Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: A randomized, double‐blind, placebo‐controlled trial in asymptomatic antiphospholipid antibody–positive individuals

Erkan, Doruk; Harrison, Melanie; Levy, Roger A.; Peterson, Margaret G. E.; Petri, Michelle; Sammaritano, Lisa R.; Ünalp–Arida, Aynur; Vilela, Verônica Silva; Yazıcı, Yusuf; Lockshin, Michael D.

doi:10.1002/art.22663

Cited by 359 publications

(214 citation statements)

References 38 publications

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“…The contrasting results observed were probably determined by the different study design, the small number of cohort analyzed and the low incidence of events [2,[4][5][6]. In particular, the APLASA study, the first multicenter double-blind placebocontrolled RCT in the area, compared a dose of 81 mg of aspirin daily with placebo in asymptomatic aPL-positive individuals concluding that aspirin was not beneficial in preventing thrombosis.…”

Section: Resultsmentioning

confidence: 99%

“…Notably, all but one of the thrombotic events occurred in patients with additional thrombotic risk factors, or autoimmune diseases. Another important limitation of APLASA study was the small simple size included, due to recruitment difficulties, leaving the study underpowered [4]. Prospective RCTs specifically designed to evaluate the use of aspirin and other non-aspirin antithrombotic therapies are required, considering larger cohorts, including also patients with high prothrombotic risk.…”

Section: Resultsmentioning

confidence: 99%

“…Much more debated is the management of asymptomatic patients with aPL positivity confirmed 12 weeks apart, without a clinical history of venous or arterial thrombosis. To date, few clinical trials have addressed the role of primary prophylaxis in asymptomatic aPL subjects, and not univocal results have been reported [2,[4][5][6]. Moreover, the limited number of patients enrolled and the low incidence of outcome events make even more difficult to draw definitive conclusions.…”

Section: Thromboprophylaxis In Apl Carriers Without Previous Thrombosismentioning

confidence: 99%

“…The only randomized, double-blind, placebo-controlled trial (the APLASA study) investigating the efficacy of low-dose aspirin (LDA) as primary prevention of thrombotic events suggested aPL-positive individuals do not benefit from primary thrombosis prophylaxis: among 98 asymptomatic aPL carriers, LDA was not more effective than placebo for primary prophylaxis of thrombotic events. aPL-positive individuals were found to develop a first vascular event when additional procoagulant risk factors were present [4]. Concordingly, retrospective cohort studies reported that 46-76% of APS patients have other thrombotic risk factors at the time of vascular events.…”

Section: Thromboprophylaxis In Apl Carriers Without Previous Thrombosismentioning

confidence: 99%

“…The Antiphospholipid Antibody Acetylsalicylic Acid (APLASA) study was a multicenter, randomized, double-blind, placebo-controlled clinical trial in which asymptomatic, persistently aPL-positive individuals were randomized to receive a daily dose of 81 mg of aspirin or placebo [4]. In this study, 98 individuals were randomized to receive aspirin (n= 48) or placebo (n= 50) (mean ± SD follow up period 2.30 ± 0.95 years).…”

Section: Clinical Studies Of Aspirin In Asymptomatic Patients With Aplmentioning

confidence: 99%

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Thromboprophylaxis in carriers of antiphospholipid antibodies (APL) without previous thrombosis: “Pros” and “Cons”

Ceccarelli

Chighizola

Finazzi

et al. 2012

Autoimmunity Reviews

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a b s t r a c t a r t i c l e i n f o Available online xxxx Keywords:Anti-phospholipid antibodies Carriers Thromboprophylaxis Risk factorsThe presence of anti-phospholipid (aPL) is necessary but not sufficient to induce a thrombotic event. The "second hit" hypothesis suggested that an additional trigger may be needed to develop a vascular event in aPL carriers. In this article, pro and con of primary thromboprophylaxis in aPL carriers is deeply discussed, concluding that univocal data are not available, due to conflicting results of available clinical trials. However, in clinical practice the primary thromboprophylaxis is not indicated in all unselected asymptomatic aPL carriers, and the best strategy begin with the assessment of the peculiar risk profile of the subject. Thus, it is mandatory to eliminate modifiable prothrombotic risk factors (i.e. smoking, oral contraceptive), to treat the irreversible risk factors (i.e. hypertension, diabetes) and to introduce an aggressive prophylaxis with subcutaneous LMWH in high-risk situations (i.e. surgical procedures with prolonged immobilization). A different evaluation should be addressed to aPL carriers with a concomitant autoimmune disease that are considered as an additional pro-thrombotic risk factor. Similarly, concomitant positivity for more than one antiphospholipid test confer a stronger risk of developing the thrombotic manifestations. Specific trials with larger cohorts of patients are needed to better clarify this issue.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Thromboprophylaxis In Apl Carriers Without Previous Thrombosismentioning

confidence: 99%

Section: Thromboprophylaxis In Apl Carriers Without Previous Thrombosismentioning

confidence: 99%

Section: Clinical Studies Of Aspirin In Asymptomatic Patients With Aplmentioning

confidence: 99%

See 3 more Smart Citations

Thromboprophylaxis in carriers of antiphospholipid antibodies (APL) without previous thrombosis: “Pros” and “Cons”

Ceccarelli

Chighizola

Finazzi

et al. 2012

Autoimmunity Reviews

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Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events

et al. 2023

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ImportanceThe prevalence of antiphospholipid antibodies (aPL) and their association with future atherosclerotic cardiovascular disease (ASCVD) risk has yet to be thoroughly investigated.ObjectiveTo determine the association between measurements of aPL at a single time point and ASCVD risk in a diverse population.Design, Setting, and ParticipantsThis cohort study measured 8 aPL (anticardiolipin [aCL] IgG/IgM/IgA, anti–beta-2 glycoprotein I [aβ2GPI] IgG/IgM/IgA, and antiphosphatidylserine/prothrombin [aPS/PT] IgG/IgM) by solid-phase assays in plasma from participants of the Dallas Heart Study (DHS) phase 2, a multiethnic, population-based cohort study. Blood samples were collected between 2007 and 2009. The median follow-up was 8 years. Statistical analysis was performed from April 2022 to January 2023.Main Outcomes and MeasuresAssociations of aPL with future ASCVD events (defined as first nonfatal myocardial infarction, first nonfatal stroke, coronary revascularization, or death from cardiovascular cause) were assessed by Cox proportional hazards models, adjusting for known risk factors, medications, and multiple comparisons.ResultsAmong the 2427 participants (mean [SD] age, 50.6 [10.3] years; 1399 [57.6%] female; 1244 [51.3%] Black, 339 [14.0%] Hispanic, and 796 [32.8%] White), the prevalence of any positive aPL tested at a single time point was 14.5% (353 of 2427), with approximately one-third of those detected at a moderate or high titer; aCL IgM had the highest prevalence (156 individuals [6.4%]), followed by aPS/PT IgM (88 [3.4%]), aβ2GPI IgM (63 [2.6%]), and aβ2GPI IgA (62 [2.5%]). The IgA of aCL (adjusted hazard ratio [HR], 4.92; 95% CI, 1.52-15.98) and aβ2GPI (HR, 2.91; 95% CI, 1.32-6.41) were independently associated with future ASCVD events. The risk further increased when applying a positivity threshold of at least 40 units (aCL IgA: HR, 9.01 [95% CI, 2.73-29.72]; aβ2GPI IgA: HR, 4.09 [95% CI, 1.45-11.54]). Levels of aβ2GPI IgA negatively correlated with cholesterol efflux capacity (r = −0.055; P = .009) and positively correlated with circulating oxidized LDL (r = 0.055; P = .007). aβ2GPI IgA–positive plasma was associated with an activated endothelial cell phenotype as evidenced by increased surface expression of surface E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1.Conclusions and RelevanceIn this population-based cohort study, aPL detectable by solid-phase assays were present in a substantial proportion of adults; positive aCL IgA and aβ2GPI IgA at a single time point were independently associated with future ASCVD events. Longitudinal studies with serial aPL measurements are needed to further explore these findings.

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Frequency of Intracranial Hemorrhage With Low-Dose Aspirin in Individuals Without Symptomatic Cardiovascular Disease

Huang

Saver

et al. 2019

JAMA Neurol

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IMPORTANCE Use of low-dose aspirin for the primary prevention of cardiovascular events remains controversial because increased risk of bleeding may offset the overall benefit. Among major bleeding events, intracranial hemorrhage is associated with high mortality rates and functional dependency. OBJECTIVE To assess the risk of intracranial hemorrhage associated with low-dose aspirin among individuals without symptomatic cardiovascular disease. DATA SOURCES PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1966 to October 30, 2018. STUDY SELECTION Randomized clinical trials that compared low-dose aspirin (daily dose Յ100 mg) vs control and recorded the end points of intracranial hemorrhage separately for active treatment and control groups were included. DATA EXTRACTION AND SYNTHESIS A random-effect estimate was computed based on the Mantel-Haenszel method. Relative risk with 95% CI was used as a measure of aspirin vs control on risk of intracranial hemorrhage. MAIN OUTCOMES AND MEASURES The main outcomes were any intracranial hemorrhage, intracerebral hemorrhage, subdural or extradural hemorrhage, and subarachnoid hemorrhage, for aspirin vs control. RESULTS The search identified 13 randomized clinical trials of low-dose aspirin use for primary prevention, enrolling 134 446 patients. Pooling the results from the random-effects model showed that low-dose aspirin, compared with control, was associated with an increased risk of any intracranial bleeding (8 trials; relative risk, 1.37; 95% CI, 1.13-1.66; 2 additional intracranial hemorrhages in 1000 people), with potentially the greatest relative risk increase for subdural or extradural hemorrhage (4 trials; relative risk, 1.53; 95% CI, 1.08-2.18) and less for intracerebral hemorrhage and subarachnoid hemorrhage. Patient baseline features associated with heightened risk of intracerebral hemorrhage with low-dose aspirin, compared with control, were Asian race/ethnicity and low body mass index. CONCLUSIONS AND RELEVANCE Among people without symptomatic cardiovascular disease, use of low-dose aspirin was associated with an overall increased risk of intracranial hemorrhage, and heightened risk of intracerebral hemorrhage for those of Asian race/ethnicity or people with a low body mass index.

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Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: A randomized, double‐blind, placebo‐controlled trial in asymptomatic antiphospholipid antibody–positive individuals

Cited by 359 publications

References 38 publications

Thromboprophylaxis in carriers of antiphospholipid antibodies (APL) without previous thrombosis: “Pros” and “Cons”

Thromboprophylaxis in carriers of antiphospholipid antibodies (APL) without previous thrombosis: “Pros” and “Cons”

Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events

Frequency of Intracranial Hemorrhage With Low-Dose Aspirin in Individuals Without Symptomatic Cardiovascular Disease

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