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Lung Cancer (Amsterdam, Netherlands) Jun 2024Complementary medicine and integrative oncology modalities (IOM) have been included in the clinical practice guidelines of the American College of Chest Physicians in...
INTRODUCTION
Complementary medicine and integrative oncology modalities (IOM) have been included in the clinical practice guidelines of the American College of Chest Physicians in the treatments of patients with lung cancer. The present study examined the impact of a patient-tailored IOM treatment program on quality of life (QoL)-related concerns among patients with non-small and small lung cancer undergoing active oncology treatment.
METHODS
This controlled study was pragmatic and prospective assessing the adherence among patients referred by their oncology healthcare provider to an integrative physician consultation, followed by 6 weekly IOM treatments addressing QoL-related concerns. High adherence to integrative care (high-AIC, vs. low-AIC) was defined as attending ≥4 IOM sessions. Symptoms were assessed using the ESAS (Edmonton Symptom Assessment Scale), EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire), and MYCAW (Measure Yourself Concerns and Wellbeing) tools, at baseline and 6 weeks.
RESULTS
Of 153 patients, 74 (48 %) were high-AIC, with baseline demographic, cancer-and QoL-related characteristics similar to those of low-AIC patients. At 6 weeks, high-AIC patients reported greater improvement on MYCAW well-being (p = 0.036), with within-group improvement observed for EORTC pain (p = 0.021) and emotional functioning (p = 0.041); and for ESAS depression (p = 0.005), with borderline significance for EORTC sleep (p = 0.06).
CONCLUSION
High adherence to a 6-week IOM program within supportive/palliative care for patients with lung cancer was found to alleviate pain and emotional concerns, improving overall QoL. Further research is needed to confirm the findings in real-life IOM practice for patients with lung cancer.
PubMed: 38941654
DOI: 10.1016/j.lungcan.2024.107857 -
JMIR Research Protocols Jun 2024Despite the potential to significantly reduce complications, many patients do not consistently receive diabetes preventive care. Our research team recently applied... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Despite the potential to significantly reduce complications, many patients do not consistently receive diabetes preventive care. Our research team recently applied user-centered design sprint methodology to develop a patient portal intervention empowering patients to address selected diabetes care gaps (eg, no diabetes eye examination in last 12 months).
OBJECTIVE
This study aims to evaluate the effect of our novel diabetes care gap intervention on completion of selected evidence-based diabetes preventive care services and secondary outcomes.
METHODS
We are conducting a pragmatic randomized controlled trial of the effect of the intervention on diabetes care gaps. Adult patients with diabetes mellitus (DM) are recruited from primary care clinics affiliated with Vanderbilt University Medical Center. Participants are eligible if they have type 1 or 2 DM, can read in English, are aged 18-75 years, have a current patient portal account, and have reliable access to a mobile device with internet access. We exclude patients with medical conditions that prevent them from using a mobile device, severe difficulty seeing, pregnant women or women who plan to become pregnant during the study period, and patients on dialysis. Participants will be randomly assigned to the intervention or usual care. The primary outcome measure will be the number of diabetes care gaps among 4 DM preventive care services (diabetes eye examination, pneumococcal vaccination, hemoglobin A, and urine microalbumin) at 12 months after randomization. Secondary outcomes will include diabetes self-efficacy, confidence managing diabetes in general, understanding of diabetes preventive care, diabetes distress, patient portal satisfaction, and patient-initiated orders at baseline, 3 months, 6 months, and 12 months after randomization. An ordinal logistic regression model will be used to quantify the effect of the intervention on the number of diabetes care gaps at the 12-month follow-up. For dichotomous secondary outcomes, a logistic regression model will be used with random effects for the clinic and provider variables as needed. For continuous secondary outcomes, a regression model will be used.
RESULTS
This study is ongoing. Recruitment was closed in February 2022; a total of 433 patients were randomized. Of those randomized, most (n=288, 66.5%) were non-Hispanic White, 33.5% (n=145) were racial or ethnic minorities, 33.9% (n=147) were aged 65 years or older, and 30.7% (n=133) indicated limited health literacy.
CONCLUSIONS
The study directly tests the hypothesis that a patient portal intervention-alerting patients about selected diabetes care gaps, fostering understanding of their significance, and allowing patients to initiate care-will reduce diabetes care gaps compared with usual care. The insights gained from this study may have broad implications for developing future interventions to address various care gaps, such as gaps in cancer screening, and contribute to the development of effective, scalable, and sustainable approaches to engage patients in chronic disease management and prevention.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04894903; https://classic.clinicaltrials.gov/ct2/show/NCT04894903.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/56123.
Topics: Humans; Patient Portals; Adult; Middle Aged; Female; Male; Aged; Adolescent; Diabetes Mellitus; Young Adult; Pragmatic Clinical Trials as Topic
PubMed: 38941148
DOI: 10.2196/56123 -
Health Technology Assessment... Jun 2024Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a non-acute anterior cruciate ligament injury can be non-surgical (rehabilitation) or surgical (reconstruction). However, insufficient evidence exists to guide treatment.
OBJECTIVE(S)
To determine in patients with non-acute anterior cruciate ligament injury and symptoms of instability whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically and cost-effective than non-surgical management (rehabilitation).
DESIGN
A pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. Due to the nature of the interventions, no blinding could be carried out.
SETTING
Twenty-nine NHS orthopaedic units in the United Kingdom.
PARTICIPANTS
Participants with a symptomatic (instability) non-acute anterior cruciate ligament-injured knee.
INTERVENTIONS
Patients in the surgical management arm underwent surgical anterior cruciate ligament reconstruction as soon as possible and without any further rehabilitation. Patients in the rehabilitation arm attended physiotherapy sessions and only were listed for reconstructive surgery on continued instability following rehabilitation. Surgery following initial rehabilitation was an expected outcome for many patients and within protocol.
MAIN OUTCOME MEASURES
The primary outcome was the Knee Injury and Osteoarthritis Outcome Score 4 at 18 months post randomisation. Secondary outcomes included return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee-specific quality of life and resource usage.
RESULTS
Three hundred and sixteen participants were recruited between February 2017 and April 2020 with 156 randomised to surgical management and 160 to rehabilitation. Forty-one per cent ( = 65) of those allocated to rehabilitation underwent subsequent reconstruction within 18 months with 38% ( = 61) completing rehabilitation and not undergoing surgery. Seventy-two per cent ( = 113) of those allocated to surgery underwent reconstruction within 18 months. Follow-up at the primary outcome time point was 78% ( = 248; surgical, = 128; rehabilitation, = 120). Both groups improved over time. Adjusted mean Knee Injury and Osteoarthritis Outcome Score 4 scores at 18 months had increased to 73.0 in the surgical arm and to 64.6 in the rehabilitation arm. The adjusted mean difference was 7.9 (95% confidence interval 2.5 to 13.2; = 0.005) in favour of surgical management. The per-protocol analyses supported the intention-to-treat results, with all treatment effects favouring surgical management at a level reaching statistical significance. There was a significant difference in Tegner Activity Score at 18 months. Sixty-eight per cent ( = 65) of surgery patients did not reach their expected activity level compared to 73% ( = 63) in the rehabilitation arm. There were no differences between groups in surgical complications ( = 1 surgery, = 2 rehab) or clinical events ( = 11 surgery, = 12 rehab). Of surgery patients, 82.9% were satisfied compared to 68.1% of rehabilitation patients. Health economic analysis found that surgical management led to improved health-related quality of life compared to non-surgical management (0.052 quality-adjusted life-years, = 0.177), but with higher NHS healthcare costs (£1107, < 0.001). The incremental cost-effectiveness ratio for the surgical management programme versus rehabilitation was £19,346 per quality-adjusted life-year gained. Using £20,000-30,000 per quality-adjusted life-year thresholds, surgical management is cost-effective in the UK setting with a probability of being the most cost-effective option at 51% and 72%, respectively.
LIMITATIONS
Not all surgical patients underwent reconstruction, but this did not affect trial interpretation. The adherence to physiotherapy was patchy, but the trial was designed as pragmatic.
CONCLUSIONS
Surgical management (reconstruction) for non-acute anterior cruciate ligament-injured patients was superior to non-surgical management (rehabilitation). Although physiotherapy can still provide benefit, later-presenting non-acute anterior cruciate ligament-injured patients benefit more from surgical reconstruction without delaying for a prior period of rehabilitation.
FUTURE WORK
Confirmatory studies and those to explore the influence of fidelity and compliance will be useful.
TRIAL REGISTRATION
This trial is registered as Current Controlled Trials ISRCTN10110685; ClinicalTrials.gov Identifier: NCT02980367.
FUNDING
This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/140/63) and is published in full in ; Vol. 28, No. 27. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Male; Female; Anterior Cruciate Ligament Injuries; Adult; United Kingdom; Cost-Benefit Analysis; Anterior Cruciate Ligament Reconstruction; Quality of Life; Quality-Adjusted Life Years; Middle Aged; Young Adult; State Medicine; Joint Instability; Adolescent; Technology Assessment, Biomedical
PubMed: 38940695
DOI: 10.3310/VDKB6009 -
Europace : European Pacing,... Jun 2024To describe the rationale, design, delivery and baseline characteristics of STEEER-AF (Stroke prevention and rhythm control Treatment: Evaluation of an Educational...
Design and deployment of the STEEER-AF trial to evaluate and improve guideline adherence: A cluster-randomised trial by the European Society of Cardiology and European Heart Rhythm Association.
AIMS
To describe the rationale, design, delivery and baseline characteristics of STEEER-AF (Stroke prevention and rhythm control Treatment: Evaluation of an Educational programme of the European Society of Cardiology [ESC] in a cluster-Randomised trial in patients with Atrial Fibrillation).
METHODS & RESULTS
STEEER-AF is a pragmatic trial designed to objectively and robustly determine whether guidelines are adhered to in routine practice, and evaluate a targeted educational programme for healthcare professionals. Seventy centres were randomised in 6 countries (France, Germany, Italy, Poland, Spain and United Kingdom; 2022-2023). STEEER-AF centres recruited 1732 patients with a diagnosis of atrial fibrillation (AF), with mean age 68.9 years (SD 11.7), CHA2DS2-VASc score 3.2 (SD 1.8) and 647 (37%) women. 843 patients (49%) were in AF and 760 (44%) in sinus rhythm at enrolment. Oral anticoagulant therapy was prescribed in 1,543 patients (89%), with the majority receiving direct oral anticoagulants (1,378; 89%). Previous cardioversion, antiarrhythmic drug therapy or ablation was recorded in 836 patients (48.3%). 551 patients (31.8%) were currently receiving an antiarrhythmic drug, and 446 (25.8%) were scheduled to receive a future cardioversion or ablation. The educational programme engaged 195 healthcare professionals across centres randomised to the intervention group, consisting of bespoke interactive online learning and reinforcement activities, supported by national expert trainers.
CONCLUSION
The STEEER-AF trial was successfully deployed across six European countries to investigate guideline adherence in real-world practice, and evaluate if a structured educational programme for healthcare professionals can improve patient-level care.
REGISTRATION
Clinicaltrials.gov NCT04396418.
PubMed: 38940494
DOI: 10.1093/europace/euae178 -
PeerJ 2024Femoroacetabular impingement syndrome (FAIS) can cause hip pain and chondrolabral damage that may be managed non-operatively or surgically. Squatting motions require... (Randomized Controlled Trial)
Randomized Controlled Trial
Squatting biomechanics following physiotherapist-led care or hip arthroscopy for femoroacetabular impingement syndrome: a secondary analysis from a randomised controlled trial.
BACKGROUND
Femoroacetabular impingement syndrome (FAIS) can cause hip pain and chondrolabral damage that may be managed non-operatively or surgically. Squatting motions require large degrees of hip flexion and underpin many daily and sporting tasks but may cause hip impingement and provoke pain. Differential effects of physiotherapist-led care and arthroscopy on biomechanics during squatting have not been examined previously. This study explored differences in 12-month changes in kinematics and moments during squatting between patients with FAIS treated with a physiotherapist-led intervention (Personalised Hip Therapy, PHT) and arthroscopy.
METHODS
A subsample ( = 36) of participants with FAIS enrolled in a multi-centre, pragmatic, two-arm superiority randomised controlled trial underwent three-dimensional motion analysis during squatting at baseline and 12-months following random allocation to PHT ( = 17) or arthroscopy ( = 19). Changes in time-series and peak trunk, pelvis, and hip biomechanics, and squat velocity and maximum depth were explored between treatment groups.
RESULTS
No significant differences in 12-month changes were detected between PHT and arthroscopy groups. Compared to baseline, the arthroscopy group squatted slower at follow-up (descent: mean difference -0.04 m∙s (95%CI [-0.09 to 0.01]); ascent: -0.05 m∙s [-0.11 to 0.01]%). No differences in squat depth were detected between or within groups. After adjusting for speed, trunk flexion was greater in both treatment groups at follow-up compared to baseline (descent: PHT 7.50° [-14.02 to -0.98]%; ascent: PHT 7.29° [-14.69 to 0.12]%, arthroscopy 16.32° [-32.95 to 0.30]%). Compared to baseline, both treatment groups exhibited reduced anterior pelvic tilt (descent: PHT 8.30° [0.21-16.39]%, arthroscopy -10.95° [-5.54 to 16.34]%; ascent: PHT -7.98° [-0.38 to 16.35]%, arthroscopy -10.82° [3.82-17.81]%), hip flexion (descent: PHT -11.86° [1.67-22.05]%, arthroscopy -16.78° [8.55-22.01]%; ascent: PHT -12.86° [1.30-24.42]%, arthroscopy -16.53° [6.72-26.35]%), and knee flexion (descent: PHT -6.62° [0.56- 12.67]%; ascent: PHT -8.24° [2.38-14.10]%, arthroscopy -8.00° [-0.02 to 16.03]%). Compared to baseline, the PHT group exhibited more plantarflexion during squat ascent at follow-up (-3.58° [-0.12 to 7.29]%). Compared to baseline, both groups exhibited lower external hip flexion moments at follow-up (descent: PHT -0.55 N∙m/BW∙HT[%] [0.05-1.05]%, arthroscopy -0.84 N∙m/BW∙HT[%] [0.06-1.61]%; ascent: PHT -0.464 N∙m/BW∙HT[%] [-0.002 to 0.93]%, arthroscopy -0.90 N∙m/BW∙HT[%] [0.13-1.67]%).
CONCLUSION
Exploratory data suggest at 12-months follow-up, neither PHT or hip arthroscopy are superior at eliciting changes in trunk, pelvis, or lower-limb biomechanics. Both treatments may induce changes in kinematics and moments, however the implications of these changes are unknown.
TRIAL REGISTRATION DETAILS
Australia New Zealand Clinical Trials Registry reference: ACTRN12615001177549. Trial registered 2/11/2015.
Topics: Humans; Femoracetabular Impingement; Arthroscopy; Male; Female; Biomechanical Phenomena; Adult; Range of Motion, Articular; Hip Joint; Middle Aged; Treatment Outcome; Physical Therapy Modalities
PubMed: 38938616
DOI: 10.7717/peerj.17567 -
JACC. Advances Jun 2023The use of statins in patients with heart failure (HF) is controversial. In patients without HF, statins reduce atherosclerotic cardiovascular disease (ASCVD) risk,...
BACKGROUND
The use of statins in patients with heart failure (HF) is controversial. In patients without HF, statins reduce atherosclerotic cardiovascular disease (ASCVD) risk, including HF-related events. However, in some large studies, no benefit was seen in statin-treated HF patients.
OBJECTIVES
The purpose of this study was to determine the impact of statin therapy in HF with reduced ejection fraction (HFrEF).
METHODS
Intermountain Healthcare medical records identified patients with a HF diagnosis and an ejection fraction of ≤40%. Patients prescribed and not prescribed a statin were compared for major adverse cardiovascular events (MACE) (death, myocardial infarction, stroke) (median of 4.5 years follow-up). Statin use was defined as use at or after a HF diagnosis but at least 60 days before MACE or end of follow-up. Cox proportional hazards regression was used to determine the relationship between statin use and outcomes.
RESULTS
A total of 15,010 patients (n = 9,641 [64%] on statins) were studied. Statin use was associated with more frequent ASCVD risk factors yet a lower risk of MACE risk (adjusted HR: 0.53; 95% CI: 0.51-0.56; < 0.0001). Benefit was similar for primary and secondary prevention patients and for prior and new statin prescriptions. Using time-varying hazard ratio analysis, the longer the patient was on a statin, the greater the reduction in risk of MACE ( < 0.0001).
CONCLUSIONS
These results suggest a potential benefit of selective statin use in the real-world management of HFrEF patients with ASCVD or at high ASCVD risk.
PubMed: 38938227
DOI: 10.1016/j.jacadv.2023.100385 -
Trials Jun 2024Randomized controlled trials (RCTs) are rigorous scientific research designs for evaluating intervention effectiveness. However, implementing RCTs in a real-world...
Strengths, challenges, and strategies for implementing pragmatic multicenter randomized controlled trials (RCTs): example of the Personalized Citizen Assistance for Social Participation (APIC) trial.
BACKGROUND
Randomized controlled trials (RCTs) are rigorous scientific research designs for evaluating intervention effectiveness. However, implementing RCTs in a real-world context is challenging. To develop strategies to improve its application, it is essential to understand the strengths and challenges of this design. This study thus aimed to explore the strengths, challenges, and strategies for improving the implementation of a pragmatic multicenter, prospective, two-arm RCT evaluating the effects of the Personalized Citizen Assistance for Social Participation (Accompagnement-citoyen Personnalisé d'Intégration Communautaire: APIC; weekly 3-h personalized stimulation sessions given by a trained volunteer over a 12-month period) on older adults' health, social participation, and life satisfaction.
METHODS
A multiple case study was conducted with 14 participants, comprising one research assistant, seven coordinators, and six managers of six community organizations serving older adults, who implemented the APIC in the context of a RCT. Between 2017 and 2023, qualitative data were extracted from 24 group meetings, seven semi-directed interviews, emails exchanged with the research team, and one follow-up document.
RESULTS
Aged between 30 and 60 (median ± SIQR: 44.0 ± 6.3), most participants were women from organizations already offering social participation interventions for older adults and working with the public sector. Reported strengths of this RCT were its relevance in assessing an innovative intervention to support healthy aging, and the sharing of common goals, expertise, and strategies with community organizations. Challenges included difficulties recruiting older adults, resistance to potential control group assignments, design complexity, and efforts to mobilize and engage volunteers. The COVID-19 pandemic lockdown and health measures exacerbated challenges related to recruiting older adults and mobilizing volunteers and complicated delivery of the intervention. The strategies that mostly overcame difficulties in recruiting older adults were reducing sample size, simplifying recruitment procedures, emphasizing the health follow-up, extending partnerships, and recognizing and supporting volunteers better. Because of the lockdown and physical distancing measures, the intervention was also adapted for remote delivery, including via telephone or videoconferencing.
CONCLUSION
Knowledge of the strengths and challenges of pragmatic RCTs can contribute to the development of strategies to facilitate implementation studies and better evaluate health and social participation interventions delivered under real-life conditions.
TRIAL REGISTRATION
NCT03161860; Pre-results. Registered on May 22, 2017.
Topics: Humans; Social Participation; Female; Male; Middle Aged; Prospective Studies; Adult; Volunteers; Research Design; COVID-19; Randomized Controlled Trials as Topic; Pragmatic Clinical Trials as Topic; Aged; Personal Satisfaction; Multicenter Studies as Topic
PubMed: 38937798
DOI: 10.1186/s13063-024-08248-w -
Trials Jun 2024Treatment of displaced distal forearm fractures in children has traditionally been closed reduction and pin fixation, although they might heal and remodel without...
Is casting of displaced paediatric distal forearm fractures non-inferior to reduction under general anaesthesia? Study protocol for a pragmatic, randomized, controlled non-inferiority multicentre trial (the casting trial).
BACKGROUND
Treatment of displaced distal forearm fractures in children has traditionally been closed reduction and pin fixation, although they might heal and remodel without surgery with no functional impairment. No randomized controlled trials have been published comparing the patient-reported functional outcome following non-surgical or surgical treatment of displaced paediatric distal forearm fractures.
METHODS
A multicentre non-inferiority randomized controlled trial. Children aged 4-10 years with a displaced distal forearm fracture will be offered inclusion, if the on-duty orthopaedic surgeon finds indication for surgical intervention. They will be allocated equally to non-surgical treatment (intervention) or surgical treatment of surgeon's choice (comparator). Follow-up will be 4 weeks and 3, 6, and 12 months. The primary outcome is the between-group difference in 12 months QuickDASH score. We will need a sample of 40 patients to show a 15-point difference with 80% power.
DISCUSSION
The results of this trial may change our understanding of the healing potential of paediatric distal forearm fractures. If non-inferiority of non-surgical treatment is shown, the results may contribute to a reduction in future surgeries on children, who in turn can be treated without the risks and psychological burdens associated with surgery.
TRIAL REGISTRATION
www.
CLINICALTRIALS
gov (ID: NCT05736068). Date of registry: 17 February 2023.
Topics: Humans; Child; Child, Preschool; Radius Fractures; Casts, Surgical; Treatment Outcome; Anesthesia, General; Pragmatic Clinical Trials as Topic; Multicenter Studies as Topic; Ulna Fractures; Equivalence Trials as Topic; Female; Male; Time Factors; Fracture Healing; Fracture Fixation; Age Factors; Forearm Injuries; Recovery of Function; Wrist Fractures
PubMed: 38937792
DOI: 10.1186/s13063-024-08253-z -
International Journal of Surgery... Jun 2024Although the benefits of post-operative rehabilitation in cancer surgery are well established, the role of prehabilitation is less defined. Oesophagogastric cancers...
The effect of a pre- and post- operative exercise program versus standard care on physical fitness of patients with oesophageal and gastric cancer undergoing neoadjuvant treatment prior to surgery (The PERIOP-OG Trial): a randomized controlled trial.
INTRODUCTION
Although the benefits of post-operative rehabilitation in cancer surgery are well established, the role of prehabilitation is less defined. Oesophagogastric cancers present a unique opportunity to study the impact of prehabilitation during the neoadjuvant window, whether with chemotherapy or chemoradiotherapy (NCT) in patients who are frequently nutritionally depleted. This trial examines the impact of a community-based exercise program on patient fitness during and after the neoadjuvant window.
METHODS
A pragmatic, randomized controlled multi-centre trial was undertaken in three centres. Inclusion criteria were patients aged ≥ 18 years planned for NCT and esophagectomy or gastrectomy. Participants were randomized 1:1 to an exercise prehabilitation group (EX) or to usual care (UC). The primary endpoint was cardiorespiratory fitness between baseline and pre-surgery timepoint using the 6-min walk test. Secondary endpoints included hand dynamometer, 10-sec sit to stand, activity behaviour, body mass index, semi-structured interviews, questionnaires assessing quality of life, surgical fear, general self-efficacy and mastery.
RESULTS
Between March 2019 and December 2020, 71 participants were recruited: EX (n=36) or UC (n=35). From baseline to pre-surgery, the difference-in-difference for EX showed a significant improvement in 6MWT of 50.7m (P=0.05) compared to UC [mean (SD): 522.1m (+/-104.3) to 582.1m (+/-108) vs. 497.5m (+/-106.3) to 506.0 m (+/-140.4). There was no statistically significant DID for secondary outcome measures.
CONCLUSIONS
This community exercise prehabilitation program significantly improves physical fitness for surgery, is feasible and provides a standardized framework for prescription of exercise in esophagogastric cancer patients undergoing NCT.
PubMed: 38935085
DOI: 10.1097/JS9.0000000000001663 -
European Journal of Heart Failure Jun 2024Cardiovascular-kidney-metabolic (CKM) multimorbidity is prevalent among individuals with heart failure (HF), but whether cardiac structure and function, clinical...
Cardiovascular-kidney-metabolic overlap in heart failure with preserved ejection fraction: Cardiac structure and function, clinical outcomes, and response to sacubitril/valsartan in PARAGON-HF.
AIMS
Cardiovascular-kidney-metabolic (CKM) multimorbidity is prevalent among individuals with heart failure (HF), but whether cardiac structure and function, clinical outcomes, and treatment response to sacubitril/valsartan vary in relation to CKM status is unknown.
METHODS AND RESULTS
In this PARAGON-HF post-hoc analysis, we evaluated the impact of CKM multimorbidity (atherosclerotic cardiovascular [CV] disease, chronic kidney disease, and type 2 diabetes) on cardiac structure and function, clinical outcomes, and treatment effects of sacubitril/valsartan versus valsartan. The primary outcome was a composite of total HF hospitalizations and CV death. Secondary outcomes included the individual components of the primary outcome and a composite kidney outcome (sustained estimated glomerular filtration rate reduction of ≥50%, end-stage kidney disease, or kidney-related death). At baseline, 35.2% had one CKM condition, 33.3% had two, 15.9% had three, and only 15.6% had HF alone. CKM multimorbidity was associated with higher septal and posterior wall thickness, lower global longitudinal strain, higher E/e', and worse right ventricular function. Total HF hospitalizations or CV death increased with greater CKM multimorbidity, with the highest relative risk observed with three CKM conditions (rate ratio 3.06, 95% confidence interval 2.33-4.03), compared with HF alone. Treatment effects of sacubitril/valsartan were consistent irrespective of the number of CKM conditions for the primary endpoint (p = 0.75), CV death (p = 0.82), total HF hospitalizations (p = 0.67), and the composite kidney endpoint (p = 0.99).
CONCLUSIONS
Cardiovascular-kidney-metabolic multimorbidity was common in PARAGON-HF and associated with adverse changes in cardiac structure and function and with a stepwise increase in risk of clinical outcomes. Treatment effects of sacubitril/valsartan were consistent irrespective of CKM burden.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov NCT01920711.
PubMed: 38932589
DOI: 10.1002/ejhf.3304