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1.
JAMA Cardiol ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33185650

RESUMO

Importance: The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH. Objective: To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. Design, Setting, and Participants: Analysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020. Intervention: Vericiguat titrated to 10 mg daily vs placebo. Main Outcomes and Measures: The primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. Results: Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms. Conclusions and Relevance: Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF. Trial Registration: ClinicalTrials.gov Identifier: NCT02861534.

2.
JACC Heart Fail ; 8(11): 931-939, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33039447

RESUMO

OBJECTIVES: The purpose of this study was to examine the treatment effect of vericiguat in relation to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at randomization. BACKGROUND: Vericiguat compared with placebo reduced the primary outcome of cardiovascular death (CVD) or heart failure hospitalization (HFH) in patients with HF with reduced ejection fraction (HFrEF) in the VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) trial. Because an interaction existed between treatment and the primary outcome according to pre-specified quartiles of NT-proBNP at randomization, we examined this further. METHODS: This study evaluated the NT-proBNP relationship with the primary outcome in 4,805 of 5,050 patients as a risk-adjusted, log-transformed continuous variable. Hazard ratios (HRs) and 95% confidence intervals (CIs) are presented. RESULTS: Median NT-proBNP was 2,816 pg/ml (25th to 75th percentile: 1,556 to 5,314 pg/ml). The study treatment effect varied across the spectrum of NT-proBNP at randomization (with log2 transformation, p for interaction = 0.002). A significant association between treatment effects existed in patients with levels <4,000 pg/ml and remained evident up to 8,000 pg/ml. A 23% relative risk reduction occurred in the primary endpoint with NT-proBNP ≤4,000 pg/ml (HR: 0.77; 95% CI: 0.68 to 0.88). For NT-proBNP values ≤4,000 pg/ml (n = 3,100), the HR was 0.78 (95% CI: 0.67 to 0.90) for HFH and 0.75 (95% CI: 0.60 to 0.94) for CVD. For NT-proBNP ≤8,000 pg/ml (n = 4,133), the HR was 0.85 (95% CI: 0.76 to 0.95) for the primary outcome, 0.84 (95% CI: 0.75 to 0.95) for HFH, and 0.84 (95% CI: 0.71 to 0.99) for CVD. For NT-proBNP >8,000 pg/ml (n = 672), the HR was 1.16 (95% CI: 0.94 to 1.41) for the primary outcome. CONCLUSIONS: A reduction in the primary composite endpoint and its CVD and HFH components was observed in patients on vericiguat compared with subjects on placebo with NT-proBNP levels up to 8,000 pg/ml. This provided new insight into the benefit observed in high-risk patients with worsening HFrEF. (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction [HFrEF] [MK-1242-001] [VICTORIA]; NCT02861534).

3.
JAMA ; 324(15): 1512-1521, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079152

RESUMO

Importance: Patients with heart failure and preserved ejection fraction (HFpEF) are at high risk of mortality, hospitalizations, and reduced functional capacity and quality of life. Objective: To assess the efficacy of the oral soluble guanylate cyclase stimulator vericiguat on the physical limitation score (PLS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ). Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled, multicenter trial of 789 patients with chronic HFpEF and left ventricular ejection fraction 45% or higher with New York Heart Association class II-III symptoms, within 6 months of a recent decompensation (HF hospitalization or intravenous diuretics for HF without hospitalization), and with elevated natriuretic peptides, enrolled at 167 sites in 21 countries from June 15, 2018, through March 27, 2019; follow-up was completed on November 4, 2019. Interventions: Patients were randomized to receive vericiguat, up-titrated to 15-mg (n = 264) or 10-mg (n = 263) daily oral dosages, compared with placebo (n = 262) and randomized 1:1:1. Main Outcomes and Measures: The primary outcome was change in the KCCQ PLS (range, 0-100; higher values indicate better functioning) after 24 weeks of treatment. The secondary outcome was 6-minute walking distance from baseline to 24 weeks. Results: Among 789 randomized patients, the mean age was 72.7 (SD, 9.4) years; 385 (49%) were female; mean EF was 56%; and median N-terminal pro-brain natriuretic peptide level was 1403 pg/mL; 761 (96.5%) completed the trial. The baseline and 24-week KCCQ PLS means for the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 60.0 and 68.3, 57.3 and 69.0, and 59.0 and 67.1, respectively, and the least-squares mean changes were 5.5, 6.4, and 6.9, respectively. The least-squares mean difference in scores between the 15-mg/d vericiguat and placebo groups was -1.5 (95% CI, -5.5 to 2.5; P = .47) and between the 10-mg/d vericiguat and placebo groups was -0.5 (95% CI, -4.6 to 3.5; P = .80). The baseline and 24-week 6-minute walking distance mean scores in the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 295.0 m and 311.8m , 292.1 m and 318.3 m, and 295.8 m and 311.4 m, and the least-squares mean changes were 5.0 m, 8.7 m, and 10.5 m, respectively. The least-squares mean difference between the 15-mg/d vericiguat and placebo groups was -5.5 m (95% CI, -19.7 m to 8.8 m; P = .45) and between the 10-mg/d vericiguat and placebo groups was -1.8 m (95% CI, -16.2 m to 12.6 m; P = .81), respectively. The proportions of patients who experienced symptomatic hypotension were 6.4% in the 15-mg/d vericiguat group, 4.2% in the 10-mg/d vericiguat group, and 3.4% in the placebo group; those with syncope were 1.5%, 0.8%, and 0.4%, respectively. Conclusions and Relevance: Among patients with HFpEF and recent decompensation, 24-week treatment with vericiguat at either 15-mg/d or 10-mg/d dosages compared with placebo did not improve the physical limitation score of the KCCQ. Trial Registration: ClinicalTrials.gov Identifier: NCT03547583.


Assuntos
Tolerância ao Exercício/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Compostos Heterocíclicos com 2 Anéis/uso terapêutico , Pirimidinas/uso terapêutico , Qualidade de Vida , Administração Oral , Idoso , Método Duplo-Cego , Feminino , Guanilato Ciclase/metabolismo , Insuficiência Cardíaca/fisiopatologia , Compostos Heterocíclicos com 2 Anéis/administração & dosagem , Compostos Heterocíclicos com 2 Anéis/efeitos adversos , Hospitalização , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Volume Sistólico , Falha de Tratamento , Teste de Caminhada
4.
J Clin Epidemiol ; 129: 60-67, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33002635

RESUMO

OBJECTIVE: To describe PCORnet, a clinical research network developed for patient-centered outcomes research on a national scale. STUDY DESIGN AND SETTING: Descriptive study of the current state and future directions for PCORnet. We conducted cross-sectional analyses of the health systems and patient populations of the 9 Clinical Research Networks and 2 Health Plan Research Networks that are part of PCORnet. RESULTS: Within the Clinical Research Networks, electronic health data are currently collected from 337 hospitals, 169,695 physicians, 3,564 primary care practices, 338 emergency departments, and 1,024 community clinics. Patients can be recruited for prospective studies from any of these clinical sites. The Clinical Research Networks have accumulated data from 80 million patients with at least one visit from 2009 to 2018. The PCORnet Health Plan Research Network population of individuals with a valid enrollment segment from 2009 to 2019 exceeds 60 million individuals, who on average have 2.63 years of follow-up. CONCLUSION: PCORnet's infrastructure comprises clinical data from a diverse cohort of patients and has the capacity to rapidly access these patient populations for pragmatic clinical trials, epidemiological research, and patient-centered research on rare diseases.

5.
Mayo Clin Proc Innov Qual Outcomes ; 4(5): 529-536, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33083701

RESUMO

Objective: To describe the intent and early outcomes of elective inotrope use during heart failure hospitalization. Patients and Methods: A prospective multisite design was used to collect data for hemodynamically stable patients started electively on inotrope therapy between January 1 and August 31, 2018. We prospectively recorded data when intravenous inotropic therapy was initiated, including survey of the attending cardiologists regarding expectations for the clinical course. Patients were followed up for events through hospital discharge and an additional survey was administered at the end of hospitalization. Results: For the 92 patients enrolled, average age was 60 years and ejection fraction was 24%±12%. At the time of inotrope initiation, attending heart failure cardiologists predicted that 50% (n=46) of the patients had a "high or very high" likelihood of becoming dependent on intravenous inotropic therapy and 58% (n=53) had a "high" likelihood of death, transplant, or durable ventricular assist device placement within the next 6 months. Provider predictions regarding death/hospice or need for continued home infusions were accurate only 51% (47 of 92) of the time. Only half the patients (n=47) had goals-of-care conversations before inotrope treatment initiation. Conclusion: More than half the patients (51 of 92) electively started on inotrope treatment without present or imminent cardiogenic shock ultimately required home inotrope therapy, died during admission, or were discharged with hospice. Heart failure clinicians could not reliably identify those patients at the time of inotrope therapy initiation and goals-of-care discussions were not frequently performed.

6.
J Card Fail ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038532

RESUMO

BACKGROUND: Prior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and postdischarge clinical outcomes, in the ASCEND-HF trial. METHODS AND RESULTS: The KH-ePVS and Duarte-ePV were calculated on admission. We assessed associations with in-hospital worsening HF, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality. There were 6373 (89.2%), and 6354 (89.0%) patients who had necessary characteristics to calculate KH-ePVS and Duarte-ePV, respectively. There was no association between PV by either formula with in-hospital worsening HF. KH-ePVS showed a weak correlation with N-terminal prohormone BNP, and with measures of decongestion such as body weight change and urine output (r < 0.3 for all). Duarte-ePV was trending toward an association with worse 30-day (adjusted odds ratio 1.07, 95% confidence interval [CI] 1.00-1.15, P = .058), but not 180-day outcomes (adjusted hazard ratio 1.03, 95% CI 0.97-1.09, P = .289). A continuous KH-ePVS of >0 (per 10-unit increase) was associated with improved 30-day outcomes (adjusted odds ratio 0.75, 95% CI 0.62-0.91, P = .004). The continuous KH-ePVS was not associated with 180-day outcomes (adjusted hazard ratio 1.05, 95% CI 0.98-1.12, P = .139). CONCLUSIONS: Baseline PV estimates had a weak association with in-hospital measures of decongestion. The Duarte-ePV trended toward an association with early clinical outcomes in decompensated HF, and may improve risk stratification in HF.

8.
Am Heart J ; 230: 35-43, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32980364

RESUMO

BACKGROUND: In PARADIGM-HF, sacubitril/valsartan improved quality of life (QOL) versus enalapril in heart failure with reduced ejection fraction (HFrEF), yet limited data are available regarding QOL changes after sacubitril/valsartan initiation in routine practice. METHODS: PROVIDE-HF was a prospective study within a national research network (Patient-Centered Outcomes Research Network) of HFrEF outpatients recently initiated on sacubitril/valsartan versus controls with recent angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation/dose change. The primary end point was mean Kansas City Cardiomyopathy Questionnaire (KCCQ) change through 12 weeks. Other end points included responder analyses: ≥5-point and ≥20-point KCCQ increase. Adjusted QOL change was estimated after propensity score weighting. RESULTS: Overall, 270 patients had both baseline and 12-week KCCQ data (151 sacubitril/valsartan; 119 control). The groups had similar demographics and HF details: median EF 28% and N-terminal pro-brain natriuretic peptide 1083 pg/mL. Sacubitril/valsartan patients had larger improvements in KCCQ (mean difference +4.76; P = .027) and were more likely to have a ≥5-point and ≥20-point response (all P < .05). Adjusted comparisons demonstrated similar numerical improvements in the change in KCCQ (+4.55; 95% CI -0.89 to 9.99; P = .101) and likelihood of ≥5-point increase (odds ratio 1.55; 95% CI: 0.84-2.86; P = .16); ≥20-point increase remained statistically significant (odds ratio 3.79; 95% CI 1.47-9.73; P = .006). CONCLUSIONS: In this prospective HFrEF study of sacubitril/valsartan initiation compared with recent angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation/dose change, the between-group difference in the primary end point, mean KCCQ change at 12 weeks was not statistically significant following adjustment, but sacubitril/valsartan initiation was associated with early improvements in QOL and a higher likelihood of ≥20-point improvement in KCCQ at 12 weeks. These data add additional real-world evidence related to patient-reported outcomes following the initiation of sacubitril/valsartan in routine clinical practice.

11.
Circulation ; 142(12): 1205-1218, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32955939

RESUMO

With worsening epidemiological trends for both the incidence and prevalence of type 2 diabetes mellitus (T2DM) and heart failure (HF) worldwide, it is critical to implement optimal prevention and treatment strategies for patients with these comorbidities, either alone or concomitantly. Several guidelines and consensus statements have recommended glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter type 2 inhibitors as add-ons to lifestyle interventions with or without metformin in those at high atherosclerotic cardiovascular disease risk. However, these recommendations are either silent about HF or fail to differentiate between the prevention of HF in those at risk versus the treatment of individuals with manifest HF. Furthermore, these documents do not differentiate among those with different HF phenotypes. This distinction, even though important, may not be critical for sodium-glucose cotransporter type 2 inhibitors in view of the consistent data for benefit for both atherosclerotic cardiovascular disease- and HF-related outcomes that have emerged from the regulatory-mandated cardiovascular outcome trials for all sodium-glucose cotransporter type 2 inhibitors and the recent DAPA-HF trial (Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction)demonstrating the benefit of dapagliflozin on HF-related outcomes in patients with HF with reduced ejection fraction with or without T2DM. However, the distinction may be crucial for glucagon-like peptide-1 receptor agonists and other antihyperglycemic agents. Indeed, in several of the new statements, glucagon-like peptide-1 receptor agonists are suggested treatment not only for patients with T2DM and atherosclerotic cardiovascular disease, but also in those with manifest HF, despite a lack of evidence for the latter recommendation. Although glucagon-like peptide-1 receptor agonists may be appropriate to use in patients at risk for HF, mechanistic insights and observations from randomized trials suggest no clear benefit on HF-related outcomes and even uncertainty regarding the safety in those with HF with reduced ejection fraction. Conversely, theoretical rationales suggest that these agents may benefit patients with HF with preserved ejection fraction. Considering that millions of patients with T2DM have HF, these concerns have public health implications that necessitate the thoughtful use of these therapies. Achieving this aim will require dedicated trials with these drugs in both patients who have HF with reduced ejection fraction and HF with preserved ejection fraction with T2DM to assess their efficacy, safety, and risk-benefit profile.

14.
Stat Med ; 39(28): 4218-4237, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-32823372

RESUMO

Cluster randomized trials (CRTs) refer to experiments with randomization carried out at the cluster or the group level. While numerous statistical methods have been developed for the design and analysis of CRTs, most of the existing methods focused on testing the overall treatment effect across the population characteristics, with few discussions on the differential treatment effect among subpopulations. In addition, the sample size and power requirements for detecting differential treatment effect in CRTs remain unclear, but are helpful for studies planned with such an objective. In this article, we develop a new sample size formula for detecting treatment effect heterogeneity in two-level CRTs for continuous outcomes, continuous or binary covariates measured at cluster or individual level. We also investigate the roles of two intraclass correlation coefficients (ICCs): the adjusted ICC for the outcome of interest and the marginal ICC for the covariate of interest. We further derive a closed-form design effect formula to facilitate the application of the proposed method, and provide extensions to accommodate multiple covariates. Extensive simulations are carried out to validate the proposed formula in finite samples. We find that the empirical power agrees well with the prediction across a range of parameter constellations, when data are analyzed by a linear mixed effects model with a treatment-by-covariate interaction. Finally, we use data from the HF-ACTION study to illustrate the proposed sample size procedure for detecting heterogeneous treatment effects.

15.
J Am Coll Cardiol ; 76(5): 580-589, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32731936

RESUMO

Concerns about the external validity of traditional randomized clinical trials (RCTs), together with the widespread availability of real-world data and advanced data analytic tools, have led to claims that common sense and clinical observation, rather than RCTs, should be the preferred method to generate evidence to support clinical decision-making. However, over the past 4 decades, results from well-done RCTs have repeatedly contradicted practices supported by common sense and clinical observation. Common sense and clinical observation fail for several reasons: incomplete understanding of pathophysiology, biases and unmeasured confounding in observational research, and failure to understand risks and benefits of treatments within complex systems. Concerns about traditional RCT models are legitimate, but randomization remains a critical tool to understand the causal relationship between treatments and outcomes. Instead, development and promulgation of tools to apply randomization to real-world data are needed to build the best evidence base in cardiovascular medicine.

16.
JACC Heart Fail ; 8(10): 789-799, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32641226

RESUMO

The PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial reported that sacubitril/valsartan (S/V), an angiotensin receptor-neprilysin inhibitor, significantly reduced mortality and heart failure (HF) hospitalization in HF patients with a reduced ejection fraction (HFrEF). However, fewer than 1% of patients in the PARADIGM-HF study had New York Heart Association (NYHA) functional class IV symptoms. Accordingly, data that informed the use of S/V among patients with advanced HF were limited. The LIFE (LCZ696 in Hospitalized Advanced Heart Failure) study was a 24-week prospective, multicenter, double-blinded, double-dummy, active comparator trial that compared the safety, efficacy, and tolerability of S/V with those of valsartan in patients with advanced HFrEF. The trial planned to randomize 400 patients ≥18 years of age with advanced HF, defined as an EF ≤35%, New York Heart Association functional class IV symptoms, elevated natriuretic peptide concentration (B-type natriuretic peptide [BNP] ≥250 pg/ml or N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥800 pg/ml), and ≥1 objective finding of advanced HF. Following a 3- to 7-day open label run-in period with S/V (24 mg/26 mg twice daily), patients were randomized 1:1 to S/V titrated to 97 mg/103 mg twice daily versus 160 mg of V twice daily. The primary endpoint was the proportional change from baseline in the area under the curve for NT-proBNP levels measured through week 24. Secondary and tertiary endpoints included clinical outcomes and safety and tolerability. Because of the COVID-19 pandemic, enrollment in the LIFE trial was stopped prematurely to ensure patient safety and data integrity. The primary analysis consists of the first 335 randomized patients whose clinical follow-up examination results were not severely impacted by COVID-19. (Entresto [LCZ696] in Advanced Heart Failure [LIFE STUDY] [HFN-LIFE]; NCT02816736).


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Tetrazóis/uso terapêutico , Betacoronavirus , Cardiotônicos/uso terapêutico , Infecções por Coronavirus , Relação Dose-Resposta a Droga , Método Duplo-Cego , Término Precoce de Ensaios Clínicos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração , Coração Auxiliar , Hospitalização/estatística & dados numéricos , Humanos , Hipotensão/induzido quimicamente , Peptídeo Natriurético Encefálico/metabolismo , Pandemias , Fragmentos de Peptídeos/metabolismo , Pneumonia Viral , Volume Sistólico
17.
Circ Cardiovasc Qual Outcomes ; 13(7): e006606, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32683985

RESUMO

The pipeline of new cardiovascular drugs is relatively limited compared with many other clinical areas. Challenges causing lagging drug innovation include the duration and expense of cardiovascular clinical trials needed for regulatory evaluation and approvals, which generally must demonstrate noninferiority to existing standards of care and measure longer-term outcomes. By comparison, there has been substantial progress in cardiovascular device innovation. There has also been progress in cardiovascular trial participation equity in recent years, especially among women, due in part to important efforts by Food and Drug Administration, National Institutes of Health, American Heart Association, and others. Yet women and especially racial and ethnic minority populations remain underrepresented in cardiovascular trials, indicating much work ahead to continue recent success. Given these challenges and opportunities, the multistakeholder Partnering with Regulators Learning Collaborative of the Value in Healthcare Initiative, a collaboration of the American Heart Association and the Robert J. Margolis, MD, Center for Health Policy at Duke University, identified how to improve the evidence generation process for cardiovascular drugs and devices. Drawing on a series of meetings, literature reviews, and analyses of regulatory options, the Collaborative makes recommendations across four identified areas for improvement. First, we offer strategies to enhance patient engagement in trial design, convenient participation, and meaningful end points and outcomes to improve patient recruitment and retention (major expenses in clinical trials). Second, new digital technologies expand the potential for real-world evidence to streamline data collection and reduce cost and time of trials. However, technical challenges must be overcome to routinely leverage real-world data, including standardizing data, managing data quality, understanding data comparability, and ensuring real-world evidence does not worsen inequities. Third, as trials are driven by evidence needs of regulators and payers, we recommend ways to improve their collaboration in trial design to streamline and standardize efficient and innovative trials, reducing costs and delays. Finally, we discuss creative ways to expand the minuscule proportion of sites involved in cardiovascular evidence generation and medical product development. These actions, paired with continued policy research into better ways to pay for and equitably develop therapies, will help reduce the cost and complexity of drug and device research, development, and trials.

20.
Eur Heart J ; 41(22): 2109-2117, 2020 06 07.
Artigo em Inglês | MEDLINE | ID: covidwho-526858

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has important implications for the safety of participants in clinical trials and the research staff caring for them and, consequently, for the trials themselves. Patients with heart failure may be at greater risk of infection with COVID-19 and the consequences might also be more serious, but they are also at risk of adverse outcomes if their clinical care is compromised. As physicians and clinical trialists, it is our responsibility to ensure safe and effective care is delivered to trial participants without affecting the integrity of the trial. The social contract with our patients demands no less. Many regulatory authorities from different world regions have issued guidance statements regarding the conduct of clinical trials during this COVID-19 crisis. However, international trials may benefit from expert guidance from a global panel of experts to supplement local advice and regulations, thereby enhancing the safety of participants and the integrity of the trial. Accordingly, the Heart Failure Association of the European Society of Cardiology on 21 and 22 March 2020 conducted web-based meetings with expert clinical trialists in Europe, North America, South America, Australia, and Asia. The main objectives of this Expert Position Paper are to highlight the challenges that this pandemic poses for the conduct of clinical trials in heart failure and to offer advice on how they might be overcome, with some practical examples. While this panel of experts are focused on heart failure clinical trials, these discussions and recommendations may apply to clinical trials in other therapeutic areas.


Assuntos
Betacoronavirus , Ensaios Clínicos como Assunto/métodos , Infecções por Coronavirus , Insuficiência Cardíaca , Pandemias , Pneumonia Viral , Projetos de Pesquisa/normas , Ensaios Clínicos como Assunto/ética , Ensaios Clínicos como Assunto/normas , Europa (Continente) , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Humanos , Consentimento Livre e Esclarecido/ética , Consentimento Livre e Esclarecido/normas , Segurança do Paciente , Seleção de Pacientes/ética
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