RESUMEN
OBJECTIVES: Digital health definitions are abundant, but often lack clarity and precision. We aimed to develop a minimum information framework to define patient-facing digital health interventions (DHIs) for outcomes research. METHODS: Definitions of digital-health-related terms (DHTs) were systematically reviewed, followed by a content analysis using frameworks, including PICOTS (population, intervention, comparator, outcome, timing, and setting), Shannon-Weaver Model of Communication, Agency for Healthcare Research and Quality Measures, and the World Health Organization's Classification of Digital Health Interventions. Subsequently, we conducted an online Delphi study to establish a minimum information framework, which was pilot tested by 5 experts using hypothetical examples. RESULTS: After screening 2610 records and 545 full-text articles, we identified 101 unique definitions of 67 secondary DHTs in 76 articles, resulting in 95 different patterns of concepts among the definitions. World Health Organization system (84.5%), message (75.7%), intervention (58.3%), and technology (52.4%) were the most frequently covered concepts. For the Delphi survey, we invited 47 members of the ISPOR Digital Health Special Interest Group, 18 of whom became the Delphi panel. The first, second, and third survey rounds were completed by 18, 11, and 10 respondents, respectively. After consolidating results, the PICOTS-ComTeC acronym emerged, involving 9 domains (population, intervention, comparator, outcome, timing, setting, communication, technology, and context) and 32 optional subcategories. CONCLUSIONS: Patient-facing DHIs can be specified using PICOTS-ComTeC that facilitates identification of appropriate interventions and comparators for a given decision. PICOTS-ComTeC is a flexible and versatile tool, intended to assist authors in designing and reporting primary studies and evidence syntheses, yielding actionable results for clinicians and other decision makers.
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Salud Digital , Envío de Mensajes de Texto , Estados Unidos , Humanos , Opinión Pública , Evaluación de Resultado en la Atención de Salud , ComunicaciónRESUMEN
OBJECTIVES: This study aimed to review definitions of digital health and understand their relevance for health outcomes research. Four umbrella terms (digital health, electronic health, mobile health, and telehealth/telemedicine) were summarized in this article. METHODS: PubMed/MEDLINE, Embase, Cochrane Library, and EconLit were searched from January 2015 to May 2020 for systematic reviews containing key Medical Subject Headings terms for digital health (n = 38) and synonyms of "definition." Independent pairs of reviewers performed each stage of the review, with reconciliation by a third reviewer if required. A single reviewer consolidated each definition for consistency. We performed text analysis via word clouds and computed document frequency-and inverse corpus frequency scores. RESULTS: The search retrieved 2610 records with 545 articles (20.9%) taken forward for full-text review. Of these, 39.3% (214 of 545) were eligible for data extraction, of which 134 full-text articles were retained for this analysis containing 142 unique definitions of umbrella terms (digital health [n = 4], electronic health [n = 36], mobile health [n = 50], and telehealth/telemedicine [n = 52]). Seminal definitions exist but have increasingly been adapted over time and new definitions were created. Nevertheless, the most characteristic words extracted from the definitions via the text analyses still showed considerable overlap between the 4 umbrella terms. CONCLUSIONS: To focus evidence summaries for outcomes research purposes, umbrella terms should be accompanied by Medical Subject Headings terms reflecting population, intervention, comparator, outcome, timing, and setting. Ultimately a functional classification system is needed to create standardized terminology for digital health interventions denoting the domains of patient-level effects and outcomes.
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Telemedicina , Envío de Mensajes de Texto , Humanos , Evaluación de Resultado en la Atención de Salud , Opinión Pública , Revisiones Sistemáticas como AsuntoRESUMEN
The optimal blood pressure (BP) to prevent major adverse outcomes (death, myocardial infarction, and stroke) for patients with hypertension and coronary artery disease who have undergone previous revascularization is unknown but might be influenced by the type of revascularization procedure. We analyzed data from the INternational VErapamil SR-Trandolapril STudy, focusing on the relation between BP and the outcomes of 6,166 previously revascularized patients, using the 16,410 nonrevascularized patients as a reference group. The previous revascularization strategy consisted of coronary artery bypass grafting (CABG, 45.2%), percutaneous coronary intervention (PCI, 42.1%), or both (CABG+PCI, 12.8%). Patients who had undergone both CABG+PCI and CABG-only had a greater adverse outcome risk (adjusted hazard ratio 1.27% and 1.20%, 95% confidence interval 1.06 to 1.53 and 1.07 to 1.35, respectively). The risk was similar for PCI-only patients (adjusted hazard ratio 1.04, 95% confidence interval 0.92 to 1.19). The relations between the adjusted hazard ratio and on-treatment BP appeared J-shaped for each revascularization strategy, accentuated for PCI and diastolic BP (DBP), but excepting CABG only and DBP for which the relation was linear and positive. In conclusion, major adverse outcomes were more frequent in patients with coronary artery disease who had undergone previous CABG, with or without PCI, compared to those with previous PCI only. This likely reflected more severe vascular disease. The relation to systolic BP was J-shaped for each strategy. Among those patients with previous CABG only, the linear relation with DBP suggested that more complete revascularization might attenuate hypoperfusion at a low DBP. The management of BP might, therefore, require modification of targets according to the revascularization strategy to improve outcomes.
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Angioplastia Coronaria con Balón , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/terapia , Hipertensión/tratamiento farmacológico , Anciano , Antihipertensivos/uso terapéutico , Presión Sanguínea , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Revascularización Miocárdica , Resultado del TratamientoRESUMEN
BACKGROUND: Our understanding of the growing population of very old patients (aged >or=80 years) with coronary artery disease and hypertension is limited, particularly the relationship between blood pressure and adverse outcomes. METHODS: This was a secondary analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable hypertensive coronary artery disease patients aged >or=50 years. The patients were grouped by age in 10-year increments (aged >or=80, n=2180; 70-<80, n=6126; 60-<70, n=7602; <60, n=6668). Patients were randomized to either verapamil SR- or atenolol-based treatment strategies, and primary outcome was first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: At baseline, increasing age was associated with higher systolic blood pressure, lower diastolic blood pressure, and wider pulse pressure (P <.001). Treatment decreased systolic, diastolic, and pulse pressure for each age group. However, the very old retained the widest pulse pressure and the highest proportion (23.6%) with primary outcome. The adjusted hazard ratio for primary outcomes showed a J-shaped relationship among each age group with on-treatment systolic and diastolic pressures. The systolic pressure at the hazard ratio nadir increased with increasing age, highest for the very old (140 mm Hg). However, diastolic pressure at the hazard ratio nadir was only somewhat lower for the very old (70 mm Hg). Results were independent of treatment strategy. CONCLUSION: Optimal management of hypertension in very old coronary artery disease patients may involve targeting specific systolic and diastolic blood pressures that are higher and somewhat lower, respectively, compared with other age groups.
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Presión Sanguínea , Enfermedad de la Arteria Coronaria/epidemiología , Hipertensión/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Diástole/fisiología , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Sístole/fisiología , Resultado del TratamientoRESUMEN
The International Verapamil SR-Trandolapril Study (INVEST), a randomized trial of 22,576 predominantly elderly patients with an average 2.7-year follow-up, compared a calcium antagonist-led strategy (verapamil SR plus trandolapril) with a beta-blocker-led strategy (atenolol plus hydrochlorothiazide) for hypertension treatment and prevention of cardiovascular outcomes in coronary artery disease patients. Patients received individualized dose and drug titration following a flexible, multi-drug, guideline-based treatment algorithm, with the objective of achieving optimal blood pressure (BP) control individualized for comorbidities (e.g., diabetes). The primary outcome (PO) was first occurrence of death (all-cause), nonfatal myocardial infarction or nonfatal stroke. The strategies resulted in significant and very similar BP reduction, with approximately 70% of patients in both strategies achieving BP control (<140/90 mmHg). Increasing number of office visits with BP in control was associated with reduced risk of the PO. Overall, there was no difference in the PO comparing the strategies; however, new-onset diabetes occurred more frequently in those assigned the atenolol strategy. This report summarizes findings from INVEST and puts them in perspective with our current state of knowledge derived from other large hypertension treatment trials. INVEST findings support that BP reduction is important for prevention of adverse cardiovascular morbidity and mortality, and selection of antihypertensive agents should be based on patient comorbidities and other risk factors (e.g., risk for diabetes) and not necessarily that any one drug be given to all.
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Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Indoles/uso terapéutico , Verapamilo/uso terapéutico , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Atenolol/uso terapéutico , Enfermedad de la Arteria Coronaria/complicaciones , Preparaciones de Acción Retardada , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diuréticos/uso terapéutico , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Hidroclorotiazida/uso terapéutico , Hipertensión/complicaciones , Masculino , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
AIM: The purpose of this study was to assess the relationship between pulse pressure (PP) and cardiovascular outcomes in a large, elderly, coronary artery disease (CAD) population with hypertension, and compare the predictive power of PP with other blood pressure measures. METHODS AND RESULTS: In INternational VErapamil-trandolapril STudy, 22,576 CAD patients with hypertension (mean age 66 years) were randomized to verapamil-SR or atenolol-based strategies and followed for 2.7 years (mean). Primary outcome (PO) was time to first occurrence of death (all-cause), non-fatal myocardial infarction (MI), or non-fatal stroke. Mean follow-up PP was summarized by 5 mmHg subgroups for association with incidence of PO. Stepwise Cox proportional hazards models were used to estimate adjusted relative hazard ratios (HR) for the risk of PO with follow-up PP as a continuous variable, with linear and quadratic terms. Similar models were constructed for follow-up systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressures (MAP). A -2 log-likelihood statistic was used to assess the predictive power of PP compared with SBP, DBP, and MAP. For follow-up PP, the incidence and adjusted HR for the PO formed a J- or U-shaped curve. After adjusting for baseline covariates, both linear and quadratic terms for PP were significant (P < 0.0001 for both), with a nadir of 54 mmHg (bootstrapping 95% CI 42-60 mmHg). Similar quadratic relationships were found between PP and all-cause mortality or MI; the relationship between PP and stroke was linear. Pulse pressure was a predictor of PO even after including SBP (P = 0.007 linear term) or DBP (P < 0.0001 for both linear and quadratic terms) or MAP (P < 0.01 for both liner and quadratic terms) in the model. Using -2 log-likelihood differences, SBP (-2 log-likelihood difference 77.1 vs. 7.3 for PP), DBP (-2 log-likelihood difference 138.5 vs. 44.6 for PP), and MAP (-2 log-likelihood difference 125.0 vs. 13.4 for PP) were stronger predictors of PO than PP. CONCLUSION: In CAD patients with hypertension, PP (on anti-hypertensive treatment) is a weaker predictor of cardiovascular outcomes than SBP, DBP, or MAP.
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Antihipertensivos/uso terapéutico , Presión Sanguínea/fisiología , Enfermedad Coronaria/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Infarto del Miocardio/prevención & control , Verapamilo/uso terapéutico , Anciano , Atenolol/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/fisiopatología , Femenino , Humanos , Hipertensión/mortalidad , Hipertensión/fisiopatología , Masculino , Infarto del Miocardio/mortalidad , Pronóstico , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/prevención & control , Resultado del TratamientoRESUMEN
Our understanding of the growing population of revascularized patients with hypertension is limited. We retrospectively analyzed the International Verapamil SR-Trandolapril Study, which randomized coronary artery disease patients with hypertension to either verapamil SR- or atenolol-based treatment strategies, focusing on characteristics and outcomes of 6166 previously revascularized patients compared with 16 410 nonrevascularized patients. Revascularized patients had a history of coronary artery bypass grafting (45.2%), percutaneous coronary intervention (42.1%), or both (12.8%). Compared with nonrevascularized patients, revascularized patients at baseline demonstrated a higher prevalence of coronary artery disease risk factors and risk conditions (P<0.001). This higher prevalence was the principal cause of a higher incidence of primary outcome (death, nonfatal myocardial infarction, or nonfatal stroke) among revascularized patients (14.2% versus 8.5% for nonrevascularized patients; P<0.001). However, both patient groups demonstrated a relatively low incidence of subsequent revascularization (5.1% versus 1.5% respectively; P<0.0001). Associations between adjusted hazard ratio for primary outcome and follow-up blood pressure appeared "J shaped" for both patient groups. Because, as a group, revascularized patients with hypertension had worse outcomes compared with nonrevascularized patients, management of blood pressure to a specific target in future studies could result in improved outcomes.
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Enfermedad de la Arteria Coronaria , Hipertensión/tratamiento farmacológico , Hipertensión/mortalidad , Indoles/uso terapéutico , Verapamilo/uso terapéutico , Anciano , Angioplastia Coronaria con Balón , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/uso terapéutico , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/terapia , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Metabolic syndrome (MS), typified by hypertension, abdominal obesity, dyslipidaemia and impaired glucose metabolism, is a precursor of type 2 diabetes. Thiazide diuretics (TD) and beta-blockers are associated with increased risk of diabetes in patients with hypertension; however, the role of these agents in development of diabetes in MS patients is unknown. We reviewed the literature regarding risk factors for diabetes development and compared this with data from the Study of Trandolapril/Verapamil SR And Insulin Resistance (STAR), which investigated the effects of two fixed-dose combinations (FDCs) [trandolapril/verapamil SR and losartan/hydrochlorothiazide (L/H)] on glucose control and new diabetes in MS patients. In STAR, logistic regression modelling identified haemoglobin A1c [odds ratio (OR) 4.21 per 1% increment; p = 0.003), L/H treatment (OR 4.04; p = 0.002) and 2-h oral glucose tolerance test glucose levels (OR 1.39 per 10 mg/dl increments; p < 0.001) as baseline predictors of diabetes. These data support prior analyses and suggest that choice of antihypertensive agent is important. Patients with MS may be at lower risk of diabetes when using a FDC calcium channel blocker + angiotensin-converting enzyme inhibitor compared with an angiotensin receptor blocker + TD.
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Antihipertensivos/efectos adversos , Diabetes Mellitus Tipo 2/inducido químicamente , Hipertensión/tratamiento farmacológico , Síndrome Metabólico/diagnóstico , Estado Prediabético/diagnóstico , Antihipertensivos/administración & dosificación , Humanos , Síndrome Metabólico/inducido químicamente , Estado Prediabético/inducido químicamente , Medición de RiesgoRESUMEN
Diabetic nephropathy management should include the use of an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker with additional antihypertensive medications to reduce proteinuria and cardiovascular events. Some studies suggest that adding a nondihydropyridine rather than a dihydropyridine calcium channel blocker (CCB) may more effectively lower proteinuria. We hypothesized that a trandolapril/verapamil SR (T/V) fixed-dose combination (FDC) was superior to a benazepril/amlodipine (B/A) FDC for reducing albuminuria in 304 hypertensive diabetic nephropathy patients when treated for 36 weeks. No statistically significant differences were observed between groups in the primary end point; adjusted percentage change in urinary albumin/creatinine ratio (UACR), which increased (mean T/V, 29.29%; mean B/A, 8.49%; difference, 20.80%; P=.34); or in change in absolute UACR, which decreased (mean [g/g] T/V, -0.11; mean [g/g] B/A, -0.08; difference -0.03; P=.78). There were significant reductions in log UACR (mean change in T/V, -0.28; P<.01; mean change in B/A, -0.31; P<.001) and diastolic blood pressure in both groups and in systolic blood pressure in the B/A group. T/V was not superior to B/A for reducing UACR. Both ACEI/CCB FDCs may reduce albuminuria; in the case of T/V, this appears to be independent of systolic blood pressure reduction in patients who had previously been treated and had baseline blood pressure levels of 142/77 mm Hg.
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Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/farmacología , Nefropatías Diabéticas/complicaciones , Proteinuria/complicaciones , Proteinuria/tratamiento farmacológico , Anciano , Albuminuria/complicaciones , Albuminuria/tratamiento farmacológico , Albuminuria/fisiopatología , Amlodipino/farmacología , Amlodipino/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Benzazepinas/farmacología , Benzazepinas/uso terapéutico , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/fisiopatología , Sinergismo Farmacológico , Quimioterapia Combinada , Femenino , Humanos , Indoles/farmacología , Indoles/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteinuria/fisiopatología , Resultado del Tratamiento , Verapamilo/farmacología , Verapamilo/uso terapéuticoRESUMEN
BACKGROUND: In patients with prior myocardial infarction (MI), beta-blockers reduce mortality by 23% to 40%. However, despite this favorable effect, adverse effects limit compliance to this medication. The purpose of the study was to compare a beta-blocker-based strategy with a heart rate-lowering calcium antagonists-based strategy in patients with prior MI. METHODS: We evaluated 7,218 patients with prior MI enrolled in the INternational VErapamil SR-Trandolapril (INVEST) substudy randomized to verapamil-sustained release (SR)- or atenolol-based strategies. Primary outcome was time to first occurrence of death (all-cause), nonfatal MI, or nonfatal stroke. Secondary outcomes included death, total MI (fatal and nonfatal), and total stroke (fatal and nonfatal) considered separately. RESULTS: During the 2.8 +/- 1.0 years of follow-up, patients assigned to the verapamil-SR-based and atenolol-based strategies had comparable blood pressure control, and the incidence of the primary outcome was equivalent. There was no difference between the 2 strategies for the outcomes of either death or total MI. However, more patients reported excellent/good well-being (82.3% vs 78.0%, P = .02) at 24 months with a trend toward less incidence of angina pectoris (12.0% vs 14.3%, adjusted P = .07), nonfatal stroke (1.4% vs 2.0%; P = .06), and total stroke (2.0% vs 2.5%, P = .18) in the verapamil-SR-based strategy group. CONCLUSIONS: In hypertensive patients with prior MI, a verapamil-SR-based strategy was equivalent to a beta-blocker-based strategy for blood pressure control and prevention of cardiovascular events, with greater subjective feeling of well-being and a trend toward lower incidence of angina pectoris and stroke in the verapamil-SR-based group.
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Antagonistas Adrenérgicos beta/uso terapéutico , Atenolol/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Hipertensión/tratamiento farmacológico , Infarto del Miocardio/tratamiento farmacológico , Accidente Cerebrovascular/prevención & control , Verapamilo/uso terapéutico , Antagonistas Adrenérgicos beta/efectos adversos , Anciano , Angina de Pecho/prevención & control , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Atenolol/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Preparaciones de Acción Retardada , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Indoles/uso terapéutico , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Infarto del Miocardio/prevención & control , Modelos de Riesgos Proporcionales , Riesgo , Método Simple Ciego , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/mortalidad , Verapamilo/efectos adversosRESUMEN
AIM: To determine the relationship between resting heart rate (RHR) and adverse outcomes in coronary artery disease (CAD) patients treated for hypertension with different RHR-lowering strategies. METHODS AND RESULTS: Time to adverse outcomes (death, non-fatal myocardial infarction, or non-fatal-stroke) and predictive values of baseline and follow-up RHR were assessed in INternational VErapamil-SR/trandolapril STudy (INVEST) patients randomized to either a verapamil-SR (Ve) or atenolol (At)-based strategy. Higher baseline and follow-up RHR were associated with increased adverse outcome risks, with a linear relationship for baseline RHR and J-shaped relationship for follow-up RHR. Although follow-up RHR was independently associated with adverse outcomes, it added less excess risk than baseline conditions such as heart failure and diabetes. The At strategy reduced RHR more than Ve (at 24 months, 69.2 vs. 72.8 beats/min; P < 0.001), yet adverse outcomes were similar [Ve 9.67% (rate 35/1000 patient-years) vs. At 9.88% (rate 36/1000 patient-years, confidence interval 0.90-1.06, P = 0.62)]. For the same RHR, men had a higher risk than women. CONCLUSION: Among CAD patients with hypertension, RHR predicts adverse outcomes, and on-treatment RHR is more predictive than baseline RHR. A Ve strategy is less effective than an At strategy for lowering RHR but has a similar effect on adverse outcomes.
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Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Indoles/uso terapéutico , Verapamilo/uso terapéutico , Anciano , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Resultado del TratamientoRESUMEN
Reversal of new-onset diabetes secondary to thiazide diuretic use remains questionable. STAR-LET was a 6-month extension of the Study of Trandolapril/Verapamil SR and Insulin Resistance (STAR), which assessed the effects of a fixed-dose renin-angiotensin system inhibitor (RASI)/hydrochlorothiazide (HCTZ) combination on changes in 2-hour oral glucose tolerance test (OGTT) results. STAR-LET explored whether the glycemic impact of HCTZ could be reversed by conversion to a RASI/verapamil combination. The primary outcome was change in 2-hour OGTT results. Fifty-one percent of the STAR patients were enrolled in STAR-LET. The 2-hour OGTT value (mmol/L) was unchanged from STAR baseline in the RASI/verapamil group (7.7+/-2.4 vs 8.1+/-3.3; P=.18) and improved in those who were switched from RASI/HCTZ to RASI/verapamil (8.5+/-3.0 vs 7.2+/-2.3; P<.001). This exploratory study suggests that the impairment in glycemic control seen with use of a thiazide diuretic combined with a RASI can be reversed by switching to a regimen that does not include a diuretic.
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Diabetes Mellitus/prevención & control , Diuréticos/efectos adversos , Hidroclorotiazida/efectos adversos , Hipertensión/tratamiento farmacológico , Indoles/uso terapéutico , Losartán/efectos adversos , Síndrome Metabólico/tratamiento farmacológico , Verapamilo/uso terapéutico , Análisis de Varianza , Distribución de Chi-Cuadrado , Diabetes Mellitus/etiología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
BACKGROUND AND PURPOSE: Our understanding of factors influencing stroke risk among patients with coronary artery disease is incomplete. Accordingly, factors predicting stroke risk in hypertensive, clinically stable coronary artery disease patients were determined with data from the INternational VErapamil SR-trandolapril STudy (INVEST). METHODS: The effect of baseline characteristics and on-treatment blood pressure (BP) were analyzed to determine the risk of stroke (fatal or nonfatal) among the 22 576 patients enrolled. Cox proportional-hazards models (unadjusted, adjusted, and time dependent) were used to identify predictors of stroke among subgroups with these characteristics present at entry and on-treatment BP. RESULTS: Excellent BP control (at 24 months, >70% <140/90 mm Hg) was achieved during 61 835 patient-years of follow-up, as 377 patients had a stroke (6.1 strokes/1000 patient-years) and 28% of those patients had a fatal stroke. Increased age, black race, US residency, and history of prior myocardial infarction, smoking, stroke/transient ischemic attack, arrhythmia, diabetes, and coronary bypass surgery were associated with an increased risk of stroke. Achieving a systolic BP <140 mm Hg and a diastolic BP <90 mm Hg was associated with a decreased risk of stroke. There was no statistically significant difference in stroke risk comparing the verapamil SR-based with the atenolol-based treatment strategy (adjusted hazard ratio=0.87; 95% CI, 0.71 to 1.06; P=0.17). CONCLUSIONS: Among hypertensive patients with chronic coronary artery disease, stroke was an important complication associated with significant mortality. Black race, US residency, and conditions associated with increased vascular disease severity and arrhythmia predicted increased stroke risk, whereas achieving a BP <140/90 mm Hg on treatment predicted a reduced stroke risk.
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Enfermedad de la Arteria Coronaria/mortalidad , Hipertensión/mortalidad , Accidente Cerebrovascular/mortalidad , Anciano , Anciano de 80 o más Años , Antihipertensivos/uso terapéutico , Atenolol/uso terapéutico , Población Negra/estadística & datos numéricos , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Hidroclorotiazida/uso terapéutico , Hipertensión/tratamiento farmacológico , Indoles/uso terapéutico , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Factores de Riesgo , Estados Unidos/epidemiología , Verapamilo/uso terapéuticoRESUMEN
PURPOSE: An obesity paradox, a "paradoxical" decrease in morbidity and mortality with increasing body mass index (BMI), has been shown in patients with heart failure and those undergoing percutaneous coronary intervention. However, whether this phenomenon exists in patients with hypertension and coronary artery disease is not known. METHODS: A total of 22,576 hypertensive patients with coronary artery disease (follow-up 61,835 patient years, mean age 66+/-9.8 years) were randomized to a verapamil-SR or atenolol strategy. Dose titration and additional drugs (trandolapril and/or hydrochlorothiazide) were added to achieve target blood pressure control according to the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure targets. Patients were classified into 5 groups according to baseline BMI: less than 20 kg/m2 (thin), 20 to 25 kg/m2 (normal weight), 25 to 30 kg/m2 (overweight), 30 to 35 kg/m2 (class I obesity), and 35 kg/m2 or more (class II-III obesity). The primary outcome was first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: With patients of normal weight (BMI 20 to<25 kg/m2) as the reference group, the risk of primary outcome was lower in the overweight patients (adjusted hazard ratio [HR] 0.77, 95% confidence interval [CI], 0.70-0.86, P<.001), class I obese patients (adjusted HR 0.68, 95% CI, 0.59-0.78, P<.001), and class II to III obese patients (adjusted HR 0.76, 95% CI, 0.65-0.88, P <.001). Class I obese patients had the lowest rate of primary outcome and death despite having smaller blood pressure reduction compared with patients of normal weight at 24 months (-17.5+/-21.9 mm Hg/-9.8+/-12.4 mm Hg vs -20.7+/-23.1 mm Hg /-10.6+/-12.5 mm Hg, P<.001). CONCLUSION: In a population with hypertension and coronary artery disease, overweight and obese patients had a decreased risk of primary outcome compared with patients of normal weight, which was driven primarily by a decreased risk of all-cause mortality. Our results further suggest a protective effect of obesity in patients with known cardiovascular disease in concordance with data in patients with heart failure and those undergoing percutaneous coronary intervention.
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Enfermedad de la Arteria Coronaria/epidemiología , Hipertensión/epidemiología , Obesidad/epidemiología , Distribución por Edad , Anciano , Antihipertensivos/uso terapéutico , Atenolol/uso terapéutico , Índice de Masa Corporal , Causalidad , Estudios de Cohortes , Comorbilidad , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad/clasificación , Evaluación de Procesos y Resultados en Atención de Salud , Factores de Riesgo , Distribución por Sexo , Análisis de Supervivencia , Estados Unidos/epidemiología , Vasodilatadores/uso terapéutico , Verapamilo/uso terapéuticoRESUMEN
Uncontrolled blood pressure (BP) increases cardiovascular risk, independent of type of treatment. In this posthoc International Verapamil SR-Trandolapril Study analysis, we determined whether adverse outcomes are related to consistency of BP control, defined as the proportion of visits in which BP was in control. A total of 22 576 patients with hypertension and coronary artery disease were divided into 4 groups according to the proportion of visits in which BP was in control (<140/90 mm Hg): <25%, 25% to <50%, 50% to <75%, and >or=75%. Risk of primary outcome (first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke), myocardial infarction, and stroke decreased progressively from the group with <25% to the group with >or=75% of visits with BP control. Adjusted risks of primary outcome (heart rate: 0.60; 95% CI: 0.53 to 0.67), myocardial infarction (heart rate: 0.58; 95% CI: 0.48 to 0.70), and stroke (heart rate: 0.50; 95% CI: 0.37 to 0.67) were less in the group with >or=75% of visits with BP control compared with the group with <25% of visits with BP control. Baseline BP was not predictive of outcomes. Proportion of visits with BP control was associated with mean follow-up systolic BP (r(2)=0.64), both being independently related to primary outcome. As proportion of visits with BP control increases, there is an associated steep reduction in cardiovascular risk, independent of baseline characteristics and mean on-treatment BP. Consistency of BP control during treatment provides additional information on the protective effect of antihypertensive treatment. Physicians need to be concerned at each visit if BP is not controlled.
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Enfermedades Cardiovasculares/prevención & control , Hipertensión/tratamiento farmacológico , Indoles/administración & dosificación , Verapamilo/administración & dosificación , Anciano , Determinación de la Presión Sanguínea , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/diagnóstico , Masculino , Persona de Mediana Edad , Probabilidad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Valores de Referencia , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: The majority of hypertensive patients require combination therapy to achieve BP goals. Guidelines recommend dual therapy in newly diagnosed patients with BP > 160/100mm Hg. Calcium channel blocker (CCB)/ACE inhibitor and beta-blocker (beta-adrenoceptor antagonists)/diuretic combinations are among regimens considered effective for BP control. ACE inhibitors, beta-blockers, and CCBs are recommended for use in patients after myocardial infarction (MI). Statistical modeling from INVEST (INternational VErapamil-Trandolapril STudy), suggests an association between dual and triple therapy and decreased risk of primary outcome ([PO] first occurrence of death, nonfatal MI, or nonfatal stroke) in patients with hypertension and coronary artery disease (CAD). OBJECTIVE AND METHODS: This study explores the utility of dual antihypertensive therapy by reporting BP and cardiovascular outcomes for INVEST patients who predominantly received either a CCB/ACE inhibitor or a beta-blocker/ diuretic regimen. RESULTS: 1170 patients were selected for analysis. After 24 months of treatment, BP control (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VI criteria) was 82.1% and 82.6% in the verapamil sustained release (SR) + trandolapril (Ve + Tr) and atenolol + hydrochlorothiazide (At + HCTZ) groups, respectively (p = 0.86). In Ve + Tr compared to At + HCTZ patients, adjusted risk for PO (hazard ratio [HR] 0.63; 95% CI 0.37, 1.05; p = 0.07) and unadjusted risks for secondary outcomes including death (HR 0.70; 95% CI 0.40, 1.25), total MI (HR 0.82; 95% CI 0.35, 1.90), total stroke (HR 0.81; 95% CI 0.25, 2.65) and new diabetes (HR 0.88; 95% CI 0.55, 1.41) were not statistically different. CONCLUSION: This analysis shows that combination treatment with either Ve+ Tr or At +- HCTZ is effective in achieving BP control and produces similar outcomes in hypertensive patients with CAD.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Enfermedad de la Arteria Coronaria/complicaciones , Hipertensión/tratamiento farmacológico , Anciano , Análisis de Varianza , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Atenolol/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Diuréticos/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Hidroclorotiazida/uso terapéutico , Hipertensión/complicaciones , Indoles/uso terapéutico , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del Tratamiento , Verapamilo/uso terapéuticoRESUMEN
BACKGROUND: Because coronary perfusion occurs mainly during diastole, patients with coronary artery disease (CAD) could be at increased risk for coronary events if diastolic pressure falls below critical levels. OBJECTIVE: To determine whether low blood pressure could be associated with excess mortality and morbidity in this population. DESIGN: A secondary analysis of data from the International Verapamil-Trandolapril Study (INVEST), which was conducted from September 1997 to February 2003. SETTING: 862 sites in 14 countries. PATIENTS: 22 576 patients with hypertension and CAD. INTERVENTIONS: Patients from INVEST were randomly assigned to a verapamil sustained-release- or atenolol-based strategy; blood pressure control and outcomes were equivalent. MEASUREMENTS: An unadjusted quadratic proportional hazards model was used to evaluate the relationship between average on-treatment blood pressure and risk for the primary outcome (all-cause death, nonfatal stroke, and nonfatal myocardial infarction [MI]), all-cause death, total MI, and total stroke. A second model adjusted for differences in baseline covariates. RESULTS: The relationship between blood pressure and the primary outcome, all-cause death, and total MI was J-shaped, particularly for diastolic pressure, with a nadir at 119/84 mm Hg. After adjustment, the J-shaped relationship persisted between diastolic pressure and primary outcome. The MI-stroke ratio remained constant over a wide blood pressure range, but at a lower diastolic blood pressure, there were substantially more MIs than strokes. An interaction between decreased diastolic pressure and history of revascularization was observed; low diastolic pressure was associated with a relatively lower risk for the primary outcome in patients with revascularization than in those without revascularization. LIMITATIONS: This is a post hoc analysis of hypertensive patients with CAD. CONCLUSIONS: The risk for the primary outcome, all-cause death, and MI, but not stroke, progressively increased with low diastolic blood pressure. Excessive reduction in diastolic pressure should be avoided in patients with CAD who are being treated for hypertension.