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1.
Clin Cardiol ; 43(1): 43-49, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31721249

RESUMO

BACKGROUND: In patients hospitalized with acute heart failure (AHF), low urine sodium concentration (UNa ) after diuretic treatment may identify patients at risk for longer length of stay (LOS) and adverse events. We investigated the prognostic significance of 24-hour cumulative postdiuretic urine sodium concentration in a multicenter clinical trial population. METHODS: The Renal Optimization Strategies Evaluation AHF (ROSE AHF) trial randomized 360 patients with AHF and renal dysfunction receiving intravenous diuretic to dopamine, nesiritide, or placebo. Sodium concentration was measured in cumulative urine sample collected during the first 24 hours after randomization in 298 patients. Based on prior studies, lower UNa was defined as ≤60 mmol/L. RESULTS: Lower UNa was present in 142 (48%) patients, who had longer LOS (7 days vs 5 days, P < .001) and less 72-hour weight loss (5.7 lb vs 9.0 lb, P < .001). These associations persisted after controlling for baseline estimated glomerular filtration rate and outpatient furosemide dose. Lower UNa did not modify the null effects of dopamine or nesiritide on clinical outcomes. Results were similar for spot rather than cumulative 24-hour UNa concentration. CONCLUSION: In patients hospitalized for AHF and renal dysfunction, UNa ≤ 60 mmol/L during the first 24 hours of diuresis identifies patients at risk for prolonged hospitalization but does not provide an indication for adjunctive dopamine or nesiritide.

2.
Eur J Heart Fail ; 21(12): 1596-1604, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31820546

RESUMO

AIM: Describe the distinguishing features of heart failure (HF) patients with reduced ejection fraction (HFrEF) in the VICTORIA (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction) trial. METHODS AND RESULTS: Key background characteristics were evaluated in 5050 patients randomized in VICTORIA and categorized into three cohorts reflecting their index worsening HF event. Differences within the VICTORIA population were assessed and compared with PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure). VICTORIA patients had increased risk of mortality and rehospitalization: New York Heart Association class (40% class III), atrial fibrillation (45%), diabetes (47%), hypertension (79%) and mean estimated glomerular filtration rate of 61.5 mL/min/1.73 m2 . Baseline standard of HF care was very good: 60% received triple therapy. Their N-terminal pro-B-type natriuretic peptide was 3377 pg/mL [interquartile range (IQR) 1992-6380]. Natriuretic peptides were 30% higher level in the 67% patients with HF hospitalization <3 months, compared to those within 3-6 months of HF hospitalization and those randomized after recent outpatient intravenous diuretic therapy. Overall the median MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) risk score in VICTORIA was 23 (IQR 18-27) as compared to the MAGGIC risk score in PARADIGM-HF of 20 (IQR 16-24). CONCLUSIONS: VICTORIA comprises a broadly generalizable high-risk population of three unique clinical strata of worsening chronic HFrEF despite very good HF therapy. VICTORIA will establish the role of vericiguat, a soluble guanylate cyclase stimulator, in HFrEF.

3.
Am Heart J ; 220: 97-107, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31805424

RESUMO

BACKGROUND: Cardiorespiratory fitness (CRF) is closely linked to health status and clinical outcomes in heart failure (HF) patients. We aimed to test whether biomarkers can reflect CRF and its change over time. METHODS: This post hoc analysis used data from ambulatory cohorts of heart failure with reduced ejection fraction (HFrEF) (IRONOUT) and heart failure with preserved ejection fraction (HFpEF) (RELAX). Cardiopulmonary exercise testing, 6-minute walk distance (6MWD), and serum biomarkers were measured at baseline and 16- or 24-week follow-up (for IRONOUT and RELAX respectively). Biomarkers included N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2, growth differentiation factor-15, and Galectin-3. RESULTS: Analysis included 225 patients with HFrEF and 216 with HFpEF. Baseline peak VO2, VE/VCO2 slope, and 6MWD showed a mild correlation with the doubling of all 4 tested biomarkers in HFrEF and HFpEF. Following multivariable adjustment (including all biomarkers), the only significant association between change in biomarker and functional parameter in HFrEF was change in NT-proBNP and change in VE/VCO2 slope (3.596% increase per doubling, 95% CI 0.779-6.492, P = .012). In HFpEF, a decrease in peak VO2 was associated with an increase in NT-proBNP (-0.726 mL/min/kg per doubling, 95% CI -1.100 to -0.353, P < .001), and a decrease in 6MWD was associated with an increase in growth differentiation factor-15 (-31.606 m per doubling, 95% CI -61.404 to -1.809, P = .038). CONCLUSIONS: In these ambulatory trial cohorts, NT-proBNP was associated with baseline and change in CRF in HFrEF and HFpEF. In contrast, novel biomarkers do not appear suitable as a reliable surrogate for serial assessment of exercise capacity in HF patients given lack of consistent independent association with CRF beyond traditional risk factors and NT-proBNP.

4.
Circulation ; 140(25): 2108-2118, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31841369

RESUMO

Following regulatory guidance set forth in 2008 by the US Food and Drug Administration for new drugs for type 2 diabetes mellitus, many large randomized, controlled trials have been conducted with the primary goal of assessing the safety of antihyperglycemic medications on the primary end point of major adverse cardiovascular events, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Heart failure (HF) was not specifically mentioned in the US Food and Drug Administration guidance and therefore it was not a focus of these studies when planned. Several trials subsequently showed the impact of antihyperglycemic drugs on HF outcomes, which were not originally specified as the primary end point of the trials. The most impressive finding has been the substantial and consistent risk reduction in HF hospitalization seen across 4 trials of sodium glucose cotransporter 2 inhibitors. However, to date, these results have not led to regulatory approval of any of these drugs for a HF indication or a recommendation for use by US HF guidelines. It is therefore important to explore to what extent persuasive treatment effects on nonprimary end points can be used to support regulatory claims and guideline recommendations. This topic was discussed by researchers, clinicians, industry sponsors, regulators, and representatives from professional societies, who convened on the US Food and Drug Administration campus on March 6, 2019. This report summarizes these discussions and the key takeaway messages from this meeting.

5.
JAMA Cardiol ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721978

RESUMO

Importance: The Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study (ARTEMIS) cluster-randomized trial found that copayment reduction for P2Y12 inhibitors improved 1-year patient persistence in taking that medication. Objective: To assess whether providing copayment reduction for P2Y12 inhibitors increases patient persistence in taking other secondary prevention cardiovascular medications. Design, Setting, and Participants: This post hoc analysis of the ARTEMIS trial includes data from 287 hospitals that enrolled patients between June 2015 and September 2016. Patients hospitalized with acute myocardial infarction were included. Data analysis occurred from May 2018 through August 2019. Interventions: Hospitals randomized to the intervention provided patients vouchers that waived copayments for P2Y12 inhibitors fills for 1 year. Hospitals randomized to usual care did not provide study vouchers. Main Outcomes and Measures: Persistence in taking ß-blocker, statin, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker medications at 1 year, defined as the absence of a gap in medication supply of 30 or more days by pharmacy fill data in the intervention-arm (intent-to-treat) population. Results: A total of 131 hospitals (with 5109 patients) were randomized to the intervention, and 156 hospitals (with 3264 patients) randomized to the control group. Patients discharged from intervention hospitals had higher persistence in taking statins (2247 [46.1%] vs 1300 [41.9%]; adjusted odds ratio, 1.11 [95% CI, 1.00-1.24]), and ß-blockers (2235 [47.6%] vs 1277 [42.5%]; odds ratio, 1.23 [95% CI, 1.10-1.38]), although the association was smaller than that seen for P2Y12 inhibitors (odds ratio, 1.47 [95% CI, 1.29-1.66]). Persistence in taking angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers were also numerically higher among patients in the intervention arm than in the usual-care arm, but this was not significant after risk adjustment (1520 [43.9%] vs 847 [40.5%]; adjusted odds ratio, 1.10 [95% CI, 0.97-1.24]). Patients in the intervention arm reported greater financial burden associated with medication cost than the patients in the usual-care arm at baseline, but these differences were no longer significant at 1 year. Conclusions and Relevance: Reducing patient copayments for 1 medication class increased persistence not only to that therapy class but may also have modestly increased persistence to other post-myocardial infarction secondary prevention medications. These findings have important implications for the clinical utility and cost-effectiveness of medication cost-assistance programs. Trial Registration: ClinicalTrials.gov Identifier: NCT02406677.

6.
J Card Fail ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31682908

RESUMO

BACKGROUND: Diastolic dysfunction (DD) is common and occurs at an earlier age among human immunodeficiency virus-infected (HIV+) individuals, but the mechanisms and consequences of DD among HIV+ individuals are unclear. METHODS AND RESULTS: The Characterization of Heart Function on Antiretroviral Therapy (CHART) study was a multicenter cross-sectional case-control study of treated and virally suppressed HIV+ individuals with (DD+) and without DD (DD-). All patients had normal ejection fraction (>50%), no significant valvular disease, and no history of coronary revascularization or persistent atrial fibrillation. Overall, 94 DD+ and 101 DD- patients were included. DD+ patients were older with higher body mass index (BMI) and more likely to have hypertension, renal dysfunction, and dyslipidemia. Groups were similar with respect to sex, race, CD4 count, and HIV RNA copies. N-terminal pro-B-type natriuretic peptide levels (median 36 [23, 85] vs 26 [12, 49] pg/mL, P < .01) and high-sensitivity troponin I (3.6 [2.6, 5.1] vs 2.5 [1.8, 3.5] pg/mL, P < .01) were higher among DD+ patients. The latter had similar left atrial size, but increased stiffness (conduit strain: 23.5 [17.5, 36.9] vs 30.0 [22.9, 37.0], P < .01) and impaired relaxation (reservoir strain: 39.7 [32.0, 58.0] vs 45.9 [37.0, 60.6], P = .04). On cardiac magnetic resonance, the prevalence of focal fibrosis was higher among DD+ patients (19.0% vs 5.3%, P < .01). DD+ patients demonstrated higher levels of carboxyl-terminal telopeptide of collagen type I (P = .04), and trends toward higher interleukin-6 and oxidized low-density lipoprotein levels (P ≤ .08). Kansas City Cardiomyopathy Questionnaire physical limitation (87.1±21.4 vs 93.1±18.1, P = .01) and symptom frequency scores were lower among DD+ patients (86.0±21.5 vs 92.5±16.8, P = .01). CONCLUSIONS: In this contemporary HIV+ population receiving antiretroviral therapy, DD was associated with multiple alterations in cardiac structure and function, including myocardial fibrosis and left atrial abnormalities, and worse quality of life. Further studies are needed to assess longitudinal changes in these parameters and their potential as therapeutic targets to prevent progressive cardiac remodeling and dysfunction in HIV.

7.
J Am Coll Cardiol ; 74(9): 1205-1217, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31466618

RESUMO

BACKGROUND: The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial demonstrated that a strategy to "guide" application of guideline-directed medical therapy (GDMT) by reducing amino-terminal pro-B-type natriuretic peptide (NT-proBNP) was not superior to GDMT alone. OBJECTIVES: The purpose of this study was to examine the prognostic meaning of NT-proBNP changes following heart failure (HF) therapy intensification relative to the goal NT-proBNP value of 1,000 pg/ml explored in the GUIDE-IT trial. METHODS: A total of 638 study participants were included who were alive and had available NT-proBNP results 90 days after randomization. Rates of subsequent cardiovascular (CV) death/HF hospitalization or all-cause mortality during follow-up and Kansas City Cardiomyopathy Questionnaire (KCCQ) overall scores were analyzed. RESULTS: A total of 198 (31.0%) subjects had an NT-proBNP ≤1,000 pg/ml at 90 days with no difference in achievement of NT-proBNP goal between the biomarker-guided and usual care arms. NT-proBNP ≤1,000 pg/ml by 90 days was associated with longer freedom from CV/HF hospitalization or all-cause mortality (p < 0.001 for both) and lower adjusted hazard of subsequent HF hospitalization/CV death (hazard ratio: 0.26; 95% confidence interval: 0.15 to 0.46; p < 0.001) and all-cause mortality (hazard ratio: 0.34; 95% confidence interval: 0.15 to 0.77; p = 0.009). Regardless of elevated baseline concentration, an NT-proBNP ≤1,000 pg/ml at 90 days was associated with better outcomes and significantly better KCCQ overall scores (p = 0.02). CONCLUSIONS: Patients with heart failure with reduced ejection fraction whose NT-proBNP levels decreased to ≤1,000 pg/ml during GDMT had better outcomes. These findings may help to understand the results of the GUIDE-IT trial. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).

8.
Artigo em Inglês | MEDLINE | ID: mdl-31358329

RESUMO

OBJECTIVE: In the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial, no differences in clinical outcomes were observed between levosimendan and placebo in a broad population of patients undergoing cardiac surgery. In previous studies, the benefits of levosimendan were most clearly evident in patients undergoing isolated coronary artery bypass grafting (CABG) surgery. In a prespecified analysis of LEVO-CTS, we compared treatment-related outcomes and costs across types of cardiac surgical procedures. METHODS: Overall, 563 (66.4%) patients underwent isolated CABG, 97 (11.4%) isolated valve, and 188 (22.2%) combined CABG/valve surgery. Outcomes included the co-primary 4-component composite (30-day mortality, 30-day renal replacement, 5-day myocardial infarction, or 5-day mechanical circulatory support), the 2-component composite (30-day mortality or 5-day mechanical circulatory support), 90-day mortality, low cardiac output syndrome (LCOS), and 30-day medical costs. RESULTS: The 4- and 2-component outcomes were not significantly different with levosimendan and placebo in patients undergoing CABG (15.2% vs 19.3% and 7.8% vs 10.4%), valve (49.0% vs 33.3% and 22.4% vs 2.1%), or combined procedures (39.6% vs 35.9% and 24.0% vs 19.6%). Ninety-day mortality was lower with levosimendan in isolated CABG (2.1% vs 7.9%; hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.11-0.64), but not significantly different in valve (8.3% vs 2.0%; HR, 4.10; 95% CI, 0.46-36.72) or combined procedures (10.4% vs 7.6%; HR, 1.39; 95% CI, 0.53-3.64; interaction P = .011). LCOS (12.0% vs 22.1%; odds ratio, 0.48; 95% CI, 0.30-0.76; interaction P = .118) was significantly lower in levosimendan-treated patients undergoing isolated CABG. Excluding study drug costs, median and mean 30-day costs were $53,707 and $65,852 for levosimendan and $54,636 and $67,122 for placebo, with a 30-day mean difference (levosimendan - placebo) of -$1270 (bootstrap 95% CI, -$8722 to $6165). CONCLUSIONS: Levosimendan was associated with lower 90-day mortality and LCOS in patients undergoing isolated CABG, but not in those undergoing isolated valve or combined CABG/valve procedures.

10.
Circ Heart Fail ; 12(5): e005998, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096775

RESUMO

Background The VITALITY-HFpEF trial (Evaluate the Efficacy and Safety of the Oral sGC Stimulator Vericiguat to Improve Physical Functioning in Daily Living Activities of Patients With Heart Failure and Preserved Ejection Fraction) is designed to determine the efficacy and safety of a novel oral soluble guanylate cyclase stimulator, vericiguat, on quality of life and exercise tolerance in heart failure patients with preserved ejection fraction (HFpEF). Impaired physical functioning reduces the quality of life in patients with HFpEF. The primary goal of HF treatment along with improving survival is to improve function, reduce symptoms, and maximize quality of life. Abnormal cyclic guanosine monophosphate signaling may contribute to physical limitations in patients with HFpEF via central and peripheral mechanisms. Exploratory post hoc analyses from a prior trial showed that vericiguat can improve patient-relevant domains of the Kansas City Cardiomyopathy Questionnaire, especially the physical limitation score. Methods and Results VITALITY-HFpEF is a placebo-controlled, double-blind, multi-center, phase IIb trial of ≈735 patients, ≥45 years with HFpEF and ejection fraction ≥45% who will be randomized 1:1:1 to placebo, 10 mg, or 15 mg vericiguat. The primary end point is change in Kansas City Cardiomyopathy Questionnaire physical limitation score from baseline to week 24 and change in 6-minute walk test from baseline to week 24 is the secondary end point. Conclusions VITALITY-HFpEF is the first trial designed to assess the efficacy of vericiguat in patients with HFpEF using the Kansas City Cardiomyopathy Questionnaire physical limitation score as a novel primary end point. This study will also extend the prior dosing experience with vericiguat in HF by studying the safety and efficacy of a 15 mg dose. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT03547583.

11.
JACC Clin Electrophysiol ; 5(5): 599-605, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31122382

RESUMO

OBJECTIVES: This study sought to determine how frequently patient-reported outcomes (PROs) are collected in registered clinical studies of atrial fibrillation (AF). BACKGROUND: Improving symptom burden and quality of life are important goals in the treatment of AF and are best measured with PROs. METHODS: Data from Clincaltrials.gov were studied to identify PROs in AF studies. All studies reporting AF as the disease condition were included, and PROs were identified by search terms within the outcome measures field. Generic and AF-specific PROs were identified and assessed by study type and year. Clinicaltrials.gov reporting was compared with published reports of linked studies in PubMed. RESULTS: From 1999 to 2018, 1,709 studies including AF patients were posted; 238 studies (14%) included PROs. Collection of PROs was reported in 22% of trials (n = 83 of 386) studying procedural interventions and 11% of all Phase 3 studies (n = 18 of 168). Among the 238 studies with PROs, most described "quality of life" (n = 194 [82%]), and most (n = 198 [83%]) included only generic (not AF-specific) PROs. Only 17% of studies (n = 40) reporting PROs specified a previously published AF-specific tool, most commonly the AFEQT (Atrial Fibrillation Effect on QualiTy-of-life) form (n = 20 [8.4%]). Among the available PubMed citations of 391 studies, 74 studies (19%) described collecting a specific PRO tool (n = 29 [7.4%]) for an AF-specific PRO. CONCLUSIONS: Despite increased emphasis on the importance of PROs in AF, a minority of registered clinical trials reported collecting PROs, with very few using validated, AF-specific PROs. Improving outcomes that are most important to patients will necessitate increased emphasis on these PROs in pivotal clinical studies.

12.
Eur J Heart Fail ; 21(6): 770-778, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30919549

RESUMO

BACKGROUND: Most heart failure (HF) risk scores have been derived from cohorts of stable HF patients and may not incorporate up to date treatment regimens or deep phenotype characterization that change baseline risk over the short- and long-term follow-up period. We undertook the current analysis of participants in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial to address these limitations. METHODS AND RESULTS: The GUIDE-IT study randomized 894 high-risk patients with HF and reduced ejection fraction (≤ 40%) to biomarker-guided treatment strategy vs. usual care. We performed risk modelling using Cox proportional hazards models and analysed the relationship between 35 baseline clinical factors and the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, the secondary endpoint of all-cause mortality, and the exploratory endpoint of 90-day HF hospitalization or death. Prognostic relationships for continuous variables were examined and key predictors were identified using a backward variable selection process. Predictive models and risk scores were developed. Over a median follow-up of 15 months, the cumulative number of HF hospitalizations and CV deaths was 328 out of 894 patients (Kaplan-Meier event rate 34.5% at 12 months). Frequency of all-cause deaths was 143 out of 894 patients (Kaplan-Meier event rate 12.2% at 12 months). Outcomes for the primary and secondary endpoints between strategy arms of the study were similar. The most important predictor that was present in all three models was the baseline natriuretic peptide level. Hispanic ethnicity, low sodium and high heart rate were present in two of the three models. Other important predictors included the presence or absence of a device, New York Heart Association class, HF duration, black race, co-morbidities (sleep apnoea, elevated creatinine, ischaemic heart disease), low blood pressure, and a high congestion score. CONCLUSION: Risk models using readily available clinical information are able to accurately predict short- and long-term CV events and may be useful in optimizing care and enriching patients for clinical trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID number NCT01685840.

13.
JAMA ; 321(13): 1275-1285, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30874716

RESUMO

Importance: Catheter ablation is more effective than drug therapy in restoring sinus rhythm in patients with atrial fibrillation (AF), but its incremental effect on long-term quality of life (QOL) is uncertain. Objective: To determine whether catheter ablation is more beneficial than conventional drug therapy for improving QOL in patients with AF. Design, Setting, and Participants: An open-label randomized clinical trial of catheter ablation vs drug therapy in 2204 symptomatic patients with AF older than 65 years or 65 years or younger with at least 1 risk factor for stroke. Patients were enrolled from November 2009 to April 2016 from 126 centers in 10 countries. Follow-up ended in December 2017. Interventions: Pulmonary vein isolation, with additional ablation procedures at the discretion of the investigators, for the catheter ablation group (n = 1108) and standard rhythm and/or rate-control drugs selected and managed by investigators for the drug therapy group (n = 1096). Main Outcomes and Measures: Prespecified co-primary QOL end points at 12 months, including the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary score (range, 0-100; 0 indicates complete disability and 100 indicates no disability; patient-level clinically important difference, ≥5 points) and the Mayo AF-Specific Symptom Inventory (MAFSI) frequency score (range, 0-40; 0 indicates no symptoms and 40 indicates the most severe symptoms; patient-level clinically important difference, ≤-1.6 points) and severity score (range, 0-30; 0 indicates no symptoms and 30 indicates the most severe symptoms; patient-level clinically important difference, ≤-1.3 points). Results: Among 2204 randomized patients (median age, 68 years; 1385 patients [63%] were men, 946 [43%] had paroxysmal AF, and 1256 [57%] had persistent AF), the median follow-up was 48.5 months, and 1968 (89%) completed the trial. The mean AFEQT summary score was more favorable in the catheter ablation group than the drug therapy group at 12 months (86.4 points vs 80.9 points) (adjusted difference, 5.3 points [95% CI, 3.7-6.9]; P < .001). The mean MAFSI frequency score was more favorable for the catheter ablation group than the drug therapy group at 12 months (6.4 points vs 8.1 points) (adjusted difference, -1.7 points [95% CI, -2.3 to -1.2]; P < .001) and the mean MAFSI severity score was more favorable for the catheter ablation group than the drug therapy group at 12 months (5.0 points vs 6.5 points) (adjusted difference, -1.5 points [95% CI, -2.0 to -1.1]; P < .001). Conclusions and Relevance: Among patients with symptomatic atrial fibrillation, catheter ablation, compared with medical therapy, led to clinically important and significant improvements in quality of life at 12 months. These findings can help guide decisions regarding management of atrial fibrillation. Trial Registration: ClinicalTrials.gov Identifier: NCT00911508.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Ablação por Cateter , Qualidade de Vida , Idoso , Fibrilação Atrial/complicações , Viés , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
14.
Stud Health Technol Inform ; 257: 86-91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30741178

RESUMO

Death, as a biological phenomenon, is well understood and a commonly employed endpoint for clinical trials. However, death identification and adjudication may be difficult for pragmatic clinical trials (PCT) that rely upon electronic health record and patient reported data. We propose a novel death identification and verification approach that is being used in the ToRsemide compArisoN with furoSemide FOR Management of Heart Failure (TRANSFORM-HF) PCT. We describe our hybrid approach that includes gathering information from clinical trial sites, a centralized call center, and National Death Index searches. Our methods detail how a possible death is triggered from each of these components and the types of information we require to verify a triggered death. Our different trigger/verification elements collectively define the TRANSFORM-HF PCT's definition of a death event.


Assuntos
Determinação de Ponto Final , Insuficiência Cardíaca , Mortalidade , Ensaios Clínicos como Assunto , Coleta de Dados , Diuréticos/uso terapêutico , Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Torasemida/uso terapêutico
15.
JAMA ; 321(1): 44-55, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30620370

RESUMO

Importance: Despite guideline recommendations, many patients discontinue P2Y12 inhibitor therapy earlier than the recommended 1 year after myocardial infarction (MI), and higher-potency P2Y12 inhibitors are underutilized. Cost is frequently cited as an explanation for both of these observations. Objective: To determine whether removing co-payment barriers increases P2Y12 inhibitor persistence and lowers risk of major adverse cardiovascular events (MACE). Design, Setting, and Participants: Cluster randomized clinical trial among 301 hospitals enrolling adult patients with acute MI (June 5, 2015, through September 30, 2016); patients were followed up for 1 year after discharge (final date of follow-up was October 23, 2017), with blinded adjudication of MACE; choice of P2Y12 inhibitor was per clinician discretion. Interventions: Hospitals randomized to the intervention (n = 131 [6436 patients]) provided patients with co-payment vouchers for clopidogrel or ticagrelor for 1 year (median voucher value for a 30-day supply, $137 [25th-75th percentile, $20-$339]). Hospitals randomized to usual care (n = 156 [4565 patients]) did not provide study vouchers. Main Outcomes and Measures: Independent coprimary outcomes were patient-reported persistence with P2Y12 inhibitor (defined as continued treatment without gap in use ≥30 days) and MACE (death, recurrent MI, or stroke) at 1 year among patients discharged with a prescription for clopidogrel or ticagrelor. Results: Among 11 001 enrolled patients (median age, 62 years; 3459 [31%] women), 10 102 patients were discharged with prescriptions for clopidogrel or ticagrelor (clopidogrel prescribed to 2317 [36.0%] in the intervention group and 2497 [54.7%] in the usual care group), 4393 of 6135 patients (72%) in the intervention group used the voucher, and follow-up data at 1 year were available for 10 802 patients (98.2%). Patient-reported persistence with P2Y12 inhibitors at 1 year was higher in the intervention group than in the control group (unadjusted rates, 5340/6135 [87.0%] vs 3324/3967 [83.8%], respectively; P < .001; adjusted difference, 2.3% [95% CI, 0.4% to 4.1%]; adjusted odds ratio, 1.19 [95% CI, 1.02 to 1.40]). There was no significant difference in MACE at 1 year between intervention and usual care groups (unadjusted cumulative incidence, 10.2% vs 10.6%; P = .65; adjusted difference, 0.66% [95% CI, -0.73% to 2.06%]; adjusted hazard ratio, 1.07 [95% CI, 0.93 to 1.25]). Conclusions and Relevance: Among patients with MI, provision of vouchers to offset medication co-payments for P2Y12 inhibitors, compared with no vouchers, resulted in a 3.3% absolute increase in patient-reported persistence with P2Y12 inhibitors and no significant reduction in 1-year MACE outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02406677.


Assuntos
Custo Compartilhado de Seguro , Adesão à Medicação , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Idoso , Clopidogrel/uso terapêutico , Custos de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Razão de Chances , Cloridrato de Prasugrel/uso terapêutico , Recidiva , Acidente Vascular Cerebral/etiologia , Ticagrelor/uso terapêutico
17.
Heart Rhythm ; 16(1): 91-97, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30059750

RESUMO

BACKGROUND: Patients with heart failure and sleep apnea are at increased risk for developing arrhythmias. Whether treatment of sleep apnea reduces arrhythmias is unknown. OBJECTIVE: The purpose of this study was to determine whether adaptive servo-ventilation (ASV) with optimal medical therapy (OMT) reduces atrial fibrillation (AF) and/or ventricular tachycardia/ventricular fibrillation (VT/VF) burden compared to OMT alone. METHODS: We conducted a prospective substudy of patients with pacemakers/defibrillators in the Cardiovascular Improvements with Minute Ventilation-Targeted ASV Therapy in Heart Failure (CAT-HF) trial. Change in arrhythmia burden was compared using a mixed model analysis to account for multiple measurements per patient. RESULTS: Among 35 randomized patients eligible and analyzed (19 ASV, 16 OMT only) in the AF cohort, mean age was 64 ± 12 years, 23% were women (n = 8), 49% had previous AF (n = 17), 89% had reduced ejection fraction (n = 31), and mean apnea hypopnea index was 41 ± 17 events per hour. Baseline characteristics were similar between groups. Change in AF burden from baseline to follow-up was -15.8% ± 36.5% with ASV vs +23.7% ± 36.2% with OMT (P = .034). There was no significant change in the AF cohort in the mean number of VT/VF events: +3.3 ± 14.9 events with ASV vs -0.3 ± 7.3 events with OMT (P = .58). Five subjects had appropriate therapies for VT/VF in the ASV arm vs 6 subjects in the OMT arm. CONCLUSION: This study provides proof of concept that treatment of sleep apnea with ASV leads to reduction in AF burden compared with OMT alone, without an increase in VT/VF events. This hypothesis should be tested in a large outcomes trial.

18.
J Am Heart Assoc ; 7(24): e010364, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30561266

RESUMO

Background We sought to study the prevalence of high-sensitivity troponin and its association with cardiac structure and outcomes in ambulatory and hospitalized patients with heart failure with a preserved ejection fraction ( HF p EF ). Methods and Results A post hoc analysis utilized data from HF p EF patients: DOSE (Diuretic Optimization Strategies Evaluation) and CARRESS - HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) enrolled patients hospitalized with acute HF p EF , and RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure With Preserved Ejection Fraction) enrolled ambulatory patients with HF p EF . High-sensitivity troponin I (hs-TnI) was measured in hospitalized patients at baseline, at 72 to 96 hours, on day 7, and on day 60. In ambulatory patients hs-TnI was measured at baseline and at week 24. In the ambulatory cohort, correlations between hs-TnI and cardiac structure and function were assessed. The association between hs-TnI and a 60-day composite of emergency room visits, readmissions, and death was assessed for hospitalized patients using multivariable Cox proportional hazard models. The study population included 139 hospitalized and 212 ambulatory patients with HF p EF and hs-TnI measured at baseline. The median (25th, 75th percentiles) baseline troponin was 17.6 (11.1, 41.0) ng/L in hospitalized patients and 9.5 (5.3, 19.7) ng/L in ambulatory patients ( P<0.001). The prevalence of elevated hs-TnI (>99% percentile upper reference limit was 86% in hospitalized patients and 53% among ambulatory patients, with stable elevation in ambulatory patients during follow-up. HF p EF patients with a hs-TnI above the median were older with worse left ventricular hypertrophy and diastolic dysfunction. Continuously valued hs-TnI (per doubling) was associated with increased risk of composite end point (adjusted hazard ratio 1.20, 95% confidence interval 1.00-1.43; P=0.042). Conclusions Hs-TnI is commonly elevated among both hospitalized and ambulatory patients with HF p EF . Increased hs-TnI levels are associated with worse cardiac structure and increased risk of adverse events.


Assuntos
Insuficiência Cardíaca/sangue , Hospitalização , Volume Sistólico , Troponina I/sangue , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
19.
JAMA ; 320(17): 1764-1773, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30398602

RESUMO

Importance: There are few effective treatments for heart failure with preserved ejection fraction (HFpEF). Short-term administration of inorganic nitrite or nitrate preparations has been shown to enhance nitric oxide signaling, which may improve aerobic capacity in HFpEF. Objective: To determine the effect of 4 weeks' administration of inhaled, nebulized inorganic nitrite on exercise capacity in HFpEF. Design, Setting, and Participants: Multicenter, double-blind, placebo-controlled, 2-treatment, crossover trial of 105 patients with HFpEF. Participants were enrolled from July 22, 2016, to September 12, 2017, at 17 US sites, with final date of follow-up of January 2, 2018. Interventions: Inorganic nitrite or placebo administered via micronebulizer device. During each 6-week phase of the crossover study, participants received no study drug for 2 weeks (baseline/washout) followed by study drug (nitrite or placebo) at 46 mg 3 times a day for 1 week followed by 80 mg 3 times a day for 3 weeks. Main Outcomes and Measures: The primary end point was peak oxygen consumption (mL/kg/min). Secondary end points included daily activity levels assessed by accelerometry, health status as assessed by the Kansas City Cardiomyopathy Questionnaire (score range, 0-100, with higher scores reflecting better quality of life), functional class, cardiac filling pressures assessed by echocardiography, N-terminal fragment of the prohormone brain natriuretic peptide levels, other exercise indices, adverse events, and tolerability. Outcomes were assessed after treatment for 4 weeks. Results: Among 105 patients who were randomized (median age, 68 years; 56% women), 98 (93%) completed the trial. During the nitrite phase, there was no significant difference in mean peak oxygen consumption as compared with the placebo phase (13.5 vs 13.7 mL/kg/min; difference, -0.20 [95% CI, -0.56 to 0.16]; P = .27). There were no significant between-treatment phase differences in daily activity levels (5497 vs 5503 accelerometry units; difference, -15 [95% CI, -264 to 234]; P = .91), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (62.6 vs 61.9; difference, 1.1 [95% CI, -1.4 to 3.5]; P = .39), functional class (2.5 vs 2.5; difference, 0.1 [95% CI, -0.1 to 0.2]; P = .43), echocardiographic E/e' ratio (16.4 vs 16.6; difference, 0.1 [95% CI, -1.2 to 1.3]; P = .93), or N-terminal fragment of the prohormone brain natriuretic peptide levels (520 vs 533 pg/mL; difference, 11 [95% CI, -53 to 75]; P = .74). Worsening heart failure occurred in 3 participants (2.9%) during the nitrite phase and 8 (7.6%) during the placebo phase. Conclusions and Relevance: Among patients with HFpEF, administration of inhaled inorganic nitrite for 4 weeks, compared with placebo, did not result in significant improvement in exercise capacity. Trial Registration: ClinicalTrials.gov Identifier: NCT02742129.


Assuntos
Tolerância ao Exercício/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Nitritos/uso terapêutico , Administração por Inalação , Idoso , Estudos Cross-Over , Método Duplo-Cego , Teste de Esforço , Tolerância ao Exercício/fisiologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Compostos Inorgânicos/farmacologia , Compostos Inorgânicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nitritos/efeitos adversos , Nitritos/farmacologia , Consumo de Oxigênio , Volume Sistólico , Falha de Tratamento
20.
J Am Coll Cardiol ; 72(21): 2551-2562, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30466512

RESUMO

BACKGROUND: The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial prospectively compared the efficacy of an N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided heart failure treatment strategy (target NT-proBNP level <1,000 pg/ml) with optimal medical therapy alone in high-risk patients with heart failure and reduced ejection fraction. When the study was stopped for futility, 894 patients had been enrolled. OBJECTIVES: The purpose of this study was to assess treatment-related quality-of-life (QOL) and economic outcomes in the GUIDE-IT trial. METHODS: The authors prospectively collected a battery of QOL instruments at baseline and 3, 6, 12, and 24 months post-randomization (collection rates 90% to 99% of those eligible). The principal pre-specified QOL measures were the Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and the Duke Activity Status Index (DASI). Cost data were collected for 735 (97%) U.S. RESULTS: Baseline variables were well balanced in the 446 patients randomized to the NT-proBNP-guided therapy and 448 to usual care. Both the KCCQ and the DASI improved over the first 6 months, but no evidence was found for a strategy-related difference (mean difference [biomarker-guided - usual care] at 24 months of follow-up 2.0 for DASI [95% confidence interval (CI): -1.3 to 5.3] and 1.1 for KCCQ [95% CI: -3.7 to 5.9]). Total winsorized costs averaged $5,919 higher in the biomarker-guided strategy (95% CI: -$1,795, +$13,602) over 15-month median follow-up. CONCLUSIONS: A strategy of NT-proBNP-guided HF therapy had higher total costs and was not more effective than usual care in improving QOL outcomes in patients with heart failure and a reduced ejection fraction. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/economia , Peptídeo Natriurético Encefálico/economia , Peptídeo Natriurético Encefálico/uso terapêutico , Fragmentos de Peptídeos/economia , Fragmentos de Peptídeos/uso terapêutico , Qualidade de Vida , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Resultado do Tratamento
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