General Hematology
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.
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.
Updated Guidelines on Perioperative Management of Anticoagulant and Antiplatelet Therapy for Interventional Techniques – Pain Physician
18 Aug, 2024 | 14:52h | UTCIntroduction: The American Society of Interventional Pain Physicians (ASIPP) has published updated guidelines for the perioperative management of patients undergoing interventional techniques while receiving antiplatelet and anticoagulant therapy. These guidelines are essential for clinicians to balance the risk of thromboembolism against the risk of bleeding during interventional procedures.
Key Points:
1 – Risk of Thromboembolic Events:
– Thromboembolic events have a higher risk of morbidity and mortality compared to the risk of epidural hematoma. Thus, interruption of antithrombotic therapy should be carefully considered.
2 – Risk Stratification of Procedures:
– Interventional techniques are classified into three categories based on risk: low, moderate, or high. For high-risk procedures, cessation of anticoagulant or antiplatelet therapy is recommended, whereas for low to moderate-risk procedures, therapy may continue under certain conditions.
3 – Management of Direct Oral Anticoagulants (DOACs):
– DOACs such as dabigatran, apixaban, rivaroxaban, and edoxaban should generally be discontinued for 2 days before high-risk procedures and one day for moderate-risk procedures. Adjustments are needed based on renal function, specially for dabigatran.
4 – Discontinuation of Aspirin:
– For high-risk interventional procedures, discontinuation of aspirin (81 or 325 mg) is recommended 6 days before the procedure. However, for low to moderate-risk procedures, aspirin therapy may be continued or stopped for 3 days depending on individual risk factors and clinical judgment.
5 – Discontinuation of Other Antiplatelet Agents:
– Clopidogrel (Plavix) and Prasugrel (Effient): These agents should be discontinued 6 days before high-risk procedures. For low-risk procedures, these medications can be continued.
– Ticagrelor (Brilinta): Discontinue for 5 days before high-risk procedures, with consideration of patient-specific risk factors.
6 – Timing for Restarting Therapy:
– Antithrombotic therapy should typically be resumed within 12-24 hours after low to moderate-risk procedures and within 24-48 hours after high-risk procedures, depending on bleeding risk and patient status.
7 – Shared Decision-Making:
– Decisions on whether to continue or discontinue antithrombotic therapy should involve shared decision-making between the patient, the interventional pain specialist, and other treating physicians, considering all associated risks.
Conclusion: These guidelines provide a comprehensive framework for managing the delicate balance between thromboembolic and bleeding risks in patients on anticoagulant or antiplatelet therapy undergoing interventional procedures. They emphasize the importance of personalized care and multidisciplinary collaboration.
Meta-Analysis: 1-Month Dual Antiplatelet Therapy Reduces Major Bleeding Without Increasing Stent Thrombosis After PCI with DES – Am J Cardiol
17 Aug, 2024 | 19:29h | UTCMain Findings: The analysis found that 1-month DAPT significantly reduced the risk of major bleeding (OR 0.66, 95% CI 0.45-0.97, p = 0.03) compared to >1-month DAPT. Additionally, there was no significant difference in stent thrombosis rates between the groups (OR 1.08, 95% CI 0.81-1.44, p = 0.60). Secondary outcomes, including all-cause mortality, cardiovascular death, myocardial infarction, stroke, and major adverse cardiovascular or cerebrovascular events were also similar between the groups.
Implications for Practice: The findings support the use of 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor as a safer alternative to longer-term DAPT in patients undergoing PCI with DES. This strategy may help reduce bleeding risks without increasing the likelihood of thrombotic events, making it a viable option for routine clinical practice, particularly in patients at high risk for bleeding.
Erythritol Ingestion Increases Platelet Reactivity and Thrombosis Potential in Healthy Adults – Arterioscler Thromb Vasc Biol
10 Aug, 2024 | 21:11h | UTCStudy Design and Population: This interventional study evaluated the effects of erythritol versus glucose on platelet reactivity and thrombosis potential in 20 healthy volunteers, with 10 participants in each group. Researchers measured erythritol plasma levels and assessed platelet function through aggregometry and granule marker analysis both before and after ingestion of 30 g of erythritol or glucose.
Main Findings: Erythritol ingestion resulted in a more than 1000-fold increase in plasma erythritol concentration and significantly enhanced stimulus-dependent platelet aggregation and release of serotonin and CXCL4, markers of platelet activation. In contrast, glucose ingestion did not significantly alter platelet reactivity or granule marker release, highlighting erythritol’s unique pro-thrombotic effects.
Implications for Practice: These findings raise concerns regarding the safety of erythritol as a non-nutritive sweetener, particularly its potential to enhance thrombosis risk. The results suggest a need to reevaluate erythritol’s safety status and consider its impact on cardiovascular health in regulatory guidelines.
RCT: Liberal vs. Restrictive Transfusion Strategy Shows No Significant Difference in Neurologic Outcomes for Traumatic Brain Injury Patients – N Engl J Med
3 Aug, 2024 | 19:06h | UTCStudy Design and Population: This randomized clinical trial evaluated the effects of liberal versus restrictive red cell transfusion strategies in 742 adults with moderate to severe traumatic brain injury (TBI) and anemia. Participants were randomized to either a liberal transfusion strategy (initiated at hemoglobin ≤10 g/dL) or a restrictive strategy (initiated at hemoglobin ≤7 g/dL). The primary outcome was an unfavorable neurologic outcome at 6 months, assessed using the Glasgow Outcome Scale–Extended.
Main Findings: The study found that 68.4% of patients in the liberal-strategy group and 73.5% in the restrictive-strategy group experienced an unfavorable outcome (adjusted absolute difference of 5.4 percentage points; 95% CI, −2.9 to 13.7). No significant difference in mortality or depression was observed between the two groups. Although some functional independence and quality of life measures were better in the liberal group among survivors, venous thromboembolic events and acute respiratory distress syndrome rates were comparable.
Implications for Practice: The findings indicate that a liberal transfusion strategy does not significantly improve neurologic outcomes at 6 months in critically ill TBI patients compared to a restrictive strategy. Clinicians may consider maintaining a restrictive transfusion strategy, given the similar outcomes and potential for fewer transfusions. Further research is needed to explore specific subgroups that might benefit from different transfusion strategies.
Randomized Controlled Trial: Mixed results with Andexanet Alfa for Factor Xa inhibitor-associated acute intracerebral hemorrhage – N Engl J Med
27 May, 2024 | 20:26h | UTCStudy Design and Population: This randomized controlled trial involved 530 patients with acute intracerebral hemorrhage who had taken factor Xa inhibitors within 15 hours before the event. They were randomly assigned to receive either andexanet alfa or usual care.
Main Findings: Hemostatic efficacy was achieved in 67% of patients receiving andexanet compared to 53.1% receiving usual care. Andexanet significantly reduced anti-factor Xa activity by 94.5%, compared to 26.9% with usual care. However, thrombotic events were more frequent in the andexanet group, including ischemic stroke.
Implications for Practice: Andexanet alfa is effective in controlling hematoma expansion in patients with factor Xa inhibitor-associated intracerebral hemorrhage but has an increased risk of thrombotic events. Further research is needed to balance efficacy and safety.
Reference (link to abstract – $ for full-text):
Randomized Crossover Trial: Prophylactic recombinant ADAMTS13 prevents acute events in congenital thrombotic thrombocytopenic purpura – N Engl J Med
6 May, 2024 | 06:22h | UTCThis study evaluates the efficacy and safety of recombinant ADAMTS13 compared to standard plasma-derived therapy in managing congenital thrombotic thrombocytopenic purpura (TTP). In a phase 3, open-label, crossover trial involving 48 patients, each participant underwent two 6-month prophylaxis periods, receiving either recombinant ADAMTS13 or standard therapy, followed by a switch to the alternate treatment. Results indicate that recombinant ADAMTS13 prevented acute TTP events during prophylaxis, with no events recorded, versus one event under standard therapy. Furthermore, recombinant ADAMTS13 was associated with significantly lower rates of thrombocytopenia and adverse events compared to standard therapy. The treatment increased ADAMTS13 activity to approximately 100% of normal levels, with no development of neutralizing antibodies. Overall, recombinant ADAMTS13 was found to be safe and more effective than standard therapy in preventing TTP events and manifestations.
Reference (link to abstract – $ for full-text):
Cohort Study: Higher serious bleeding rates linked to diltiazem in elderly atrial fibrillation patients on anticoagulation
26 Apr, 2024 | 12:35h | UTCStudy Design and Population:
This retrospective cohort study analyzed data from 204,155 Medicare beneficiaries aged 65 years or older diagnosed with atrial fibrillation. The study focused on new users of the anticoagulants apixaban or rivaroxaban who commenced treatment with either diltiazem or metoprolol between January 2012 and November 2020, with follow-up extending up to 365 days.
Main Findings:
Patients treated with diltiazem exhibited a significantly increased risk of serious bleeding, including bleeding-related hospitalization and death, compared to those treated with metoprolol. The hazard ratio (HR) for serious bleeding events was 1.21, with a rate difference (RD) of 10.6 per 1000 person-years. Notably, the risk escalated with diltiazem doses exceeding 120 mg/day, indicating a dose-response relationship. Secondary outcomes, such as ischemic stroke or systemic embolism, did not show significant differences between the treatment groups.
Implications for Practice:
The findings suggest that in older adults with atrial fibrillation treated with apixaban or rivaroxaban, diltiazem increases the risk of serious bleeding, especially at higher doses. These results underscore the importance of cautious medication management and might influence clinical decisions regarding the choice of ventricular rate control in this population.
Reference (link to abstract – $ for full-text):
High efficacy of exagamglogene autotemcel in achieving transfusion independence in β-Thalassemia
25 Apr, 2024 | 23:29h | UTCStudy Design and Population:
This open-label, single-group, phase 3 trial investigated the efficacy of exagamglogene autotemcel (exa-cel), a nonviral CRISPR-Cas9 gene-edited cell therapy, in patients aged 12 to 35 with transfusion-dependent β-thalassemia. Various genotypes were included, and participants underwent myeloablative conditioning followed by exa-cel infusion. The primary endpoint was to achieve and maintain transfusion independence.
Main Findings:
Of the 52 patients treated, 35 with sufficient follow-up showed that 32 (91%) achieved transfusion independence for at least 12 months, significantly surpassing the study’s efficacy threshold. The average total hemoglobin during this period was 13.1 g/dL, with fetal hemoglobin averaging 11.9 g/dL and widely distributed across red cells. The treatment’s safety profile was compatible with the expected outcomes of myeloablative conditioning and autologous hematopoietic stem cell transplantation, with no reported deaths or cancer developments.
Implications for Practice:
The successful achievement of transfusion independence in a high percentage of patients suggests that exa-cel is a promising treatment option for transfusion-dependent β-thalassemia. This study supports the potential for gene-edited cell therapies to significantly improve outcomes in genetic blood disorders. Continued monitoring and further research are recommended to fully understand the long-term implications and safety of such treatments.
Reference:
CRISPR-Cas9 gene editing in sickle cell disease shows high efficacy in preventing vaso-occlusive crises
25 Apr, 2024 | 23:21h | UTCStudy Design and Population: This phase 3, single-group, open-label randomized clinical trial investigated the efficacy of exagamglogene autotemcel (exa-cel), a nonviral CRISPR-Cas9 gene-edited therapy, in patients aged 12 to 35 years with severe sickle cell disease. The study included patients who experienced at least two severe vaso-occlusive crises annually in the two years prior to screening. The therapeutic intervention involved editing CD34+ hematopoietic stem and progenitor cells (HSPCs) and administering a myeloablative conditioning regimen with busulfan.
Main Findings: Of the 44 participants treated, 30 with sufficient follow-up demonstrated a significant response. Ninety-seven percent (29 of 30) remained free from severe vaso-occlusive crises for at least 12 consecutive months, and 100% (30 of 30) avoided hospitalization for these crises over the same period. The intervention showed a high safety profile, consistent with myeloablative busulfan conditioning and autologous HSPC transplantation, with no cancers reported during the follow-up.
Implications for Practice: The results suggest that exa-cel can effectively eliminate severe vaso-occlusive crises in patients with sickle cell disease, marking a substantial advance in treatment options. These findings may pave the way for broader application of gene-editing therapies in hematologic diseases, pending further research on long-term outcomes and safety.
Nested Case-Control Study: Increased risk of major bleeding in atrial fibrillation patients with concomitant SSRI and oral anticoagulant use
23 Mar, 2024 | 20:48h | UTCStudy Design and Population
This nested case-control study investigated the association between the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and oral anticoagulants (OACs) on the risk of major bleeding among patients with atrial fibrillation. Conducted within the UK’s Clinical Practice Research Datalink, the study included 42,190 cases of major bleeding matched to 1,156,641 controls based on age, sex, cohort entry date, and follow-up duration. Patients initiating OACs between January 2, 1998, and March 29, 2021, were included, with risk-set sampling utilized for control selection.
Main Findings
The study found that concomitant use of SSRIs and OACs was associated with a 33% increased risk of major bleeding compared to OAC use alone, with the highest risk observed within the first 30 days of concurrent use. The increased risk was consistent across different ages, sexes, and patient histories, including those with chronic kidney disease or previous bleeding events. Notably, the elevated risk of bleeding extended up to 6 months of concomitant use but did not vary significantly with the potency of SSRIs or the type of OAC used (direct OACs or vitamin K antagonists).
Implications for Practice
These findings underscore the need for healthcare professionals to closely monitor patients with atrial fibrillation who are prescribed SSRIs in addition to OACs, particularly during the initial months of treatment. This study highlights the importance of managing bleeding risk factors and suggests reconsidering the necessity and duration of concomitant SSRI and OAC use. Future research should focus on strategies to mitigate this bleeding risk and explore alternative treatments for managing depression in patients requiring anticoagulation.
Reference
Phase 2 RCT: Low-dose aspirin significantly reduces hepatic fat in MASLD patients without cirrhosis
20 Mar, 2024 | 17:48h | UTCStudy Design and Population: This phase 2, randomized, double-blind, placebo-controlled clinical trial was carried out over six months at a single hospital in Boston, Massachusetts. The study included 80 participants aged 18 to 70 years diagnosed with metabolic dysfunction–associated steatotic liver disease (MASLD) but without cirrhosis. Participants were randomly assigned to receive either 81 mg of daily aspirin (n=40) or placebo (n=40).
Main Findings: The trial revealed that aspirin significantly reduced the mean absolute change in hepatic fat content by -10.2% compared with placebo, as measured by proton magnetic resonance spectroscopy (MRS), with a statistically significant difference (P=0.009). Furthermore, aspirin treatment notably decreased relative hepatic fat content, increased the proportion of patients achieving a 30% or greater reduction in hepatic fat, and reduced both absolute and relative hepatic fat content as assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Adverse events were mostly minor, with upper respiratory infections and arthralgias being the most common.
Implications for Practice: These findings suggest that low-dose aspirin may be an effective intervention for reducing liver fat in adults with MASLD without cirrhosis, potentially offering a simple, accessible treatment option. However, the results are preliminary and call for further confirmation in larger, more diverse populations. The study underscores the importance of considering low-dose aspirin as part of management strategies for MASLD, pending further research.
Reference
Simon TG et al. (2024). Randomized Clinical Trial: Low-Dose Aspirin Significantly Reduces Hepatic Fat in MASLD Patients Without Cirrhosis. JAMA, 331(11), 920-929. DOI: 10.1001/jama.2024.1215. Access the study here: [Link]
RCT | Restrictive vs. liberal red blood cell transfusion strategy for critically injured patients
11 Aug, 2023 | 15:08h | UTC
NICE Updated Guideline | Venous thromboembolic diseases
7 Aug, 2023 | 15:05h | UTC
Global prevalence, years lived with disability, and trends in anemia burden by severity and cause, 1990–2021
3 Aug, 2023 | 13:43h | UTC
Commentary on Twitter
NEW #GBD study by @IHME_UW on the #anaemia burden by severity and cause, 1990–2021?https://t.co/NbiEDSkbGI
Despite a decrease in prevalence, the number of people with anaemia increased globally
In every region females had a higher #anemia YLDs than males pic.twitter.com/oFx4vHRhs1
— The Lancet Haematology (@TheLancetHaem) August 1, 2023
RCT | Ferric derisomaltose plus tranexamic acid may reduce blood transfusion risk by 50% in hip surgery
3 Aug, 2023 | 13:18h | UTCFerric derisomaltose and tranexamic acid, combined or alone, for reducing blood transfusion in patients with hip fracture (the HiFIT trial): a multicentre, 2 × 2 factorial, randomised, double-blind, controlled trial – The Lancet Haematology (link to abstract – $ for full-text)
BSH guideline for anticoagulant management of pregnant individuals with mechanical heart valves
2 Aug, 2023 | 14:01h | UTC
Review | Perioperative iron deficiency anemia
31 Jul, 2023 | 14:02h | UTCPerioperative iron deficiency anaemia – BJA Education
Systematic Review | Monocyte distribution width as a diagnostic marker for infection
26 Jul, 2023 | 13:26h | UTCMonocyte Distribution Width as a Diagnostic Marker for Infection – CHEST
Commentary on Twitter
What is the diagnostic performance of monocyte distribution width across multiple infectious disease outcomes and care settings? Read the full original research in the July issue to learn more: https://t.co/iJxzNwdlgq#JournalCHEST #MedEd #CHESTCritCare pic.twitter.com/epYYOJA9wt
— CHEST® Journal (@journal_CHEST) July 7, 2023
Cohort Study | The role of antiphospholipid syndrome and specific antibodies in predicting SLE pregnancy complications
25 Jul, 2023 | 13:44h | UTCPregnancy outcomes in 1869 pregnancies in a large cohort from the Spanish Society of Rheumatology Lupus Register (RELESSER) – Seminars in Arthritis and Rheumatism (link to abstract – $ for full-text)
Commentary: SLE and Pregnancy Outcomes – RheumNow
Consensus Paper | De-escalation or abbreviation of dual antiplatelet therapy in acute coronary syndromes and PCI
24 Jul, 2023 | 13:08h | UTCDe-escalation or abbreviation of dual antiplatelet therapy in acute coronary syndromes and percutaneous coronary intervention: a Consensus Statement from an international expert panel on coronary thrombosis – Nature Reviews Cardiology (if the link is paywalled, try this one)
Guideline Synopsis | Diagnosis and management of priapism
21 Jul, 2023 | 13:47h | UTCDiagnosis and Management of Priapism – JAMA (free for a limited period)
Original Guideline: The Diagnosis and Management of Recurrent Ischemic Priapism, Priapism in Sickle Cell Patients, and Non-Ischemic Priapism: An AUA/SMSNA Guideline – Journal of Urology