December 2023: New In Coagulation
by Donna Castellone, MS, MT(ASCP)S • November 29, 2023
Our Monthly complilation of the latest studies, guidelines and discussions in coagulation.
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Using Statins With Blood Thinners Linked With Less GI Bleeding Risk
A retrospective analysis using the Epic Cosmos database found that people who took statins along with blood thinners had a lower risk of GI bleeding. This was seen regardless of the type of blood thinner. A review of 17 million people on blood thinners, 11.2% presented with a GI bleed compared with 4.4% of people who were simultaneously on a blood thinner and statin suggesting a correlation between the two. Additionally, when different types of blood thinners were investigated there was a difference: aspirin versus aspirin and statin (11.5% vs 4.6%), warfarin versus warfarin with statins (16.9% vs 7.8%) and DOACs versus DOACs with aspirin (15.5% vs 7.1%). It was not known it the patients presented with upper or lower GI bleeding, and will be investigated as well as if higher doses of statins have a great effect in reducing GI bleeding. Since the study is retrospective, no recommendations can be made as to whether statins should be prescribed. However, the role that statins play in decreasing inflammation may be a venue to investigate.
Even Less Aspirin With Ticagrelor-Based DAPT Safe After Stenting for ACS
The T-PASS study showed that stopping ticagrelor post drug eluting stent implantation for ACS was safer that continuing. Ticagrelor monotherapy after less than 1 month of DAPT saw a 2.8% composite rate of death, MI, stent thrombosis, stroke, and major bleeding at 1 year compared with 5.2% in those with 12 months of DAPT. This met both noninferiority and superiority criteria for greater net clinical benefit with dropping aspirin early. There was also a significant reduction in major bleeding with decreased aspirin (1.2% vs 3.4%). This supports the experience of approximately 22,000 patients in dropping aspirin from ticagrelor based DAPT across five trials. Results show also demonstrate no increase in ischemic events after PCI.
The participants in this trial were at a higher risk than other studies. Almost 40% had ST-segmented MI as well as the even shorter durantion and the use of ticagrelor instead of clopidogrel which had shown an increased risk of ischemia in some studies. All this supports reviewing the current US guidelines to shorten DAPT due to the safety of the third and fourth generation of drug eluting stents.
The trial included 2850 patients at 24 centers in South Korea who had received the Orsiro biodegradable polymer sirolimus-eluting stent for ACS within 4 weeks prior to implementation. Subjects received a loading dose of aspirin and ticagrelor twice daily and randomized to either receive DAPT or to discontinue aspirin and just continue ticagrelor 90 mg twice daily alone up to 12 months. Results showed that discontinuing aspirin did alter the occurrence of major adverse cardiac events as well as ischemia.
Study was limited due to lack of statistical power for primary endpoint as well as open label design.
First Treatment Approved for Genetic Clotting Disorder
Adzynma has been approved by the FDA as prophylactic or on demand enzyme replacement therapy for patients with congenital thrombocytopenic purpura (cTTP). This is a rare, chronic blood clotting disorder cause by a mutation in the ADAMTS13 gene. It affects less than 1000 people in the US annually. This leads to a deficiency in the ADAMTS13 enzyme which results in blood clots for form in the small blood vessels throughout the body and they may experience severe bleeding episodes, strokes and damage to vital organs. Unless treated it is fatal.
Approval of the drug was based on a randomized open label crossover phase II trial that showed reductions in acute and subacute TTP events compared with plasma based therapy. Subjects received 40IU/kg of recombinant ADAMTS 13 produce by IV or plasma based therapy every other week or weekly based on their regimen at enrollment for months 1 to 6 (period 1), crossing over to the alternate therapy for months 7 to 12 (period 2), with all patients receiving the protein product for months 13 to 18 (period 3). No acute TTP events occurred among 37 patients who had recombinant prophylaxis therapy versus one event in 38 patients with plasma based therapy. And no subacute TTP events were reported in patients receiving the recombinant form of ADAMTS13 during periods 1 and 2, compared with five subacute TTP events in four patients receiving plasma-based therapies.
The mean annualized event of thrombocytopenia manifestations was 2.0 for recombinant verses 4.44 with plasma based therapies.
Consequences of Oral Anticoagulant Choice Magnified in the Frail
Better outcomes in frail patients were found in patients taking apixaban when compared with other OACs. Rivaroxaban was associated with significantly increased risk of hospitalization or nursing care within 1 year after initiation. There was also a higher composite risk of stroke, systemic embolism, major bleeding or death. The same results were found in warfarin versus apixaban. This supports the use of apixaban as the preferred OAC for older frail adults with AF.
Costs were less with apixaban than rivaroxaban but higher than warfarin based on OAC costs, however when looking at other costs apixaban was the lowest. Frail adults are a complex population that require more rehospitalization and discharge to another facility. They are underrepresented in clinical trials. This study did not compare dabigatran and edoxaban.
The study looked at Afib patients prescribed OAC sue to risk of ischemic stroke. A total of 136,551 participants with a mean age of 77.6 year, with a triality index observed in 23% of the cohort. Factors that may favor the use of apixaban include adherence to OAC, drug interaction and the impact of reduced doses of DOACs. Additionally, results were only observed 1 year post initiation.
Study Finds No Signals for CV, VTE Risk With JAK Inhibitors for Skin Diseases
A review of PubMed and ClinicalTrials.gov looked for phase 3 dermatology RCT's to look at the risk of MACE, VTE and all cause mortality with JAK inhibitors versus placebo or an active comparator in the treatment of immune mediated inflammatory skin diseases. Results revealed 35 RCTs with a total of 20,651 patients, 54% male with a mean age of 38.5. Disorders included atopic dermatitis, psoriasis and alopecia and vitiligo.
Previous studies have suggested that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors. Results found no significant differences between using JAK inhibitor and placebo comparator. Results were similar in those with psoriatic arthritis, as well as comparing topical versus oral JAK inhibitors, as there were no significant differences in short term use.
The limitations of the review included the lack of access to patient-level data as well as short term follow up, as well as being able to generalize to an older population. It is hard to evaluate if the cardiovascular risk of the JAK inhibitors are due to the drug or the patient level of cardiovascular risk.
Impressive Bleeding Profile With Factor XI Inhibitor in AF: AZALEA
Abelacimab, the factor XI inhibitor which is a monoclonal antibody given by subcutaneous injection monthly, showed significant reductions in major and clinically relevant bleeding when compared with rivaroxaban in patients with AF and moderate to high risk of stroke. These results were from the phase 2b AZALEA trial which was stopped because of the overwhelming reduction in major bleeding of up to 74% and GI bleeding up to 93%.
AF is one of the most common medical conditions and results in an increased risk of stroke up to 30-60% of patients are not prescribed an OAC or discontinue if because of bleeding. Using a factor XI inhibitor should reduce thrombotic events without causing excess bleeding. AZALEA enrolled 1287 adults with AF at a high risk of stroke assigned to oral rivaroxaban 20 mg daily; abelacimab 90 mg; or abelacimab 150 mg. Abelacimab was given monthly by injection.Both doses of abelacimab inhibited factor XI almost completely; 97% inhibition was achieved with the 90-mg dose, and 99% inhibition was achieved with the 150-mg dose. A clear reduction in bleeding was seen during a median follow up of 1.8 years. There were only 25 strokes in the group which is a rate of 1% versus 7% in patients without anticoagulation.
A phase 3 trial would be required to determine how effective factor XI inhibition with abelacimab is compared to NOACs in reducing stroke rates.
Apixaban Cuts Stroke but Ups Bleeding in Subclinical AF: ARTESIA
The ARTESIA study demonstrated that in patients with subclinical AF apixaban resulted in a lower risk of stroke but a higher risk of major bleeding. In a meta analysis two trials revealed that both edoxaban or apixaban reduced stroke by one third and doubles the risk of major bleeding. Investigator from the ARTESIA trial believes the risk and benefit should be evaluated by individual patient. Databases with more information may help to define patients where the benefits outweight the risk and if anticoagulation should be given.
The ARTESIA study of 4012 patients with device detected AF and other clinical risk factor for stroke were randomly assigned to treatment with apixaban or aspirin. A follow up of 3.5 years, occurred in 86 patients in the aspirin group and 55 patients in the apixaban group, which was 37% lower and disabling or fatal stroke was reduced by A0.94% ( 8 were fatal) in the aspirin group.
The NOAH-AFNET 6 subgroup analysis randomly assigned 2538 patients with subclinical AF as well as additional risk factors for stroke to edoxaban or placebo. The trial was stopped early due to being underpowered, however the endpoint of stroke systemic embolism or death from cardiovascular causes had no difference in outcomes, but there was a higher risk of major bleeding. There was only 49 strokes in the entire study.
The meta analysis of the two trials demonstrated that results are consistent with overall reduction in ischemic stroke with OAC. There was no significant difference in cardiovascular death but significantly increased major bleeding.
Researchers explore origins of lupus, find reason for condition's prevalence among women
Lupus, an auto immune condition, has always occurred nine times more frequently in women than in men. It has been found that a number of dysregulated genetic and biological pathways contribute to the development of lupus and it's symptoms. This includes muscle and joint pain, skin rashes, kidney problems. A toll-like receptor 7 (TLR7) which is a protein in the immune system that reacts to the body's own RNA which triggers an immune response that damages healthy tissue. A piece of genetic material that is found only in women called X-inactive transcript (XIST) which is a type of RNA that plays a role in inactivating one of the tow X chromosomes found in female cells so that females do not have imbalanced gene expression and can trigger TLR7's immune response. XIST can strongly bind to TLR7 and trigger the production of interferons and immune system protein which is at high levels in lupus. This contributes to tissue damage and was found to drive the process of an overactive immune response and contributed to lupus development. It was found the higher the levels of XIST in blood cells the greater the severity and symptoms of lupus.
Silent Gastrointestinal Bleeds Track With Antiplatelet Choice After PCI
Gastrointestinal (GI) injury post coronary intervention (PCI) is dependent on what patients took as antiplatelet therapy from the OPT-PEACE trial. After 6 month DAPT, patient who received aspirin monotherapy had the lowest rate of progressive gastric injury by 12 months when compared to clopidogrel monotherapy or continued DAPT. As well as patients with progressive small intestinal injury. This supports that patients without a high risk of GI bleeding may progress to a high risk when using continuous antiplatelet therapy.
Antiplatelets are given to prevent subsequent cardiac events, but can result in GI bleeding in particular in those with clinically silent gastric or small intestinal injury which makes them predisposed to developing overt GI bleeding which is a strong predictor of mortality. These patients may require gastrointestinal prophylaxis of shortened DAPT if ischemic risk is low.
Guidelines recommend DAPT for at least 6-12 months after PCI in those without bleeding risk. New evidence suggests a shorter course of DAPT followed by monotherapy can be good enough for ischemic protection without excessive bleeding.
A post hoc analysis of the OPT-PEACE study included patients who underwent successful PCI with drug eluting stents and who did not have a high GI bleeding risk. After 6 months of DAPT those without GI ulcers or bleeding were randomized to aspirin plus matching placebo aspirin alone; n=132), clopidogrel plus matching placebo (clopidogrel alone; n=132), or DAPT (n=130) for an additional 6 months.
The main result of OPT-PEACE is that all subjects (n=394, mean age 56.9, 75% male) on antiplatelets after PCI developed dome form of GI injury with a year, but in patients who switched to monotherapy had less GI injury. Clopidogrel was found to exacerbate aspirin related small intestinal injury or prevents healing however the mechanism is uncertain. This study was not powered for this group of patients and results should be validated in a broader range of patients.
Alteplase Not Harmful in NOAC Users, Even in a More Bleeding-Prone Cohort
In an Asian cohort study,( 7,483 adults (mean age 67.4 years, 38.9% women) it was found that stroke patients treated with alteplase did not result in having more ICH is they had taken NOACs. Asians are thought to have a higher bleeding risk during thrombolytic therapy. There was only a small difference in bleeding and mortality in those who did not receive treatment and there was no statistical significance. Intracranial hemorrhage during hospitalization after alteplase administration: 9.9% with NOACs vs 7.4% with no anticoagulants. Major bleeding during the index hospitalization: 13.2% vs 8.2%, All-cause 30-day mortality: 8.8% vs 11.0% and in-hospital mortality: 4.4% vs 9.3% There were also no differences in warfarin groups. These results may aid in updating current stroke guidelines which do not support alteplase for these patients and recommend waiting 48 hours to reduce the risk of bleeding.
The study looked at patients on dabigatran, rivaroxaban, apixaban or edoxaban, two ThNOAC levels measured nor received any antidote. The NOAC group was of disproportionately older age and comprised more women. This group also had a higher prevalence of prior stroke and coronary artery disease. The NOAC group was of disproportionately older age and comprised more women. This group also had a higher prevalence of prior stroke and coronary artery disease. Due to the retrospective nature of the study there is room for residual confounding.
Apixaban Prophylaxis Fails to Reduce Clots in Pediatric ALL
The PREVAPIX-ALL study was an open-label trial and included 512 patients ages 1 to 17 with newly diagnosed ALL (pre-B cell or T cell) or lymphoblastic lymphoma (B cell or T cell immunophenotype), with a new central venous line inserted between days -7 and 4 of induction to remain in place until at least day 29 of therapy. These patients are known to be at a higher risk of thrombosis during this time. Patients were randomly assigned 1:1 to weight-adjusted twice-daily apixaban during induction (median age 6, 55% boys, and 76% white) or standard of care (median age 6, 58% boys, and 76% white).
Results showed that apixaban failed to reduce the rate of VTE in this population. During the follow up of 27 days, 12% of patients on DOACs had a composite VTE versus 18% who did not receive anticoagulation. Two major bleeding events occurred in each group and non major bleeding occurred more frequently in the apixaban (4%) versus standard of care group (1%).
The study doesn't support uniform use of pharmacological thrombophylaxis in these patients and the safety of apixaban during induction chemotherapy and requires more studies but it does provide encouraging safety data when the benefit outways the risk of bleeding.
JOURNAL CLUB
Nitrous Oxide-induced Polyneuropathy, Pancytopenia and Pulmonary Embolism
Guillaume Parein; Benjamin Bollens, J Med Case Reports. 2023;17(350)
Abstract
Background: Nitrous oxide is a medical and household gas that has seen its use drift to recreational purpose among the young population in recent years. Significant neurological, hematological and psychiatric side effects, generally related to an induced functional vitamin B12 deficiency, have been described separately in the literature.
Case Report: A 22-year-old woman of North African origin experienced an exceptional combination of polyneuropathy, bilateral pulmonary embolism and severe pancytopenia related to vitamin B12 deficiency and hyperhomocysteinemia induced by recreational nitrous oxide use. After treatment with vitamin B12 supplementation and intensive rehabilitative management, the patient progressively regained the ability to walk and her biological parameters gradually returned to normal. The pathophysiological mechanisms related to a decrease in vitamin B12 activity are the reduction of products needed for synthesis of deoxyribonucleic acid, carbohydrate or fatty acids, and the increase of hyperhomocysteinemia. Other mechanisms involving a direct action of N2O are also suspected.
Conclusion: This case report brings elements to support our knowledge about pathological pathway, recovery and prognosis of recreational N2O abuse complications. The general and medical population should be aware to the serious consequences of this type of consumption.
Comparative Safety and Effectiveness of Warfarin or Rivaroxaban Versus Apixaban in Patients With Advanced CKD and Atrial Fibrillation: Nationwide US Cohort Study
Edouard L Fu, Rishi J Desai, Julie M Paik, Dae Hyun Kim, Yichi Zhang, Julianna M Mastrorilli, Alexander Cervone, Kueiyu Joshua Lin
Am J Kidney Dis. 2023 Oct 13:S0272-6386(23)00859-4.
Abstract
Rationale & objective: Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced CKD are lacking. We compared the safety and effectiveness of warfarin or rivaroxaban vs. apixaban in patients with AF and non-dialysis CKD stages 4-5.
Study design: Propensity score matched cohort study.
Setting & Participants: Two nationwide U.S. claims databases, Medicare and Optum's de-identified Clinformatics® Data Mart Database (01/01/2013-03/31/2022). New initiators of warfarin vs. apixaban (N = 12,488) and rivaroxaban vs. apixaban (N = 5720) with nonvalvular AF and CKD stage 4-5.
Exposures: Warfarin, rivaroxaban or apixaban.
Outcomes: Primary outcomes included major bleeding and ischemic stroke. Secondary outcomes included all-cause mortality, major gastrointestinal bleeding, and intracranial bleeding.
Analytical approach: Cox regression was used to estimate hazard ratios (HR) and 1:1 propensity score matching was used to adjust for 80 potential confounders.
Results: Compared with apixaban, warfarin initiation was associated with a higher rate of major bleeding (HR 1.85; 95% CI 1.59-2.15), including major gastrointestinal bleeding (1.86; 1.53-2.25) and intracranial bleeding (2.15; 1.42-3.25). Rivaroxaban vs. apixaban was also associated with a higher rate of major bleeding (1.69; 1.33-2.15). All-cause mortality was similar for warfarin (1.08; 0.98-1.18) or rivaroxaban (0.94; 0.81-1.10) vs. apixaban. Furthermore, no statistically significant differences for ischemic stroke were observed for warfarin (1.14; 0.83-1.57) or rivaroxaban (0.71; 0.40-1.24) vs. apixaban, although confidence intervals were wide. Similar results were observed for warfarin vs. apixaban in the positive control cohort of patients with CKD stage 3, consistent with randomized trial findings.
Limitations: Few ischemic stroke events, potential residual confounding.
Conclusions: In patients with AF and advanced CKD, rivaroxaban and warfarin were associated with a higher rate of major bleeding compared with apixaban, suggesting a superior safety profile for apixaban in this high-risk population.
Effects of oral anticoagulation in people with atrial fibrillation after spontaneous intracranial haemorrhage (COCROACH): prospective, individual participant data meta-analysis of randomised trials
Rustam Al-Shahi Salman, Jacqueline Stephen, Jayne F Tierney, Steff C Lewis, David E Newby, Adrian R Parry-Jones, Philip M White, Stuart J Connolly, Oscar R Benavente, Dar Dowlatshahi, Charlotte Cordonnier, Catherine M Viscoli, Kevin N Sheth, Hooman Kamel, Roland Veltkamp, Kristin T Larsen, Jeannette Hofmeijer, Henk Kerkhoff, Floris H B M Schreuder, Ashkan Shoamanesh , Catharina J M Klijn, H Bart van der Worp; Collaboration of Controlled Randomised Trials of Long-Term Oral Antithrombotic Agents After Spontaneous Intracranial Haemorrhage (COCROACH)
Lancet Neurol 2023 Oct 11:S1474-4422(23)
Abstract
Background: The safety and efficacy of oral anticoagulation for prevention of major adverse cardiovascular events in people with atrial fibrillation and spontaneous intracranial haemorrhage are uncertain. We planned to estimate the effects of starting versus avoiding oral anticoagulation in people with spontaneous intracranial haemorrhage and atrial fibrillation.
Methods: In this prospective meta-analysis, we searched bibliographic databases and trial registries using the strategies of a Cochrane systematic review (CD012144) on June 23, 2023. We included clinical trials if they were registered, randomised, and included participants with spontaneous intracranial haemorrhage and atrial fibrillation who were assigned to either start long-term use of any oral anticoagulant agent or avoid oral anticoagulation (ie, placebo, open control, another antithrombotic agent, or another intervention for the prevention of major adverse cardiovascular events). We assessed eligible trials using the Cochrane Risk of Bias tool. We sought data for individual participants who had not opted out of data sharing from chief investigators of completed trials, pending completion of ongoing trials in 2028. The primary outcome was any stroke or cardiovascular death. We used individual participant data to construct a Cox regression model of the time to the first occurrence of outcome events during follow-up in the intention-to-treat dataset supplied by each trial, followed by meta-analysis using a fixed-effect inverse-variance model to generate a pooled estimate of the hazard ratio (HR) with 95% CI. This study is registered with PROSPERO, CRD42021246133.
Findings: We identified four eligible trials; three were restricted to participants with atrial fibrillation and intracranial haemorrhage (SoSTART, with 203 participants) or intracerebral haemorrhage (APACHE-AF, with 101 participants, and NASPAF-ICH, with 30 participants), and one included a subgroup of participants with previous intracranial haemorrhage (ELDERCARE-AF], with 80 participants). After excluding two participants who opted out of data sharing, we included 412 participants (310 [75%] aged 75 years or older, 249 [60%] with CHA2DS2-VASc score ≤4, and 163 [40%] with CHA2DS2-VASc score >4). The intervention was a direct oral anticoagulant in 209 (99%) of 212 participants who were assigned to start oral anticoagulation, and the comparator was antiplatelet monotherapy in 67 (33%) of 200 participants assigned to avoid oral anticoagulation. The primary outcome of any stroke or cardiovascular death occurred in 29 (14%) of 212 participants who started oral anticoagulation versus 43 (22%) of 200 who avoided oral anticoagulation (pooled HR 0·68 [95% CI 0·42-1·10]; I2=0%). Oral anticoagulation reduced the risk of ischaemic major adverse cardiovascular events (nine [4%] of 212 vs 38 [19%] of 200; pooled HR 0·27 [95% CI 0·13-0·56]; I2=0%). There was no significant increase in haemorrhagic major adverse cardiovascular events (15 [7%] of 212 vs nine [5%] of 200; pooled HR 1·80 [95% CI 0·77-4·21]; I2=0%), death from any cause (38 [18%] of 212 vs 29 [15%] of 200; 1·29 [0·78-2·11]; I2=50%), or death or dependence after 1 year (78 [53%] of 147 vs 74 [51%] of 145; pooled odds ratio 1·12 [95% CI 0·70-1·79]; I2=0%).
Interpretation: For people with atrial fibrillation and intracranial haemorrhage, oral anticoagulation had uncertain effects on the risk of any stroke or cardiovascular death (both overall and in subgroups), haemorrhagic major adverse cardiovascular events, and functional outcome. Oral anticoagulation reduced the risk of ischaemic major adverse cardiovascular events, which can inform clinical practice. These findings should encourage recruitment to, and completion of, ongoing trials.
Balancing the risk of stroke and bleeding in atrial fibrillation patients with a history of falls
Nang Khaing Zar Latt, Peter Calvert, Gregory Y H Lip
Expert Opin Drug Saf 2023 Oct 20:1-8.
Abstract
Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and can lead to serious consequences such as ischemic stroke and systemic thromboembolism. The risk of thromboembolism can be reduced by anticoagulation, however many patients with high falls risk do not receive oral anticoagulation.
Areas covered: In this narrative literature review, performed with searches of the PubMed database, we discuss the factors predisposing AF patients to falls, ways to optimize bleeding risk with individualized assessment, and clarify misconceptions around falls risk and anticoagulation therapy.
Expert opinion: In general, the advantages of stroke prevention with oral anticoagulation outweigh the risk of bleeding resulting from falls, especially with the increasing use of non-vitamin K oral anticoagulants, which are associated with fewer intracranial hemorrhages and thromboembolic complications than vitamin K anticoagulants. Most studies in this field are observational and randomized controlled studies would be beneficial.
Enoxaparin for symptomatic COVID-19 managed in the ambulatory setting: An individual patient level analysis of the OVID and ETHIC trials
Stefano Barco, Saverio Virdone, Andrea Götschi, Walter Ageno, Juan I Arcelus, Roland Bingisser, Giuseppe Colucci, Frank Cools, Daniel Duerschmied, Harry Gibbs, Riccardo M Fumagalli, Bernhard Gerber, Sylvia Haas, Jelle C L Himmelreich, Richard Hobbs, Lukas Hobohm, Barry Jacobson, Gloria Kayani, Renato D Lopes, Peter MacCallum, Evy Micieli, Marc Righini, Helia Robert-Ebadi, Ana Thereza Rocha, Thomas Rosemann, Jitendra Sawhney, Sebastian Schellong, Tim Sebastian, David Spirk, Stefan Stortecky, Alexander G G Turpie, Davide Voci, Nils Kucher, Karen Pieper, Ulrike Held, Ajay K Kakkar; OVID and ETHIC Investigators.
Thromb Res 2023 Oct:230:27-32. Epub 2023 Aug 18.
Abstract
Background: Antithrombotic treatment may improve the disease course in non-critically ill, symptomatic COVID-19 outpatients.M
Methods: We performed an individual patient-level analysis of the OVID and ETHIC randomized controlled trials, which compared enoxaparin thromboprophylaxis for either 14 (OVID) or 21 days (ETHIC) vs. no thromboprophylaxis for outpatients with symptomatic COVID-19 and at least one additional risk factor. The primary efficacy outcome included all-cause hospitalization and all-cause death within 30 days from randomization. Both studies were prematurely stopped for futility. Secondary efficacy outcomes were major symptomatic venous thromboembolic events, arterial cardiovascular events, or their composite occurring within 30 days from randomization. The same outcomes were assessed over a 90-day follow-up. The primary safety outcome was major bleeding (ISTH criteria).
Results: A total of 691 patients were randomized: 339 to receive enoxaparin and 352 to the control group. Over 30-day follow-up, the primary efficacy outcome occurred in 6.0 % of patients in the enoxaparin group vs. 5.8 % of controls for a risk ratio (RR) of 1.05 (95%CI 0.57-1.92). The incidence of major symptomatic venous thromboembolic events and arterial cardiovascular events was 0.9 % vs. 1.8 %, respectively (RR 0.52; 95%CI 0.13-2.06). Most cardiovascular thromboembolic events were represented by symptomatic venous thromboembolic events, occurring in 0.6 % vs. 1.5 % of patients, respectively. A similar distribution of outcomes between the treatment groups was observed over 90 days. No major bleeding occurred in the enoxaparin group vs. one (0.3 %) in the control group.
Conclusions: We found no evidence for the clinical benefit of early administration of enoxaparin thromboprophylaxis in outpatients with symptomatic COVID-19. These results should be interpreted taking into consideration the relatively low occurrence of events.
Defining heparin resistance: communication from the ISTH SSC Subcommittee of Perioperative and Critical Care Thrombosis and Hemostasis
Jerrold H Levy, Roman M Sniecinski, Bianca Rocca, Kamrouz Ghadimi, James Douketis, Corinne Frere, Julie Helms, Toshiaki Iba, Andreas Koster, Tara K Lech, Cheryl L Maier, Mathew D Neal, Ecatarina Scarlestscu, Alex Spyropoulos, Marie E Steiner, Alfonso J Tafur, Kenichi A Tanaka, Jean M Connors
J Thromb Haemost 2023 Aug 22:S1538-7836(23)00641-4.
Abstract
The term heparin resistance (HR) is used by clinicians without specific criteria. We performed a literature search and surveyed our SSC membership to better define the term when applied to medical and intensive care unit patients. The most common heparin dosing strategy reported in the literature (53%) and by survey respondents (80.4%) was the use of weight-based dosing. Heparin monitoring results were similar based on the proportion of publications and respondents that reported the use of anti-Xa and activated partial thromboplastin time. The most common literature definition of HR was >35 000 U/d, but no consensus was reported among survey respondents regarding weight-based and the total dose of heparin when determining resistance. Respondent consensus on treating HR included antithrombin supplementation, direct thrombin inhibitors, or administering more heparin as the strategies available for treating HR. A range of definitions for HR exist. Given the common use of heparin weight-based dosing, future publications employing the term HR should include weight-based definitions, monitoring assay, and target level used. Further work is needed to develop a consensus for defining HR.
Abbreviated or Standard Dual Antiplatelet Therapy by Sex in Patients at High Bleeding Risk. A Prespecified Secondary Analysis of a Randomized Clinical Trial
Antonio Landi, MD; Mirvat Alasnag, MD; Dik Heg, PhD; et alEnrico Frigoli, MD; Fazila Tun Nesa Malik, MBBS; Ivan Gomez-Blazquez, MD; Suzanne Pourbaix, MD; Alaide Chieffo, MD; Christian Spaulding, MD, PhD; Fermin Sainz, MD; Helen Routledge, MD; Giuseppe Andò, MD; Luca Testa, MD; Alessandro Sciahbasi, MD, PhD; Hussain Contractor, MD; Nigel Jepson, MD; Juan Mieres, MD; Syed Saqib Imran, MD; Husam Noor, MD; Pieter C. Smits, MD, PhD; Marco Valgimigli, MD, PhD; for the MASTER DAPT Investigators
JAMA Cardiol. /jamacardio.2023.4316
Abstract
Importance Abbreviated dual antiplatelet therapy (DAPT) reduces bleeding with no increase in ischemic events in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI).
Objectives To evaluate the association of sex with the comparative effectiveness of abbreviated vs standard DAPT in patients with HBR.
Design, Setting, and Patients This prespecified subgroup comparative effectiveness analysis followed the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated vs Standard DAPT Regimen (MASTER DAPT) trial, a multicenter, randomized, open-label clinical trial conducted at 140 sites in 30 countries and performed from February 28, 2017, to December 5, 2019. A total of 4579 patients with HBR were randomized at 1 month after PCI to abbreviated or standard DAPT. Data were analyzed from July 1 to October 31, 2022.
Interventions Abbreviated (immediate DAPT discontinuation, followed by single APT for ≥6 months) or standard (DAPT for ≥2 additional months, followed by single APT for 11 months) treatment groups.
Main Outcomes and Measures One-year net adverse clinical events (NACEs) (a composite of death due to any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (MACCEs) (a composite of death due to any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding (MCB).
Results Of the 4579 patients included in the analysis, 1408 (30.7%) were women and 3171 (69.3%) were men (mean [SD] age, 76.0 [8.7] years). Ischemic and bleeding events were similar between sexes. Abbreviated DAPT was associated with comparable NACE rates in men (hazard ratio [HR], 0.97 [95% CI, 0.75-1.24]) and women (HR, 0.87 [95% CI, 0.60-1.26];
Conclusions and Relevance These findings suggest that women with HBR did not experience higher rates of ischemic or bleeding events compared with men and may derive particular benefit from abbreviated compared with standard DAPT owing to these numerically lower rates of events.