Randomized Trials
RCT: High-Intensity NPPV Reduced Criteria for Intubation in Acute COPD Exacerbations
16 Sep, 2024 | 16:50h | UTCBackground: Acute exacerbations of chronic obstructive pulmonary disease (COPD) often lead to hypercapnic respiratory failure requiring ventilatory support. Noninvasive positive pressure ventilation (NPPV) is standard care, commonly delivered at low intensity with lower inspiratory pressures. However, approximately 15% of patients still require endotracheal intubation despite low-intensity NPPV. High-intensity NPPV, using higher inspiratory pressures to achieve greater reductions in PaCO₂, has shown benefits in stable hypercapnic COPD patients, but its effect during acute exacerbations is unclear.
Objective: To determine whether high-intensity NPPV reduces the need for endotracheal intubation in patients with acute COPD exacerbations and persistent hypercapnia compared to low-intensity NPPV.
Methods: In a multicenter, randomized clinical trial conducted at 30 respiratory wards in China from January 2019 to January 2022, 300 patients with acute COPD exacerbations and PaCO₂ greater than 45 mm Hg after 6 hours of low-intensity NPPV were enrolled. Participants were randomized 1:1 to receive either high-intensity NPPV (inspiratory positive airway pressure [IPAP] adjusted to achieve tidal volumes of 10–15 mL/kg predicted body weight, typically IPAP 20–30 cm H₂O) or to continue low-intensity NPPV (IPAP adjusted for tidal volumes of 6–10 mL/kg, maximum IPAP 20 cm H₂O). Patients in the low-intensity group meeting prespecified criteria for intubation were allowed to crossover to high-intensity NPPV. The primary outcome was the need for endotracheal intubation during hospitalization, defined by prespecified clinical and gas exchange criteria. Secondary outcomes included actual endotracheal intubation rates, mortality, length of hospital stay, and adverse events.
Results: Of the 300 patients (mean age 73 years; 68% male), the primary outcome occurred in 4.8% of the high-intensity group versus 13.7% of the low-intensity group (absolute difference –9.0%; 95% CI, –15.4% to –2.5%; one-sided P = .004; adjusted risk ratio [RR], 0.35; 95% CI, 0.14–0.76). However, actual endotracheal intubation rates did not differ significantly between groups (3.4% vs 3.9%; absolute difference –0.5%; 95% CI, –4.8% to 3.7%; P = .81). The high-intensity group had greater reductions in PaCO₂ levels over 72 hours (mean PaCO₂ at 72 hours: 53 mm Hg vs 64 mm Hg; P < .001) and higher rates of achieving normocapnia (21.8% vs 4.6%; P < .001). Abdominal distension occurred more frequently in the high-intensity group (37.4% vs 25.5%; absolute difference 11.9%; 95% CI, 1.5%–22.4%; P = .03), but other adverse events and serious adverse events were similar between groups.
Conclusions: High-intensity NPPV reduced the proportion of patients meeting criteria for endotracheal intubation compared to low-intensity NPPV in patients with acute COPD exacerbations and persistent hypercapnia. However, actual intubation rates did not differ, possibly due to crossover from low- to high-intensity NPPV in patients meeting intubation criteria.
Implications for Practice: High-intensity NPPV may be considered for patients with acute COPD exacerbations who remain hypercapnic after initial low-intensity NPPV, as it may reduce progression to severe respiratory failure requiring intubation criteria. Clinicians should monitor for abdominal distension and potential alkalosis, although these did not significantly affect overall tolerance or safety.
Study Strengths and Limitations: Strengths include the multicenter randomized design, clear enrollment criteria, and standardized protocols. Limitations include early trial termination, unblinded interventions, potential bias due to allowed crossover, and lack of power to detect differences in mortality or actual intubation rates.
Future Research: Further large-scale trials are needed to confirm these findings, assess the impact on actual intubation rates and mortality, and explore the efficacy of high-intensity NPPV in different clinical settings and patient populations, including those without prior NPPV exposure or with more severe respiratory distress.
RCT: Tenecteplase Noninferior to Alteplase in Acute Ischemic Stroke
14 Sep, 2024 | 20:03h | UTCBackground: Acute ischemic stroke (AIS) is a leading cause of morbidity and mortality globally, with a particularly high burden in China. Intravenous thrombolysis with alteplase, administered within 4.5 hours of symptom onset, is the current standard of care. Tenecteplase, a genetically modified variant of alteplase with greater fibrin specificity and a longer half-life, allows for single-bolus administration, potentially simplifying and expediting treatment. Prior studies suggest tenecteplase may be as effective as alteplase in AIS, but data specific to Chinese patients are limited.
Objective: To determine whether tenecteplase is noninferior to alteplase in achieving excellent functional outcomes in Chinese patients with AIS treated within 4.5 hours of symptom onset.
Methods:
- Design: Multicenter, randomized, open-label, blinded-endpoint, noninferiority trial conducted at 55 centers in China between July 2021 and July 2023.
- Participants: 1,489 Chinese adults aged ≥18 years with AIS, National Institutes of Health Stroke Scale (NIHSS) scores of 1–25, measurable neurological deficits, and symptom onset within 4.5 hours.
- Interventions: Patients were randomized 1:1 to receive either:
- Tenecteplase: 0.25 mg/kg intravenous single bolus (maximum 25 mg).
- Alteplase: 0.9 mg/kg intravenous (maximum 90 mg), with 10% as an initial bolus and the remainder infused over 1 hour.
- Outcomes:
- Primary Outcome: Proportion of patients achieving a modified Rankin Scale (mRS) score of 0 or 1 at 90 days (indicating no symptoms or no significant disability).
- Secondary Outcomes: Major neurological improvement at 24 hours, mRS scores of 0–2 at 90 days, change in NIHSS score at 90 days, Barthel Index score ≥95 at 90 days.
- Safety Outcomes: Symptomatic intracerebral hemorrhage (sICH) per ECASS III definition and all-cause mortality at 90 days.
Results:
- Participants: 1,465 patients were included in the full analysis set (732 tenecteplase; 733 alteplase). Median age was 66 years, median NIHSS score was 6, and 30.4% were female.
- Primary Outcome:
- 72.7% in the tenecteplase group achieved mRS 0 or 1 at 90 days compared to 70.3% in the alteplase group.
- Adjusted risk ratio (RR): 1.03 (95% CI, 0.97–1.09), meeting the predefined noninferiority margin (RR ≥0.937).
- Secondary Outcomes:
- Major Neurological Improvement at 24 Hours: 48.0% (tenecteplase) vs. 45.0% (alteplase); RR, 1.07 (95% CI, 0.96–1.19).
- mRS 0–2 at 90 Days: 80.9% (tenecteplase) vs. 79.9% (alteplase); RR, 1.01 (95% CI, 0.96–1.06).
- Change in NIHSS Score at 90 Days: Mean change of –3.70 (tenecteplase) vs. –3.02 (alteplase); adjusted difference, –0.45 (95% CI, –1.40 to 0.50).
- Barthel Index ≥95 at 90 Days: 75.7% (tenecteplase) vs. 73.9% (alteplase); RR, 1.02 (95% CI, 0.96–1.08).
- Safety Outcomes:
- sICH: Occurred in 1.2% of patients in both groups; RR, 1.01 (95% CI, 0.37–2.70).
- 90-Day Mortality: 4.6% (tenecteplase) vs. 5.8% (alteplase); RR, 0.80 (95% CI, 0.51–1.23).
Conclusions: Tenecteplase was noninferior to alteplase in achieving excellent functional outcomes (mRS 0 or 1) at 90 days in Chinese patients with AIS treated within 4.5 hours of symptom onset. Safety profiles, including rates of sICH and mortality, were similar between the two treatments. These findings support tenecteplase as a suitable alternative to alteplase for intravenous thrombolysis in AIS.
Implications for Practice:
- Administration Advantage: Tenecteplase’s single-bolus administration could streamline treatment workflows and reduce door-to-needle times.
- Efficacy and Safety: Comparable efficacy and safety profiles suggest tenecteplase can be confidently used in place of alteplase.
- Patient Selection: Results are applicable to a broad range of AIS patients, including those with varying stroke severities and ages.
Study Strengths and Limitations:
- Strengths: Large sample size, multicenter design, and inclusion of a real-world patient population enhance the generalizability of findings.
- Limitations: Open-label design may introduce bias despite blinded endpoint assessments. The relatively low proportion of patients undergoing thrombectomy limits conclusions about combined therapy.
Future Research:
- Further studies could explore the effectiveness of tenecteplase in specific subgroups, such as patients with large vessel occlusions or those requiring endovascular interventions.
- Investigations into long-term outcomes beyond 90 days and real-world implementation strategies may provide additional insights.
RCT: Liraglutide for Children Aged 6 to <12 Years with Obesity
14 Sep, 2024 | 19:40h | UTCSummary:
A recent phase 3a randomized, double-blind, placebo-controlled trial published in the New England Journal of Medicine examined the efficacy and safety of liraglutide in children aged 6 to less than 12 years with obesity. Currently, no medications are approved for treating nonmonogenic, nonsyndromic obesity in this age group, making this study particularly noteworthy.
Methods:
- Participants: 82 children with obesity (BMI ≥95th percentile for age and sex).
- Design: Participants were randomized in a 2:1 ratio to receive once-daily subcutaneous liraglutide (up to 3.0 mg) or placebo, alongside lifestyle interventions, over a 56-week treatment period, followed by a 26-week follow-up.
- Primary Endpoint: Percentage change in BMI from baseline to week 56.
- Secondary Endpoints: Percentage change in body weight and the proportion achieving a ≥5% reduction in BMI.
Results:
- BMI Reduction: At week 56, the liraglutide group experienced a mean BMI reduction of –5.8%, compared to a +1.6% increase in the placebo group. The estimated difference was –7.4 percentage points (95% CI, –11.6 to –3.2; P<0.001).
- Body Weight: Mean body weight increased by 1.6% in the liraglutide group versus 10.0% in the placebo group, a difference of –8.4 percentage points (95% CI, –13.4 to –3.3; P=0.001).
- BMI Reduction ≥5%: Achieved by 46% of participants in the liraglutide group versus 9% in the placebo group (adjusted odds ratio, 6.3; 95% CI, 1.4 to 28.8; P=0.02).
- Adverse Events: Reported in 89% of the liraglutide group and 88% of the placebo group. Gastrointestinal events were more common with liraglutide (80% vs. 54%).
Discussion:
While the study suggests that liraglutide can lead to a statistically significant reduction in BMI among children aged 6 to less than 12 years with obesity, several considerations should temper our enthusiasm:
- Sample Size and Diversity: The trial included only 82 participants, with a predominantly White population (72%), which may limit the generalizability of the findings to broader, more diverse populations.
- Duration and Long-Term Effects: The study spanned 56 weeks, with a 26-week follow-up. The long-term efficacy and safety of liraglutide in this age group remain uncertain, particularly concerning growth, development, and potential rebound weight gain after discontinuation.
- Clinical Significance: Although the reduction in BMI was statistically significant, the clinical significance—especially regarding long-term health outcomes and obesity-related comorbidities—is less clear. Obesity is a chronic and relapsing condition, and a modest reduction in BMI may not translate into substantial health benefits without sustained intervention.
- Adverse Events: The high incidence of gastrointestinal adverse events raises questions about the tolerability of liraglutide in young children. Managing these side effects in a pediatric population can be challenging and may affect adherence.
- Lack of Consensus on BMI Reduction: There’s no international consensus on what constitutes a clinically meaningful BMI reduction in children, complicating the interpretation of the results.
Conclusion:
This trial provides preliminary evidence that liraglutide, combined with lifestyle interventions, may help reduce BMI in children under 12 with obesity. However, given the limitations—including small sample size, short duration, and safety concerns—it’s prudent to approach these findings with cautious optimism. More extensive studies with longer follow-up periods and more diverse populations are necessary to fully assess the long-term efficacy and safety of liraglutide in this vulnerable age group.
Takeaway:
While liraglutide shows promise as an adjunct therapy for pediatric obesity, it’s essential to weigh the benefits against the potential risks and uncertainties. Clinicians should continue to prioritize established lifestyle interventions and consider pharmacotherapy on a case-by-case basis, pending further evidence.
RCT: PCI Reduces Major Adverse Cardiac Events in Patients Undergoing TAVI with Significant Coronary Artery Disease
14 Sep, 2024 | 19:09h | UTCBackground:
Severe aortic stenosis and coronary artery disease (CAD) frequently coexist, particularly in the elderly population. Approximately 50% of patients undergoing transcatheter aortic valve implantation (TAVI) have concurrent CAD. The optimal management of significant coronary lesions in patients undergoing TAVI remains uncertain, with guidelines providing no clear recommendations. Understanding whether percutaneous coronary intervention (PCI) improves outcomes in this setting is crucial for guiding clinical practice.
Objective:
To evaluate whether routine PCI of physiologically significant coronary lesions improves clinical outcomes compared to conservative management in patients with stable CAD undergoing TAVI.
Methods:
- Design: International, multicenter, open-label, randomized controlled trial (NOTION-3).
- Participants: 455 patients with severe symptomatic aortic stenosis scheduled for TAVI and at least one significant coronary lesion (defined as fractional flow reserve [FFR] ≤0.80 or diameter stenosis ≥90%).
- Interventions:
- PCI Group (n=227): Underwent PCI of all eligible lesions followed by TAVI.
- Conservative Treatment Group (n=228): Received TAVI without prior PCI.
- Primary Endpoint: Major adverse cardiac events (MACE), a composite of death from any cause, myocardial infarction (MI), or urgent revascularization.
- Secondary Endpoints: Included individual components of the primary endpoint, bleeding events, stroke, hospital admissions for heart failure, and procedural complications.
- Follow-Up: Median of 2 years (interquartile range, 1 to 4 years).
Results:
- Baseline Characteristics: Median age was 82 years; 67% were men; median Society of Thoracic Surgeons–Procedural Risk of Mortality (STS-PROM) score was 3%.
- Primary Endpoint (MACE):
- Occurred in 26% of patients in the PCI group versus 36% in the conservative group.
- Hazard Ratio (HR): 0.71 (95% Confidence Interval [CI], 0.51 to 0.99; P=0.04), indicating a 29% relative risk reduction with PCI.
- Components of MACE:
- Myocardial Infarction:
- Lower incidence in the PCI group.
- Urgent Revascularization:
- Reduced need in the PCI group.
- Myocardial Infarction:
- All-Cause Mortality:
- No significant difference between groups.
- Bleeding Events:
- Higher in the PCI group (28% vs. 20%; HR, 1.51; 95% CI, 1.03 to 2.22).
- Bleeding assessed according to Valve Academic Research Consortium–2 criteria.
- Procedural Complications:
- PCI-related complications occurred in 3% of patients in the PCI group.
- Safety Endpoints:
- Similar rates of stroke and stent thrombosis between groups.
- Acute kidney injury was less frequent in the PCI group (5% vs. 11%; HR, 0.45; 95% CI, 0.23 to 0.89).
Conclusions:
In patients with stable CAD and severe symptomatic aortic stenosis undergoing TAVI, performing PCI on significant coronary lesions resulted in a statistically significant reduction in MACE over a median follow-up of 2 years compared to conservative management. The benefit was primarily due to reductions in myocardial infarction and urgent revascularization rates. However, this advantage was accompanied by an increased risk of bleeding events.
Clinical Implications:
- Patient Selection: PCI should be considered in patients with physiologically significant coronary lesions (FFR ≤0.80 or diameter stenosis ≥90%) undergoing TAVI.
- Risk–Benefit Analysis: Clinicians should balance the reduction in MACE against the increased bleeding risk when deciding on PCI.
- Treatment Strategy: The findings support a strategy of routine revascularization in this patient population to improve cardiovascular outcomes.
- Future Considerations: Further research is needed to determine the optimal timing of PCI relative to TAVI and to identify which patient subgroups may derive the most benefit.
Recommendations:
- Guideline Update: The results may inform future guidelines to provide clearer recommendations on managing CAD in patients undergoing TAVI.
- Individualized Care: Decisions regarding PCI should be individualized, considering patient comorbidities, anatomical complexity, and bleeding risk.
- Antithrombotic Therapy: Attention to antiplatelet and anticoagulation strategies is important to mitigate bleeding risks.
Study Limitations:
- Exclusion of patients with recent acute coronary syndromes and left main coronary artery disease limits the generalizability.
- Changes in antithrombotic regimens over the study period reflect evolving clinical practice but may affect outcomes.
- Majority of patients had low to intermediate SYNTAX scores, so results may not apply to those with more complex CAD.
Final Note:
The NOTION-3 trial provides valuable evidence supporting the use of PCI in patients with significant CAD undergoing TAVI, emphasizing the importance of comprehensive cardiovascular care in this high-risk population.
RCT: Comparing Perioperative Chemotherapy Alone to Perioperative Chemotherapy Plus Preoperative Chemoradiotherapy in Resectable Gastric Cancer
14 Sep, 2024 | 18:23h | UTCBackground:
In the management of resectable gastric cancer, perioperative chemotherapy—chemotherapy administered both before (neoadjuvant) and after (adjuvant) surgery—is the standard of care in many Western countries. This approach is based on trials like MAGIC and FLOT4-AIO, which demonstrated improved survival with perioperative chemotherapy compared to surgery alone.
Preoperative chemoradiotherapy (the combination of chemotherapy and radiotherapy before surgery) has shown benefits in other gastrointestinal cancers, such as esophageal cancer, by downstaging tumors and potentially improving surgical outcomes. However, its efficacy in gastric cancer, especially when added to perioperative chemotherapy, has not been well-established.
Objective:
To determine whether adding preoperative chemoradiotherapy to standard perioperative chemotherapy improves overall survival compared to perioperative chemotherapy alone in patients with resectable gastric and gastroesophageal junction adenocarcinoma.
Methods:
- Study Design: International, phase 3, randomized controlled trial (TOPGEAR).
- Participants: 574 patients with resectable adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II or III), clinical stage T3 or T4, and considered suitable for curative surgery.
- Interventions:
1. Perioperative Chemotherapy Group (Control Group):
- Definition of Perioperative Chemotherapy: Chemotherapy administered both before (preoperative/neoadjuvant) and after (postoperative/adjuvant) surgery.
- Chemotherapy Regimens:
- Before 2017: Patients received three cycles before surgery and three cycles after surgery of either:
- ECF: Epirubicin, Cisplatin, and continuous-infusion Fluorouracil.
- ECX: Epirubicin, Cisplatin, and Capecitabine (an oral prodrug of fluorouracil).
- After 2017 Amendment: Patients received four cycles before surgery and four cycles after surgery of:
- FLOT: Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel.
- Before 2017: Patients received three cycles before surgery and three cycles after surgery of either:
2. Perioperative Chemotherapy Plus Preoperative Chemoradiotherapy Group (Experimental Group):
- Modifications to Chemotherapy:
- Received one less cycle of preoperative chemotherapy compared to the control group to accommodate the addition of radiotherapy.
- Postoperative chemotherapy was the same as in the control group.
- Preoperative Chemoradiotherapy:
- Chemoradiotherapy Definition: Concurrent administration of chemotherapy and radiotherapy before surgery.
- Radiotherapy Regimen:
- Total dose of 45 Gy, delivered in 25 fractions over 5 weeks (1.8 Gy per fraction, 5 days per week).
- Target Area: Entire stomach, any perigastric tumor extension, and regional lymph nodes.
- Concurrent Chemotherapy During Radiotherapy:
- Continuous infusion of Fluorouracil (200 mg/m² per day) 7 days a week during radiotherapy.
- Alternatively, Capecitabine (825 mg/m² twice daily on days 1–5 of each radiotherapy week) could be used.
- Surgical Procedure:
- Surgery was performed 4–6 weeks after completion of preoperative therapy.
- Recommended surgery included total gastrectomy, subtotal distal gastrectomy, or esophagogastrectomy with D2 lymphadenectomy (removal of additional lymph node stations beyond the immediate perigastric nodes).
Endpoints:
- Primary Endpoint: Overall survival (time from randomization to death from any cause).
- Secondary Endpoints: Progression-free survival, pathological complete response rate (no residual tumor in the resected specimen), treatment-related toxic effects, and quality of life.
Results:
- Pathological Findings:
- Pathological Complete Response Rate:
- Higher in the experimental group (preoperative chemoradiotherapy) at 17% compared to 8% in the control group.
- Tumor Downstaging:
- More patients in the experimental group had their tumors downstaged to a lower T category and had fewer involved lymph nodes.
- Pathological Complete Response Rate:
- Survival Outcomes:
- Overall Survival:
- Median Overall Survival:
- Experimental Group: 46 months.
- Control Group: 49 months.
- Hazard Ratio for Death: 1.05 (95% CI, 0.83–1.31), indicating no significant difference between the groups.
- Median Overall Survival:
- Progression-Free Survival:
- Median progression-free survival was similar between the groups (31 months vs. 32 months).
- Overall Survival:
- Treatment Adherence:
- Preoperative Therapy Completion:
- High completion rates in both groups for preoperative chemotherapy.
- Slightly lower in the experimental group due to the addition of radiotherapy.
- Postoperative Chemotherapy Completion:
- Lower completion rates overall, with fewer patients in the experimental group completing postoperative chemotherapy (48% vs. 59%).
- Preoperative Therapy Completion:
- Adverse Events:
- Similar rates of grade 3 or higher toxic effects in both groups.
- No significant differences in surgical complications or postoperative mortality.
Conclusion:
Adding preoperative chemoradiotherapy to standard perioperative chemotherapy did not improve overall survival or progression-free survival in patients with resectable gastric and gastroesophageal junction adenocarcinoma, despite achieving higher pathological complete response rates and increased tumor downstaging. These findings suggest that the routine addition of preoperative chemoradiotherapy to perioperative chemotherapy does not confer additional survival benefits and should not change the current standard of care.
Clinical Implications:
- Standard Treatment Remains Perioperative Chemotherapy:
- Perioperative chemotherapy alone continues to be the standard approach for resectable gastric cancer.
- Regimens like FLOT are preferred due to their demonstrated efficacy.
- Role of Radiotherapy:
- Routine use of preoperative radiotherapy in addition to chemotherapy is not supported by this trial’s findings.
- Radiotherapy may still have a role in specific clinical scenarios, but not as a standard addition to perioperative chemotherapy.
- Future Directions:
- Further research may focus on identifying subgroups of patients who might benefit from chemoradiotherapy.
- Biomarker-driven approaches and personalized treatment strategies could optimize outcomes.
Polled Analysis: Semaglutide Reduces Heart Failure Events in Obese Patients with HFpEF
12 Sep, 2024 | 13:39h | UTCStudy Design and Population: This post-hoc pooled analysis combined data from four randomized, placebo-controlled trials (SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM) involving 3,743 participants with heart failure and preserved or mildly reduced ejection fraction (HFpEF). The participants had various comorbidities including obesity, diabetes, and atherosclerotic cardiovascular disease. They were randomized to receive either semaglutide or placebo.
Main Findings: Semaglutide significantly reduced the risk of the composite endpoint of cardiovascular death or worsening heart failure events compared to placebo (HR 0.69, 95% CI 0.53–0.89, p=0.0045). It also reduced worsening heart failure events alone (HR 0.59, 95% CI 0.41–0.82, p=0.0019). However, no significant reduction in cardiovascular death alone was observed (HR 0.82, 95% CI 0.57–1.16, p=0.25). Semaglutide was generally well tolerated, with fewer serious adverse events compared to placebo.
Implications for Practice: These findings suggest semaglutide may be an effective therapy to reduce heart failure-related events in obese patients with HFpEF. Although semaglutide did not reduce cardiovascular death, its ability to lower the risk of heart failure hospitalizations makes it a potential therapeutic option for managing HFpEF in this population, a condition with limited treatment choices.
RCT: 24-Hour Oxygen Therapy Does Not Reduce Hospitalization or Mortality Compared to 15-Hour Therapy in Severe Hypoxemia
12 Sep, 2024 | 13:21h | UTCStudy Design and Population: This multicenter, registry-based randomized controlled trial compared the effects of 24-hour versus 15-hour daily oxygen therapy in 241 patients with chronic, severe hypoxemia. Patients, recruited between 2018 and 2022, were assigned to either 24 hours (117 patients) or 15 hours (124 patients) of oxygen therapy daily. The study’s primary outcome was the composite of hospitalization or death from any cause within 1 year.
Main Findings: After 12 months, the results showed no significant difference between the two groups in the primary outcome. The event rates for hospitalization or death were similar in the 24-hour and 15-hour groups (124.7 vs. 124.5 events per 100 person-years, hazard ratio 0.99, 95% CI, 0.72-1.36). Secondary outcomes, including individual rates of hospitalization and mortality, also showed no meaningful differences, and adverse event rates were comparable between groups.
Implications for Practice: These findings suggest that increasing oxygen therapy from 15 to 24 hours per day does not reduce hospitalization or mortality in patients with severe hypoxemia. Therefore, the less burdensome 15-hour regimen may be preferable in clinical practice, as it is equally effective while reducing patient burden.
RCT: Once-Weekly Insulin Efsitora Non-Inferior to Insulin Degludec for HbA1c Control but Increases Hypoglycemia in Adults with Type 1 Diabetes
12 Sep, 2024 | 13:06h | UTCStudy Design and Population: This 52-week, randomized, open-label non-inferiority trial included 692 adults with type 1 diabetes from 82 global sites. Participants were randomly assigned to receive once-weekly insulin efsitora (n=343) or once-daily insulin degludec (n=349), both in combination with insulin lispro. The primary objective was to assess the change in HbA1c from baseline to week 26, with a non-inferiority margin of 0.4%.
Main Findings: HbA1c reduction was similar between the groups at 26 weeks (–0.51% for efsitora vs. –0.56% for degludec; p=0.43). However, participants on efsitora experienced higher rates of level 2 or 3 hypoglycemia (14.03 vs. 11.59 events per patient year, p=0.016) and a greater incidence of severe hypoglycemia (10% for efsitora vs. 3% for degludec). Overall, the safety profile was similar, with no treatment-related deaths.
Implications for Practice: Once-weekly insulin efsitora offers comparable glycemic control to daily degludec, but its association with increased hypoglycemia, especially during dose titration, indicates that closer monitoring and optimization are necessary. This treatment could reduce the burden of daily injections, but its hypoglycemia risks must be managed carefully.
RCT: Transcatheter Repair Noninferior to Mitral-Valve Surgery for Secondary Mitral Regurgitation
12 Sep, 2024 | 12:13h | UTCStudy Design and Population: This noninferiority trial, conducted in Germany, enrolled 210 patients with heart failure and secondary mitral regurgitation who remained symptomatic despite medical therapy. Patients were randomized to undergo either transcatheter edge-to-edge repair or mitral-valve surgery, with outcomes assessed over a one-year period.
Main Findings: Transcatheter repair was found to be noninferior to mitral-valve surgery regarding the primary efficacy outcome—a composite of death, heart failure hospitalization, mitral-valve reintervention, assist device implantation, or stroke at one year (16.7% in the transcatheter group vs. 22.5% in the surgery group; mean difference, -6%; 95% CI, -17 to 6; P<0.001 for noninferiority). The transcatheter group experienced fewer major adverse events within 30 days (14.9% vs. 54.8%; mean difference, -40%; 95% CI, -51 to -27; P<0.001).
Implications for Practice: Transcatheter edge-to-edge repair offers a similar efficacy to mitral-valve surgery at one year with a lower rate of short-term adverse events, suggesting it may be a suitable alternative, particularly for patients with higher surgical risk.
RCT: Olanzapine Improves Nausea and Vomiting Control in Moderately Emetogenic Chemotherapy but Increases Somnolence
7 Sep, 2024 | 19:28h | UTCStudy Design and Population: This phase 3, multicenter, open-label randomized clinical trial involved 560 chemotherapy-naive patients aged 18 years or older with solid malignant tumors. The trial, conducted at three institutes in India, compared the efficacy of adding olanzapine to standard antiemetic therapy in patients receiving moderately emetogenic chemotherapy (MEC) based on oxaliplatin, carboplatin, or irinotecan.
Main Findings: The group receiving olanzapine in addition to standard antiemetic therapy showed significantly higher complete response (CR) rates (91% vs 82%, P = .005) compared to the observation group. The olanzapine group also demonstrated superior control of nausea (96% vs 87%, P < .001) and chemotherapy-induced nausea and vomiting (CINV) (96% vs 91%, P = .02). The use of rescue medications was significantly lower in the olanzapine group. Grade 1 somnolence occurred in 10% of patients receiving olanzapine but was absent in the observation group.
Implications for Practice: The results support the inclusion of olanzapine in antiemetic regimens for MEC to improve CINV outcomes. However, mild somnolence should be considered when prescribing olanzapine as part of antiemetic prophylaxis. Further research could explore dose optimization to minimize adverse effects.
Reference: Ostwal, V. et al. (2024). Olanzapine as antiemetic prophylaxis in moderately emetogenic chemotherapy: a phase 3 randomized clinical trial. JAMA Network Open. DOI: http://doi.org/10.1001/jamanetworkopen.2024.26076
Link: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2822027
RCT: Pulmonary Vein Isolation Reduces Atrial Fibrillation Burden and Improves Quality of Life vs. Sham Procedure
7 Sep, 2024 | 17:24h | UTCStudy Design and Population: This double-blind, randomized clinical trial (SHAM-PVI) compared pulmonary vein isolation (PVI) via cryoablation to a sham procedure in 126 patients with symptomatic paroxysmal or persistent atrial fibrillation (AF). The study, conducted in two UK tertiary centers, enrolled patients between January 2020 and March 2024. Major exclusions included long-standing persistent AF, prior left atrial ablation, and ejection fraction below 35%. Patients were monitored using implantable loop recorders.
Main Findings: At 6 months, the PVI group demonstrated a significant reduction in AF burden (60.31%) compared to the sham group (35.0%), with a geometric mean difference of 0.25 (95% CI, 0.15-0.42; P < .001). Quality-of-life scores also improved more in the PVI group, with an 18.39-point difference (95% CI, 11.48-25.30). Symptom improvement was also marked, with a reduction in the Mayo AF-Specific Symptom Inventory frequency score of −6.36 points (95% CI, −8.46 to −4.26).
Implications for Practice: PVI significantly reduces AF burden and improves both symptoms and quality of life in patients with symptomatic AF, compared to a sham procedure. These findings support the efficacy of PVI beyond a placebo effect, making it a compelling option for managing AF in patients not responsive to antiarrhythmic drugs.
Reference: Dulai, R., Sulke, N., Freemantle, N., Lambiase, P. D., Farwell, D., Srinivasan, N. T., et al. (2024). Pulmonary vein isolation vs sham intervention in symptomatic atrial fibrillation: The SHAM-PVI randomized clinical trial. JAMA. http://doi.org/10.1001/jama.2024.17921
Link: https://jamanetwork.com/journals/jama/fullarticle/2823283
RCT: Optical Coherence Tomography (OCT)-Guided PCI Lowers Adverse Cardiac Events Compared to Angiography in Complex Lesions
7 Sep, 2024 | 17:08h | UTCStudy Design and Population: This multicenter, randomized, open-label superiority trial (OCCUPI) compared optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) with angiography-guided PCI in patients with complex coronary lesions. The trial was conducted across 20 hospitals in South Korea, enrolling 1,604 patients aged 19–85 years requiring drug-eluting stents. Participants were randomized into OCT-guided PCI (n=803) or angiography-guided PCI (n=801), with outcomes assessed over 1 year.
Main Findings: At 1 year, major adverse cardiac events (MACE), including cardiac death, myocardial infarction, stent thrombosis, and ischemia-driven target-vessel revascularization, occurred in 5% of patients in the OCT-guided group compared to 7% in the angiography-guided group. The reduction in events was mainly driven by lower rates of spontaneous myocardial infarction and target-vessel revascularization in the OCT group. Secondary outcomes, such as stroke or contrast-induced nephropathy, showed no significant differences between groups.
Implications for Practice: OCT-guided PCI was associated with a lower incidence of MACE in patients with complex coronary lesions. These findings suggest that OCT guidance may provide additional benefit in stent optimization compared to angiography alone.
Reference: Hong SJ et al. (2024). Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention for patients with complex lesions (OCCUPI): an investigator-initiated, multicentre, randomised, open-label, superiority trial in South Korea. The Lancet. DOI: https://doi.org/10.1016/S0140-6736(24)01454-5
link: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01454-5/fulltext
Meta-Analysis: Ticagrelor Monotherapy Reduces Bleeding Without Increasing Ischemic Risk in Coronary Stent Patients
7 Sep, 2024 | 15:06h | UTCStudy Design and Population: This systematic review and individual patient-level meta-analysis pooled data from six randomized trials, comparing ticagrelor monotherapy after short-term dual antiplatelet therapy (DAPT) with standard 12-month DAPT in patients who underwent percutaneous coronary intervention with drug-eluting stents. The analysis included 23,256 patients in the per-protocol population and 24,407 in the intention-to-treat population, excluding those requiring long-term anticoagulants.
Main Findings: Ticagrelor monotherapy was found to be noninferior to 12-month DAPT for major adverse cardiovascular or cerebrovascular events (MACCE), with a hazard ratio (HR) of 0.91 (95% CI 0.78-1.07). It also reduced the risk of major bleeding (HR 0.43, p<0.0001) and all-cause mortality (HR 0.76, p=0.034). Subgroup analyses suggested possible benefits in women for mortality and in patients with acute coronary syndrome (ACS) for bleeding reduction.
Implications for Practice: Ticagrelor monotherapy may offer a safer alternative to prolonged DAPT by reducing bleeding risks without increasing ischemic events, particularly in ACS patients. Further research is needed to fully explore potential survival benefits, especially in women.
Reference: Valgimigli M, Hong S-J, Gragnano F, et al. (2024). De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: a systematic review and individual patient-level meta-analysis of randomised trials. Lancet. http://doi.org/10.1016/S0140-6736(24)01616-7
Link: https://www.sciencedirect.com/science/article/pii/S0140673624016167
RCT: Invasive Strategy Does Not Significantly Improve Cardiovascular Outcomes Over Conservative Management in Older Adults with NSTEMI
7 Sep, 2024 | 13:25h | UTCStudy Design and Population: This was a prospective, multicenter, randomized trial conducted across 48 sites in the UK, enrolling 1,518 patients aged 75 years or older with non-ST-segment elevation myocardial infarction (NSTEMI). Patients were randomly assigned to receive either the best available medical therapy alone (conservative strategy) or in combination with invasive treatment (coronary angiography and revascularization). The population included individuals who were frail or had high comorbidities, with a mean age of 82 years.
Main Findings: Over a median follow-up of 4.1 years, the primary outcome (a composite of cardiovascular death or nonfatal myocardial infarction) occurred in 25.6% of the invasive-strategy group and 26.3% of the conservative-strategy group (HR, 0.94; 95% CI, 0.77–1.14; P=0.53), showing no significant difference. Cardiovascular death rates were similar between the two groups, but nonfatal myocardial infarction was lower in the invasive group (11.7% vs. 15.0%; HR, 0.75; 95% CI, 0.57–0.99). Procedural complications were rare, affecting less than 1% of patients.
Implications for Practice: This trial suggests that in older adults with NSTEMI, an invasive strategy does not significantly reduce the risk of cardiovascular death or nonfatal myocardial infarction compared to a conservative approach. The findings support the consideration of conservative management in frail elderly patients or those with significant comorbidities, given the minimal additional benefit of invasive treatment.
Reference: Kunadian, V., Mossop, H., Shields, C., Bardgett, M., Watts, P., Teare, M. D., Pritchard, J., et al. (2024). Invasive treatment strategy for older patients with myocardial infarction. New England Journal of Medicine. http://doi.org/10.1056/NEJMoa2407791
Link: https://www.nejm.org/doi/10.1056/NEJMoa2407791
RCT: Edoxaban Monotherapy Reduces Bleeding Events in Atrial Fibrillation with Stable CAD Compared to Dual Therapy
7 Sep, 2024 | 13:03h | UTCStudy Design and Population: This multicenter, open-label, adjudicator-masked randomized trial enrolled 1,040 patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) across 18 sites in South Korea. Patients were randomly assigned to receive either edoxaban monotherapy (n=524) or dual antithrombotic therapy (edoxaban plus a single antiplatelet agent; n=516). The mean age was 72.1 years, with a mean CHA2DS2-VASc score of 4.3, reflecting a moderate to high stroke risk.
Main Findings: At 12 months, the primary composite outcome occurred in fewer patients in the edoxaban monotherapy group (6.8%) than in the dual therapy group (16.2%) (HR, 0.44; 95% CI, 0.30–0.65; P<0.001). The reduction was largely driven by a significantly lower incidence of major bleeding or clinically relevant non-major bleeding (4.7% vs. 14.2%; HR, 0.34; 95% CI, 0.22–0.53). In contrast, the incidence of major ischemic events was similar between the two groups.
Implications for Practice: Edoxaban monotherapy provides a safer antithrombotic option for patients with AF and stable CAD by significantly reducing bleeding without increasing ischemic events compared to dual therapy. These findings suggest that monotherapy could be a preferable long-term treatment strategy in this population.
RCT: Interruption of Oral Anticoagulation during TAVI Reduces Bleeding Without Increasing Thromboembolic Events
7 Sep, 2024 | 12:43h | UTCStudy Design and Population: This international, open-label, randomized noninferiority trial examined 858 patients undergoing transcatheter aortic-valve implantation (TAVI) who had an indication for oral anticoagulation due to concomitant diseases. Patients were randomized 1:1 to either continue or interrupt their oral anticoagulation during the procedure, with the primary outcome being a composite of cardiovascular death, stroke, myocardial infarction, major vascular complications, or major bleeding within 30 days.
Main Findings: Primary outcome events occurred in 16.5% of the continuation group and 14.8% of the interruption group, showing a non-significant risk difference of 1.7 percentage points (95% CI, -3.1 to 6.6). Thromboembolic events were similar between groups (8.8% in continuation vs. 8.2% in interruption). However, bleeding events were significantly higher in the continuation group (31.1% vs. 21.3%; risk difference, 9.8 percentage points; 95% CI, 3.9 to 15.6).
Implications for Practice: Interrupting oral anticoagulation during TAVI significantly reduces bleeding without increasing thromboembolic risks, suggesting it may be a safer strategy for patients undergoing TAVI. These findings could influence clinical decision-making regarding anticoagulation management in this population.
Reference: van Ginkel, D.J. et al. (2024). Continuation versus Interruption of Oral Anticoagulation during TAVI. The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2407794
RCT: Continuing Aspirin vs. Antiplatelet Cessation Before Surgery Did Not Reduce Ischemic Events in Patients With Coronary Stents Over 1 Year Post-Implantation
7 Sep, 2024 | 12:29h | UTCStudy Design and Population: This randomized controlled trial (ASSURE-DES) investigated the perioperative management of antiplatelet therapy in 926 patients with coronary drug-eluting stents (DES) undergoing low-to-intermediate-risk noncardiac surgery. The patients, at least one year post-stent implantation, were randomized to continue aspirin monotherapy or stop all antiplatelet therapy five days prior to surgery.
Main Findings: The study found no significant difference in the primary composite outcome (death, myocardial infarction, stent thrombosis, or stroke) between the aspirin monotherapy group (0.6%) and the no antiplatelet group (0.9%). However, minor bleeding was more frequent in the aspirin group (14.9% vs 10.1%, P=0.027), with no difference in major bleeding.
Implications for Practice: These results suggest that for stable patients with DES undergoing noncardiac surgery, temporarily discontinuing aspirin may be a safe option, as continuing aspirin did not reduce ischemic events but did increase minor bleeding risk. Further research is needed to assess outcomes in higher-risk surgical settings.
News Release: SCOFF Trial Confirms Fasting Not Necessary Before Cardiac Catheterisation Procedures
7 Sep, 2024 | 10:10h | UTC1 September 2024 – London, United Kingdom – New findings from the SCOFF trial, presented at ESC Congress 2024, suggest that fasting prior to minimally invasive cardiac catheterisation procedures under conscious sedation does not increase the risk of complications. The trial supports reconsidering current guidelines on pre-procedural fasting.
Key Points for Physicians:
– No increased complications: The SCOFF trial found no significant difference in adverse outcomes, such as aspiration pneumonia or hypoglycemia, between patients who fasted and those who ate normally before cardiac catheterisation.
– Improved patient satisfaction: Patients who did not fast reported higher satisfaction, with fewer complaints of discomfort and hunger.
– Potential guideline change: These findings, in line with previous studies like CHOW-NOW and TONIC, challenge the necessity of fasting before such procedures.
The trial’s lead investigator, Dr. David Ferreira (John Hunter Hospital, Australia), emphasized that avoiding fasting may improve patient experience without increasing risks, making it time to reconsider fasting guidelines for these procedures.
Study Overview:
– Trial design: Prospective, randomized, open-label, with blinded endpoint assessment.
– Participants: 716 patients undergoing coronary angiography, coronary intervention, or cardiac implantable electronic device procedures.
– Primary endpoint: Composite of hypotension, aspiration pneumonia, hyperglycemia, and hypoglycemia, showing a lower event rate in the non-fasting group (12.0%) compared to the fasting group (19.1%).
These results are likely to influence future clinical practice, providing greater flexibility for both patients and healthcare systems.
RCT: More Extensive Lymph Node Removal Does Not Improve Outcomes in Right-Sided Colon Cancer Surgery
7 Sep, 2024 | 09:56h | UTCStudy Design and Population: This multicenter, open-label, randomized controlled trial (RELARC) evaluated the efficacy of complete mesocolic excision (CME) versus D2 lymphadenectomy for right-sided colon cancer. Conducted across 17 hospitals in China, the study enrolled 1,072 patients with stage T2-T4aNanyM0 or TanyN+M0 disease. Participants were randomized (1:1) to undergo either CME or D2 dissection, and the primary outcome was 3-year disease-free survival (DFS), with 3-year overall survival (OS) as the main secondary outcome.
Main Findings: Among 995 analyzed patients, no significant differences were observed between CME and D2 groups in 3-year DFS (86.1% vs. 81.9%, HR 0.74, P = 0.06) or 3-year OS (94.7% vs. 92.6%, HR 0.70, P = 0.17). While CME trended toward better DFS, the results were not statistically significant.
Implications for Practice: Given the lack of significant survival benefit, the trial supports D2 dissection as the standard surgical approach for right-sided colon cancer. CME may be reserved for cases with evident mesocolic lymph node involvement.
RCT: Zasocitinib Achieves Significant Psoriasis Improvement in Moderate to Severe Plaque Psoriasis
6 Sep, 2024 | 22:48h | UTCStudy Design and Population: This phase 2b, double-blind, placebo-controlled trial evaluated the efficacy, safety, and tolerability of zasocitinib, a selective tyrosine kinase 2 (TYK2) inhibitor, in patients with moderate to severe plaque psoriasis. Conducted across 55 centers in the US and Canada, the study enrolled 287 patients aged 18 to 70 years with a Psoriasis Area and Severity Index (PASI) score ≥12, and ≥10% of body surface area affected. Patients were randomized to receive zasocitinib at doses of 2 mg, 5 mg, 15 mg, or 30 mg, or a placebo, over 12 weeks.
Main Findings: At week 12, significant improvements in PASI were observed across all doses of zasocitinib. The primary endpoint of PASI 75 was achieved in 18%, 44%, 68%, and 67% of patients in the 2 mg, 5 mg, 15 mg, and 30 mg zasocitinib groups, respectively, compared to 6% in the placebo group. Higher PASI 90 and PASI 100 responses were also observed, particularly in the 15 mg and 30 mg groups. Adverse events were mild to moderate and occurred in 53% to 62% of patients receiving zasocitinib, compared to 44% for placebo.
Implications for Practice: Zasocitinib shows promise as an effective and well-tolerated oral treatment for moderate to severe plaque psoriasis. Its efficacy in achieving skin clearance (PASI 75 and above) at higher doses suggests potential for broader clinical use, with phase 3 trials warranted for further validation.
RCT: Azithromycin Increases Asthma Remission Rates in Adults With Persistent Uncontrolled Asthma
6 Sep, 2024 | 22:35h | UTCStudy Design and Population: This secondary analysis stems from the Asthma and Macrolides: Azithromycin Efficacy and Safety (AMAZES) trial, a randomized, double-anonymized, placebo-controlled trial. The study involved 335 adults with persistent uncontrolled asthma, who were treated with either azithromycin (500 mg, 3 times weekly) or placebo for 12 months. The goal was to evaluate azithromycin’s impact on asthma remission, defined through clinical and lung function measures.
Main Findings: Azithromycin significantly increased the rate of clinical remission compared to placebo (50.6% vs. 38.9%; P = .032). Clinical remission combined with lung function criteria was also higher in the azithromycin group (50.8% vs. 37.1%; P = .029). Although the complete remission rate (including sputum eosinophil count <3%) trended higher, it did not reach statistical significance (23% vs. 13.7%; P = .058).
Implications for Practice: This secondary analysis suggests that azithromycin, when added to standard asthma therapy, could significantly increase remission rates in adults with persistent uncontrolled asthma, including both eosinophilic and noneosinophilic subtypes.
RCT: AF Screening Does Not Reduce Stroke Hospitalizations in Elderly Patients
6 Sep, 2024 | 22:18h | UTCStudy Design and Population: The GUARD-AF trial was a prospective, randomized controlled trial conducted across 149 primary care sites in the U.S. It enrolled 11,905 participants aged 70 and older, with a median age of 75 years, 56.6% of whom were female. Participants were randomized 1:1 to either screening for atrial fibrillation (AF) using a 14-day continuous electrocardiographic patch monitor or usual care. The primary outcome was all-cause stroke hospitalization, with bleeding as a key safety outcome.
Main Findings: After a median follow-up of 15.3 months, AF diagnosis was higher in the screening group (5%) compared to the usual care group (3.3%), and anticoagulation initiation was also more frequent (4.2% vs. 2.8%). However, the risk of stroke hospitalization was not significantly different between the screening and usual care groups (0.7% vs. 0.6%; HR: 1.10, 95% CI: 0.69-1.75). Similarly, there was no significant difference in bleeding risk (1.0% vs. 1.1%; HR: 0.87, 95% CI: 0.60-1.26).
Implications for Practice: The findings suggest that screening for AF using continuous electrocardiographic monitoring in elderly patients does not reduce stroke hospitalizations despite an increased detection of AF. Given the low event rates and premature termination of enrollment due to COVID-19, further studies are needed to confirm these results and explore alternative strategies for stroke prevention in this population.
RCT: Finerenone Reduces Worsening Heart Failure Events in Patients with Mildly Reduced or Preserved Ejection Fraction
6 Sep, 2024 | 22:03h | UTCStudy Design and Population: This international, double-blind, randomized clinical trial included 6,001 patients with heart failure and a left ventricular ejection fraction of 40% or greater. Patients were randomly assigned to receive either finerenone (20 mg or 40 mg daily) or placebo in addition to standard therapy, with a median follow-up period of 32 months.
Main Findings: The finerenone group experienced a 16% reduction in the composite primary outcome of worsening heart failure events and death from cardiovascular causes compared to placebo (rate ratio, 0.84; 95% CI, 0.74 to 0.95; P=0.007). Specifically, total worsening heart failure events were lower in the finerenone group (rate ratio, 0.82; 95% CI, 0.71 to 0.94; P=0.006), but cardiovascular mortality did not significantly differ between the groups (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Finerenone was linked to an increased risk of hyperkalemia.
Implications for Practice: Finerenone reduces worsening heart failure events in patients with mildly reduced or preserved ejection fraction, making it a viable addition to standard heart failure therapy. However, clinicians should monitor for hyperkalemia, a known side effect, and the lack of significant mortality benefit highlights the need for further investigation into long-term cardiovascular outcomes.
RCT: Vutrisiran Reduces Mortality and Cardiovascular Events in Patients with Transthyretin Amyloidosis Cardiomyopathy
6 Sep, 2024 | 21:57h | UTCStudy Design and Population: This double-blind, randomized clinical trial evaluated the efficacy of vutrisiran in 655 patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Participants were randomly assigned to receive either vutrisiran (25 mg) or placebo every 12 weeks for up to 36 months. The study population included patients both with and without baseline tafamidis treatment.
Main Findings: Vutrisiran treatment significantly reduced the risk of death from any cause and recurrent cardiovascular events compared to placebo (HR: 0.72, 95% CI: 0.56–0.93, p=0.01). In monotherapy patients (no tafamidis), the hazard ratio was 0.67 (95% CI: 0.49–0.93, p=0.02). Vutrisiran also preserved physical function, showing less decline in the 6-minute walk test distance (mean difference: 26.5 meters, p<0.001) and quality of life (mean KCCQ-OS difference: 5.8 points, p<0.001). Adverse events were comparable between groups.
Implications for Practice: Vutrisiran offers a promising treatment option for reducing mortality, cardiovascular events, and functional decline in ATTR-CM patients. Its favorable safety profile supports its potential use in long-term management.
RCT: No Difference in Postoperative Complications Between Continuation and Discontinuation of Renin-Angiotensin System Inhibitors Before Major Surgery – JAMA
31 Aug, 2024 | 19:12h | UTCStudy Design and Population: This multicenter randomized clinical trial included 2,222 patients who had been treated with renin-angiotensin system inhibitors (RASIs) for at least 3 months and were scheduled for major noncardiac surgery at 40 hospitals in France between January 2018 and April 2023. The participants were randomly assigned to either continue RASIs until the day of surgery or to discontinue them 48 hours before surgery.
Main Findings: The trial found no significant difference in the primary outcome—a composite of all-cause mortality and major postoperative complications within 28 days—between the continuation and discontinuation groups (22% in both groups, RR 1.02, 95% CI 0.87-1.19). However, the continuation group experienced a higher incidence of intraoperative hypotension (54% vs. 41%, RR 1.31, 95% CI 1.19-1.44).
Implications for Practice: Continuation of RASIs before major noncardiac surgery does not increase the risk of postoperative mortality or major complications, but it does elevate the risk of intraoperative hypotension. Clinicians should weigh these risks when deciding whether to continue or discontinue RASIs before surgery.