end of 2006, using passive surveillance via national databases. For this secondary analysis, which used an intention-to-treat approach, data were analyzed from February 1, 1994, through December 31, 2006. MAIN OUTCOMES AND MEASURES: Hip and pelvic fracture hospitalizations. RESULTS: A total of 22 180 participants (mean [SD] age, 70.4 [6.7] years; 43.0% female; and 49.9% white non-Hispanic, 31.2% African American, and 19.1% other ethnic groups) were followed for up to 8 years (mean [SD], 4.9 [1.5] years) during masked therapy. After trial completion, 16 622 participants for whom claims data were available were followed for up to 5 additional years (mean [SD] total follow-up, 7.8 [3.1] years). During the trial, 338 fractures occurred. Participants randomized to receive chlorthalidone vs amlodipine or lisinopril had a lower risk of fracture on adjusted analyses (hazards ratio [HR], 0.79; 95% CI, 0.63-0.98; P = .04). Risk of fracture was significantly lower in participants randomized to receive chlorthalidone vs lisinopril (HR, 0.75; 95% CI, 0.58-0.98; P = .04) but not significantly different compared with those randomized to receive amlodipine (HR, 0.82; 95% CI, 0.63-1.08; P = .17). During the entire trial and posttrial period of follow-up, the cumulative incidence of fractures was nonsignificantly lower in participants randomized to receive chlorthalidone vs lisinopril or amlodipine (HR, 0.87; 95% CI, 0.74-1.03; P = .10) and vs each medication separately. In sensitivity analyses, when 1 year after randomization was used as the baseline (to allow for the effects of medications on bone to take effect), similar results were obtained for in-trial and in-trial plus posttrial follow-up. CONCLUSIONS AND RELEVANCE: These findings from a large randomized clinical trial provide evidence of a beneficial effect of thiazide-type diuretic therapy in reducing hip and pelvic fracture risk compared with treatment with other antihypertensive medications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000542.

Asunto(s)

Amlodipino/uso terapéutico , Antihipertensivos/uso terapéutico , Clortalidona/uso terapéutico , Fracturas de Cadera/epidemiología , Fracturas de Cadera/prevención & control , Lisinopril/uso terapéutico , Huesos Pélvicos/lesiones , Anciano , Femenino , Estudios de Seguimiento , Humanos , Análisis de Intención de Tratar , Masculino , Medición de Riesgo , Factores de Riesgo , Estados Unidos/epidemiología

RESUMEN

BACKGROUND: Although hypertension guidelines define treatment-resistant hypertension as blood pressure uncontrolled by ≥3 antihypertensive medications, including a diuretic, it is unknown whether patient prognosis differs when a diuretic is included. METHODS: Participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) were randomly assigned to first-step therapy with chlorthalidone, amlodipine, or lisinopril. At a Year 2 follow-up visit, those with average blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic on ≥3 antihypertensive medications, or blood pressure <140/90 mm Hg on ≥4 antihypertensive medications were identified as having apparent treatment-resistant hypertension. The prevalence of treatment-resistant hypertension and its association with ALLHAT primary (combined fatal coronary heart disease or nonfatal myocardial infarction) and secondary (all-cause mortality, stroke, heart failure, combined coronary heart disease, and combined cardiovascular disease) outcomes were identified for each treatment group. RESULTS: Of participants assigned to chlorthalidone, amlodipine, or lisinopril, 9.6%, 11.4%, and 19.7%, respectively, had treatment-resistant hypertension. During mean follow-up of 2.9 years, primary outcome incidence was similar for those assigned to chlorthalidone compared with amlodipine or lisinopril (amlodipine- vs chlorthalidone-adjusted hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.53-1.39; P = .53; lisinopril- vs chlorthalidone-adjusted HR = 1.06; 95% CI, 0.70-1.60; P = .78). Secondary outcome risks were similar for most comparisons except coronary revascularization, which was higher with amlodipine than with chlorthalidone (HR 1.86; 95% CI, 1.11-3.11; P = .02). An as-treated analysis based on diuretic use produced similar results. CONCLUSIONS: In this study, which titrated medications to a goal, participants assigned to chlorthalidone were less likely to develop treatment-resistant hypertension. However, prognoses in those with treatment-resistant hypertension were similar across treatment groups.

Asunto(s)

Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Anciano , Amlodipino/administración & dosificación , Amlodipino/uso terapéutico , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/etiología , Clortalidona/administración & dosificación , Clortalidona/uso terapéutico , Diuréticos/administración & dosificación , Diuréticos/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Hipertensión/complicaciones , Lisinopril/administración & dosificación , Lisinopril/uso terapéutico , Masculino , Insuficiencia del Tratamiento , Resultado del Tratamiento

RESUMEN

BACKGROUND/OBJECTIVES: Chronic kidney disease (CKD) and cancer are both common in older patients; whether CKD increases risk for cancer is unclear. This study evaluated CKD as a risk factor for cancer mortality in a large cohort of hypertensive patients. STUDY DESIGN: We did post-hoc analyses of in-trial and post-trial data from participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). SETTING AND PARTICIPANTS: Participants were ≥ 55 years old with hypertension and one other additional risk factor for coronary heart disease. PREDICTOR: Baseline estimated glomerular filtration rate (eGFR). OUTCOMES: Cancer mortality was ascertained by cancer-related deaths reported in national databases during and after the trial. Cox proportional hazard models were used to calculate hazard ratios (HRs) adjusted for possible confounders and were stratified by baseline GFR. RESULTS: Participants' mean age was 66.9 years. After a mean follow-up of 8.9 years, there were 2,338 reported cancer-related deaths. Participants with GFR < 45 mL/min/1.73 m2 were at increased risk of cancer mortality compared to those with GFR ≥ 90 mL/min/1.73 m2 (adjusted HR 1.54 (1.22 - 1.94), p-value for trend 0.004). These findings were consistent across subgroups defined by race, gender, and diabetes. Participants with GFR < 45 mL/min/1.73 m2 were at higher risk for mortality related to colon cancer (p-value for trend 0.048, HR 2.28 (1.12 - 4.62)) and urinary tract cancer (p-value for trend 0.001, adjusted HR 2.95 (1.14 - 7.65)). LIMITATIONS: This is a post hoc analysis of clinical trial data. CONCLUSIONS: In a large cohort of hypertensive patients, GFR < 45 mL/min/1.73 m2 was associated with a higher risk of cancer-related mortality.

Asunto(s)

Tasa de Filtración Glomerular , Hipertensión/complicaciones , Neoplasias/mortalidad , Insuficiencia Renal Crónica/fisiopatología , Anciano , Antihipertensivos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal Crónica/complicaciones , Factores de Riesgo

RESUMEN

BACKGROUND: In this study, we aimed to translate the average relative effect of statin therapy from trial data to the individual patient with type 2 diabetes mellitus by developing and validating a model to predict individualized absolute risk reductions (ARR) of cardiovascular events. METHODS AND RESULTS: Data of 2725 patients with type 2 diabetes mellitus from the Lipid Lowering Arm of the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT-LLA) study (atorvastatin 10 mg versus placebo) were used for model derivation. The model was based on 8 clinical predictors including treatment allocation (statin/placebo). Ten-year individualized ARR on major cardiovascular events by statin therapy were calculated for each patient by subtracting the estimated on-treatment risk from the estimated off-treatment risk. Predicted 10-year ARR by statin therapy was <2% for 13% of the patients. About 30% had an ARR of >4% (median ARR, 3.2%; interquartile range, 2.5%-4.3%; 95% confidence interval for 3.2% ARR, -1.4% to 6.8%). Addition of treatment interactions did not improve model performance. Therefore, the wide distribution in ARR was a consequence of the underlying distribution in cardiovascular risk enrolled in these trials. External validation of the model was performed in data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT; pravastatin 40 mg versus usual care) and Collaborative Atorvastatin Diabetes Study (CARDS; atorvastatin 10 mg versus placebo) of 3878 and 2838 patients with type 2 diabetes mellitus, respectively. Model calibration was adequate in both external data sets, discrimination was moderate (ALLHAT-LLT: c-statistics, 0.64 [95% confidence interval, 0.61-0.67] and CARDS: 0.68 [95% confidence interval, 0.64-0.72]). CONCLUSIONS: ARRs of major cardiovascular events by statin therapy can be accurately estimated for individual patients with type 2 diabetes mellitus using a model based on routinely available patient characteristics. There is a wide distribution in ARR that may complement informed decision making. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00327418 (CARDS) and NCT00000542 (ALLHAT).

Asunto(s)

Antihipertensivos/uso terapéutico , Atorvastatina/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Técnicas de Apoyo para la Decisión , Diabetes Mellitus Tipo 2/complicaciones , Dislipidemias/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipertensión/tratamiento farmacológico , Infarto del Miocardio/prevención & control , Adulto , Anciano , Antihipertensivos/efectos adversos , Atorvastatina/efectos adversos , Biomarcadores/sangre , Toma de Decisiones Clínicas , Diabetes Mellitus Tipo 2/diagnóstico , Dislipidemias/sangre , Dislipidemias/complicaciones , Dislipidemias/diagnóstico , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Lípidos/sangre , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/etiología , América del Norte/epidemiología , Valor Predictivo de las Pruebas , Factores Protectores , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Países Escandinavos y Nórdicos , Factores de Tiempo , Resultado del Tratamiento , Reino Unido

RESUMEN

Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH) trial is a randomized, open-label comparison of hydroxycarbamide (also termed hydroxyurea) versus continued chronic transfusion therapy for primary stroke prevention in patients with sickle cell anaemia (SCA) and abnormal TCD. Severity and location of iron overload is an important secondary outcome measure. We report the baseline findings of abdominal organ iron burden in 121 participants. At enrollment, patients were young (9·8 ± 2·9 years), predominantly female (60:40), and previously treated with transfusions (4·1 ± 2·4 years) and iron chelation (3·1 ± 2·1 years). Liver iron concentration (LIC; 9·0 ± 6·6 mg/g dry weight) and serum ferritin were moderately elevated (2696 ± 1678 µg/l), but transferrin was incompletely saturated (47·2 ± 23·6%). Spleen R2* was 509 ± 399 Hz (splenic iron ~13·9 mg/g) and correlated with LIC (r(2)  = 0·14, P = 0·0008). Pancreas R2* was increased in 38·3% of patients but not to levels associated with endocrine toxicity. Kidney R2* was increased in 80·7% of patients; renal iron correlated with markers of intravascular haemolysis and was elevated in patients with increased urine albumin-creatinine ratios. Extra-hepatic iron deposition is common among children with SCA who receive chronic transfusions, and could potentiate oxidative stress caused by reperfusion injury and decellularized haemoglobin.

Asunto(s)

Anemia de Células Falciformes/terapia , Sobrecarga de Hierro/etiología , Reacción a la Transfusión , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/metabolismo , Antidrepanocíticos/uso terapéutico , Niño , Femenino , Ferritinas/sangre , Humanos , Hidroxiurea/uso terapéutico , Hierro/metabolismo , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Imagen por Resonancia Magnética , Masculino , Páncreas/metabolismo , Bazo/metabolismo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Ultrasonografía Doppler Transcraneal

RESUMEN

Thiazide-type diuretics have been recommended for initial treatment of hypertension in most patients, but should this recommendation differ for patients with and without coronary heart disease (CHD)? The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind hypertension treatment trial in 42,418 participants with high risk of combined cardiovascular disease (CVD) (25% with preexisting CHD). This post hoc analysis compares long-term major clinical outcomes in those assigned amlodipine (n = 9048) or lisinopril (n = 9,054) with those assigned chlorthalidone (n = 15,255), stratified by CHD status. After 4 to 8 years, randomized treatment was discontinued. Total follow-up (active treatment + passive surveillance using national databases for deaths and hospitalizations) was 8 to 13 years. For most CVD outcomes, end-stage renal disease, and total mortality, there were no differences across randomized treatment arms regardless of baseline CHD status. In-trial rates of CVD were significantly higher for lisinopril compared with chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared with chlorthalidone in those with and without CHD (overall hazard ratios [HRs] 1.10, p <0.001, and 1.38, p <0.001, respectively). During extended follow-up, significant outcomes according to CHD status interactions (p = 0.012) were noted in amlodipine versus chlorthalidone comparison for CVD and CHD mortality (HR 0.88, p = 0.04, and 0.84, p = 0.04, respectively) in those with CHD at baseline (HR 1.06, p = 0.15, and 1.08, p = 0.17) and in those without. The results of the overall increased stroke mortality in lisinopril compared with chlorthalidone (HR 1.2; p = 0.03) and hospitalized heart failure in amlodipine compared with chlorthalidone (HR 1.12; p = 0.01) during extended follow-up did not differ by baseline CHD status. In conclusion, these results provide no reason to alter our previous recommendation to include a properly dosed diuretic (such as chlorthalidone 12.5 to 25 mg/day) in the initial antihypertensive regimen for most hypertensive patients.

Asunto(s)

Antihipertensivos/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Dislipidemias/complicaciones , Hipertensión/tratamiento farmacológico , Infarto del Miocardio/prevención & control , Guías de Práctica Clínica como Asunto/normas , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/complicaciones , Método Doble Ciego , Dislipidemias/sangre , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/complicaciones , Lípidos/sangre , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Estudios Retrospectivos , Factores de Riesgo

RESUMEN

Although hemoglobin SC (HbSC) disease is usually considered less severe than sickle cell anemia (SCA), which includes HbSS and HbS/ß(0) -thalassemia genotypes, many patients with HbSC experience severe disease complications, including vaso-occlusive pain, acute chest syndrome, avascular necrosis, retinopathy, and poor quality of life. Fully 20 years after the clinical and laboratory efficacy of hydroxyurea was proven in adult SCA patients, the safety and utility of hydroxyurea treatment for HbSC patients remain unclear. Recent NHLBI evidence-based guidelines highlight this as a critical knowledge gap, noting HbSC accounts for ∼30% of sickle cell patients within the United States. To date, only 5 publications have reported short-term, incomplete, or conflicting laboratory and clinical outcomes of hydroxyurea treatment in a total of 71 adults and children with HbSC. We now report on a cohort of 133 adult and pediatric HbSC patients who received hydroxyurea, typically for recurrent vaso-occlusive pain. Hydroxyurea treatment was associated with a stable hemoglobin concentration; increased fetal hemoglobin (HbF) and mean corpuscular volume (MCV); and reduced white blood cell count (WBC), absolute neutrophil count (ANC), and absolute reticulocyte count (ARC). Reversible cytopenias occurred in 22% of patients, primarily neutropenia and thrombocytopenia. Painful events were reduced with hydroxyurea, more in patients >15 years old. These multicenter data support the safety and potentially salutary effects of hydroxyurea treatment for HbSC disease; however, a multicenter, placebo-controlled, Phase 3 clinical trial is needed to determine if hydroxyurea therapy has efficacy for patients with HbSC disease.

Asunto(s)

Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/uso terapéutico , Hidroxiurea/uso terapéutico , Adolescente , Anemia de Células Falciformes/genética , Antidrepanocíticos/administración & dosificación , Antidrepanocíticos/efectos adversos , Niño , Femenino , Humanos , Hidroxiurea/administración & dosificación , Hidroxiurea/efectos adversos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (≥ 200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01425307. FINDINGS: Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140-146) in children who received standard transfusions and 138 cm/s (135-142) in those who received hydroxycarbamide, with a difference of 4·54 (0·10-8·98). Non-inferiority (p=8·82 × 10(-16)) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five [8%] patients with hydroxycarbamide and three events in one [2%] patient for transfusions). INTERPRETATION: For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke. FUNDING: National Heart, Lung, and Blood Institute, National Institutes of Health.

Asunto(s)

Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/uso terapéutico , Transfusión Sanguínea/métodos , Hidroxiurea/uso terapéutico , Adolescente , Anemia de Células Falciformes/fisiopatología , Velocidad del Flujo Sanguíneo , Circulación Cerebrovascular/fisiología , Niño , Preescolar , Terapia Combinada , Sustitución de Medicamentos , Femenino , Humanos , Masculino , Accidente Cerebrovascular/etiología , Resultado del Tratamiento , Ultrasonografía Doppler Transcraneal

RESUMEN

Noninvasive, quantitative, and accurate assessment of liver iron concentration (LIC) by MRI is useful for patients receiving transfusions, but R2 and R2* MRI techniques have not been systematically compared in sickle cell anemia (SCA). We report baseline LIC results from the TWiTCH trial, which compares hydroxyurea with blood transfusion treatment for primary stroke prophylaxis assessed by transcranial Doppler sonography in pediatric SCA patients. Liver R2 was collected and processed using a FDA-approved commercial process (FerriScan®), while liver R2* quality control and processing were performed by a Core Laboratory blinded to clinical site and patient data. Baseline LIC studies using both MRI techniques were available for 120 participants. LICR2* and LICR2 results were highly correlated (r(2) = 0.93). A proportional bias of LIC(R2*)/LIC(R2), decreasing with average LIC, was observed. Systematic differences between LICR2* and LICR2 were also observed by MRI manufacturer. Importantly, LICR2* and LICR2 estimates had broad 95% limits of agreement with respect to each other. We recommend LICR2 and LICR2* not be used interchangeably in SCA patients to follow individual patient trends in iron burden.

Asunto(s)

Anemia de Células Falciformes/terapia , Bioensayo/normas , Sobrecarga de Hierro/metabolismo , Hierro/análisis , Hígado/química , Reacción a la Transfusión , Adolescente , Anemia de Células Falciformes/patología , Antidrepanocíticos/uso terapéutico , Benzoatos/uso terapéutico , Niño , Preescolar , Deferasirox , Deferoxamina/uso terapéutico , Femenino , Humanos , Hidroxiurea/uso terapéutico , Hierro/metabolismo , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/patología , Hígado/metabolismo , Imagen por Resonancia Magnética , Masculino , Accidente Cerebrovascular/prevención & control , Triazoles/uso terapéutico , Ultrasonografía Doppler Transcraneal

RESUMEN

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in 33,357 high-risk hypertensive participants. ALLHAT compared cardiovascular disease outcomes in participants initially treated with an angiotensin-converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), or a thiazide-type diuretic (chlorthalidone). We report stroke outcomes in 1517 participants in-trial and 1596 additional participants during post-trial passive surveillance, for a total follow-up of 8-13 years. Stroke rates were higher with lisinopril (6-year rate/100 = 6.4) than with chlorthalidone (5.8) or amlodipine (5.5) in-trial but not including post-trial (10-year rates/100 = 13.2 [chlorthalidone], 13.1[amlodipine], and 13.7 [lisinopril]). In-trial differences were driven by race (race-by-lisinopril/chlorthalidone interaction P = .005, race-by-amlodipine/lisinopril interaction P = .012) and gender (gender-by-lisinopril/amlodipine interaction P = .041), separately. No treatment differences overall, or by race or gender, were detected over the 10-year period. No differences appeared among treatment groups in adjusted risk of all-cause mortality including post-trial for participants with nonfatal in-trial strokes. Among Blacks and women, lisinopril was less effective in preventing stroke in-trial than either chlorthalidone or amlodipine, even after adjusting for differences in systolic blood pressure. These differences abated by the end of the post-trial period.

Asunto(s)

Amlodipino/administración & dosificación , Clortalidona/administración & dosificación , Hipertensión/tratamiento farmacológico , Lisinopril/administración & dosificación , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/prevención & control , Factores de Edad , Anciano , Amlodipino/efectos adversos , Causas de Muerte , Clortalidona/efectos adversos , Intervalos de Confianza , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/mortalidad , Estimación de Kaplan-Meier , Lisinopril/efectos adversos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/fisiopatología , Tasa de Supervivencia , Resultado del Tratamiento

RESUMEN

Apparent treatment-resistant hypertension (aTRH) is defined as uncontrolled hypertension despite the use of ≥3 antihypertensive medication classes or controlled hypertension while treated with ≥4 antihypertensive medication classes. Although a high prevalence of aTRH has been reported, few data are available on its association with cardiovascular and renal outcomes. We analyzed data on 14 684 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants to determine the association between aTRH (n=1870) with coronary heart disease, stroke, all-cause mortality, heart failure, peripheral artery disease, and end-stage renal disease. We defined aTRH as blood pressure not at goal (systolic/diastolic blood pressure ≥140/90 mm Hg) while taking ≥3 classes of antihypertensive medication or taking ≥4 classes of antihypertensive medication with blood pressure at goal during the year 2 ALLHAT study visit (1996-2000). Use of a diuretic was not required to meet the definition of aTRH. Follow-up occurred through 2002. The multivariable adjusted hazard ratios (95% confidence intervals) comparing participants with versus without aTRH were as follows: coronary heart disease (1.44 [1.18-1.76]), stroke (1.57 [1.18-2.08]), all-cause mortality (1.30 [1.11-1.52]), heart failure (1.88 [1.52-2.34]), peripheral artery disease (1.23 [0.85-1.79]), and end-stage renal disease (1.95 [1.11-3.41]). aTRH was also associated with the pooled outcomes of combined coronary heart disease (hazard ratio, 1.47; 95% confidence interval, 1.26-1.71) and combined cardiovascular disease (hazard ratio, 1.46; 95% confidence interval, 1.29-1.64). These results demonstrate that aTRH increases the risk for cardiovascular disease and end-stage renal disease. Studies are needed to identify approaches to prevent aTRH and reduce risk for adverse outcomes among individuals with aTRH.

Asunto(s)

Antihipertensivos/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Resistencia a Medicamentos , Hipertensión/tratamiento farmacológico , Fallo Renal Crónico/epidemiología , Infarto del Miocardio/prevención & control , Anciano , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Hipolipemiantes/uso terapéutico , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Insuficiencia del Tratamiento , Resultado del Tratamiento