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Phase 2b RCT: Abelacimab Significantly Reduces Bleeding Events Compared with Rivaroxaban in Patients with Atrial Fibrillation

27 Jan, 2025 | 11:00h | UTC

Background: Atrial fibrillation (AF) elevates stroke risk roughly fivefold, necessitating anticoagulation therapy to reduce embolic events. Direct oral anticoagulants (DOACs) have replaced vitamin K antagonists as the preferred agents, given their comparable efficacy and lower risk of intracranial hemorrhage. However, significant bleeding—especially gastrointestinal bleeding—still occurs with DOACs, prompting ongoing efforts to develop safer anticoagulants. Abelacimab, a fully human monoclonal antibody targeting factor XI (and its active form, XIa), is hypothesized to “uncouple” thrombosis from hemostasis, potentially lowering bleeding risk. Early data in knee arthroplasty prevention suggested reduced venous thromboembolism (VTE) without increased bleeding. This trial (AZALEA–TIMI 71) aimed to compare the bleeding rates of monthly subcutaneous abelacimab with once-daily rivaroxaban in patients with AF and moderate-to-high stroke risk.

Objective: To evaluate whether subcutaneous abelacimab at two doses (150 mg or 90 mg monthly) leads to fewer major or clinically relevant nonmajor bleeding events than rivaroxaban (20 mg or 15 mg daily) in patients with AF.

Methods: In this phase 2b, parallel-group, partially blind, randomized trial, 1287 adults with AF (CHA $_2$ DS $_2$ -VASc ≥3–4 and moderate/high stroke risk) were assigned 1:1:1 to abelacimab 150 mg, abelacimab 90 mg, or open-label rivaroxaban. Treatment continued for a median of 2.1 years. The primary endpoint was major or clinically relevant nonmajor bleeding, adjudicated by a blinded events committee. Levels of free factor XI were measured to gauge abelacimab’s pharmacodynamics. The trial was halted early based on a recommendation from the independent data monitoring committee due to unexpectedly large reductions in bleeding with abelacimab.

Results: Median age was 74 years, and 44% of participants were female. In the final analysis of the complete dataset, major or clinically relevant nonmajor bleeding occurred at rates of 3.2 and 2.6 events per 100 person-years for abelacimab 150 mg and 90 mg, respectively, versus 8.4 per 100 person-years for rivaroxaban. Corresponding hazard ratios were 0.38 (95% CI, 0.24–0.60) for the 150-mg dose and 0.31 (95% CI, 0.19–0.51) for the 90-mg dose (P<0.001 for both comparisons). The incidence of major gastrointestinal bleeding was notably lower with abelacimab (0.5% in both arms) compared with rivaroxaban (4.2%). Although not powered for stroke prevention, ischemic stroke rates were numerically higher with abelacimab, underscoring the need for larger efficacy trials.

Conclusions: Monthly abelacimab led to substantial and sustained reduction of free factor XI and demonstrated significantly lower bleeding rates than rivaroxaban in patients with AF. While these findings suggest a potentially safer profile for abelacimab, definitive conclusions about stroke prevention require phase 3 studies.

Implications for Practice: Should abelacimab maintain efficacy in preventing thromboembolism in forthcoming trials, it may offer an alternative to existing DOACs, particularly for patients at elevated bleeding risk (e.g., gastrointestinal). However, clinicians must consider real-world factors such as possible high drug cost, insurance coverage, and the logistics of monthly subcutaneous injections. Abelacimab is investigational and not yet approved; its role will depend on phase 3 efficacy and cost-effectiveness outcomes.

Study Strengths and Limitations: Strengths include randomized design, relatively long follow-up (median 2.1 years), and direct comparison to an established DOAC. The major limitation is that the trial was not sufficiently powered to evaluate stroke or systemic embolism. Moreover, the open-label design between abelacimab and rivaroxaban could introduce bias, partly mitigated by blinded dose assignments for abelacimab and blinded endpoint adjudication. The predominantly White population may limit generalizability.

Future Research: Ongoing phase 3 studies (e.g., LILAC–TIMI 76) will clarify abelacimab’s efficacy and safety in larger cohorts, particularly regarding stroke prevention. Comparative cost analyses, real-world adherence, and exploration of subcutaneous administration logistics will be crucial in determining abelacimab’s long-term clinical value. Additional investigations into factor XIa inhibitors (e.g., small molecules, antisense oligonucleotides) may further expand this therapeutic class.

Reference:

Ruff CT, Patel SM, Giugliano RP, Morrow DA, Hug B, Kuder JF, et al. “Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation.” New England Journal of Medicine. 2025;392:361–371. DOI: https://doi.org/10.1056/NEJMoa2406674
Angiolillo DJ, Capodanno D. “Uncoupling Thrombosis and Hemostasis by Inhibiting Factor XI.” New England Journal of Medicine. 2025;392:400–403. DOI: https://doi.org/10.1056/NEJMe2414209
Mandrola JM. “Factor XI Inhibitors May Not Be Dead.” This Week in Cardiology Podcast. January 24, 2025. https://www.medscape.com/viewarticle/1002184#vp_3

2024 ACC/AHA Guideline for the Management of Lower Extremity Peripheral Artery Disease

21 Jan, 2025 | 12:44h | UTC

Introduction:
This summary highlights key points from the 2024 ACC/AHA guideline on managing patients with lower extremity peripheral artery disease (PAD). It addresses diagnosis, risk stratification, and treatment strategies to reduce major adverse cardiovascular events (MACE) and major adverse limb events (MALE), focusing on four clinical subsets of PAD—asymptomatic PAD, chronic symptomatic PAD, chronic limb-threatening ischemia (CLTI), and acute limb ischemia (ALI). Its overarching goal is to optimize cardiovascular risk reduction, preserve limb function, and improve quality of life (QOL).

Key Recommendations:

Clinical Assessment and Diagnosis
- Perform a thorough history and physical examination in patients at risk of PAD (e.g., older adults, those with diabetes, hypertension, dyslipidemia, smokers, or known atherosclerosis).
- Measure the ankle-brachial index (ABI) to establish the diagnosis of PAD; use toe-brachial index (TBI) for patients with noncompressible arteries.
- Obtain imaging (e.g., duplex ultrasound, CT angiography, MR angiography) when planning revascularization or in cases with inconclusive ABI.
Risk Factor Management (Guideline-Directed Medical Therapy)
- Antiplatelet and Antithrombotic Therapy:
  - Recommend single antiplatelet therapy (e.g., aspirin or clopidogrel) for symptomatic PAD to reduce MACE.
  - Consider low-dose rivaroxaban (2.5 mg twice daily) plus low-dose aspirin in patients at low bleeding risk to reduce MALE.
- Lipid-Lowering Therapy:
  - Initiate high-intensity statin therapy in all patients with PAD to reduce cardiovascular and limb events.
  - Add ezetimibe or a PCSK9 inhibitor if LDL-C levels remain above target (≥70 mg/dL).
- Blood Pressure Control:
  - Target a systolic blood pressure <130 mm Hg in patients with PAD; ACE inhibitors or angiotensin-receptor blockers can further reduce cardiovascular risk.
- Diabetes Management:
  - Optimize glycemic control, especially in CLTI; newer agents (e.g., SGLT2 inhibitors, GLP-1 receptor agonists) can reduce cardiovascular risk in PAD with type 2 diabetes.
- Smoking Cessation:
  - Strongly advise cessation of all forms of tobacco and nicotine; offer pharmacotherapy (e.g., varenicline, bupropion, nicotine replacement) and behavioral counseling.
Exercise Therapy
- Supervised Exercise Therapy (SET):
  - A cornerstone of care for patients with claudication to improve walking performance and quality of life.
  - Generally performed 3 times per week for at least 12 weeks in a supervised setting (e.g., cardiac rehab facility).
- Structured Community-Based (Home-Based) Programs:
  - Include regularly prescribed walking regimens, with periodic clinical follow-up and coaching to promote adherence.
Revascularization for Chronic Symptomatic PAD
- Initial Approach:
  - Offer revascularization (endovascular, surgical, or hybrid) if patients have functionally limiting claudication that fails to improve with medical therapy and structured exercise.
- Endovascular vs. Surgical:
  - Select a strategy based on lesion characteristics, availability of adequate vein conduit, and patient comorbidities.
  - Combining revascularization with supervised exercise generally yields better functional outcomes.
- Common Femoral Disease:
  - Surgical endarterectomy remains a highly durable option.
  - Endovascular approaches can be considered for select cases, particularly where surgical risk is high or anatomy is favorable.
Management of Chronic Limb-Threatening Ischemia (CLTI)
- Team-Based Care:
  - Collaborate with vascular specialists, podiatrists, wound-care experts, and other clinicians for optimal outcomes.
- Revascularization Goals:
  - Prevent amputation, heal wounds, and reduce rest pain.
  - Both endovascular and surgical methods can be effective; selection depends on anatomy, available vein conduit, and patient risk profile (e.g., the BEST-CLI and BASIL-2 trials guide decisions).
- Adjunctive Wound Care:
  - Use local wound management (e.g., debridement, negative pressure therapy, offloading) to facilitate healing.
  - Treat infection aggressively; urgent revascularization plus antibiotics is essential.
- Pressure Offloading:
  - Custom footwear and casts/shoes reduce plantar pressure and help prevent or heal foot ulcers.
Acute Limb Ischemia (ALI)
- Immediate Recognition:
  - Suspect ALI in patients with sudden onset of pain, pallor, pulselessness, paresthesia, and paralysis.
  - Determine limb viability (categories I–III) rapidly.
- Treatment:
  - Begin anticoagulation (e.g., IV unfractionated heparin) unless contraindicated.
  - Urgent revascularization (surgical embolectomy, catheter-directed thrombolysis, or mechanical thrombectomy) for salvageable limbs.
  - Monitor for compartment syndrome and consider fasciotomy if needed.
Preventive Foot Care
- Educate patients on self-inspection, daily hygiene, and protective footwear.
- Screen regularly for high-risk conditions (neuropathy, calluses, deformities, infection).
- Promptly address any foot lesions to avoid progression to ulceration, infection, or gangrene.
Longitudinal Follow-Up
- Schedule regular visits to monitor:
  - Cardiovascular risk factor control (lipids, blood pressure, glycemic targets, smoking).
  - Lower extremity symptoms, functional status, and foot health.
  - Need for repeat ABI, duplex ultrasound, or imaging after revascularization to detect restenosis.
- Reinforce adherence to structured exercise, medication regimens, and foot care strategies.

Conclusion:
These recommendations underscore the importance of personalized, multidisciplinary care that addresses both cardiovascular and limb-related outcomes in patients with lower extremity PAD. A combination of comprehensive risk-factor modification, supervised or structured exercise programs, and strategic use of revascularization can significantly reduce the risk of major limb loss, improve symptoms, and enhance QOL. Ongoing follow-up is critical to detect disease progression, optimize therapy, and maintain patient engagement in preventative care.

Reference:
2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024; DOI: https://doi.org/10.1161/CIR.0000000000001251

Management of Cervical Artery Dissection: Key Points From the AHA Scientific Statement

21 Jan, 2025 | 11:05h | UTC

Introduction:
This document summarizes the American Heart Association (AHA) scientific statement on cervical artery dissection (CAD), an important cause of ischemic stroke, especially in younger and middle-aged adults. Cervical artery dissection often presents with nonspecific symptoms—such as headache, neck pain, or partial Horner syndrome—but can lead to serious neurological deficits. Early recognition, targeted imaging, appropriate acute treatment, and well-informed decisions on antithrombotic therapy are essential to optimize patient outcomes.

Key Recommendations:

Epidemiology and Risk Factors
- CAD accounts for up to 25% of ischemic strokes in adults under 50 years of age, with a slightly higher incidence in men but lower peak age in women.
- Risk factors include genetic predispositions (eg, connective tissue disorders), anatomic variants (elongated styloid process, vascular tortuosity), minor cervical trauma, and comorbidities such as hypertension or fibromuscular dysplasia.
Diagnosis and Imaging
1. Clinical Suspicion
  - Suspect CAD in younger adults with new or worsening neck pain, headache, pulsatile tinnitus, partial Horner syndrome, or cranial nerve involvement, especially if there is a history of recent minor neck trauma or manipulation.
  - Up to 8%–12% of patients may have isolated neck or head pain with no initial ischemic signs.
2. Imaging Modalities
  - Magnetic Resonance Imaging (MRI)/Magnetic Resonance Angiography (MRA): High-resolution, fat-suppressed T1-weighted sequences are useful for detecting intramural hematoma.
  - Computed Tomography Angiography (CTA): Good sensitivity and specificity for luminal abnormalities and can detect intraluminal thrombus. Avoid false positives by distinguishing imaging artifacts from true double lumens or intimal flaps.
  - Conventional Digital Subtraction Angiography (DSA): Historically the gold standard but reserved for equivocal cases because of procedure-related risks (eg, iatrogenic dissection).
  - Ultrasound with Color Doppler: Operator-dependent but helpful for serial follow-up of vessel remodeling.
3. Additional Diagnostic Testing
  - Connective Tissue Disorders: Consider genetic counseling if physical exam, family history, or recurrent dissections suggest a monogenic disorder (eg, vascular Ehlers-Danlos).
  - Screening for Fibromuscular Dysplasia (FMD): Patients with CAD, especially those with hypertension or evidence of FMD in other vascular beds, may warrant renal artery imaging.
  - Aortic and Intracranial Imaging: Aortic root dilation and cerebral aneurysms may be more prevalent in CAD; consider advanced imaging (eg, MRA) based on clinical judgment.
Hyperacute and Acute Stroke Management
1. Intravenous Thrombolysis (IVT):
  - IVT (alteplase or tenecteplase) remains reasonable for otherwise eligible acute ischemic stroke patients, with no specific evidence of higher hemorrhagic risk in CAD. Caution is advised if there is intracranial extension of the dissection or other significant bleeding risk factors.
2. Mechanical Thrombectomy:
  - Recommended for large-vessel occlusion in CAD patients who meet standard thrombectomy criteria. Tandem lesions (extracranial dissection and intracranial occlusion) can be addressed via retrograde (intracranial first) or antegrade (extracranial first) approach, with similar overall outcomes reported.
3. Acute or Subacute Stenting:
  - May be considered in selected cases of severe flow-limiting stenosis leading to distal hypoperfusion or in persistent ischemia despite optimal medical therapy. Stenting in tandem occlusions can improve reperfusion but carries added risks (in-stent restenosis, stent thrombosis, or need for dual antiplatelet therapy).
Antithrombotic Therapy for Secondary Stroke Prevention
1. Rationale for Early Treatment:
  - Artery-to-artery embolization underpins most CAD-related ischemic events. Early initiation of antithrombotics (ideally within the first 24–72 hours) reduces further embolic risk.
2. Choice of Agent: Antiplatelet vs Anticoagulant
  - When to Prefer Anticoagulation:
    - Patients with high-risk imaging features: severe stenosis (>50%–70%), intraluminal thrombus, occlusion, multiple or early recurrent dissections.
    - Traditional option is heparin bridging to Vitamin K antagonist (target INR ≈2–3), but direct oral anticoagulants (DOACs) can be considered based on patient profile and preference.
  - When to Prefer Antiplatelet Therapy:
    - Patients with lower stroke risk (no significant stenosis, no intraluminal thrombus) or higher bleeding risk (large infarct, hemorrhagic transformation, intradural extension).
    - Aspirin monotherapy is typical; a short course of dual antiplatelet therapy (aspirin + clopidogrel) for 21–90 days can be considered if minor stroke/TIA criteria apply and bleeding risk is acceptable.
3. Practical Start-Up and Monitoring:
  - Begin therapy as soon as deemed safe, ideally after hemorrhagic complications are excluded.
  - For VKA: bridge with heparin (IV unfractionated or low–molecular-weight) for at least 5 days until INR is therapeutic for ≥24 hours.
  - Regularly monitor clinical response and, if relevant, INR in anticoagulated patients.
4. Duration of Therapy:
  - Minimum 3–6 months of antithrombotics, with vessel imaging at follow-up (eg, 3 or 6 months) to assess for healing or persistent dissection.
  - Decisions to extend antithrombotic therapy past the 6-month mark may be considered in the context of an individual’s overall vascular risk factor profile and in the context of neuroimaging features as remodeling occurs.
  - Consider extended or indefinite therapy (often antiplatelet) if persistent stenosis, high-risk anatomic factors, or recurrent dissections occur.
Risk of Recurrent Dissection and Lifestyle Precautions
- Recurrence rates range from 1% to 2% per year but are higher in the first few months post-dissection. Fibromuscular dysplasia and younger age are associated with increased recurrence risk.
- It is reasonable to advise patients to avoid high-risk neck activities (eg, contact sports, extreme neck manipulation) for 1–6 months or until imaging confirms vessel healing. In those with a known connective tissue disorder or recurrent dissection, lifelong caution is appropriate.
Follow-Up Imaging and Management of Dissecting Aneurysms
- Recanalization most often occurs by 6–12 months; persistent occlusions or stenoses beyond 12 months rarely recanalize further.
- Dissecting aneurysms form or enlarge in some cases but seldom rupture. Antithrombotic choice does not appear to affect aneurysm resolution rates.
- Endovascular or surgical interventions are reserved for enlarging or symptomatic aneurysms causing compression or other complications.

Conclusion: Cervical artery dissection warrants vigilant clinical recognition, prompt imaging, and individualized treatment strategies. Early antithrombotic therapy—whether anticoagulation or antiplatelet—plays a critical role in preventing stroke. Decisions should reflect both the patient’s hemorrhagic risk and the presence of imaging features predictive of stroke. Mechanical thrombectomy and, in selected cases, stenting are viable acute interventions for high-risk presentations. Although recurrences are uncommon, thoughtful follow-up imaging, patient education, and avoidance of high-risk neck activities are central to minimizing future dissections and optimizing outcomes.

Reference: Yaghi S, Engelter S, Del Brutto VJ, Field TS, Jadhav AP, Kicielinski K, Madsen TE, Mistry EA, Salehi Omran S, Pandey A, Raz E, on behalf of the American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Council on Peripheral Vascular Disease. Treatment and Outcomes of Cervical Artery Dissection in Adults: A Scientific Statement From the American Heart Association. Stroke. 2024;55(3). DOI: https://doi.org/10.1161/STR.0000000000000457

AGA Clinical Practice Update on Managing Portal Vein Thrombosis in Cirrhotic Patients: Expert Review

3 Jan, 2025 | 10:00h | UTC

Introduction: This summary highlights key recommendations from an AGA expert review on portal vein thrombosis (PVT) in cirrhotic patients. PVT is common in cirrhosis, with an estimated five-year incidence of around 11%, and may worsen portal hypertension and elevate mortality. Management is challenging because of limited evidence, the potential complications of both PVT and anticoagulation, and significant heterogeneity regarding clot characteristics, host factors, and cirrhosis severity. This review presents the latest guidance on identifying clinically relevant PVT, selecting anticoagulation, and considering endovascular interventions, including TIPS (transjugular intrahepatic portosystemic shunt).

Key Recommendations:

No Routine Screening: Asymptomatic patients with compensated cirrhosis do not require regular screening for PVT in the absence of suggestive clinical changes.
Imaging Confirmation: When Doppler ultrasound reveals suspected PVT, contrast-enhanced CT or MRI is recommended to confirm the diagnosis, exclude malignancy, and characterize clot extent and occlusion.
Hypercoagulability Testing: Extensive thrombophilia workup is not indicated unless there is family or personal history of thrombotic events, or associated laboratory abnormalities.
Intestinal Ischemia Management: Patients who develop PVT with evidence of intestinal ischemia should receive prompt anticoagulation and, ideally, multidisciplinary team care involving gastroenterology, hepatology, interventional radiology, hematology, and surgery.
Observation of Minor or Recent Thrombi: In cirrhotic patients without ischemia, with recent (<6 months) thrombi that are <50% occlusive, close imaging follow-up every three months is a reasonable option to track potential spontaneous clot regression.
Anticoagulation for Significant PVT: Consider anticoagulation for more extensive or obstructive (>50%) recent PVT, especially if the main portal vein or mesenteric vessels are involved. Candidates for liver transplantation and those with inherited thrombophilia may derive additional benefit.
Chronic Cavernous PVT: Anticoagulation is generally not advised in patients with long-standing (>6 months) complete occlusion and well-formed collateral channels.
Variceal Screening: Perform endoscopic screening or ensure prophylaxis for varices. Avoid delays in initiating anticoagulation, as timeliness is essential for better recanalization outcomes.
Choice of Anticoagulant: Vitamin K antagonists, low-molecular-weight heparin, and direct oral anticoagulants (DOACs) are all viable options in cirrhosis. DOACs may be appropriate in well-compensated (Child-Turcotte-Pugh class A or certain class B) cirrhosis but should be avoided in class C. Treatment selection should consider patient preferences, monitoring feasibility, and risk of bleeding.
Duration of Therapy: Reassess clot status with cross-sectional imaging every three months. Continue anticoagulation for transplant-eligible individuals who show partial or complete recanalization, and consider discontinuation in nonresponders after six months if futility is evident.
TIPS Revascularization: Portal vein revascularization using TIPS may be pursued in patients who have other TIPS indications (like refractory ascites or variceal bleeding) or to improve transplant feasibility by recanalizing portal flow.

Conclusion: PVT in cirrhosis remains a complex clinical issue requiring careful evaluation of clot extent, timing, and the potential need for transplantation. The recommendations presented here underscore prompt imaging, timely anticoagulation for high-risk thrombi, and individualized therapy based on Child-Turcotte-Pugh classification and bleeding risk. When necessary, multidisciplinary collaboration is key to achieving optimal patient outcomes. Prospective randomized trials and standardized classifications of PVT will be instrumental in refining future guidelines.

Reference:
Davis JPE, Lim JK, Francis FF, Ahn J. AGA Clinical Practice Update on Management of Portal Vein Thrombosis in Patients With Cirrhosis: Expert Review. Gastroenterology. 2024. DOI: http://doi.org/10.1053/j.gastro.2024.10.038

Meta-Analysis: Endovascular Therapy for Vertebrobasilar Occlusion Improves Functional Outcomes

19 Dec, 2024 | 22:56h | UTC

Background: Acute vertebrobasilar artery occlusion (VBAO) is associated with high mortality and severe neurological deficits. Previous randomized trials of endovascular therapy (EVT) for VBAO have shown inconsistent results, leaving uncertainty about its efficacy across different patient subgroups.

Objective: To determine whether EVT confers improved 90-day functional outcomes compared with standard medical therapy alone in patients with acute VBAO and to explore treatment effect heterogeneity in prespecified subgroups.

Methods: This individual patient data meta-analysis included all four major randomized controlled trials (ATTENTION, BAOCHE, BASICS, BEST) that enrolled patients with VBAO treated within 24 hours of estimated onset. Participants received either EVT or best medical therapy. The primary outcome was a favorable functional status at 90 days (modified Rankin Scale [mRS] score 0–3). Secondary outcomes included functional independence (mRS 0–2), distribution of mRS scores (shift analysis), symptomatic intracranial hemorrhage (sICH), and all-cause mortality at 90 days.

Results: Among 988 patients (556 EVT; 432 control), median age 67 years, EVT significantly increased the proportion achieving mRS 0–3 (45% vs 30%; adjusted odds ratio [aOR] 2.41, 95% CI 1.78–3.26) and mRS 0–2 (35% vs 21%; aOR 2.52, 95% CI 1.82–3.48). EVT improved the overall distribution of functional outcomes (aOR for mRS shift 2.09, 95% CI 1.61–2.71) and reduced 90-day mortality (36% vs 45%; aOR 0.60, 95% CI 0.45–0.80). Although sICH was more common with EVT (5% vs <1%; aOR 11.98, 95% CI 2.82–50.81), the net clinical benefit remained strongly in favor of EVT. Subgroup analyses showed broadly consistent benefit, though the advantage was uncertain for patients with mild baseline severity (NIHSS <10).

Conclusions: EVT for acute VBAO significantly improves functional outcomes and reduces mortality despite a higher sICH risk. These results support EVT as a standard consideration in appropriately selected patients with moderate-to-severe VBAO. The benefit’s magnitude is comparable to that seen in anterior circulation large vessel occlusions, although caution is advised in mild cases and those with extensive baseline infarction.

Implications for Practice: Clinicians should consider EVT for most patients presenting with acute VBAO. While sICH risk is increased, the substantial improvements in function and survival justify its use in suitable candidates. Careful imaging and clinical assessment remain critical for optimal patient selection.

Study Strengths and Limitations: Strengths include a pooled individual patient dataset from all major VBAO EVT trials, allowing detailed subgroup analyses. Limitations involve early trial termination, underrepresentation of women, predominance of Asian populations, and exclusion of patients with very mild symptoms or large baseline infarcts, potentially limiting generalizability.

Future Research: Further trials are needed to define EVT’s role in patients with mild symptoms, isolated vertebral occlusion, large infarcts, or those presenting beyond 24 hours. Additional studies should assess real-world applicability and diverse patient populations.

Reference: Nogueira RG, et al. Endovascular therapy for acute vertebrobasilar occlusion (VERITAS): a systematic review and individual patient data meta-analysis. DOI: http://doi.org/10.1016/S0140-6736(24)01820-8

Review: Nonsurgical Management of Chronic Venous Insufficiency

19 Dec, 2024 | 16:45h | UTC

Introduction: This summary highlights key points from a recent review on the nonsurgical management of chronic venous insufficiency, a condition characterized by persistent venous hypertension leading to edema, skin changes, and venous ulcers. Chronic venous insufficiency is influenced by both structural factors (e.g., venous reflux, obstruction) and functional elements (e.g., obesity, impaired calf-muscle pump). While interventional procedures may improve symptoms in patients with significant structural abnormalities, most cases require comprehensive nonsurgical strategies targeting venous hypertension and improving quality of life.

Key Recommendations:

Comprehensive Assessment: Distinguish between structural and functional components of venous disease. Structural issues may warrant endovenous procedures, whereas functional insufficiency (e.g., due to obesity, weak calf muscles) requires behavioral and medical interventions.
Compression Therapy (Class 1A for Venous Ulcers): Use tailored compression stockings or wraps to reduce venous pressure, alleviate swelling, and aid ulcer healing. Compression levels above 30 mm Hg can facilitate healing, but lower levels (20–30 mm Hg) may improve adherence.
Lifestyle Modifications: Implement weight reduction measures in obese patients to lower central venous pressure and improve venous return. Consider evaluating and managing obstructive sleep apnea or cardiac dysfunction that may elevate venous pressure.
Exercise and Leg Elevation: Encourage exercises that strengthen calf and foot muscles, thereby enhancing the venous pump function and reducing stasis. Advise regular leg elevation to alleviate edema and discomfort.
Medication Review: Assess current medications (e.g., calcium-channel blockers, gabapentinoids) that may cause edema and consider alternatives. Avoid unnecessary diuretics unless true volume overload is confirmed.
Venous Interventions for Structural Lesions (Class IB for Varicose Veins): In patients with symptomatic varicose veins and axial reflux, procedural interventions (e.g., endovenous ablation, sclerotherapy, or surgical stripping) can be more effective than long-term compression alone. Early intervention may expedite ulcer healing in selected cases.
Cautious Use of Venoactive Agents: Although certain supplements (e.g., flavonoids, horse chestnut) are widely available, current guidelines provide only weak recommendations, with limited evidence for clinically meaningful outcomes.

Conclusion: Nonsurgical management of chronic venous insufficiency emphasizes reducing venous hypertension, improving calf muscle pump function, and addressing central factors such as obesity and cardiac conditions. By combining compression therapy, exercise, weight reduction, and appropriate medication adjustments, clinicians can alleviate symptoms, enhance patient comfort, and potentially improve wound healing. Procedural interventions remain essential adjuncts for selected structural abnormalities, but long-term functional management is key to sustained clinical benefit.

Reference: Fukaya E, Kolluri R. Nonsurgical Management of Chronic Venous Insufficiency. The New England Journal of Medicine. 2024;391:2350–2359. DOI: https://doi.org/10.1056/NEJMcp2310224

RCT: Adjunctive Middle Meningeal Artery Embolization Reduces Reoperation in Subdural Hematoma

24 Nov, 2024 | 13:53h | UTC

Background: 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.

Reference: Davies JM, et al. Adjunctive Middle Meningeal Artery Embolization for Subdural Hematoma. New England Journal of Medicine. 2024; DOI: http://doi.org/10.1056/NEJMoa2313472

Cohort Study: Oral Hormone Therapy and Tibolone Increase Cardiovascular Risk in Menopausal Women

28 Nov, 2024 | 18:42h | UTC

Background: 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.

Reference: Johansson T, Karlsson T, Bliuc D, et al. Contemporary menopausal hormone therapy and risk of cardiovascular disease: Swedish nationwide register based emulated target trial. BMJ. 2024;387:e078784. DOI: http://doi.org/10.1136/bmj-2023-078784

Cohort Study: High Rate of Preventable Adverse Events in Surgical Inpatients

16 Nov, 2024 | 17:29h | UTC

Background: Adverse events during hospital admissions, particularly in surgical settings, remain a significant cause of patient harm despite efforts to improve patient safety since the “To Err is Human” report. Advances in surgical techniques and patient care necessitate an updated assessment of the current state of perioperative safety.

Objective: To estimate the frequency, severity, and preventability of adverse events associated with perioperative care in surgical inpatients and to identify the settings and healthcare professionals involved.

Methods: A multicenter retrospective cohort study was conducted across 11 US hospitals in Massachusetts. A weighted random sample of 1,009 patients was selected from 64,121 adults admitted for surgery in 2018. Trained nurses reviewed electronic health records to identify adverse events, which were then adjudicated by physicians. Adverse events were classified by type, severity, preventability, setting, and professions involved.

Results: Adverse events occurred in 38.0% of patients (95% CI, 32.6–43.4%), with major adverse events in 15.9% (12.7–19.0%). Among 593 adverse events identified, 59.5% were potentially preventable, and 20.7% were definitely or probably preventable. The most common events were surgery-related (49.3%), adverse drug events (26.6%), healthcare-associated infections (12.4%), and patient care events (11.2%). Adverse events most frequently occurred in general care units (48.8%) and involved attending physicians (89.5%) and nurses (58.9%).

Conclusions: More than one-third of surgical inpatients experienced adverse events, with nearly half classified as major and most potentially preventable. These findings highlight the critical need for ongoing improvement in patient safety throughout perioperative care involving all healthcare professionals.

Implications for Practice: Healthcare providers should enhance patient safety protocols across all perioperative settings, not just in operating rooms. Emphasis should be placed on preventing surgery-related complications, adverse drug events, and healthcare-associated infections by fostering teamwork and continuous monitoring.

Study Strengths and Limitations: Strengths include a comprehensive review of medical records and systematic classification of adverse events by trained professionals. Limitations involve the study’s confinement to Massachusetts hospitals in 2018, potential variability in documentation practices, and limited sample size affecting generalizability and specialty-specific estimates.

Future Research: Further studies are needed to assess adverse event rates in diverse geographic locations and healthcare systems, explore effective interventions to reduce preventable harm, and evaluate long-term trends in surgical patient safety.

Reference: Duclos A, Frits ML, Iannaccone C, Lipsitz SR, Cooper Z, Weissman JS, Bates DW. Safety of inpatient care in surgical settings: cohort study. BMJ. 2024; DOI: http://doi.org/10.1136/bmj-2024-080480

Review: Endovascular Management of Acute Stroke

20 Oct, 2024 | 14:43h | UTC

Introduction: Stroke due to large vessel occlusion (LVO) remains a leading cause of disability and mortality worldwide. Endovascular therapy has revolutionized acute ischemic stroke management by enhancing recanalization rates and improving patient outcomes. This review outlines the evolution of endovascular treatments, expansion of therapeutic indications, current best practices, and ongoing research in the endovascular management of acute stroke.

Key Recommendations:

Early Time Window Therapy (0–6 Hours): Robust evidence from randomized controlled trials demonstrates that mechanical thrombectomy significantly improves functional outcomes in patients with anterior circulation LVO presenting within 6 hours of symptom onset. Patients are selected based on moderate-to-severe neurological deficits and small infarct cores identified via imaging.
Extended Time Window Therapy (6–24 Hours): Trials such as DAWN and DEFUSE3 have extended thrombectomy benefits to patients up to 24 hours after symptom onset. Advanced imaging techniques, like CT perfusion and MRI, identify patients with substantial penumbral tissue, indicating potential for recovery.
Large Ischemic Core Infarcts: Recent studies (e.g., SELECT2, ANGEL-ASPECT) suggest that patients with large core infarcts can benefit from endovascular therapy, challenging previous contraindications. Individualized patient selection is crucial to balance risks and benefits.
Basilar Artery Occlusion: New evidence supports thrombectomy for basilar artery occlusions, especially in patients with moderate-to-severe symptoms. This intervention improves outcomes in a condition historically associated with high morbidity and mortality.
Bridging Thrombolysis: The necessity of intravenous thrombolysis before thrombectomy in patients directly admitted to endovascular centers is under debate. Meta-analyses indicate that omitting thrombolysis may not adversely affect outcomes, although it remains standard for patients at non-thrombectomy centers.
Simplified Imaging for Patient Selection: The use of non-contrast CT and CT angiography alone has proven effective for patient selection, reducing treatment delays and expanding access to thrombectomy, particularly in resource-limited settings.

Conclusion: Advancements in endovascular therapy have markedly improved outcomes for patients with acute ischemic stroke due to LVO. Expanded treatment indications and simplified imaging protocols have broadened patient eligibility for thrombectomy. Ongoing research into adjunctive therapies and optimization of management strategies holds promise for further reducing stroke-related disability and mortality.

Reference: Nguyen TN, et al. (2024) Endovascular management of acute stroke. Lancet. DOI: http://doi.org/10.1016/S0140-6736(24)01410-7

RCT: Renal Denervation Reduces Blood Pressure in Chinese Patients With Uncontrolled Hypertension

7 Sep, 2024 | 14:57h | UTC

Study Design and Population: This was a prospective, multicenter, randomized, sham-controlled trial investigating the efficacy and safety of catheter-based radiofrequency renal denervation (RDN) in Chinese patients with uncontrolled hypertension despite standardized triple antihypertensive therapy. A total of 217 patients (mean age 45.3 years, 21% female) were randomized 1:1 to receive RDN or a sham procedure.

Main Findings: At 6 months, patients who underwent RDN showed a significantly greater reduction in 24-hour ambulatory systolic blood pressure (−13.0 mm Hg) compared to the sham group (−3.0 mm Hg), with a baseline-adjusted difference of −9.4 mm Hg (P<0.001). Significant reductions were also observed in 24-hour diastolic BP and office systolic and diastolic BP. One access site complication occurred in the RDN group but resolved without further issues.

Implications for Practice: This trial demonstrates that RDN is an effective and safe option for reducing blood pressure in patients with uncontrolled hypertension, offering a potential adjunct to antihypertensive therapy in this population. Further research may solidify its role in managing resistant hypertension.

Reference: Jiang X et al. (2024). Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.124.069215

Link: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.069215

RCT: Thrombectomy improves outcomes in acute stroke with large infarcts – N Engl J Med

25 May, 2024 | 19:35h | UTC

Study Design and Population: This randomized clinical trial investigated the efficacy of thrombectomy in combination with standard medical care versus medical care alone in patients with acute stroke and large infarcts. Participants included 333 patients with proximal cerebral vessel occlusion in the anterior circulation, presenting within 6.5 hours of symptom onset. They were randomized in a 1:1 ratio to either undergo thrombectomy or receive only medical care. An Alberta Stroke Program Early Computed Tomographic Score of ≤5 was used to define large infarcts.

Main Findings: The primary outcome, assessed by the modified Rankin scale score at 90 days, showed a median score of 4 in the thrombectomy group compared to 6 in the control group, indicating better functional outcomes with thrombectomy (generalized odds ratio, 1.63; 95% CI, 1.29 to 2.06; P<0.001). Mortality at 90 days was significantly lower in the thrombectomy group (36.1%) compared to the control group (55.5%) with an adjusted relative risk of 0.65. However, thrombectomy was associated with a higher rate of symptomatic intracerebral hemorrhage (9.6% vs. 5.7% in the control group).

Implications for Practice: The findings suggest that thrombectomy, when added to standard medical care, can significantly improve functional outcomes and reduce mortality in patients with large infarct strokes. However, the increased risk of symptomatic intracerebral hemorrhage must be considered when deciding on this intervention. These results support the broader use of thrombectomy in clinical settings with similar patient profiles but underscore the need for careful risk-benefit analysis due to the potential for serious hemorrhagic complications.

Reference (link to abstract – $ for full-text):

Costalat, V. et al. (2024). Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size. N Engl J Med, 390(18), 1677-1689. DOI: 10.1056/NEJMoa2314063

New ACC/AHA Guidelines for the Management of Lower Extremity Peripheral Artery Disease

16 May, 2024 | 11:05h | UTC

Introduction

The 2024 ACC/AHA guidelines, along with several associated societies, highlight the significance of peripheral artery disease (PAD) as a major public health issue, often underestimated, and linked to high risks of amputation and serious cardiovascular events. This document is crucial for clinicians seeking to optimize treatment and improve the quality of life for affected patients.

Key Points

1 – Risk Assessment: It is crucial to evaluate risks associated with PAD and health disparities that may impact treatment outcomes.

2 – Diagnosis: Diagnosis of PAD typically involves physical examination, medical history, and the resting ankle-brachial index.

3 – Medical Therapy: Management includes antiplatelet therapy (usually single), high-intensity statins, antihypertensive therapy, diabetes management, and smoking cessation. Rivaroxaban (2.5 mg twice daily) combined with low-dose aspirin (81 mg) has proven effective and can be included in the therapy for patients at low risk of bleeding.

4 – Structured Exercise: A central component of care, including supervised exercise therapy and community-based programs.

5 – Revascularization: Indicated to prevent limb loss in chronic limb-threatening ischemia and can improve quality of life in cases of claudication.

6 – Multidisciplinary Care: Optimized care involves a team of multiple specialties, especially for chronic limb-threatening ischemia.

Reference: Gornik HL, et al. (2024). 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for the management of lower extremity peripheral artery disease. J Am Coll Cardiol. Available at: https://doi.org/10.1016/j.jacc.2024.02.013