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OBJECTIVES: To evaluate whether the effectiveness and safety of low (81 mg daily) versus high-dose (325 mg daily) aspirin is consistent across races among patients with established atherosclerotic cardiovascular disease (ASCVD). DESIGN: A secondary analysis of the randomised controlled trial ADAPTABLE was performed. SETTING: The study was conducted in 40 centres and one health plan participating in the National Patient-Centred Clinical Research Network (PCORnet) in the USA. PARTICIPANTS: Among 15 076 participants with established ASCVD, 14 096 had self-reported race available and were included in the analysis. Participants were divided according to self-reported race as Black (n=1311, 9.3%), White (n=11 990, 85.1%) or other race (n=795, 5.6%). INTERVENTIONS: Participants were randomised to open-label daily aspirin doses of 81 mg versus 325 mg in a 1:1 ratio for a median of 26.2 months. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary effectiveness endpoint was a composite of death from any cause, hospitalisation for myocardial infarction or hospitalisation for stroke. The primary safety endpoint was hospitalisation for bleeding requiring blood product transfusion. RESULTS: Estimated cumulative incidence of the primary effectiveness endpoint at median follow-up with the 81 mg and the 325 mg daily doses were 6.70% and 7.12% in White participants (adjusted HR: 1.00 [95% CI: 0.88 to 1.15]); 12.27% and 10.69% in Black participants (adjusted HR: 1.40 [95% CI: 1.02 to 1.93]); and 6.88% and 7.69% in other participants (adjusted HR: 0.86 [95% CI: 0.54 to 1.39]) (p-interaction=0.12), respectively. There was no significant interaction between self-reported race and assigned aspirin dose regarding the secondary effectiveness and the primary safety endpoints. CONCLUSION: Race is not an effect modifier on the impact of aspirin dosing on effectiveness and safety in patients with established ASCVD. In clinical practice, treatment decisions regarding aspirin dose in secondary prevention of ASCVD should not be influenced by race. TRIAL REGISTRATION NUMBER: NCT02697916.
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Aspirina , Aterosclerosis , Inhibidores de Agregación Plaquetaria , Prevención Secundaria , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Aterosclerosis/prevención & control , Enfermedades Cardiovasculares/prevención & control , Relación Dosis-Respuesta a Droga , Hemorragia/inducido químicamente , Hospitalización/estadística & datos numéricos , Infarto del Miocardio/prevención & control , Infarto del Miocardio/etnología , Infarto del Miocardio/epidemiología , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevención Secundaria/métodos , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento , Estados Unidos/epidemiología , Blanco , Negro o AfroamericanoRESUMEN
Importance: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the US. Although aspirin is recommended for secondary prevention of ASCVD, there was no difference in safety and effectiveness of aspirin dosed daily at 81 mg or 325 mg in the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) randomized clinical trial. However, it is unknown whether differences by sex exist in the safety and effectiveness of the different aspirin doses. Objective: To evaluate sex-specific differences in the safety and effectiveness of 2 aspirin doses in the ADAPTAPLE trial. Design, Setting, and Participants: The ADAPTABLE study was an open-label, pragmatic, randomized clinical trial that randomly assigned participants with chronic, stable ASCVD to 81 mg vs 325 mg of aspirin daily. Using Cox proportional-hazard models, male and female participants were compared for outcomes. In addition, it was assessed whether sex was an effect modifier in the association between aspirin dose and outcomes. The ADAPTABLE trial was conducted at 40 medical centers and 1 health plan. Eligible patients were 18 years and older and had established ASCVD. Study data were analyzed from December 2021 to March 2024. Interventions: Patients received 81 mg or 325 mg of aspirin daily for the secondary prevention of ASCVD. Main Outcomes and Measures: The primary effectiveness outcomes included all-cause death and hospitalization for myocardial infarction (MI) or stroke. The primary safety outcome was hospitalization for major bleeding requiring transfusion. Results: A total of 15â¯076 patients (median [IQR] age, 67.6 [60.7-73.6] years; 10â¯352 male [68.7%]) were followed up for a median (IQR) of 26.2 (19.0-34.9) months. Overall, 4724 (31.3%) were female, and 2307 of the female participants (48.8%) received aspirin 81 mg. Compared with males, female participants were younger (median [IQR] age, 66.3 [59.4-72.6] years vs 68.2 (61.4-73.9) years, less likely to self-report White race (3426 [72.5%] vs 8564 [82.7%]), more likely to smoke (564 [12.9%] vs 818 [8.4%]), and more likely to have a history of peripheral arterial disease (1179 [25.7%] vs 2314 [23.0%]). The primary effectiveness outcome of all-cause death and hospitalization for MI or stroke occurred in 379 female participants (8.1%) and 780 male participants (7.1%). There was no significant interaction by sex for the primary effectiveness end point between the 2 aspirin doses (female adjusted hazard ratio [aHR], 1.01; 95% CI, 0.82-1.26 and male aHR, 1.06; 95% CI, 0.91-1.23; P interaction term for sex = .74). During the trial, female participants had fewer revascularization procedures (237 [5.0%] vs 680 [6.6%]; aHR, 0.79; 95% CI, 0.68-0.92; P = .002) but had a higher risk of hospitalization for stroke (aHR, 1.72; 95% CI, 1.27-2.33; P < .001). Among female participants, there was a slightly higher rate of bleeding in the 81-mg aspirin cohort compared with the 325-mg cohort (20 [0.83%] vs 13 [0.52%]; aHR, 2.21; 95% CI, 1.04-4.70; P interaction term for sex = .07). There were no significant differences between female and male participants regarding aspirin dose adherence. Conclusions and Relevance: In this secondary analysis of the ADAPTABLE trial, there were no significant sex-specific differences in the effectiveness and safety of 2 aspirin doses for secondary prevention of ASCVD events. Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.
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This JAMA Clinical Guidelines Synopsis summarizes the 2023 American Heart Association (AHA)/American College of Cardiology (ACC) guideline on management of patients with chronic coronary disease.
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Enfermedad Coronaria , Humanos , Enfermedad Crónica , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/prevención & control , Enfermedad Coronaria/terapia , Inhibidores de Hidroximetilglutaril-CoA Reductasas/normas , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Ejercicio Físico/normas , Dieta Saludable/normas , Procedimientos Endovasculares/normas , Inhibidores del Cotransportador de Sodio-Glucosa 2/normas , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Antagonistas Adrenérgicos beta/normas , Antagonistas Adrenérgicos beta/uso terapéutico , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Volumen SistólicoRESUMEN
BACKGROUND: In patients with atherosclerotic cardiovascular disease, increasing age is concurrently associated with higher risks of ischemic and bleeding events. The objectives are to determine the impact of aspirin dose on clinical outcomes according to age in atherosclerotic cardiovascular disease. METHODS AND RESULTS: In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) trial, patients with atherosclerotic cardiovascular disease were randomized to daily aspirin doses of 81 mg or 325 mg. The primary effectiveness end point was death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety end point was hospitalization for bleeding requiring transfusion. A total of 15 076 participants were randomized to aspirin 81 mg (n=7540) or 325 mg (n=7536) daily (median follow-up: 26.2 months; interquartile range: 19.0-34.9 months). Median age was 67.6 years (interquartile range: 60.7-73.6 years). Among participants aged <65 years (n=5841 [38.7%]), a primary end point occurred in 226 (7.54%) in the 81 mg group, and in 191 (6.80%) in the 325 mg group (adjusted hazard ratio [HR], 1.23 [95% CI, 1.01-1.49]). Among participants aged ≥65 years (n=9235 [61.3%]), a primary end point occurred in 364 (7.12%) in the 81 mg group, and in 378 (7.96%) in the 325 mg group (adjusted HR, 0.95 [95% CI, 0.82-1.10]). The age-dose interaction was not significant (P=0.559). There was no significant interaction between age and the randomized aspirin dose for the secondary effectiveness and the primary safety bleeding end points (P>0.05 for all). CONCLUSIONS: Age does not modify the impact of aspirin dosing (81 mg or 325 mg daily) on clinical end points in secondary prevention of atherosclerotic cardiovascular disease.
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Aterosclerosis , Enfermedades Cardiovasculares , Anciano , Humanos , Aspirina/uso terapéutico , Aterosclerosis/complicaciones , Aterosclerosis/diagnóstico , Aterosclerosis/prevención & control , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , Hemorragia/inducido químicamente , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevención Secundaria , Persona de Mediana EdadRESUMEN
OBJECTIVE: Patients with diabetes mellitus (DM) and concomitant atherosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events. RESEARCH DESIGN AND METHODS: ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this prespecified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome. RESULTS: Of 15,076 patients, 5,676 (39%) had DM of whom 2,820 (49.7%) were assigned to 81 mg aspirin and 2,856 (50.3%) to 325 mg aspirin. Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% vs. 0.50%; P < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs. 10.0%; hazard ratio [HR] 0.98 [95% CI 0.83-1.16]; P = 0.265) or safety outcome (0.87% vs. 0.69%; subdistribution HR 1.25 [95% CI 0.72-2.16]; P = 0.772). CONCLUSIONS: This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest that a higher dose of aspirin yields no added clinical benefit, even in a more vulnerable population.
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Aterosclerosis , Enfermedades Cardiovasculares , Diabetes Mellitus , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Aspirina/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/inducido químicamente , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/inducido químicamente , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/epidemiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Accidente Cerebrovascular/epidemiologíaRESUMEN
OBJECTIVE: Among people with peripheral artery disease (PAD), perceived change in walking difficulty over time, compared with people without PAD, is unclear. Among people reporting no change in walking difficulty over time, differences in objectively measured change in walking performance between people with and without PAD are unknown. METHODS: A total of 1289 participants were included. Eight hundred seventy-four participants with PAD (aged 71.1 ± 9.1 years) were identified from noninvasive vascular laboratories and 415 without PAD (aged 69.9 ± 7.6 years) were identified from people with normal vascular laboratory testing or general medical practices in Chicago. The Walking Impairment Questionnaire and 6-minute walk were completed at baseline and 1-year follow-up. The Walking Impairment Questionnaire assessed perceived difficulty walking due to symptoms in the calves or buttocks on a Likert scale (range, 0-4). Symptom change was determined by comparing difficulty reported at 1-year follow-up to difficulty reported at baseline. RESULTS: At 1-year follow-up, 31.9% of participants with and 20.6% of participants without PAD reported walking difficulty that was improved (P < .01), whereas 41.2% vs 55%, respectively, reported walking difficulty that was unchanged (P < .01). Among all reporting no change in walking difficulty, participants with PAD declined in 6-minute walk, whereas participants without PAD improved (-10 vs +15 meters; mean difference, -25; 95% confidence interval, -38 to -13; P < .01). CONCLUSIONS: Most people with PAD reported improvement or no change in walking difficulty from calf or buttock symptoms at one-year follow-up. Among all participants who perceived stable walking ability, those with PAD had significant greater declines in objectively measured walking performance, compared with people without PAD.
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Enfermedad Arterial Periférica , Humanos , Pierna , Limitación de la Movilidad , Medición de Resultados Informados por el Paciente , Enfermedad Arterial Periférica/diagnóstico , Caminata , Persona de Mediana Edad , Anciano , Anciano de 80 o más AñosRESUMEN
Objective: Age is the strongest contributor to 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk. Some older adults have a predicted ASCVD risk ≥7.5 %, without established risk factors. We sought to compare ASCVD incidence among adults with predicted ASCVD risk ≥7.5 %, with and without established ASCVD risk factors, to adults with predicted risk <7.5 %. Methods: We analyzed data from REasons for Geographic and Racial Differences in Stroke study participants, 45-79 years old, without ASCVD or diabetes, not taking statins and with low-density lipoprotein cholesterol 70-189 mg/dL. Participants were categorized into 3 groups based on their 10-year predicted ASCVD risk and presence of established risk factors: <7.5 %, ≥7.5 % with established risk factors and ≥7.5 % without established risk factors. Established risk factors included smoking, systolic blood pressure ≥130 mmHg or antihypertensive medication use, total cholesterol ≥200 mg/dL, or high-density lipoprotein cholesterol <50 mg/dL for women (<40 mg/dL for men). Participants were followed for ASCVD events. Results: Among 11,115 participants, 911 incident ASCVD events occurred over a median of 11.1 years. ASCVD incidence rates were 3.6, 12.8, and 9.8 per 1,000 person-years for participants with predicted risk <7.5 %, predicted risk ≥7.5 % with established risk factors and predicted risk ≥7.5 % without established risk factors, respectively. Compared to adults with predicted risk <7.5 %, hazard ratios for incident ASCVD in participants with risk ≥7.5 % with and without established risk factors were 3.58 (95 %CI 3.03 - 4.21) and 2.72 (95 %CI 1.91-3.88), respectively. Conclusions: Adults with a 10-year predicted ASCVD risk ≥7.5 % but without established risk factors had a high ASCVD incidence.
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BACKGROUND: A strategy of administering a transfusion only when the hemoglobin level falls below 7 or 8 g per deciliter has been widely adopted. However, patients with acute myocardial infarction may benefit from a higher hemoglobin level. METHODS: In this phase 3, interventional trial, we randomly assigned patients with myocardial infarction and a hemoglobin level of less than 10 g per deciliter to a restrictive transfusion strategy (hemoglobin cutoff for transfusion, 7 or 8 g per deciliter) or a liberal transfusion strategy (hemoglobin cutoff, <10 g per deciliter). The primary outcome was a composite of myocardial infarction or death at 30 days. RESULTS: A total of 3504 patients were included in the primary analysis. The mean (±SD) number of red-cell units that were transfused was 0.7±1.6 in the restrictive-strategy group and 2.5±2.3 in the liberal-strategy group. The mean hemoglobin level was 1.3 to 1.6 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary-outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive-strategy group and in 255 of 1755 patients (14.5%) in the liberal-strategy group (risk ratio modeled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval [CI], 0.99 to 1.34; P = 0.07). Death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy (risk ratio, 1.19; 95% CI, 0.96 to 1.47); myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively (risk ratio, 1.19; 95% CI, 0.94 to 1.49). CONCLUSIONS: In patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days. However, potential harms of a restrictive transfusion strategy cannot be excluded. (Funded by the National Heart, Lung, and Blood Institute and others; MINT ClinicalTrials.gov number, NCT02981407.).
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Anemia , Transfusión Sanguínea , Infarto del Miocardio , Humanos , Anemia/sangre , Anemia/etiología , Anemia/terapia , Transfusión Sanguínea/métodos , Transfusión de Eritrocitos/efectos adversos , Transfusión de Eritrocitos/métodos , Hemoglobinas/análisis , Infarto del Miocardio/sangre , Infarto del Miocardio/complicaciones , Infarto del Miocardio/mortalidad , Infarto del Miocardio/terapia , RecurrenciaRESUMEN
Background The ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high- versus low-dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods and Results Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22-1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91-2.22]). We found no interaction in the relative effectiveness and safety of high- versus low-dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high-dose compared with low-dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. Conclusions In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high- versus low-dose aspirin was not modified by baseline P2Y12 inhibitor use. Registration https://www.clinical.trials.gov. Unique identifier: NCT02697916.
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Síndrome Coronario Agudo , Aterosclerosis , Enfermedades Cardiovasculares , Humanos , Clopidogrel/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/efectos adversos , Ticlopidina/uso terapéutico , Prevención Secundaria , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/inducido químicamente , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Aspirina/uso terapéutico , Hemorragia/inducido químicamente , Aterosclerosis/diagnóstico , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & controlRESUMEN
Importance: Clinicians recommend enteric-coated aspirin to decrease gastrointestinal bleeding in secondary prevention of coronary artery disease even though studies suggest platelet inhibition is decreased with enteric-coated vs uncoated aspirin formulations. Objective: To assess whether receipt of enteric-coated vs uncoated aspirin is associated with effectiveness or safety outcomes. Design, Setting, and Participants: This is a post hoc secondary analysis of ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic study of 15â¯076 patients with atherosclerotic cardiovascular disease having data in the National Patient-Centered Clinical Research Network. Patients were enrolled from April 19, 2016, through June 30, 2020, and randomly assigned to receive high (325 mg) vs low (81 mg) doses of daily aspirin. The present analysis assessed the effectiveness and safety of enteric-coated vs uncoated aspirin among those participants who reported aspirin formulation at baseline. Data were analyzed from November 11, 2019, to July 3, 2023. Intervention: ADAPTABLE participants were regrouped according to aspirin formulation self-reported at baseline, with a median (IQR) follow-up of 26.2 (19.8-35.4) months. Main Outcomes and Measures: The primary effectiveness end point was the cumulative incidence of the composite of myocardial infarction, stroke, or death from any cause, and the primary safety end point was major bleeding events (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage). Cumulative incidence at median follow-up for primary effectiveness and primary safety end points was compared between participants taking enteric-coated or uncoated aspirin using unadjusted and multivariable Cox proportional hazards models. All analyses were conducted for the intention-to-treat population. Results: Baseline aspirin formulation used in ADAPTABLE was self-reported for 10â¯678 participants (median [IQR] age, 68.0 [61.3-73.7] years; 7285 men [68.2%]), of whom 7366 (69.0%) took enteric-coated aspirin and 3312 (31.0%) took uncoated aspirin. No significant difference in effectiveness (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.80-1.09; P = .40) or safety (AHR, 0.82; 95% CI, 0.49-1.37; P = .46) outcomes between the enteric-coated aspirin and uncoated aspirin cohorts was found. Within enteric-coated aspirin and uncoated aspirin, aspirin dose had no association with effectiveness (enteric-coated aspirin AHR, 1.13; 95% CI, 0.88-1.45 and uncoated aspirin AHR, 0.99; 95% CI, 0.83-1.18; interaction P = .41) or safety (enteric-coated aspirin AHR, 2.37; 95% CI, 1.02-5.50 and uncoated aspirin AHR, 0.89; 95% CI, 0.49-1.64; interaction P = .07). Conclusions and Relevance: In this post hoc secondary analysis of the ADAPTABLE randomized clinical trial, enteric-coated aspirin was not associated with significantly higher risk of myocardial infarction, stroke, or death or with lower bleeding risk compared with uncoated aspirin, regardless of dose, although a reduction in bleeding with enteric-coated aspirin cannot be excluded. More research is needed to confirm whether enteric-coated aspirin formulations or newer formulations will improve outcomes in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.
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Enfermedades Cardiovasculares , Infarto del Miocardio , Accidente Cerebrovascular , Masculino , Humanos , Anciano , Aspirina/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Método Doble Ciego , Infarto del Miocardio/epidemiología , Accidente Cerebrovascular/epidemiología , Hemorragia GastrointestinalRESUMEN
Background Menstrual cycle irregularities are associated with cardiovascular and cardiometabolic disease. We tested associations between age at menarche and cycle irregularity in adolescence and cardiometabolic health in early adulthood in a subsample from the Pittsburgh Girls Study. Methods and Results Data from annual interviews were used to assess age at menarche and cycle irregularity (ie, greater or less than every 27-29 days) at age 15 years. At ages 22 to 25 years, cardiometabolic health was measured in a subsample of the Pittsburgh Girls Study (n=352; 68.2% Black), including blood pressure, waist circumference, and fasting serum insulin, glucose, and lipids. T tests were used for continuous data and odds ratios for dichotomous data to compare differences in cardiometabolic health as a function of onset and regularity of menses. Early menarche (ie, before age 11 years; n=52) was associated with waist circumference (P=0.043). Participants reporting irregular cycles (n=50) in adolescence had significantly higher levels of insulin, glucose, and triglycerides, and higher systolic and diastolic blood pressure (P values range from 0.035 to 0.005) and were more likely to have clinical indicators of cardiometabolic predisease in early adulthood compared with women who reported regular cycles (odds ratios ranged from 1.89 to 2.56). Conclusions Increasing rates and earlier onset of cardiovascular and metabolic disease among women, especially among Black women, highlights the need for identifying early and reliable risk indices. Menstrual cycle irregularity may serve this purpose and help elucidate the role of women's reproductive health in protecting and conferring risk for later cardiovascular and cardiometabolic diseases.
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Población Negra , Factores de Riesgo Cardiometabólico , Enfermedades Cardiovasculares , Ciclo Menstrual , Trastornos de la Menstruación , Enfermedades Metabólicas , Adolescente , Adulto , Niño , Femenino , Humanos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etnología , Enfermedades Cardiovasculares/etiología , Glucosa , Insulina/sangre , Enfermedades Metabólicas/diagnóstico , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/etnología , Enfermedades Metabólicas/etiología , Adulto Joven , Trastornos de la Menstruación/complicaciones , Trastornos de la Menstruación/epidemiología , Trastornos de la Menstruación/etnologíaRESUMEN
Importance: Few people with lower extremity peripheral artery disease (PAD) participate in supervised treadmill exercise covered by the Center for Medicare and Medicaid Services. In people with PAD, the benefits of home-based walking exercise, relative to supervised exercise, remain unclear. Objective: To study whether home-based walking exercise improves 6-minute walk (6MW) more than supervised treadmill exercise in people with PAD (defined as Ankle Brachial Index ≤0.90). Data Sources: Data were combined from 5 randomized clinical trials of exercise therapy for PAD using individual participant data meta-analyses, published from 2009 to 2022. Study Selection: Of the 5 clinical trials, 3 clinical trials compared supervised treadmill exercise to nonexercise control (N = 370) and 2 clinical trials compared an effective home-based walking exercise intervention to nonexercise control (N = 349). Data Extraction and Synthesis: Individual participant-level data from 5 randomized clinical trials led by 1 investigative team were combined. The 5 randomized clinical trials included 3 clinical trials of supervised treadmill exercise and 2 effective home-based walking exercise interventions. Main Outcomes and Measures: Change in 6MW distance, maximum treadmill walking distance, and Walking Impairment Questionnaire at 6-month follow-up. The supervised treadmill exercise intervention consisted of treadmill exercise in the presence of an exercise physiologist, conducted 3 days weekly for up to 50 minutes per session. Home-based walking exercise consisted of a behavioral intervention in which a coach helped participants walk for exercise in or around home for up to 5 days per week for 50 minutes per session. Results: A total of 719 participants with PAD (mean [SD] age, 68.8 [9.5] years; 46.5% female) were included (349 in a home-based exercise clinical trial and 370 in a supervised exercise trial). Compared with nonexercise control, supervised treadmill exercise was associated with significantly improved 6MW by 32.9 m (95% CI, 20.6-45.6; P < .001) and home-based walking exercise was associated with significantly improved 6MW by 50.7 m (95% CI, 34.8-66.7; P < .001). Compared with supervised treadmill exercise, home-based walking exercise was associated with significantly greater improvement in 6MW distance (between-group difference: 23.8 m [95% CI, 3.6, 44.0; P = .02]) but significantly less improvement in maximum treadmill walking distance (between-group difference:-132.5 m [95% CI, -192.9 to -72.1; P < .001]). Conclusions and Relevance: In this individual participant data meta-analyses, compared with supervised exercise, home-based walking exercise was associated with greater improvement in 6MW in people with PAD. These findings support home-based walking exercise as a first-line therapy for walking limitations in PAD.
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Medicare , Enfermedad Arterial Periférica , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ejercicio Físico , Terapia por Ejercicio , Enfermedad Arterial Periférica/terapia , Estados Unidos , Caminata , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background Overweight and obesity are associated with adverse functional outcomes in people with peripheral artery disease (PAD). The effects of weight loss in people with overweight/obesity and PAD are unknown. Methods The PROVE (Promote Weight Loss in Obese PAD Patients to Prevent Mobility Loss) Trial is a multicentered randomized clinical trial with the primary aim of testing whether a behavioral intervention designed to help participants with PAD lose weight and walk for exercise improves 6-minute walk distance at 12-month follow-up, compared with walking exercise alone. A total of 212 participants with PAD and body mass index ≥25 kg/m2 will be randomized. Interventions are delivered using a Group Mediated Cognitive Behavioral intervention model, a smartphone application, and individual telephone coaching. The primary outcome is 12-month change in 6-minute walk distance. Secondary outcomes include total minutes of walking exercise/wk at 12-month follow-up and 12-month change in accelerometer-measured physical activity, the Walking Impairment Questionnaire distance score, and the Patient-Reported Outcomes Measurement Information System mobility questionnaire. Tertiary outcomes include 12-month changes in perceived exertional effort at the end of the 6-minute walk, diet quality, and the Short Physical Performance Battery. Exploratory outcomes include changes in gastrocnemius muscle biopsy measures of mitochondrial cytochrome C oxidase activity, mitochondrial biogenesis, capillary density, and inflammatory markers. Conclusions The PROVE randomized clinical trial will evaluate the effects of exercise with an intervention of coaching and a smartphone application designed to achieve weight loss, compared with exercise alone, on walking performance in people with PAD and overweight/obesity. Results will inform optimal treatment for the growing number of patients with PAD who have overweight/obesity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04228978.
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Obesidad , Enfermedad Arterial Periférica , Programas de Reducción de Peso , Humanos , Obesidad/complicaciones , Obesidad/terapia , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/terapia , Proyectos de Investigación , Programas de Reducción de Peso/métodos , Terapia por Ejercicio , Caminata , Estudios de Seguimiento , Masculino , Femenino , Persona de Mediana EdadRESUMEN
Background Internet-based participation has the potential to enhance pragmatic and decentralized trials, where representative study populations and generalizability to clinical practice are key. We aimed to study the differences between internet and noninternet/telephone participants in a large remote, pragmatic trial. Methods and Results In a subanalysis of the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) study, we compared internet participants with those who opted for noninternet participation. Study process measures examined included participant characteristics at consent, study medication adherence, and study retention. The clinical outcome examined was a composite of all-cause mortality, hospitalization for myocardial infarction, or hospitalization for stroke. Noninternet participants were older (mean 69.4 versus 67.4 years), more likely to be female (38.9% versus 30.2%), more likely to be Black (27.3% versus 6.0%) or Hispanic (11.1% versus 2.0%), and had a higher number of comorbid conditions. The composite clinical outcome was more than twice as high in noninternet participants. The hazard of nonadherence to the assigned aspirin dosage was 46% higher in noninternet participants than internet participants. Conclusions Noninternet participants differed from internet participants in notable demographic characteristics while having poorer baseline health. Over the course of ADAPTABLE, they also had worse clinical outcomes and greater likelihood of study drug nonadherence. These results suggest that trials focused on internet participation select for younger, healthier participants with a higher proportion of traditionally overrepresented patients. Allowing noninternet participation enhances diversity; however, additional steps may be needed to promote study retention and study medication adherence. Registration Information clinicaltrials.gov. Identifier: NCT02697916.
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Infarto del Miocardio , Accidente Cerebrovascular , Femenino , Humanos , Masculino , Aspirina/uso terapéutico , Internet , Infarto del Miocardio/tratamiento farmacológico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/tratamiento farmacológico , AncianoRESUMEN
BACKGROUND: Among patients with established cardiovascular disease, the ADAPTABLE trial found no significant differences in cardiovascular events and bleeding rates between 81 mg and 325 mg of aspirin (ASA) daily. In this secondary analysis from the ADAPTABLE trial, we studied the effectiveness and safety of ASA dosing in patients with a history of chronic kidney disease (CKD). METHODS: ADAPTABLE participants were stratified based on the presence or absence of CKD, defined using ICD-9/10-CM codes. Within the CKD group, we compared outcomes between patients taking ASA 81 mg and 325 mg. The primary effectiveness outcome was defined as a composite of all cause death, myocardial infarction, or stroke and the primary safety outcome was hospitalization for major bleeding. Adjusted Cox proportional hazard models were utilized to report differences between the groups. RESULTS: After excluding 414 (2.7%) patients due to missing medical history, a total of 14,662 patients were included from the ADAPTABLE cohort, of whom 2,648 (18%) patients had CKD. Patients with CKD were older (median age 69.4 vs 67.1 years; P < .0001) and less likely to be white (71.5% vs 81.7%; P < .0001) when compared to those without CKD. At a median follow-up of 26.2 months, CKD was associated with an increased risk of both the primary effectiveness outcome (adjusted HR 1.79 [1.57, 2.05] P < .001 and the primary safety outcome (adjusted HR 4.64 (2.98, 7.21), P < .001 and P < .05, respectively) regardless of ASA dose. There was no significant difference in effectiveness (adjusted HR 1.01 95% CI 0.82, 1.23; P = .95) or safety (adjusted HR 0.93; 95% CI 0.52, 1.64; P = .79) between ASA groups. CONCLUSIONS: Patients with CKD were more likely than those without CKD to have adverse cardiovascular events or death and were also more likely to have major bleeding requiring hospitalization. However, there was no association between ASA dose and study outcomes among these patients with CKD.
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Enfermedades Cardiovasculares , Infarto del Miocardio , Insuficiencia Renal Crónica , Humanos , Anciano , Prevención Secundaria , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Infarto del Miocardio/etiología , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Hemorragia/complicaciones , Aspirina/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/complicacionesRESUMEN
Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated. Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], pinteraction <0.001). Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).
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OBJECTIVE: To explore trends in blood pressure (BP) control before and during the COVID-19 pandemic. PATIENTS AND METHODS: Health systems participating in the National Patient-Centered Clinical Research Network (PCORnet) Blood Pressure Control Laboratory Surveillance System responded to data queries, producing 9 BP control metrics. Averages of the BP control metrics (weighted by numbers of observations in each health system) were calculated and compared between two 1-year measurement periods (January 1, 2019, through December 31, 2019, and January 1, 2020, through December 31, 2020). RESULTS: Among 1,770,547 hypertensive persons in 2019, BP control to <140/<90 mm Hg varied across 24 health systems (range, 46%-74%). Reduced BP control occurred in most health systems with onset of the COVID-19 pandemic; the weighted average BP control was 60.5% in 2019 and 53.3% in 2020. Reductions were also evident for BP control to <130/<80 mm Hg (29.9% in 2019 and 25.4% in 2020) and improvement in BP (reduction of 10 mm Hg in systolic BP or achievement of systolic BP <140 mm Hg; 29.7% in 2019 and 23.8% in 2020). Two BP control process metrics exhibited pandemic-associated disruption: repeat visit in 4 weeks after a visit with uncontrolled hypertension (36.7% in 2019 and 31.7% in 2020) and prescription of fixed-dose combination medications among those with 2 or more drug classes (24.6% in 2019 and 21.5% in 2020). CONCLUSION: BP control decreased substantially during the COVID-19 pandemic, with a corresponding reduction in follow-up health care visits among persons with uncontrolled hypertension. It is unclear whether the observed decline in BP control during the pandemic will contribute to future cardiovascular events.
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COVID-19 , Hipertensión , Humanos , Presión Sanguínea , Antihipertensivos/uso terapéutico , Antihipertensivos/farmacología , Pandemias , COVID-19/epidemiología , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiologíaRESUMEN
Whether initiation of statins could increase survival free of dementia and disability in adults aged ≥75 years is unknown. PREVENTABLE, a double-blind, placebo-controlled randomized pragmatic clinical trial, will compare high-intensity statin therapy (atorvastatin 40 mg) with placebo in 20,000 community-dwelling adults aged ≥75 years without cardiovascular disease, disability, or dementia at baseline. Exclusion criteria include statin use in the prior year or for >5 years and inability to take a statin. Potential participants are identified using computable phenotypes derived from the electronic health record and local referrals from the community. Participants will undergo baseline cognitive testing, with physical testing and a blinded lipid panel if feasible. Cognitive testing and disability screening will be conducted annually. Multiple data sources will be queried for cardiovascular events, dementia, and disability; survival is site-reported and supplemented by a National Death Index search. The primary outcome is survival free of new dementia or persisting disability. Co-secondary outcomes are a composite of cardiovascular death, hospitalization for unstable angina or myocardial infarction, heart failure, stroke, or coronary revascularization; and a composite of mild cognitive impairment or dementia. Ancillary studies will offer mechanistic insights into the effects of statins on key outcomes. Biorepository samples are obtained and stored for future study. These results will inform the benefit of statins for increasing survival free of dementia and disability among older adults. This is a pioneering pragmatic study testing important questions with low participant burden to align with the needs of the growing population of older adults.
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Demencia , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Accidente Cerebrovascular/epidemiología , Demencia/prevención & control , Demencia/tratamiento farmacológico , LípidosRESUMEN
BACKGROUND: We aimed to understand the effects of aspirin dose on outcomes in patients with peripheral artery disease (PAD) as well as their participation in a pragmatic randomized controlled trial. METHODS: In a subanalysis of the Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness (ADAPTABLE) study, we compared aspirin doses (81 vs 325 mg) among participants with PAD and study participation metrics in patients with and without PAD. The primary outcome composite was all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: Among 14,662 participants enrolled in ADAPTABLE with PAD status available, 3493 (23.8%) had PAD. Participants with PAD were more likely to experience the primary composite (13.76% vs 5.31%, p < 0.001), all-cause mortality (7.55% vs 3.01%, p < 0.001), myocardial infarction (5.71% vs 2.09%, p < 0.001), stroke (2.45% vs 0.86%, p < 0.001), and major bleeding (1.19% vs 0.44%, p < 0.001). A higher aspirin dose did not reduce the primary outcome in patients with PAD (13.68% vs 13.84% in 81 mg and 325 mg groups; OR 1.05, 95% CI 0.88-1.25). Participants with PAD were less likely to enroll via email (33.0% vs 41.9%, p < 0.0001), less likely to choose internet follow-up (79.2% vs 89.5%, p < 0.0001), and were more likely to change their aspirin doses (39.7% vs 30.7%, p < 0.0001). CONCLUSIONS: ADAPTABLE participants with PAD did not benefit from a higher dose of aspirin and participated in the study differently from those without PAD. These results reinforce the need for additional PAD-specific research and suggest that different trial strategies may be needed for optimal engagement of patients with PAD. (ClinicalTrials.gov Identifier: NCT02697916).