January 2025: New In Coagulation
by Donna Castellone • January 21, 2025
Our Monthly complilation of the latest studies, guidelines and discussions in coagulation.
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Eltrombopag Improves Outcomes in Kids With Newly Diagnosed ITP
ITP is a rare bleeding disorder that affects 5-10/100,000 children annually. Many of the patients experience spontaneous remission within 6-12 months of diagnosis. Some require treatment for bleeding and impact on quality of life. Eltrombopag is a small molecule non-peptide thrombopoietin receptor agonist.
The PINES trial enrolled children of at least 1 year of age with a median enrollment age of 7.9 years in the eltrombopag group and 8.7 year in the standard group, 54% and 45% were girls. The median platelet count were 4 × 109/L and 8 × 109/L. A little over a third of patients in both groups had received upfront treatment before enrollment, and 63% of both groups had experienced treatment failure.
When 108 newly diagnosed ITP children were treated with eltrombopag results showed a significantly higher response rate of platelets when compared to first line treatment with standard therapy (intravenous immunoglobulin, prednisone, or anti-D immunoglobulin) (63 vs 35% respectively). The z-score for the superiority of eltrombopag versus standard of care was 2.78, which crossed the pre-defined efficacy monitoring boundary. Based on these results it was recommended that the trial be closed early for efficacy. The primary endpoint was defined as three out of four platelet counts >50 109/L without rescue treatment (weeks 6-12) was met by 65% of those in the eltromobpag arm. A composite endpoint of platelets >30 × 109/L with at least a twofold increase from baseline and no bleeding was achieved earlier in the standard treatment group (14 days vs 21 days in the eltrombopag arm).
The eltromobopag arm had 14 grade ≥3 adverse events including 6 serious events versus 6, 3 of them serious in the standard arm. The most common adverse event was headache, however quality of life improved in both arms.
Longer Admissions for IBD Flares Linked to VTE Risk
A small retrospective study (7/519 who experienced VTE) showed that a longer hospital stay doubled the odds of VTE in 6 months post discharge in patients with flares of inflammatory bowel disease (IBD) (OR 2.0, 95% CI 1.3-4.2,
An IBD database from the University of Iowa using EPIC medical records from 2010-2023 were reviewed for cases of VTE post hospitalization in patients with IBD to determine possible additional risk factors to identify ones that need VTE prophylaxis. In the 519 patients identified, 487 were excluded due to a history of VTE, a hypercoagulable comorbidity, or surgery leaving 7 patients. VTE occurred in an average of 20 days (9-25) with 14% having a PE and DVT in 86%. These were paired to matched controls. The average age of VTE was 55 years compared with 32 for the controls, average age of diagnosis was 31 in control versus 22 in controls with average duration of disease 4-6 years. The cohorts each comprised 43% patients with ulcerative colitis and 57% with Crohn's disease.
There were two risk factors that differentiated the risk of VTE: average length of stay 10 vs 4 and the albumin was 2.7 in the VTE cohort vs 3.4 in the control.
Cognitive Decline in AF Not Reduced by Anticoagulation
The BRAIN-AF trial was a randomized placebo-controlled trial testing DOAC for the prevention of cognitive decline in patients with AF. It included 1235 patients from 53 sites with a median age of 53, 96% were white, 25% female and 78% has a history of paroxysmal AF. After a follow up of 3.7 years, no difference was found between 15mg rivaroxaban and placebo that included cognitive decline, stroke, and TIA. There were 18% of study participants that met the definition of cognitive loss. As a result, it was halted for futility.
A limitation of the study was that it enrolled patients with a risk for stroke that did not meet the guidelines for OAC. The included age range of 30-62 years of age, with exclusions for previous stroke, hypertension, diabetes, and congestive heart failure the population was at a very low risk but not without risk. The observed rates of cognitive loss that accrued during a median follow-up of less than 4 years, the estimated stroke rate in this low-risk population was 0.5%-1.0% per year. The observed incidence was 2.5%.
The dose of rivaroxaban was 15mg versus the normal dose of 20 mg used in stroke prevention due to the concern of increased bleeding. There were no fatal bleeding events in either group, the differences in major bleeding (0.3% vs 0.8%) and stroke (2.5% vs 2.7%) were not significant when compared to the placebo group.
New Gel Stops Severe Bleeding in Seconds
Controlling hemorrhage in most cases is passive, that is using a material with either gauze or impregnated gauze where the mode of action is absorbing blood using pressure by a first responder or clinician. The idea is to stop the flow of blood to concentrate blood factors on the surface of the gauze and to promote platelet activation or the formation of fibrin to form a clot. These type of technologies are inefficient since they can be difficult to get into wounds and the form of bleeding. Also if the patient clotting is compromised the ability to create a durable clot that will not be ripped off when you remove the product is also concerning.
Currently, Traumagel is FDA cleared for prescription use only, but the goal is to make this product available for use by someone without medical training. The gel comes in a syringe that can be used to just point and shoot to control hemorrhage. Traumagel's indication must be removed within 24 hours. The patient produces a blood clot underneath but does not incorporate into the gel as opposed to using gauze in which the clot ends up wrapped around the fibers of the gauze which is porous and which results in the clot adhering to the gauze and coming off when it is removed.
Traumagel is nonporous so when a blood clot or fibrin is formed next to or on top of Traumagel it doesn't end up in the polymers. Since it is a hydrogel, there is less adhesion to the clot over time, when it is time to remove it, it has lost almost all of its adhesive ability resulting in the clot sticking to the tissue better than the gel.
Traumagel is made of two polysaccharides derived from plants. One is a polysaccharide that is polyanionic (positive charges) and the other is polycationic (negative charges) creating a mechanical barrier against bleeding.
This product has been tested using the US military model for lethal hemorrhage, also tested in carotid artery, aortic applications as well as venous and arterial bleeds. Failure rates have been low using Traumagel when it is used correctly. In a deep wound where you cannot visualize the source of the bleed, pressure is used to seat Traumagel into the source of bleeding where you're over wrapping with gauze, and you're providing a pressure wrapping to ensure that the Traumagel is in contact with the bleed while it's doing what it's doing. Traumagel is a sterile biocompatible product.
Traumagel is the next generation hemostatic agent in trauma care and emergency medicine allowing for faster control of hemorrhage with better patient outcomes.
Anticoagulant Considered After Bioprosthetic Valve Surgery
The ENBALV trial showed that edoxaban appeared to be as effective as or more effective than warfarin in preventing thromboembolism such as stroke systemic embolism or intracardiac thrombus in patients who had undergone bioprosthetic valve replacement surgery. This was the first large scale trial that looked at the use of DOAC in this cohort suggesting that edoxaban could be an alternative to warfarin offering more flexibility and convenience. Current guidelines recommend therapy with vitamin K antagonists such as warfarin. However, warfarin requires monitoring, has a narrow therapeutic range and interacts with other drugs and foods. Using DOACs would be easier for patients.
The study included 410 patients randomized to edoxaban or warfarin for 12 weeks. Up to 20% had AF, outcome measures were evaluated 12 weeks post-surgery. The primary outcome of stroke an embolism occurred in one patient in the edoxaban group and 3 patients in the warfarin group. No intracardiac thrombus was seen in the edoxaban group but occurred in 1% of the warfarin group. The edoxaban group had a higher frequency of bleeding, including more GI bleeding (2.1% vs 0.0%), but no fatal nor ICH occurred, but there was one fatal intracranial hemorrhage occurred in the warfarin group.
But the event rate was so low that definitive conclusions could not be determined.
Large study links air pollution to deep vein blood clotting
An observation study found that longer exposure to air pollution has been linked to a greater risk for deep vein blood clotting. The study was funded by the NIH. A total of 6651 participants were followed for 17 years and lived in or near New York, Baltimore, Chicago, Los Angeles, Minneapolis, and Winston-Salem. Three different types of air pollutants were researched. Results showed that adults that had greater exposure to pollution from smoke from coal-burning power plants, forest fires, and motor vehicle exhaust results in a 39% increased risk for VTE. While those with a higher exposure to oxides of nitrogen and nitrogen dioxide, pollutants most often found from vehicle exhaust, had a respective 121% to 174% increased risk.
What Now for Factor XI Inhibitors in AF?
The use of FXI inhibition as an anticoagulant target held the promise of a reduction of thrombotic risk without a significant increase in bleeding. An initial phase 2 data using orthopedic patients looked good. The phase 3 OCEANIC-AF study compared asundexian with apixaban in patients with AF was stopped early for futility.
Currently DOACs include Xa targeted drugs (apixaban, rivaroxaban, edoxaban) and target factor IIa (dabigatran) have improved patient management when compared to warfarin. Up to 30-40% of AF patients are not receiving anticoagulation and up to 5-8% come off of anticoagulation within the first 6 months. Many patients do not receive anticoagulation due to the risk of bleeding. Having a new targeted DOAC that reduces the risk of bleeding could fill an unmet need. The reason this target may work is factor XI is primarily involved with hemostatic thrombus formation via the tissue factor pathway but is not involved to a significant degree in the development of pathologic thrombi.
Results showed that asundexian was inferior to apixaban. Patients had a several fold higher risk for ischemic stroke. This may be attributed to insufficient dosing. The PACIFIC-AF phase 2 study used a dose of 50mg/day resulted in 92-94% reduction in FXI activity, while in the AXALEA-TIMI 71 trial of abelacimab (a monoclonal antibody that uniquely inhibits both factor XI and its active form factor XIa) a dose of 150mg results in 99% inhibition of FXI. The LIBREXIA-AF phase 3 trial using 100 mg dose of FXI a milvexian resulting in a 95% inhibition.
The issue with the study may be either insufficient dosing and complete suppression of factor XI may be required. It may also be that both FXI and XIa need to be inhibited. The study may be biased because patients were previously on anticoagulant, results may have been different if patients were not previously on therapy.
Lentiviral Gene Therapy Shows Promise in Severe Hemophilia A
A small study of 5 patients showed that gene therapy involving the use of lentiviral vector-transduced autologous hematopoietic stem cells (HSCs) increased factor VIII levels in patients with severe hemophilia A. The participants had severe hemophilia A (<1% measurable factor VIII activity), who ranged in age from 22 to 41. Each received CD68-ET3-LV-transduced autologous CD34+ HSCs at doses of 5.0 × 106 to 6.1 × 106 per kg of body weight. The vector copy numbers in the final drug product were 1.0 and 0.6 copies/cell for the two participants in group 1 and 1.5, 0.6, and 2.2 copies/cell for the three participants in group 2. The median follow up was 14 months. Levels of FVIII went to 5.2 and 1.7 IU/dL with a peripheral-blood vector copy number of 0.2 and 0.1 copies/cell, respectively, in the two participants in group 1 (who did not receive a transduction enhancer), and 37.1, 19.3, and 39.9 IU/dL with a peripheral-blood vector copy number of 4.4, 3.2, and 4.8 copies/cell, respectively, in the three participants in group 2 (who received a transduction enhancer). Over 81 months there was a median annualized bleeding rate of zero.
This study validated a new approach to gene therapy through transplantation after myeloablative conditioning of autologous HSCs transduced with a lentiviral vector encoding a novel factor VIII transgene driven by a CD68 promoter. This resulted in mild and well tolerated regimen related toxicities with a significant and sustained expression for Factor VIII activity. But it is a complex procedure that required individual product manufacturing as well as stem cell transplantation. Efficacy needs to be evaluated in larger numbers.
These results may be better than the results from the AVV delivered FVIII. A liver directed AAV vector based gene therapy has been approved for hemophilia. And two other AAV vector-based gene therapies, fidanacogene elaparvovec and anetranacogene dezaparvovec, for hemophilia B. Several limitations have been observed with these including an unpredictable initial levels ofexpression and a progressive drop of levels after 6-12 months mostly in hemophilia A. This is associated with transaminitis that needs immunosuppression and the exclusion of patients due to pre-existing anti-AVV antibodies and children under the age of 12 due to liver immaturity making a need for an alternative approach to gene therapy.
JOURNAL CLUB
Long-Term Aspirin vs Clopidogrel After Coronary Stenting by Bleeding Risk and Procedural Complexity
Jeehoon Kang, MD; Jaewook Chung, MD; Kyung Woo Park, MD; et alJang-Whan Bae, MD; Huijin Lee, MD; Doyeon Hwang, MD; Han-Mo Yang, MD; Kyoo-Rok Han, MD; Keon-Woong Moon, MD; Ung Kim, MD; Moo-Yong Rhee, MD; Doo-Il Kim, MD; Song-Yi Kim, MD; Sung-Yun Lee, MD; Seung Uk Lee, MD; Sang-Wook Kim, MD; Seok Yeon Kim, MD; Jung-Kyu Han, MD; Eun-Seok Shin, MD; Bon-Kwon Koo, MD; Hyo-Soo Kim, MD
Abstract
Importance Antiplatelet monotherapy in the chronic maintenance period for patients with high bleeding risk (HBR) and those who have undergone complex percutaneous coronary intervention (PCI) has not yet been explored.
Objective To compare clopidogrel vs aspirin monotherapy in patients with HBR and/or PCI complexity.
Design, Setting, and Participants This post hoc analysis of the multicenter HOST-EXAM Extended study, an open-label trial conducted across 37 sites in South Korea, enrolled patients from 2014 to 2018 with up to 5.9 years of follow-up. The analysis was conducted from February to November 2023. Patients who maintained dual antiplatelet therapy (DAPT) event-free for 6 to 18 months following PCI were included.
Interventions Patients were randomized to receive either clopidogrel or aspirin in a 1:1 ratio. Those with sufficient data to assess HBR or complex PCI were analyzed.
Main Outcomes and Measures Coprimary end points were thrombotic composite end point (cardiovascular death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and definite/probable stent thrombosis) and any bleeding (Bleeding Academic Research Consortium type 2 to 5).
Results Of 3974 patients included (mean [SD] age, 63.4 [10.7] years; 2976 male [74.9%]), 866 had HBR (21.8%), and 849 underwent complex PCI (21.4%). Clopidogrel as compared with aspirin was associated with lower rates of thrombotic and bleeding events regardless of HBR and/or PCI complexity. For the thrombotic composite end point, the hazard ratio (HR) was 0.75 (95% CI, 0.53-1.04) among HBR vs 0.62 (95% CI, 0.48-0.80) among patients without HBR (
Conclusions and Relevance In this study, in patients who experienced PCI and were event-free during 6 to 18 months of DAPT, the beneficial impact of clopidogrel monotherapy over aspirin monotherapy was consistent, regardless of bleeding risk and/or PCI complexity.
Clinical practice guidelines for management of disseminated intravascular coagulation in Japan 2024. Part 1: sepsis
Kazuma Yamakawa, Kohji Okamoto, Yoshinobu Seki, Takayuki Ikezoe, Takashi Ito, Toshiaki Iba, Satoshi Gando, Noritaka Ushio, Takaaki Totoki, Takeshi Wada, Hidesaku Asakura, Hiroyasu Ishikura, Mitsuhiro Uchiba, Toshimasa Uchiyama, Kaoru Kawasaki, Noriaki Kawano, Shigeki Kushimoto, Shin Koga, Yuichiro Sakamoto, Toshihisa Tamura, Kenji Nishio, Mineji Hayakawa, Takeshi Matsumoto, Seiji Madoiwa, Toshihiko Mayumi, Shinya Yamada, Hideo Wada; Committee of the Clinical Practice Guidelines for Management of Disseminated Intravascular Coagulation 2024, the Japanese Society on Thrombosis and Hemostasis
Int J Hematology, 2024 Dec 16.
Abstract
The Japanese Society on Thrombosis and Hemostasis (JSTH) published the first-ever disseminated intravascular coagulation (DIC) guidelines in 2009. Fifteen years later, the JSTH developed new guidelines covering DIC associated with various underlying conditions. These guidelines were developed in accordance with the GRADE system to determine the strength of the recommendations and certainty of the evidence. This article was drafted as Part 1 of an overall DIC guideline covering various underlying conditions, with sepsis as the subject. In this section, seven key clinical issues (questions) are set. Question 1, regarding DIC diagnosis, introduces several diagnostic criteria, such as the JAAM-2, ISTH overt, SIC, and JSTH DIC criteria and recommends choosing the appropriate diagnostic criteria for DIC based on an understanding of their diagnostic properties. For pharmacotherapy in DIC patients with sepsis, we recommend the administration of antithrombin (Question 2) and recombinant thrombomodulin (Question 3) (both GRADE 1B). However, we do not make a clear recommendation regarding the administration of heparin (Question 6) and serine protease inhibitors (Question 7) because of the lack of evidence. Combination therapy, order of administration, and other administration methods for antithrombin and recombinant thrombomodulin are proposed as important future research questions.
Demystifying autoimmune HIT: what it is, when to test, and how to treat
Marie Scully , William A Lester
Hematology Am Soc Hematol Educ Program 2024 Dec 6;2024(1):403-408.
Abstract
Antibodies to platelet factor 4 (PF4) have been primarily linked to classical heparin-induced thrombocytopenia (cHIT). However, during the rollout of the COVID-19 vaccine program a new condition, vaccine-induced thrombocytopenia and thrombosis (VITT), was identified, related to adenoviral-based COVID-19 vaccines. The differences between these 2 conditions, both clinically and in laboratory testing, set the scene for the development of a new rapid anti-PF4 assay that is not linked with heparin (as relevant for cHIT). Concurrently, there has been a reassessment of those cases described as autoimmune HIT. Such scenarios do not follow cHIT, but there is now a clearer differentiation of heparin-dependent and heparin-independent anti-PF4 conditions. The importance of this distinction is the identification of heparin-independent anti-PF4 antibodies in a new subgroup termed VITT-like disorder. Cases appear to be rare, precipitated by infection and in a proportion of cases, orthopaedic surgery, but are associated with high mortality and the need for a different treatment pathway, which includes immunomodulation therapy.
Practical guide to the diagnosis and management of heparin-induced thrombocytopenia
Jori May , Adam Cuker
Hematology Am Soc Hematol Educ Program. 2024 Dec 6;2024(1):388-395.
Abstract
Heparin-induced thrombocytopenia (HIT) is an immune reaction to heparin associated with thrombocytopenia, thrombotic risk, and a high risk of morbidity and mortality. Given the frequent use of heparin and the common occurrence of thrombocytopenia in hospitalized patients, the diagnosis and management of HIT is a recurrent challenge in everyday inpatient care. This article presents practical guidance and tools to support the individual clinician providing evidence-based care to patients with suspected or confirmed HIT. The optimal diagnostic evaluation requires the stepwise use of risk-stratification tools and laboratory assays. Management requires the selection and use of nonheparin anticoagulation in these complex patients with both increased thrombotic risk and possible concurrent increased bleeding risk due to thrombocytopenia. Each step in the diagnostic and management process has important nuances and complexities, many of which vary based on patient characteristics and institutional resources. Given the many challenges of HIT care, truly practical management is best achieved when tools are implemented to support the delivery of consistent, high quality, and cost-effective care across health systems.
Troubleshooting heparin resistance
Cheryl L Maier , Jean M Connors , Jerrold H Levy
Hematology Am Soc Hematol Educ Program. 2024 Dec 6;2024(1):186-191.
Abstract
The term heparin resistance is likely best defined as the failure of an appropriate dose of unfractionated heparin (UFH) to achieve a predetermined level of anticoagulation. Unfortunately, and despite many prior reports, there is no established consensus as to what either the appropriate dose or the predetermined level should be. Traditionally, assays used to monitor anticoagulation with UFH have been clot based, including the activated partial thromboplastin time, used for patients on the ward or intensive care unit, and the activated clotting time, used for patients undergoing vascular interventions and cardiopulmonary bypass. Unfortunately, these tests may be highly influenced by other factors occurring in many patients, especially those with inflammation or acute infection, as noted during the COVID-19 pandemic. Many hospitals have thus moved to anti-Xa testing for heparin monitoring. Another important factor in defining heparin resistance includes dosing, whether weight-based or total daily dosing is used, as initial reports of heparin resistance described daily doses independent of body weight. Multiple causes of apparent heparin resistance include hypercoagulability, antithrombin deficiency, andexanet alfa used for direct oral anticoagulant reversal, thrombocytosis, and antiphospholipid antibody syndromes. Treatment options for managing patients with heparin resistance include weight-based dosing and administration of additional UFH, antithrombin supplementation, or the use of an alternative anticoagulant such as the direct thrombin inhibitors bivalirudin or argatroban.
Warfarin and heparin monitoring in antiphospholipid syndrome
Prabal Mittal , Zara Sayar, Hannah Cohen
Hematology Am Soc Hematol Educ Program 2024 Dec 6;2024(1):192-199.
Abstract
Anticoagulation is central to the management of antiphospholipid syndrome (APS), an acquired thrombo-inflammatory disorder characterized by thrombosis (venous, arterial, or microvascular) or pregnancy morbidity, in association with persistent antiphospholipid antibodies (aPL; ie, 1 or more of lupus anticoagulant [LA], anticardiolipin, anti-beta-2- glycoprotein I, IgG, or IgM antibodies). The mainstay of anticoagulation in patients with thrombotic APS is warfarin or an alternative vitamin K antagonist (VKA) and, in certain situations, low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). Accurate assessment of anticoagulation intensity underpins optimal anticoagulant dosing for thrombus treatment or primary/secondary prevention. In patients with APS on warfarin, the international normalized ratio (INR) may not be representative of anticoagulation intensity due to an interaction between LA and the thromboplastin reagent used in the INR determination. In this review, we summarize the use of warfarin/VKA in patients with APS, along with venous and point-of-care INR monitoring. We also discuss the role and monitoring of LMWH/UFH, including in the anticoagulant refractory setting and during pregnancy.
DOACs Not Linked to Increased Intracranial Hemorrhage Risk
TOPLINE:
Direct oral anticoagulant (DOAC) therapy is not associated with a significantly higher risk for intracranial hemorrhage than single-agent antiplatelet therapy. However, DOACs are linked to an increased risk for major hemorrhage.
METHODOLOGY:
- Researchers conducted a systematic review and meta-analysis of nine randomized clinical trials involving 45,494 participants (mean age, 67.5 years; mean follow-up duration, 17.2 months) with various cardiovascular conditions.
- Data were extracted from PubMed and Embase databases, covering studies from database inception to February 7, 2024.
- Trials were selected on the basis of criteria such as a comparison of DOAC therapy with antiplatelet therapy (aspirin was the comparator in all included trials), reporting of bleeding events, enrollment of more than 200 participants, and a minimum follow-up of 30 days.
- The primary outcome was the occurrence of intracranial hemorrhage.
- The secondary outcomes included major, fatal, and gastrointestinal hemorrhage; ischemic stroke; and cardiovascular mortality.
TAKEAWAY:
- DOAC therapy was not associated with a significantly increased risk for intracranial hemorrhage compared with antiplatelet therapy (odds ratio [OR], 1.15; 95% CI, 0.71-1.88).
- DOAC therapy was linked to a 39% higher risk for major (95% CI, 1.07-1.80) and gastrointestinal hemorrhage (95% CI, 1.11-1.73) and a 42% higher risk for all hemorrhages (95% CI, 1.25-1.62) than antiplatelet therapy.
- Among the DOAC agents, rivaroxaban was associated with a significantly increased risk for intracranial hemorrhage (OR, 2.09; 95% CI, 1.20-3.64) and major hemorrhage (OR, 1.91; 95% CI, 1.22-3.00), whereas dabigatran and apixaban were not linked to a significant increase in risk.
- DOAC therapy was associated with a lower risk for ischemic stroke than antiplatelet therapy (OR, 0.74; 95% CI, 0.58-0.94), with no significant difference in the risk for cardiovascular mortality between the groups.
LIMITATIONS:
The intervention groups included a combination of different DOAC agents. The enrolled populations varied between trials, including those with atrial fibrillation and those with embolic stroke of undetermined source. The variability in the definition of major hemorrhage across trials may affect the comparability of results. The low rates of occurrence for certain outcomes, including fatal hemorrhage, may have resulted in summary estimates that were not precise.
The study was led by Mark Coyle, MSc, of the National University of Ireland Galway. It was published online on December 4, 2024, in
Clopidogrel Tops Aspirin Post-PCI, Even in High-Risk Cases
TOPLINE:
The beneficial effect of clopidogrel monotherapy over aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) and remained event free for 6-18 months on dual antiplatelet therapy (DAPT) is consistent, regardless of bleeding risk or PCI complexity, according to a post hoc analysis of the HOST-EXAM trial.
METHODOLOGY:
- The HOST-EXAM Extended study conducted across 37 sites in South Korea included patients who underwent PCI with drug-eluting stents and remained free of clinical events for 6-18 months post-PCI, while receiving DAPT.
- This post hoc analysis of the HOST-EXAM Extended study compared the effectiveness of long-term daily clopidogrel (75 mg) with that of aspirin monotherapy (100 mg) after PCI, according to bleeding risk and procedural complexity in 3974 patients (mean age, 63 years; 75% men) who were followed for up to 5.9 years.
- High bleeding risk was reported in 866 patients, and 849 patients underwent complex PCI.
- Patients were classified into four distinct risk groups: No bleeding risk and noncomplex PCI, no bleeding risk and complex PCI, high bleeding risk and noncomplex PCI, and high bleeding risk and complex PCI.
- The co-primary endpoints were thrombotic composite events (cardiovascular death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and definite/probable stent thrombosis) and any bleeding event.
TAKEAWAY:
- Thrombotic composite events (hazard ratio [HR], 2.15;
P < .001) and any bleeding event (HR, 3.64;P < .001) were more frequent in patients with a high bleeding risk than in those without. - However, there was no difference in the risk for thrombotic composite events or any bleeding event by PCI complexity.
- The long-term benefits of clopidogrel monotherapy over aspirin monotherapy were seen in all patients, regardless of bleeding risks (
P for interaction = .38 for thrombotic composite events andP for interaction = .20 for any bleeding event) or PCI complexity (P for interaction = .12 for thrombotic composite events andP for interaction = .62 for any bleeding event). - The greatest risk reduction in thrombotic composite events with clopidogrel monotherapy occurred in patients with a high bleeding risk who underwent complex PCI (HR, 0.46;
P = .03).
LIMITATIONS:
As this study is a post hoc analysis, the findings should be considered primarily hypothesis generating. This study was conducted exclusively in an East Asian population and may not be generalizable to other ethnic groups. The definitions of high bleeding risk and complex PCI used in this analysis were not prespecified in the study protocol of the HOST-EXAM trial. Certain criteria defining high bleeding risk were not analyzed as they fell under the exclusion criteria of the HOST-EXAM trial or were not recorded in the study case report form.
This study was led by Jeehoon Kang, MD, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea. It was published online on November 27, 2024, in