Geriatrics
RCT: Transcatheter Edge-to-edge Repair Improves Outcomes in Severe Tricuspid Regurgitation
29 Nov, 2024 | 12:37h | UTCBackground: Severe tricuspid regurgitation (TR) is linked to poor quality of life and increased mortality. Traditional medical therapy offers limited symptom relief, and surgical options carry high risks. Transcatheter tricuspid valve therapies like transcatheter edge-to-edge repair (T-TEER) have emerged as less invasive alternatives, but their impact on patient outcomes needs further exploration.
Objective: To determine if T-TEER combined with optimized medical therapy (OMT) enhances patient-reported outcomes and clinical events compared to OMT alone in patients with severe, symptomatic TR.
Methods: In this multicenter, prospective, randomized (1:1) trial, 300 adults with severe, symptomatic TR despite stable OMT were enrolled from 24 centers in France and Belgium between March 2021 and March 2023. Participants were randomized to receive either T-TEER plus OMT or OMT alone. The primary outcome was a composite clinical endpoint at 1 year, including changes in New York Heart Association (NYHA) class, patient global assessment (PGA), or occurrence of major cardiovascular events. Secondary outcomes encompassed TR severity, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and a composite of death, tricuspid valve surgery, KCCQ improvement, or hospitalization for heart failure.
Results: At 1 year, 74.1% of patients in the T-TEER plus OMT group improved in the composite endpoint versus 40.6% in the OMT-alone group (P < .001). Massive or torrential TR persisted in 6.8% of the T-TEER group compared to 53.5% of the OMT group (P < .001). The mean KCCQ score was higher in the T-TEER group (69.9 vs 55.4; P < .001). The win ratio for the composite secondary outcome was 2.06 (95% CI, 1.38-3.08; P < .001). No significant differences were observed in major cardiovascular events or cardiovascular death between groups.
Conclusions: Adding T-TEER to OMT significantly reduces TR severity and improves patient-reported outcomes at 1 year in patients with severe, symptomatic TR, without increasing adverse events.
Implications for Practice: T-TEER may offer a valuable addition to OMT for selected patients with severe TR, enhancing symptoms and quality of life. However, the absence of significant differences in hard clinical endpoints and the open-label design suggest cautious interpretation. Clinicians should weigh the benefits against potential biases in patient-reported outcomes.
Study Strengths and Limitations: Strengths include the randomized design and multicenter participation, enhancing the study’s validity. Limitations involve the open-label design without a sham control, potentially introducing bias in subjective outcomes. The short follow-up period and selective patient population based on anatomical suitability for T-TEER may limit generalizability.
Future Research: Longer-term studies are necessary to assess T-TEER’s impact on survival and heart failure hospitalization. Comparative studies of different transcatheter devices and investigations into optimal patient selection criteria are also recommended.
Cohort Study: Oral Hormone Therapy and Tibolone Increase Cardiovascular Risk in Menopausal Women
28 Nov, 2024 | 18:42h | UTCBackground: Cardiovascular disease is the leading cause of mortality worldwide, with incidence in women increasing notably during the menopausal transition. Menopausal hormone therapy (MHT) effectively alleviates menopausal symptoms but has been associated with cardiovascular risks in previous studies. The impact of contemporary MHT formulations and administration routes on cardiovascular disease risk in women aged 50–58 remains unclear.
Objective: To assess the effect of different types of contemporary MHT on the risk of cardiovascular disease, focusing on various hormone combinations and administration methods.
Methods: This nationwide register-based emulated target trial included 919,614 Swedish women aged 50–58 years between 2007 and 2020 who had not used MHT in the previous two years. Participants were assigned to one of eight treatment groups—including oral and transdermal therapies—or to a non-initiator group. The primary outcomes were hazard ratios (HRs) for venous thromboembolism (VTE), ischemic heart disease (IHD), cerebral infarction, and myocardial infarction, analyzed separately and as a composite cardiovascular disease outcome.
Results: Among the participants, 77,512 were MHT initiators and 842,102 were non-initiators. During follow-up, 24,089 cardiovascular events occurred. In intention-to-treat analyses, tibolone was associated with an increased risk of cardiovascular disease (HR 1.52, 95% CI 1.11 to 2.08) compared with non-initiators. Initiation of tibolone or oral estrogen-progestin therapy was linked to a higher risk of IHD (HRs 1.46 and 1.21, respectively). A higher risk of VTE was observed with oral continuous estrogen-progestin therapy (HR 1.61), sequential therapy (HR 2.00), and estrogen-only therapy (HR 1.57). Per protocol analyses showed that tibolone use was associated with increased risks of cerebral infarction (HR 1.97) and myocardial infarction (HR 1.94).
Conclusions: Use of oral estrogen-progestin therapy was associated with increased risks of IHD and VTE, while tibolone was linked to higher risks of IHD, cerebral infarction, and myocardial infarction but not VTE. These findings underscore the varying cardiovascular risks associated with different MHT types and administration methods.
Implications for Practice: Clinicians should exercise caution when prescribing oral estrogen-progestin therapy or tibolone for menopausal symptom relief, considering the elevated cardiovascular risks. Alternative MHT options, such as transdermal therapies, may offer a safer profile and should be considered.
Study Strengths and Limitations: Strengths include the large, nationwide cohort and the emulated target trial design, which reduces selection bias and confounding. Limitations involve the lack of data on menopausal status, smoking, and body mass index, which may affect cardiovascular risk. Potential misclassification of exposure and adherence could also impact results.
Future Research: Further studies should investigate the cardiovascular effects of specific progestins within MHT formulations and explore the impact of different doses and durations of therapy.
Review: Acute Respiratory Distress Syndrome
28 Nov, 2024 | 13:06h | UTCIntroduction: Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung condition characterized by diffuse alveolar damage, leading to hypoxemia and respiratory failure. Since its initial description in 1967, the understanding and definition of ARDS have significantly evolved, integrating advances in basic science and clinical practice. A newly recommended global definition expands diagnostic criteria to enhance early recognition and management, especially in resource-limited settings. This review summarizes current insights into the epidemiology, pathophysiology, and evidence-based management of ARDS, highlighting key updates and future research priorities.
Key Recommendations:
- New Global Definition of ARDS: Adoption of an expanded definition that includes patients receiving high-flow nasal oxygen (HFNO) support and allows diagnosis using pulse oximetry and thoracic ultrasonography. This makes ARDS identification feasible in diverse clinical environments, including those with limited resources.
- Established Critical Care Interventions: Emphasis on early implementation of proven strategies such as low tidal volume ventilation (6 mL/kg predicted body weight) with plateau pressures ≤30 cm H₂O, prone positioning for patients with PaO₂/FiO₂ <150 mm Hg, and conservative fluid management after initial resuscitation. These interventions have consistently reduced mortality and are recommended as standard care.
- Personalized Approaches and Phenotyping: Recognition of the heterogeneity in ARDS pathophysiology underscores the need for personalized treatment strategies. Identification of hyper-inflammatory and hypo-inflammatory phenotypes may guide targeted therapies and improve outcomes, although prospective validation is required.
- Impact of COVID-19 on ARDS: Acknowledgment of the significant increase in ARDS incidence due to the COVID-19 pandemic. While COVID-19 ARDS shares similarities with traditional ARDS, notable differences in endothelial dysfunction and immune response highlight the necessity for tailored management approaches in these patients.
- Pharmacologic Interventions: Updated guidelines provide conditional recommendations for the use of corticosteroids in ARDS, particularly in early moderate to severe cases. Ongoing research into pharmacologic agents such as statins, mesenchymal stromal cells, and other cell-based therapies shows potential but requires further clinical trials to establish efficacy.
- Future Research Priorities: Identification of key areas for investigation, including the long-term sequelae of ARDS, optimization of non-invasive and invasive ventilation strategies, exploration of genetic and environmental risk factors, and development of rapid biomarker assays for real-time phenotyping and targeted therapy.
Conclusion: The evolving definition and understanding of ARDS aim to improve early detection and standardization of care across various clinical settings. Reinforcing established critical care interventions while advancing personalized and novel therapeutic approaches holds promise for reducing mortality and enhancing long-term patient outcomes. Continuous research into the pathophysiology and management of ARDS, enriched by insights from the COVID-19 pandemic, is essential to address ongoing challenges and improve patient care.
Review: Management of Degenerative Rotator-Cuff Disorders
28 Nov, 2024 | 12:48h | UTCIntroduction: Degenerative rotator-cuff disorders are a leading cause of shoulder pain, especially in adults over 40 years of age, involving tendon degeneration from tendinopathy to full-thickness tears. Recognizing the need for clear clinical guidance, Jain and Khazzam provide a comprehensive review aimed at informing clinicians on evidence-based strategies for the evaluation and management of degenerative rotator-cuff tears to optimize patient outcomes.
Key Recommendations:
- First-Line Nonoperative Management: Initiate treatment with nonoperative measures, primarily structured physical therapy. The therapy should focus on strengthening periscapular muscles, correcting scapular posture, and improving rotator-cuff muscle strength and endurance. (Evidence Level: Expert consensus)
- Pharmacologic Therapy: Employ topical NSAIDs for pain relief due to their favorable safety profile. Oral NSAIDs may offer modest pain relief but should be used cautiously because of potential adverse effects. Opioids are generally not recommended due to associated risks and lack of superior efficacy. (Evidence Level: Moderate)
- Glucocorticoid Injections: Consider a single subacromial glucocorticoid injection to provide short-term pain relief, which may facilitate participation in physical therapy. (Evidence Level: Limited)
- Selective Imaging Use: Reserve imaging modalities like ultrasonography or MRI for cases with diagnostic uncertainty, potential surgical candidates, or when detailed assessment of tear extent and muscle degeneration is required. Routine imaging is not recommended in primary care settings. (Evidence Level: Consensus)
- Surgical Intervention Criteria: Surgery is not the initial treatment and should be considered for patients not improving with nonoperative measures. Factors favoring surgery include younger age, smaller tear size, and absence of significant psychosocial barriers. The decision should be individualized due to debated surgical indications. (Evidence Level: Observational studies)
- Avoidance of Unproven Therapies: Current evidence does not support the use of orthobiologic therapies, such as platelet-rich plasma or stem cells, in treating rotator-cuff disorders. (Evidence Level: Insufficient)
Conclusion: Implementing these recommendations can enhance patient care by emphasizing effective nonoperative strategies and judicious use of surgery for degenerative rotator-cuff disorders. Early initiation of physical therapy and appropriate pain management can lead to significant improvements in pain and function, potentially reducing the need for surgical intervention and improving patients’ quality of life.
Meta-analysis: Low/Moderate-Intensity Statins with Ezetimibe May Offer Better LDL-C Reduction and Safety over High-Intensity Statins
24 Nov, 2024 | 20:01h | UTCBackground: Despite widespread use of high-intensity statin therapy, achieving target LDL-C levels and reducing cardiovascular events remain challenging in patients with or at high risk of atherosclerotic cardiovascular disease (ASCVD). High-intensity statins can have dose-dependent adverse effects, limiting their tolerability. Combining low/moderate-intensity statins with ezetimibe, a cholesterol absorption inhibitor, may enhance lipid-lowering efficacy with fewer side effects.
Objective: To compare the clinical effectiveness and safety of low/moderate-intensity statins combined with ezetimibe versus high-intensity statin monotherapy in reducing major adverse cardiovascular events (MACEs) and lowering LDL-C levels.
Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. Fifteen studies (6 randomized controlled trials [RCTs] and 9 observational studies) encompassing 251,450 participants were included. The primary outcome was a composite of cardiovascular death or major cardiovascular events. Secondary outcomes included lipid-lowering efficacy and safety measures such as muscle-related adverse events and liver enzyme elevations.
Results: Observational studies indicated that combination therapy was associated with lower rates of the primary composite outcome (HR = 0.76; 95% CI [0.73, 0.80]), cardiovascular death (HR = 0.80; 95% CI [0.74, 0.88]), all-cause death (HR = 0.84; 95% CI [0.78, 0.91]), and non-fatal stroke (HR = 0.81; 95% CI [0.75, 0.87]). RCTs showed that combination therapy resulted in a greater number of patients achieving LDL-C levels < 70 mg/dL (RR = 1.27; 95% CI [1.21, 1.34]) and significant reductions in LDL-C (MD = –7.95 mg/dL; 95% CI [–10.02, –5.89]) and total cholesterol (MD = –26.77 mg/dL; 95% CI [–27.64, –25.89]). Combination therapy also reduced muscle-related adverse events (RR = 0.52; 95% CI [0.32, 0.85]) and liver enzyme elevations (RR = 0.51; 95% CI [0.29, 0.89]) in RCTs.
Conclusions: Combining low/moderate-intensity statins with ezetimibe may offer superior lipid-lowering effects and better safety profiles compared to high-intensity statin monotherapy. While observational studies suggest improved clinical outcomes, these findings need confirmation from large-scale, long-term RCTs.
Implications for Practice: The combination therapy could be a viable option for patients intolerant to high-intensity statins or those requiring additional LDL-C lowering to reach target levels. However, clinicians should interpret these potential benefits cautiously due to reliance on observational data for clinical outcomes and the lack of robust RCT evidence.
Study Strengths and Limitations: Strengths include a comprehensive search strategy and a large patient population. Limitations involve heavy reliance on observational studies for clinical outcomes.
Future Research: Large, well-designed RCTs with longer follow-up periods are needed to confirm the clinical benefits and safety of the combination therapy over high-intensity statin monotherapy across diverse populations.
Review: Candida auris Infections
24 Nov, 2024 | 19:50h | UTCIntroduction: Candida auris, first identified in Japan in 2009, has rapidly emerged as a global public health threat due to its multidrug resistance and propensity to cause difficult-to-control outbreaks in healthcare settings. This review by Lionakis and Chowdhary aims to provide clinicians with an in-depth understanding of the mycologic features, immune responses, epidemiology, risk factors, clinical manifestations, diagnosis, antifungal resistance, treatment, and prevention strategies associated with C. auris infections to inform effective patient care and containment measures.
Key Points:
- Mycologic Features: C. auris is a budding yeast that thrives in high-salt and high-temperature environments. It is divided into five clades (I–V) with distinct geographic distributions and varying virulence and resistance profiles.
- Immune Response: The interleukin-17 pathway is crucial in reducing skin colonization by C. auris, while phagocytes like monocytes, macrophages, and neutrophils are essential for clearing bloodstream and organ infections.
- Epidemiology: Reported in over 45 countries, C. auris is known for causing outbreaks in healthcare facilities due to its persistence on skin and surfaces and challenges in accurate identification. The CDC classifies it as an urgent threat, and the WHO places it in the “critical” group of human fungal pathogens.
- Risk Factors: Key risk factors include advanced age, indwelling medical devices, immunocompromised states, diabetes, recent surgery, use of broad-spectrum antibiotics or antifungals, prolonged hospitalization, and severe COVID-19.
- Clinical Manifestations: Primarily causing invasive infections like candidemia, C. auris is associated with high morbidity and mortality rates (30–60%). Up to 25% of critically ill colonized patients may develop invasive infections.
- Diagnosis: Accurate identification is challenging due to misidentification with other Candida species on conventional tests. Reliable methods include MALDI-TOF mass spectrometry, sequencing of rDNA regions, and molecular assays like PCR.
- Antifungal Resistance: C. auris exhibits clade-specific multidrug resistance, with most strains resistant to fluconazole and some resistant to echinocandins and amphotericin B. Resistance mechanisms involve mutations in the ERG11 and FKS1 genes.
- Treatment: Echinocandins are recommended as first-line treatment for invasive C. auris infections. Close monitoring is essential due to potential treatment failure and emergence of resistance. Amphotericin B formulations may be used in neonates or if echinocandin resistance is present.
- Prevention: Strict infection control measures are critical, including contact precautions, environmental cleaning with EPA-registered disinfectants effective against C. auris, surveillance screening, and cohorting of patients to prevent nosocomial transmission.
Conclusion: The rapid global spread of multidrug-resistant C. auris presents significant challenges for clinical management and infection control. Early and accurate diagnosis, appropriate antifungal therapy, and stringent prevention strategies are essential to improve patient outcomes and prevent further dissemination of this pathogen.
RCT: Fezolinetant Reduces Vasomotor Symptoms in Menopausal Individuals Unfit for Hormone Therapy
24 Nov, 2024 | 19:29h | UTCBackground: Vasomotor symptoms (VMS), including hot flushes and night sweats, are prevalent and often debilitating during menopause. Hormone therapy (HT) is effective but contraindicated or unsuitable for many due to medical conditions or personal choice, creating a need for safe, non-hormonal treatments.
Objective: To evaluate the efficacy and safety of fezolinetant, a non-hormonal neurokinin 3 receptor antagonist, in treating moderate to severe VMS in menopausal individuals unsuitable for HT.
Methods: This phase 3b, randomized, double-blind, placebo-controlled trial was conducted across 16 countries. A total of 453 individuals aged 40-65 years with moderate to severe VMS unsuitable for HT were randomized 1:1 to receive fezolinetant 45 mg once daily or placebo for 24 weeks. The primary endpoint was the mean change in daily frequency of moderate to severe VMS from baseline to week 24. Secondary endpoints included changes in VMS severity, sleep disturbance, and safety evaluations.
Results: Of the 452 participants who received at least one dose of the study drug (fezolinetant n=226, placebo n=226), 370 (81.7%) completed the study. The mean age was 54.5 years, and most participants were white (96.7%) and categorized as either HT averse or requiring caution with HT. At week 24, fezolinetant significantly reduced the frequency of VMS compared with placebo (least squares mean difference [LSMD] –1.93 episodes/day; 95% CI –2.64 to –1.22; P<0.001). It also significantly reduced VMS severity (LSMD –0.39; 95% CI –0.57 to –0.21; P<0.001) and improved sleep disturbance scores (LSMD –2.5; 95% CI –3.9 to –1.1; P<0.001). Improvements were observed as early as week 1 and sustained throughout the study. The incidence of treatment-emergent adverse events (TEAEs) was similar between the fezolinetant and placebo groups (65.0% vs. 61.1%, respectively). No significant safety concerns, including liver toxicity, were identified.
Conclusions: Fezolinetant was effective and well-tolerated over 24 weeks in reducing moderate to severe VMS in menopausal individuals unsuitable for HT.
Implications for Practice: Fezolinetant offers a promising alternative for managing VMS in individuals who cannot or choose not to use HT. Clinicians should consider this option but remain cautious due to limited long-term safety data. Individual patient preferences, risk factors, and the novelty of the medication should be weighed in clinical decision-making.
Study Strengths and Limitations: Strengths include the large sample size and extended placebo-controlled duration. Limitations involve the predominantly white study population, potentially limiting generalizability to more diverse groups. The exclusion of individuals over 65 years old and the lack of direct comparison with other non-hormonal treatments also constrain the applicability of the findings.
Future Research: Further studies are needed to assess the long-term safety and efficacy of fezolinetant, particularly in diverse populations and older individuals.
RCT: Adjunctive Middle Meningeal Artery Embolization Reduces Reoperation in Subdural Hematoma
24 Nov, 2024 | 13:53h | UTCBackground: Subacute and chronic subdural hematomas are common neurosurgical conditions with a high recurrence rate after surgical evacuation, affecting 8% to 20% of patients. Middle meningeal artery embolization (MMAE) is a minimally invasive procedure targeting the blood supply to these membranes. Preliminary studies suggest that adjunctive MMAE may reduce hematoma recurrence, but its impact on reoperation risk remains unclear.
Objective: To determine whether adjunctive MMAE reduces the risk of hematoma recurrence or progression leading to repeat surgery within 90 days compared to surgery alone in patients with symptomatic subacute or chronic subdural hematoma.
Methods: In this prospective, multicenter, randomized controlled trial, 400 patients aged 18 to 90 years with symptomatic subacute or chronic subdural hematoma requiring surgical evacuation were randomly assigned to receive either MMAE plus surgery (n=197) or surgery alone (n=203). The primary endpoint was hematoma recurrence or progression leading to repeat surgery within 90 days after the index treatment. The secondary endpoint was deterioration of neurologic function at 90 days, assessed using the modified Rankin Scale.
Results: Hematoma recurrence or progression requiring repeat surgery occurred in 8 patients (4.1%) in the MMAE plus surgery group versus 23 patients (11.3%) in the surgery-alone group (relative risk, 0.36; 95% CI, 0.11 to 0.80; P=0.008). Functional deterioration at 90 days was similar between groups (11.9% vs. 9.8%; risk difference, 2.1 percentage points; 95% CI, −4.8 to 8.9). Mortality at 90 days was 5.1% in the MMAE group and 3.0% in the control group. Serious adverse events related to the embolization occurred in 4 patients (2.0%), including disabling stroke in 2 patients.
Conclusions: Adjunctive MMAE combined with surgery significantly reduced the risk of hematoma recurrence or progression requiring reoperation within 90 days compared to surgery alone. However, there was no significant difference in neurologic functional deterioration, and the procedure was associated with procedural risks.
Implications for Practice: MMAE may be considered as an adjunct to surgical evacuation in patients with subacute or chronic subdural hematoma to reduce reoperation risk. Clinicians should carefully weigh the potential benefits against the risks of procedural complications, including stroke.
Study Strengths and Limitations: Strengths include the randomized controlled design and multicenter approach, enhancing generalizability. Limitations involve the open-label design, introducing potential bias since the primary endpoint was based on surgeon judgment. A substantial loss to follow-up (13.2%) could affect results, and the study was not powered to detect differences in mortality or serious adverse events.
Future Research: Further studies with larger sample sizes are needed to fully evaluate the safety and efficacy of MMAE, including long-term outcomes. Research should focus on optimizing patient selection and assessing the procedure’s impact on mortality and serious adverse events.
News Release: Anticoagulation Does Not Prevent Cognitive Decline in Younger Low-Risk AFib Patients
20 Nov, 2024 | 20:17h | UTCIntroduction: A recent large-scale trial has found that anticoagulation therapy does not reduce the risk of cognitive decline, stroke, or transient ischemic attack (TIA) in adults under 65 years old with atrial fibrillation (AFib) who have no additional stroke risk factors. AFib is the most common type of irregular heart rhythm and is known to increase the risk of stroke, especially in older individuals or those with comorbidities. This study aimed to determine if blood thinners could offer neurocognitive and cerebrovascular protection in younger, low-risk AFib patients.
Highlights: The Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF) enrolled over 1,200 participants with an average age of 53 years, none of whom had standard indications for anticoagulation therapy. Participants were randomly assigned to receive either rivaroxaban (15 mg daily) or a placebo and were followed for an average of 3.7 years.
Key findings from the trial include:
- No Significant Difference in Primary Outcomes: There was no significant difference between the rivaroxaban and placebo groups in the combined outcome of cognitive decline (a decrease of two or more points on the Montreal Cognitive Assessment), stroke, or TIA. The annual rates were 7% for rivaroxaban and 6.4% for placebo.
- High Rate of Cognitive Decline: Approximately 1 in 5 participants experienced cognitive decline, accounting for 91% of the primary outcome events. Despite this high rate, anticoagulation did not mitigate the risk.
- Low Incidence of Stroke: The incidence of stroke was low in this population, at less than 1 in 100 participants per year.
- Early Termination of the Trial: The study was terminated early due to futility, as continuing was unlikely to demonstrate a benefit from anticoagulation in preventing cognitive decline or stroke in this group.
- Safety Profile: Major bleeding events were rare and did not differ significantly between the rivaroxaban and placebo groups.
These results confirm that younger AFib patients without additional stroke risk factors have a low incidence of stroke and that anticoagulation does not reduce the risk of cognitive decline or cerebrovascular events in this population.
Conclusion: The BRAIN-AF trial supports current clinical guidelines that do not recommend anticoagulation therapy for AFib patients under 65 years old without other stroke risk factors. The findings suggest that anticoagulation is not effective in preventing cognitive decline or stroke in this low-risk group. Clinicians should continue to focus on standard recommendations for maintaining cognitive health, such as promoting a healthy lifestyle, engaging in brain-stimulating activities, and encouraging regular physical activity, rather than prescribing anticoagulation therapy for neurocognitive protection in these patients.
Source: This study was conducted by researchers at the Montreal Heart Institute and Université de Montréal and was presented at the American Heart Association’s Scientific Sessions 2024.
- American Heart Association News Release: https://newsroom.heart.org/news/blood-thinners-didnt-reduce-cognitive-decline-in-adults-65-and-younger-with-afib
Additional commentaries:
- TCTMD: https://www.tctmd.com/news/rivaroxaban-doesnt-cut-cognitive-decline-stroke-or-tia-younger-af-patients
- American College of Cardiology: https://www.acc.org/latest-in-cardiology/clinical-trials/2024/11/15/15/17/brain-af
News Release: Edoxaban Comparable to Warfarin for Stroke Prevention After Bioprosthetic Valve Surgery
20 Nov, 2024 | 20:05h | UTCIntroduction: A recent multicenter trial from Japan, presented at the American Heart Association’s Scientific Sessions 2024, has found that edoxaban, a direct oral anticoagulant, is as effective as warfarin in preventing stroke and systemic embolism in patients following bioprosthetic heart valve replacement surgery. This addresses the ongoing need for alternative anticoagulant therapies that simplify post-surgical management and enhance patient quality of life.
Highlights: The ENBALV trial enrolled approximately 400 adults aged 41 to 84 who underwent bioprosthetic valve replacement at the aortic and/or mitral position. Participants were randomly assigned to receive either edoxaban (60 mg or 30 mg once daily) or warfarin for 12 weeks post-surgery. Unlike warfarin, edoxaban does not require regular blood tests to monitor clotting activity and has fewer interactions with food and other medications.
Key findings include:
- Efficacy: Stroke or systemic embolism occurred in 0.5% of patients receiving edoxaban compared to 1.5% in the warfarin group, indicating comparable effectiveness.
- Thrombus Formation: No intracardiac thrombus was observed in the edoxaban group, whereas it occurred in 1% of patients on warfarin.
- Bleeding Risks: Major bleeding events were higher in the edoxaban group (4.1% vs. 1% with warfarin). While no fatal bleeding or intracranial hemorrhage occurred with edoxaban, one fatal cerebral hemorrhage was reported in the warfarin group. Gastrointestinal bleeding was more common with edoxaban (2.1% vs. 0% with warfarin).
Lead author Dr. Chisato Izumi noted that edoxaban’s fixed dosing and minimal dietary interactions reduce the treatment burden, potentially improving patient adherence during the critical post-operative period.
Conclusion: The findings suggest that edoxaban is a viable alternative to warfarin for anticoagulation after bioprosthetic valve surgery, offering similar protection against stroke and blood clots with the convenience of simplified management. However, the increased incidence of bleeding events with edoxaban underscores the need for careful patient selection and further research to identify individuals at higher risk. These results may inform future clinical guidelines and improve patient care by providing more flexible anticoagulant options.
Source: This study was conducted by the National Cerebral and Cardiovascular Center in Suita, Japan, and presented at the American Heart Association’s Scientific Sessions 2024. The full news release is available at: http://newsroom.heart.org/news/patients-taking-edoxoban-after-heart-valve-surgery-had-lower-risk-of-stroke-blood-clots
Additional commentaries can be found at:
- American College of Cardiology: https://www.acc.org/latest-in-cardiology/articles/2024/11/13/21/17/sun-935am-enbalv-aha-2024
- TCTMD: https://www.tctmd.com/news/enbalv-edoxaban-matches-warfarin-after-bioprosthetic-valve-surgery
News Release: Sacubitril/Valsartan May Reduce Chemotherapy-Induced Cardiotoxicity in High-Risk Cancer Patients
20 Nov, 2024 | 18:38h | UTCIntroduction: A recent study presented at the American Heart Association’s Scientific Sessions 2024 introduces sacubitril/valsartan, a widely used heart failure medication, as a potential protective agent against heart damage in high-risk cancer patients undergoing anthracycline chemotherapy. Anthracyclines, while effective for treating various cancers such as breast cancer, leukemia, and lymphoma, carry a significant risk of cardiotoxicity, leading to cardiomyopathy and heart failure. The SARAH trial aimed to evaluate whether sacubitril/valsartan could mitigate this risk and preserve cardiac function during chemotherapy.
Highlights: The SARAH trial was a randomized, double-blind, placebo-controlled study involving 114 high-risk cancer patients at Erasto Gaertner Hospital in Curitiba, Brazil. High risk was defined by elevated high-sensitivity troponin I levels post-anthracycline infusion, indicating early signs of cardiac injury. Participants, predominantly women with breast cancer (81%), were randomized to receive sacubitril/valsartan or a placebo over 24 weeks.
Key findings include:
- Significant Reduction in Cardiotoxicity: Sacubitril/valsartan was associated with a 77% reduction in the relative risk of cardiotoxicity compared to placebo. Cardiotoxicity was measured as a ≥15% reduction in global longitudinal strain (GLS), a sensitive marker of left ventricular function.
- Improvement in Cardiac Function: Patients in the sacubitril/valsartan group experienced an average improvement in GLS by 2.55%, whereas those in the placebo group showed an average decline of 6.65%.
- Dose Titration and Tolerance: The medication was initiated at a dose of 24/26 mg twice daily and titrated every two weeks to a target of 97/103 mg twice daily or the highest tolerated dose without side effects. It was generally well tolerated, with hypotension being more common in the treatment group (14% vs. 1.8%) but no significant differences in other adverse events.
- Independent of Other Factors: The protective effect of sacubitril/valsartan was consistent regardless of cumulative anthracycline dose, HER2 status, presence of hypertension, or patient age.
Conclusion: The findings from the SARAH trial suggest that sacubitril/valsartan may offer a promising strategy to prevent chemotherapy-induced cardiotoxicity in high-risk cancer patients. By preserving cardiac function during anthracycline treatment, this medication has the potential to improve patient outcomes, enhance quality of life, and reduce the long-term burden of heart failure among cancer survivors. Further research with larger, more diverse populations and extended follow-up is warranted to confirm these results and assess the impact on long-term clinical outcomes.
Source: This research was conducted by the Heart Institute at the University of São Paulo, Brazil, and presented at the American Heart Association Scientific Sessions 2024.
Primary Source: American Heart Association News Release
https://newsroom.heart.org/news/a-common-heart-failure-medication-may-help-prevent-heart-damage-related-to-chemotherapy-6906417
Secondary Sources:
- American College of Cardiology Summary of the SARAH Trial
https://www.acc.org/Latest-in-Cardiology/Articles/2024/11/13/21/17/mon-915am-sarah-aha-2024 - TCTMD Article: “ARNI Lessens Anthracycline Cardiotoxicity in High-Risk Patients: SARAH”
https://www.tctmd.com/news/arni-lessens-anthracycline-cardiotoxicity-high-risk-patients-sarah
RCT: 7-Day Antibiotic Therapy Noninferior to 14-Day for Bloodstream Infections
20 Nov, 2024 | 18:19h | UTCBackground: Bloodstream infections are a significant cause of morbidity and mortality worldwide. Early and appropriate antibiotic therapy is essential, but the optimal duration remains uncertain. Prolonged antibiotic use can lead to adverse events, Clostridioides difficile infection, antimicrobial resistance, and increased healthcare costs.
Objective: To determine whether a 7-day course of antibiotic treatment is noninferior to a 14-day course in hospitalized patients with bloodstream infections regarding 90-day all-cause mortality.
Methods: In this multicenter, noninferiority randomized controlled trial, 3,608 hospitalized patients from 74 hospitals in seven countries were enrolled. Eligible patients had bloodstream infections but were excluded if they had severe immunosuppression, infections requiring prolonged therapy, possible contaminants, or Staphylococcus aureus bacteremia. Participants were randomized to receive either 7 days (n=1,814) or 14 days (n=1,794) of adequate antibiotic therapy, with antibiotic selection at the clinicians’ discretion. The primary outcome was death from any cause by 90 days post-diagnosis, with a noninferiority margin of 4 percentage points.
Results: At 90 days, mortality was 14.5% in the 7-day group and 16.1% in the 14-day group (difference: –1.6 percentage points; 95.7% CI, –4.0 to 0.8), demonstrating noninferiority of the shorter duration. Noninferiority was confirmed in per-protocol and modified intention-to-treat analyses. Secondary outcomes, including relapse rates, adverse events, and hospital length of stay, were similar between groups. Findings were consistent across subgroups based on infection source, pathogen type, and patient characteristics.
Conclusions: A 7-day antibiotic regimen is noninferior to a 14-day regimen for treating hospitalized patients with bloodstream infections, without increasing mortality or relapse rates.
Implications for Practice: Implementing a 7-day antibiotic course could reduce antibiotic exposure, minimize adverse events, and potentially limit antimicrobial resistance development. Clinicians should consider individual patient factors, such as infection severity and comorbidities, before universally adopting shorter treatment durations.
Study Strengths and Limitations: Strengths include a large, diverse patient population and inclusion of critically ill patients, enhancing generalizability. Limitations involve the open-label design and nonadherence to assigned durations in some cases (23.1% in the 7-day group continued antibiotics longer). Exclusion of S. aureus bacteremia limits applicability to that subgroup. The study may not have been powered to detect differences in rare adverse outcomes like C. difficile infection or antimicrobial resistance emergence.
Future Research: Further studies should explore the efficacy of even shorter antibiotic durations, individualized treatment strategies based on patient response, and the long-term impact on antimicrobial resistance and healthcare costs.
RCT: Colchicine Does Not Reduce Cardiovascular Events After Myocardial Infarction
20 Nov, 2024 | 18:12h | UTCBackground: Inflammation is a key contributor to atherosclerosis and adverse cardiovascular events. Previous trials have suggested that anti-inflammatory agents like colchicine may reduce cardiovascular risks in patients with coronary artery disease.
Objective: To evaluate whether colchicine reduces the incidence of major cardiovascular events when initiated soon after a myocardial infarction.
Methods: In this multicenter, randomized, placebo-controlled trial with a 2-by-2 factorial design, 7,062 patients who experienced a myocardial infarction were assigned to receive colchicine (0.5 mg daily) or placebo, and spironolactone or placebo. The colchicine results are reported here. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization. Median follow-up was 3 years.
Results: A primary outcome event occurred in 9.1% of patients in the colchicine group and 9.3% in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.16; P=0.93). Individual components of the primary outcome were similar between groups. Colchicine significantly reduced C-reactive protein levels at 3 months (adjusted mean difference of –1.28 mg/L; 95% CI, –1.81 to –0.75). Diarrhea was more frequent with colchicine (10.2% vs. 6.6%; P<0.001), but serious infections did not differ significantly.
Conclusions: Among patients post-myocardial infarction, colchicine did not reduce the incidence of major cardiovascular events over a median of 3 years compared to placebo.
Implications for Practice: These findings suggest that initiating colchicine after myocardial infarction may not provide additional cardiovascular benefits. Clinicians should weigh the lack of efficacy and potential gastrointestinal side effects when considering colchicine for secondary prevention in this population.
Study Strengths and Limitations: Strengths include a large sample size and extended follow-up. Limitations involve a higher-than-expected discontinuation rate and underrepresentation of women and diverse populations. The predominance of STEMI patients may limit applicability to NSTEMI cases.
Future Research: Further studies are needed to identify if specific subgroups might benefit from colchicine or if different dosing strategies could be more effective in reducing cardiovascular events post-myocardial infarction.
RCT: Routine Spironolactone Post-MI Does Not Reduce Cardiovascular Events
20 Nov, 2024 | 18:03h | UTCBackground: Mineralocorticoid receptor antagonists (MRAs), such as spironolactone, have demonstrated mortality benefits in patients with heart failure following myocardial infarction (MI). However, the efficacy of routine spironolactone use in all patients post-MI, regardless of heart failure status, remains uncertain.
Objective: To evaluate whether routine administration of spironolactone reduces cardiovascular events in patients after MI who have undergone percutaneous coronary intervention (PCI).
Methods: In a multicenter, double-blind, placebo-controlled trial with a 2-by-2 factorial design, 7,062 patients with MI undergoing PCI were randomized to receive spironolactone (25 mg daily) or placebo, and colchicine or placebo. The two primary outcomes were: (1) a composite of death from cardiovascular causes or new or worsening heart failure, assessed as the total number of events; and (2) a composite of the first occurrence of MI, stroke, new or worsening heart failure, or death from cardiovascular causes. Median follow-up was 3 years.
Results: No significant differences were observed between the spironolactone and placebo groups in the primary outcomes. For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group versus 220 events (2.1 per 100 patient-years) in the placebo group (hazard ratio [HR] adjusted for competing risk, 0.91; 95% confidence interval [CI], 0.69–1.21; P=0.51). For the second primary outcome, events occurred in 280 patients (7.9%) in the spironolactone group and 294 patients (8.3%) in the placebo group (HR adjusted for competing risk, 0.96; 95% CI, 0.81–1.13; P=0.60). Serious adverse events were similar between groups.
Conclusions: Routine use of spironolactone after MI did not reduce cardiovascular mortality or new or worsening heart failure compared to placebo.
Implications for Practice: These findings suggest that routine prescription of spironolactone for all patients after MI may not be beneficial and should be reconsidered. Clinicians should carefully evaluate the indication for MRAs post-MI, particularly in patients without heart failure, and remain cautious about routine use without clear evidence of benefit.
Study Strengths and Limitations: Strengths of the study include its large sample size, multicenter international design, and long follow-up period, enhancing the generalizability of the findings. However, limitations include lower-than-expected event rates, potentially reducing statistical power to detect significant differences. The high rate of discontinuation of the trial regimen and underrepresentation of women and certain racial and ethnic groups may also limit the applicability of the results. Additionally, the possibility of a type II error due to reduced power cannot be excluded.
Future Research: Further studies are warranted to identify specific subgroups of patients who may benefit from spironolactone post-MI and to explore alternative therapies that effectively reduce cardiovascular events after MI.
RCT: Left Atrial Appendage Closure May Reduce Bleeding Without Increasing Stroke Risk After AF Ablation
20 Nov, 2024 | 16:28h | UTCBackground: Catheter ablation is an effective treatment for symptomatic atrial fibrillation (AF), but patients at high risk for stroke require ongoing oral anticoagulation (OAC) due to the potential for asymptomatic AF recurrence. Left atrial appendage closure (LAAC) is a mechanical alternative to OAC, but its efficacy and safety post-AF ablation are not well established.
Objective: To compare the safety and efficacy of LAAC versus continued OAC in patients with AF undergoing catheter ablation.
Methods: In this international, randomized trial, 1,600 patients with AF and elevated CHA₂DS₂-VASc scores (≥2 in men, ≥3 in women) who underwent or were scheduled for catheter ablation were assigned to either LAAC (n=803) or OAC (n=797). The primary safety endpoint was non–procedure-related major bleeding or clinically relevant nonmajor bleeding through 36 months. The primary efficacy endpoint was a composite of death from any cause, stroke, or systemic embolism at 36 months. The secondary endpoint was major bleeding, including procedure-related bleeding.
Results: At 36 months, bleeding events occurred in 8.5% of the LAAC group versus 18.1% of the OAC group (P<0.001 for superiority). The primary efficacy endpoint occurred in 5.3% of the LAAC group and 5.8% of the OAC group (P<0.001 for noninferiority). Major bleeding, including procedure-related bleeding, occurred in 3.9% of the LAAC group and 5.0% of the OAC group (P<0.001 for noninferiority). Device-related complications occurred in 23 patients, and incomplete device closure was noted in up to 20% of patients.
Conclusions: Among patients undergoing AF ablation, LAAC reduced the risk of bleeding compared to OAC without increasing the risk of death, stroke, or systemic embolism over 36 months.
Implications for Practice: LAAC may be considered as an alternative to long-term OAC in patients undergoing AF ablation who are at moderate to high risk of stroke. However, clinicians should exercise caution due to potential device-related complications, such as incomplete closure and peri-device leaks, which may increase stroke risk. The decision to use LAAC should involve a thorough discussion with the patient about the benefits and risks.
Study Strengths and Limitations: Strengths include the randomized design and large sample size. Limitations involve the exclusion of procedure-related bleeding from the primary safety endpoint, potentially underestimating the true bleeding risk of LAAC. The inclusion of all-cause mortality in the primary efficacy endpoint may dilute the ability to detect differences in stroke risk. Additionally, missing data and a significant rate of incomplete device closure raise concerns about the generalizability and safety of LAAC.
Future Research: Further large-scale, randomized trials are needed to address these limitations, especially to assess stroke risk adequately and the impact of procedural complications. Studies should also evaluate long-term outcomes and the cost-effectiveness of LAAC compared to OAC in diverse patient populations.
References:
- Wazni OM, Saliba WI, Nair DG, et al. Left Atrial Appendage Closure after Ablation for Atrial Fibrillation. New England Journal of Medicine. Published November 16, 2024. DOI: http://doi.org/10.1056/NEJMoa2408308
- Mandrola J. Electrophysiology is on the brink of a possible disaster. November 19, 2024. Available at: https://johnmandrola.substack.com/p/electrophysiology-is-on-the-brink
Meta-Analysis: Moderately Rapid Sodium Correction Linked to Better Outcomes in Severe Hyponatremia
20 Nov, 2024 | 16:10h | UTCBackground: Severe hyponatremia is a critical condition that can lead to hyponatremic encephalopathy, necessitating prompt treatment to prevent neurological damage or death. Traditional guidelines recommend limiting sodium correction rates to prevent osmotic demyelination syndrome (ODS). However, emerging evidence suggests that slower correction rates may be associated with increased mortality.
Objective: To evaluate the association between sodium correction rates and mortality among hospitalized adults with severe hyponatremia.
Methods: This systematic review and meta-analysis included 16 cohort studies published between January 2013 and October 2023, involving 11,811 hospitalized adults with severe hyponatremia (serum sodium <120 mEq/L or <125 mEq/L with severe symptoms). Patients were categorized based on sodium correction rates: rapid (≥8-10 mEq/L per 24 hours), slow (<8 or 6-10 mEq/L per 24 hours), and very slow (<4-6 mEq/L per 24 hours). Primary outcomes were in-hospital and 30-day mortality; secondary outcomes included hospital length of stay (LOS) and incidence of ODS.
Results: Rapid correction was associated with significantly lower in-hospital mortality compared to slow correction (odds ratio [OR], 0.67; 95% CI, 0.55-0.82) and very slow correction (OR, 0.29; 95% CI, 0.11-0.79), corresponding to 32 and 221 fewer deaths per 1,000 patients, respectively. At 30 days, rapid correction was associated with 61 and 134 fewer deaths per 1,000 patients compared to slow and very slow correction, respectively. Rapid correction also resulted in shorter hospital LOS by 1.20 days (95% CI, 0.51-1.89) compared to slow correction and 3.09 days (95% CI, 1.21-4.94) compared to very slow correction. There was no statistically significant increase in ODS risk with rapid correction.
Conclusions: In hospitalized adults with severe hyponatremia, rapid sodium correction was associated with reduced mortality and shorter hospital stays without a significant increase in ODS risk.
Implications for Practice: These findings suggest that more aggressive sodium correction may benefit patients with severe hyponatremia, challenging current guidelines that recommend slower correction rates to prevent ODS. Clinicians should weigh the potential benefits of rapid correction against the traditionally emphasized risks, although caution is still warranted given the seriousness of ODS.
Study Strengths and Limitations: Strengths include a large sample size and inclusion of recent studies reflecting current practices. Limitations involve the observational nature of included studies, potential confounding factors, heterogeneity in correction rate definitions, and possible underreporting of ODS due to its rarity and diagnostic challenges.
Future Research: Randomized controlled trials are needed to establish causality and optimal correction rates, as well as to identify patient subgroups that may benefit most from rapid correction while minimizing ODS risk.
RCT: Linear Ablation Plus Ethanol infusion of the vein of Marshall Enhances Rhythm Outcomes in Persistent AF
20 Nov, 2024 | 15:48h | UTCBackground: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation for atrial fibrillation (AF) but has modest efficacy in persistent AF. Previous randomized trials have not demonstrated additional benefit from adding linear ablation to PVI, possibly due to challenges in achieving durable lesions. Ethanol infusion of the vein of Marshall (EIVOM) may facilitate linear ablation, especially at the mitral isthmus, potentially improving outcomes.
Objective: To determine whether adding linear ablation combined with EIVOM to PVI improves maintenance of sinus rhythm compared with PVI alone in patients with persistent AF.
Methods: PROMPT-AF was an investigator-initiated, multicenter, open-label randomized trial involving 12 hospitals in China. The study included 498 patients aged 18–80 years with persistent AF lasting >3 months undergoing first-time ablation. Participants were randomized to either PVI alone or PVI plus EIVOM and linear ablation targeting the left atrial roof, mitral isthmus, and cavotricuspid isthmus. Primary outcomes included freedom from atrial arrhythmias lasting >30 seconds without antiarrhythmic drugs over 12 months. Patients were monitored weekly with wearable ECG patches and periodic Holter monitoring.
Results: Among 495 patients analyzed (mean age, 61.1 years; 72.9% male), the intervention group demonstrated significantly higher freedom from atrial arrhythmias without antiarrhythmic drugs (70.7% vs 61.5%; HR, 0.73; 95% CI, 0.54–0.99; P = .045). Secondary outcomes showed no significant differences in quality of life or arrhythmia recurrence with antiarrhythmic drugs. Linear ablation increased procedural time (188.0 vs 140.8 minutes, P < .001) and fluoroscopy exposure. Serious adverse events were comparable between groups, though pericarditis or pericardial effusion occurred in 7 intervention patients versus none in the control.
Conclusions: Adding linear ablation and EIVOM to PVI significantly improves freedom from atrial arrhythmias in patients with persistent AF compared with PVI alone.
Implications for Practice: The combination of linear ablation and EIVOM addresses limitations of PVI alone by enhancing lesion durability and targeting challenging areas such as the mitral isthmus. However, the increased procedural complexity and longer operative times highlight the need for skilled operators. Adoption should be balanced against risks and resource demands.
Study Strengths and Limitations: Strengths include the randomized, multicenter design and high procedural adherence. Limitations involve the open-label design and potential underestimation of arrhythmia recurrence due to intermittent rhythm monitoring rather than continuous monitoring. The increased procedural time and fluoroscopy exposure are concerns, and the findings may not be generalizable to all persistent AF patients, especially those with episodes lasting less than 3 months.
Future Research: Further studies are needed to optimize ablation strategies, assess long-term outcomes, and evaluate the safety, efficacy, and cost-effectiveness of incorporating EIVOM and linear ablation in diverse patient populations.
Review: Comparative Analysis of ESC and ESH Hypertension Guidelines
20 Nov, 2024 | 15:03h | UTCIntroduction: Hypertension remains a significant global health challenge with increasing prevalence and substantial morbidity and mortality rates. To address this, the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) have independently published updated guidelines on hypertension management. This review provides a pragmatic comparison of these guidelines, highlighting their major similarities and differences to assist clinicians in optimizing patient care.
Key Recommendations:
Shared Recommendations:
- Diagnosis Criteria: Both guidelines recommend diagnosing hypertension based on office systolic and diastolic blood pressures of ≥140/90 mmHg.
- Blood Pressure Targets: Both advocate aiming for an optimal blood pressure of <130/80 mmHg. The ESH emphasizes personalized targets for specific populations like the elderly, while the ESC adopts the ALARA (as low as reasonably achievable) principle.
- Out-of-Office Measurements: Emphasis is placed on home blood pressure monitoring and ambulatory measurements to confirm diagnoses and tailor treatments.
- Comprehensive Assessment: Both recommend thorough initial evaluations, including screening for orthostatic hypotension, comorbidities, and hypertension-mediated organ damage (HMOD).
- Early Treatment Initiation: Both suggest starting antihypertensive therapy promptly, preferably using a single-pill combination of two agents after lifestyle interventions.
- Treatment Goals and Follow-Up: Both aim for patients to reach blood pressure targets within three months, underscoring the importance of close monitoring.
- Adjunctive Therapies: The use of SGLT-2 inhibitors is recommended for patients with chronic kidney disease and/or heart failure. Renal denervation is considered for true resistant hypertension.
Differences:
- Blood Pressure Classification: The ESC introduces a new category of “elevated blood pressure,” altering patient classification but with minimal impact on practical management.
- Screening for Secondary Hypertension: The ESC strongly encourages screening for secondary hypertension, particularly primary aldosteronism; the ESH does not emphasize this as strongly.
- Age Stratification: Different age thresholds for the very elderly are used (ESH: ≥80 years; ESC: ≥85 years), with the ESH providing more detailed treatment personalization for this group.
- Treatment Targets Philosophy: The ESC supports the ALARA principle for blood pressure targets, aiming for the lowest achievable levels without adverse effects, while the ESH provides specific target ranges.
- Beta-Blocker Use: The ESH includes beta-blockers as first-line therapy options, whereas the ESC positions them as third-line agents.
Conclusion: Despite minor discrepancies, the ESC and ESH hypertension guidelines are largely concordant and based on the same evidence base. Both sets provide clear, pragmatic recommendations emphasizing early diagnosis, personalized treatment, and close follow-up. Clinicians can confidently use either guideline to inform practice, as both aim to improve patient outcomes by effectively managing hypertension in the primary care setting.
RCT: Catheter Ablation Superior to Antiarrhythmic Drugs in Ischemic Cardiomyopathy with Ventricular Tachycardia
20 Nov, 2024 | 14:32h | UTCBackground: Patients with ventricular tachycardia and ischemic cardiomyopathy face high risks of adverse outcomes, including death and recurrent arrhythmias. While catheter ablation is commonly used when antiarrhythmic drugs fail to suppress ventricular tachycardia, its effectiveness as a first-line therapy compared to antiarrhythmic drugs remains uncertain.
Objective: To compare the efficacy of catheter ablation versus antiarrhythmic drug therapy as a first-line treatment in patients with ischemic cardiomyopathy and ventricular tachycardia who have an implantable cardioverter–defibrillator (ICD).
Methods: In this multicenter, randomized controlled trial (VANISH2), 416 patients with previous myocardial infarction, clinically significant ventricular tachycardia, and an ICD were randomly assigned to receive catheter ablation within 14 days or antiarrhythmic drug therapy with sotalol or amiodarone based on prespecified criteria. The primary endpoint was a composite of death from any cause during follow-up or, more than 14 days after randomization, ventricular tachycardia storm, appropriate ICD shock, or sustained ventricular tachycardia treated by medical intervention.
Results: Over a median follow-up of 4.3 years, the primary endpoint occurred in 50.7% of patients in the catheter ablation group and 60.6% in the drug therapy group (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.58–0.97; P=0.03). Adverse events within 30 days post-ablation included death in 1.0% and nonfatal events in 11.3% of patients. In the drug therapy group, adverse events attributed to antiarrhythmic drugs included death from pulmonary toxicity in 0.5% and nonfatal events in 21.6% of patients.
Conclusions: Catheter ablation as an initial therapy significantly reduced the risk of the composite primary endpoint compared to antiarrhythmic drug therapy in patients with ischemic cardiomyopathy and ventricular tachycardia.
Implications for Practice: These findings support considering catheter ablation as a first-line treatment option for patients with ischemic cardiomyopathy and ventricular tachycardia, potentially leading to improved clinical outcomes over initial antiarrhythmic drug therapy.
Study Strengths and Limitations: Strengths include the randomized, multicenter design and long-term follow-up. Limitations involve the inability to assess effects on individual components of the primary endpoint, such as mortality. Operator experience with catheter ablation may affect outcomes, potentially influencing the generalizability of the results.
Future Research: Further studies are needed to evaluate the long-term benefits and risks of catheter ablation, particularly with advancements in ablation technology. Research into new antiarrhythmic drugs and alternative ICD programming strategies may also provide additional insights.
Phase 2 RCT: Oral Muvalaplin Significantly Reduces Lipoprotein(a) Levels in High-Risk Patients
20 Nov, 2024 | 14:22h | UTCBackground: Elevated lipoprotein(a) [Lp(a)] levels are an independent risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Current therapeutic options to lower Lp(a) are limited, and no approved pharmacotherapies specifically target Lp(a) reduction.
Objective: To evaluate the efficacy and safety of muvalaplin, an oral small-molecule inhibitor of Lp(a) formation, in reducing Lp(a) levels in patients at high risk of cardiovascular events.
Methods: In this phase 2, randomized, double-blind, placebo-controlled trial, 233 adults aged 40 years or older with Lp(a) concentrations of 175 nmol/L or greater and high cardiovascular risk (due to atherosclerotic cardiovascular disease, diabetes, or familial hypercholesterolemia) were enrolled across 43 sites worldwide. Participants were randomized to receive muvalaplin at doses of 10 mg/d (n = 34), 60 mg/d (n = 64), or 240 mg/d (n = 68), or placebo (n = 67) for 12 weeks. The primary endpoint was the placebo-adjusted percentage change from baseline in Lp(a) levels at week 12, measured using both an intact Lp(a) assay and a traditional apolipoprotein(a)-based assay.
Results
At week 12, muvalaplin achieved significant, dose-dependent reductions in Lp(a) levels compared with placebo. Using the intact Lp(a) assay, placebo-adjusted reductions were:
- 47.6% (95% CI, 35.1%-57.7%) for 10 mg/d
- 81.7% (95% CI, 78.1%-84.6%) for 60 mg/d
- 85.8% (95% CI, 83.1%-88.0%) for 240 mg/d
Using the apolipoprotein(a)-based assay, reductions were:
- 40.4% (95% CI, 28.3%-50.5%) for 10 mg/d
- 70.0% (95% CI, 65.0%-74.2%) for 60 mg/d
- 68.9% (95% CI, 63.8%-73.3%) for 240 mg/d
Dose-dependent decreases in apolipoprotein B levels were also observed, with placebo-adjusted reductions ranging from 8.9% to 16.1%. Muvalaplin was well tolerated across all doses, with no significant safety or tolerability concerns reported.
Conclusions: Muvalaplin significantly reduced Lp(a) levels in high-risk patients over a 12-week period and was well tolerated. These findings suggest that muvalaplin could be an effective oral therapy for lowering Lp(a) levels.
Implications for Practice: Muvalaplin may offer a convenient oral option to reduce elevated Lp(a) levels, potentially lowering cardiovascular risk in high-risk patient populations.
Study Strengths and Limitations: Strengths of the study include its randomized, double-blind, placebo-controlled design and the use of both traditional and novel assays to accurately measure Lp(a) levels. Limitations involve the short duration of the trial, the relatively small sample size for each dosage group, and the lack of assessment of long-term cardiovascular outcomes and safety.
Future Research: Long-term studies are necessary to determine whether the reduction in Lp(a) levels with muvalaplin translates into decreased cardiovascular events. Future research should also explore optimal dosing strategies and assess the long-term safety profile of muvalaplin.
RCT: Intensive Systolic Blood Pressure Target Reduces Cardiovascular Events in Type 2 Diabetes
16 Nov, 2024 | 16:49h | UTCBackground: Patients with type 2 diabetes frequently have elevated systolic blood pressure, heightening their risk for cardiovascular disease. Optimal systolic blood-pressure targets in this population remain unclear due to inconclusive results from previous trials.
Objective: To determine whether intensive treatment targeting a systolic blood pressure of less than 120 mm Hg reduces major cardiovascular events compared to standard treatment targeting less than 140 mm Hg in patients with type 2 diabetes.
Methods: In this randomized controlled trial conducted at 145 sites in China, 12,821 patients aged 50 or older with type 2 diabetes, elevated systolic blood pressure, and increased cardiovascular risk were assigned to intensive treatment (target <120 mm Hg) or standard treatment (target <140 mm Hg). The primary outcome was a composite of nonfatal stroke, nonfatal myocardial infarction, treatment or hospitalization for heart failure, or death from cardiovascular causes.
Results: Over a median follow-up of 4.2 years, the intensive-treatment group achieved a mean systolic blood pressure of 121.6 mm Hg versus 133.2 mm Hg in the standard-treatment group at 1 year. Primary outcome events occurred in 393 patients in the intensive group (1.65 events per 100 person-years) versus 492 patients in the standard group (2.09 events per 100 person-years) (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). Serious adverse events were similar between groups, but symptomatic hypotension and hyperkalemia were more frequent in the intensive-treatment group.
Conclusions: Intensive systolic blood-pressure control to less than 120 mm Hg significantly reduced major cardiovascular events in patients with type 2 diabetes compared to standard treatment.
Implications for Practice: These findings support adopting more aggressive systolic blood-pressure targets in patients with type 2 diabetes to prevent cardiovascular events. Clinicians should balance the benefits with potential risks, monitoring for hypotension and hyperkalemia.
Study Strengths and Limitations: Strengths include a large sample size, multicenter design, and sufficient power to detect differences in cardiovascular outcomes. Limitations involve unblinded treatment assignment, which may introduce bias, and reliance on self-reported home blood-pressure measurements during the COVID-19 pandemic, potentially affecting data accuracy. The exclusive enrollment of Chinese patients may limit generalizability to other populations. The increased incidence of hypotension and hyperkalemia raises concerns about the safety of intensive blood-pressure lowering in broader practice.
Future Research: Further studies should assess the long-term safety and efficacy of intensive blood-pressure control in diverse populations and explore strategies to minimize adverse events. Investigations into personalized blood-pressure targets based on patient characteristics may enhance clinical outcomes.
RCT: Tirzepatide Reduces Heart Failure Events and Improves Health Status in Obese HFpEF Patients
16 Nov, 2024 | 16:42h | UTCBackground: Obesity significantly increases the risk of heart failure with preserved ejection fraction (HFpEF) due to visceral adiposity-induced systemic inflammation affecting the myocardium. Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, induces substantial weight loss. However, its effects on cardiovascular outcomes in obese HFpEF patients were previously unknown.
Objective: To assess the impact of tirzepatide on cardiovascular events and health status in patients with HFpEF and obesity.
Methods: In this international, double-blind, randomized, placebo-controlled trial, 731 patients with HFpEF (ejection fraction ≥50%), a body-mass index (BMI) of at least 30, and New York Heart Association class II–IV symptoms were assigned to receive tirzepatide (up to 15 mg subcutaneously once weekly) or placebo for at least 52 weeks. The two primary endpoints were the composite of adjudicated death from cardiovascular causes or worsening heart-failure events, and the change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS).
Results: Over a median follow-up of 104 weeks, death from cardiovascular causes or worsening heart-failure events occurred in 9.9% of patients in the tirzepatide group versus 15.3% in the placebo group (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.41 to 0.95; P=0.026). Worsening heart-failure events occurred in 8.0% with tirzepatide versus 14.2% with placebo (HR, 0.54; 95% CI, 0.34 to 0.85). At 52 weeks, the mean increase in KCCQ-CSS was 19.5 points in the tirzepatide group compared to 12.7 points in the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P<0.001). Adverse events leading to discontinuation occurred in 6.3% of tirzepatide patients versus 1.4% of placebo patients, mainly due to gastrointestinal symptoms.
Conclusions: Tirzepatide significantly reduced the risk of cardiovascular death or worsening heart failure and improved health status in patients with HFpEF and obesity.
Implications for Practice: These findings suggest that tirzepatide may be an effective therapeutic option for reducing heart failure events and enhancing quality of life in obese patients with HFpEF. Its benefits may be attributed to significant weight loss and anti-inflammatory effects, offering a potential new approach in managing this patient population.
Study Strengths and Limitations: Strengths include the randomized, double-blind design and a long median follow-up of 104 weeks. Limitations involve the exclusion of patients with BMI less than 30, which may limit applicability to non-obese HFpEF patients with increased visceral adiposity. Additionally, the higher rate of gastrointestinal adverse events leading to discontinuation in the tirzepatide group warrants cautious consideration.
Future Research: Further studies are needed to evaluate tirzepatide’s effects in HFpEF patients with lower BMI but increased visceral adiposity and to elucidate the mechanisms underlying its cardiovascular benefits.
Retrospective Cohort Study: Midline Catheters Associated with Lower Major Complications Than PICCs in Outpatient Antimicrobial Therapy
16 Nov, 2024 | 14:35h | UTCBackground: Outpatient parenteral antimicrobial therapy (OPAT) requires reliable vascular access for administering intravenous antibiotics post-hospitalization. Peripherally inserted central catheters (PICCs) are commonly used due to their versatility and ease of placement. Recently, midline catheters have emerged as potential alternatives for OPAT, offering less invasive access. However, limited evidence exists comparing the safety and complication rates of midline catheters versus PICCs in OPAT patients.
Objective: To compare the risk of major and minor device complications associated with midline catheters versus PICCs in patients receiving OPAT.
Methods: This retrospective cohort study analyzed data from 2,824 hospitalized patients across 69 Michigan hospitals who received either a midline catheter (n=1,999) or a PICC (n=825) for OPAT between January 2017 and November 2023. Patients receiving vancomycin were excluded. The primary outcome was major device complications, defined as catheter-related bloodstream infection (CRBSI) or catheter-related venous thromboembolism (CR-VTE). Secondary outcomes included minor device complications (e.g., catheter dislodgement, occlusion) and device failure, defined as catheter removal due to any complication.
Results: Midline catheters were associated with a lower risk of major complications compared to PICCs (0.8% vs 3.4%; adjusted hazard ratio [aHR], 0.46; 95% CI, 0.23-0.91; P < .001). This difference was more pronounced for devices with dwell times of 14 days or fewer (aHR, 0.29; 95% CI, 0.12-0.68). There were no significant differences in minor complications (10.3% vs 13.8%; aHR, 1.07; 95% CI, 0.83-1.38) or device failure rates (9.6% vs 12.1%; aHR, 1.26; 95% CI, 0.96-1.65) between midline catheters and PICCs.
Conclusions: Midline catheters are associated with a lower risk of major complications compared to PICCs in patients receiving OPAT, particularly for treatment durations of 14 days or fewer. These findings suggest that midline catheters are a safe and effective alternative to PICCs for short-term OPAT.
Implications for Practice: Clinicians should consider using midline catheters for OPAT when the anticipated therapy duration is 14 days or less and the infusate is peripherally compatible. This may reduce the risk of major complications such as CRBSI and CR-VTE, potentially improving patient outcomes and reducing healthcare costs.
Study Strengths and Limitations: Strengths of this study include a large, diverse patient population across multiple hospitals and rigorous data collection methods. Limitations include its retrospective design, potential for unmeasured confounding, and exclusion of patients receiving vancomycin, which may limit generalizability. Additionally, complications occurring after 30 days or post-device removal may have been missed.
Future Research: Further studies are needed to evaluate the safety and efficacy of midline catheters for OPAT durations exceeding 14 days and to explore factors influencing long-term device performance and patient outcomes.
Test-Negative Study: RSV Vaccine May Reduce Hospitalizations and ED Visits in Adults Aged ≥60
16 Nov, 2024 | 14:18h | UTCBackground: Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality among older adults in the USA, with an estimated 100,000–160,000 RSV-associated hospitalizations annually in those aged 60 years and older. In 2023, RSV vaccines were recommended for this population, showing efficacy in clinical trials. However, real-world effectiveness data, particularly against severe outcomes like hospitalizations in high-risk groups, are limited.
Objective: To assess the real-world effectiveness of RSV vaccination against RSV-associated hospitalizations and emergency department (ED) encounters among adults aged 60 years and older during the 2023–24 RSV season in the USA.
Methods: A test-negative design analysis was conducted using data from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network (VISION), encompassing eight states. Adults aged ≥60 presenting with RSV-like illness and tested for RSV from Oct 1, 2023, to Mar 31, 2024, were included. Vaccination status was determined through electronic health records, immunization registries, and medical claims. Vaccine effectiveness (VE) was estimated by comparing the odds of vaccination among RSV-positive cases and RSV-negative controls, adjusting for age, sex, race and ethnicity, comorbidities, and geographic region.
Results: Among 28,271 hospitalizations for RSV-like illness in immunocompetent adults aged ≥60, VE against RSV-associated hospitalization was 80% (95% CI 71–85). VE against RSV-associated critical illness (ICU admission or death) was 81% (95% CI 52–92). In 8,435 hospitalizations among immunocompromised adults, VE was 73% (95% CI 48–85) against RSV-associated hospitalization. Among 36,521 ED encounters in immunocompetent adults, VE against RSV-associated ED visits was 77% (95% CI 70–83). VE estimates were consistent across age groups and vaccine products.
Conclusions: RSV vaccination effectively prevented RSV-associated hospitalizations and ED visits among adults aged ≥60 during the first season post-approval, including those at highest risk due to advanced age or immunocompromise.
Implications for Practice: These findings support recommending RSV vaccination for adults aged ≥60 to reduce severe RSV-related morbidity and mortality. Clinicians should consider advising eligible patients to receive the RSV vaccine to prevent hospitalizations and critical illness.
Study Strengths and Limitations: Strengths include a large, geographically diverse cohort and integrated medical, laboratory, and vaccination data, allowing robust VE estimates across subgroups. Limitations involve potential misclassification of vaccination status, residual confounding, and reliance on clinician-directed RSV testing, which may introduce bias.
Future Research: Further studies are needed to evaluate the duration of vaccine protection over multiple RSV seasons and to assess VE in other high-risk populations and settings.
Phase 3 RCT: Resmetirom Significantly Improves NASH Resolution and Liver Fibrosis
16 Nov, 2024 | 13:56h | UTCBackground: Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatments. It significantly increases the risk of liver-related complications, especially in patients with type 2 diabetes. Resmetirom, a thyroid hormone receptor beta-selective agonist, is being investigated for its potential to treat NASH and liver fibrosis.
Objective: To evaluate the efficacy and safety of resmetirom in resolving NASH and improving fibrosis in adults with biopsy-confirmed NASH and fibrosis stages F1B to F3.
Methods: This double-blind, placebo-controlled phase 3 trial randomized 966 adults with NASH to receive once-daily resmetirom (80 mg or 100 mg) or placebo for 52 weeks. Primary endpoints included (1) NASH resolution with no fibrosis worsening and (2) fibrosis improvement by at least one stage without NAFLD activity score worsening. Secondary outcomes included changes in lipid profiles and liver biomarkers.
Results: At 52 weeks, NASH resolution occurred in 25.9% of patients receiving 80 mg and 29.9% receiving 100 mg of resmetirom, compared with 9.7% in the placebo group (P<0.001 for both doses vs. placebo). Fibrosis improved by at least one stage in 24.2% (80 mg) and 25.9% (100 mg) of resmetirom-treated patients versus 14.2% for placebo (P<0.001). LDL cholesterol reductions were −13.6% (80 mg) and −16.3% (100 mg) at 24 weeks versus 0.1% for placebo (P<0.001). Improvements were also noted in triglycerides, liver enzymes, and imaging biomarkers. Adverse events, primarily mild gastrointestinal symptoms, were more frequent with resmetirom. Serious adverse events were similar across groups (10.9%–12.7%).
Conclusions: Resmetirom significantly improved NASH resolution and fibrosis compared to placebo, demonstrating its potential as a treatment for NASH with liver fibrosis.
Implications for Practice: Resmetirom offers a promising treatment option for NASH, potentially altering the disease course and improving outcomes. Clinicians should monitor for regulatory approval and long-term safety data.
Study Strengths and Limitations: Strengths include robust biopsy-confirmed endpoints and a large sample size. Limitations include short follow-up and lack of clinical-outcome data.
Future Research: Long-term studies are needed to assess durability, safety, and effects on clinical outcomes like cirrhosis and liver-related mortality.