Treatment of Vascular Thrombosis in Antiphospholipid Syndrome: An Update

AbstractThe antiphospholipid syndrome (APS) is an acquired autoimmune disorder associated with arterial, venous, or microvascular thrombosis and/or pregnancy complications mainly in young age. The diagnosis is made by the persistent detection of anticardiolipin antibodies, β2-glycoprotein I antibodies (β2GPIA), and/or lupus anticoagulants (LAs) for at least 12 weeks. Patients should present with at least one clinical and one laboratory criterion. Patients presenting with all three types of antibodies and vascular events are high-risk patients and should receive vitamin K antagonists (VKAs) as long as the antibodies persist. In patients with prior arterial thrombosis, VKA with or without low-dose aspirin is the current treatment of choice. The international normalized ratio (INR) should be between 2 and 3 although in some cases keeping the target INR above 3 may be necessary. Patients with venous thrombosis and negative LA may alternatively be treated with direct oral anticoagulants although more data are needed. Minimizing vascular risk factors is always necessary in APS patients. Aspirin can be given as primary prevention in asymptomatic patients with positive antiphospholipid antibodies without thrombosis or pregnancy complications especially when additional vascular risk factors are present. Catastrophic APS occurs in less than 1% of APS patients and presents as a thrombotic storm. Early use of a combined triple therapy such as anticoagulation, plasma exchange, and steroids with either or not addition of immunoglobulins is important to reduce mortality.

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Vascular Events, Vascular Disease and Vascular Risk Factors—Strongly Intertwined with COVID-19

Current Treatment Options in Neurology ◽

10.1007/s11940-020-00648-y ◽

2020 ◽

Vol 22 (11) ◽

Author(s):

Adrian Scutelnic ◽

Mirjam R. Heldner

Keyword(s):

Risk Factors ◽

Vascular Disease ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Vascular Events ◽

Increased Risk ◽

Clinical Benefits ◽

Infection And Inflammation ◽

Unhealthy Diet ◽

New Perspective

Abstract Purpose of review To elucidate the intertwining of vascular events, vascular disease and vascular risk factors and COVID-19. Recent findings Strokes are a leading cause of disability and death worldwide. Vascular risk factors are important drivers of strokes. There are unmodifiable vascular risk factors such as age and ethnicity and modifiable vascular risk factors. According to the INTERSTROKE study, the 10 most frequent modifiable vascular risk factors are arterial hypertension, physical inactivity, overweight, dyslipidaemia, smoking, unhealthy diet, cardiac pathologies, diabetes mellitus, stress/depression and overconsumption of alcohol. Also, infection and inflammation have been shown to increase the risk of stroke. There is high-quality evidence for the clinical benefits of optimal primary and secondary stroke prevention. The COVID-19 pandemic brought a new perspective to this field. Vascular events, vascular disease and vascular risk factors—and COVID-19—are strongly intertwined. An increased risk of vascular events—by multifactorial mechanisms—has been observed in COVID-19 patients. Also, a higher rate of infection with COVID-19, severe COVID-19 and bad outcome has been demonstrated in patients with pre-existing vascular disease and vascular risk factors. Summary At present, we suggest that regular interactions between healthcare professionals and patients should include education on COVID-19 and on primary and secondary vascular prevention in order to reduce the burden of disease in our ageing populations.

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Direct oral anticoagulants versus vitamin K antagonists in patients with antiphospholipid syndrome: systematic review and meta-analysis

RMD Open ◽

10.1136/rmdopen-2021-001678 ◽

2021 ◽

Vol 7 (2) ◽

pp. e001678

Author(s):

Nazariy Koval ◽

Mariana Alves ◽

Rui Plácido ◽

Ana G Almeida ◽

João Eurico Fonseca ◽

...

Keyword(s):

Systematic Review ◽

Antiphospholipid Syndrome ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Thromboembolic Events ◽

Bleeding Events ◽

Prevention Of Thromboembolic Events

BackgroundDespite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral anticoagulants/direct oral anticoagulants (DOACs) have been used off-label.ObjectiveWe aimed to perform a systematic review comparing DOACs to VKA regarding prevention of thromboembolic events, occurrence of bleeding events and mortality in patients with APS.MethodsAn electronic database search was performed through MEDLINE, CENTRAL and Web of Science. After data extraction, we pooled the results using risk ratio (RR) and 95% CI. Heterogeneity was assessed using the I². The outcomes considered were all thromboembolic events as primary, and major bleeding, all bleeding events and mortality as secondary. Evidence confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology.ResultsWe included 7 studies and a total of 835 patients for analyses. Thromboembolic events were significantly increased in DOACs arm, compared with VKA—RR 1.69, 95% CI 1.09 to 2.62, I²—24%, n=719, 6 studies. In studies using exclusively rivaroxaban, which was the most representative drug in all included studies, the thromboembolic risk was increased threefold (RR 3.36, 95% CI 1.53 to 7.37). The risks of major bleeding, all bleeding events and mortality were not significantly different from control arm. The grade of certainty of our results is very low.ConclusionsCurrent evidence suggests DOACs use, particularly rivaroxaban, among patients with APS, is less effective than VKA since it is associated with 69% increased risk of thromboembolic events.Trial registration numberCRD42020216178.

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Direct oral anticoagulants in patients with antiphospholipid syndrome: a cohort study

Lupus ◽

10.1177/0961203319889156 ◽

2019 ◽

Vol 29 (1) ◽

pp. 37-44 ◽

Cited By ~ 9

Author(s):

K Malec ◽

E Broniatowska ◽

A Undas

Keyword(s):

Cohort Study ◽

Antiphospholipid Syndrome ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Real Life ◽

Double Positive ◽

Increased Risk ◽

Long Term Follow Up

Objectives Despite controversies, direct oral anticoagulants (DOACs) are increasingly used in antiphospholipid syndrome (APS). We investigated the safety and efficacy of DOACs versus vitamin K antagonists (VKAs) in real-life consecutive APS patients. Patients and methods In a cohort study of 176 APS patients, which included 82 subjects who preferred DOACs or had unstable anticoagulation with VKAs, we recorded venous thromboembolism (VTE), cerebrovascular ischemic events or myocardial infarction, along with major bleeding or clinically relevant non-major bleeding (CRNMB). Results APS patients were followed for a median time of 51 (interquartile range 43–63) months. Patients on DOACs and those on VKAs were similar with regard to baseline characteristics. APS patients treated with DOACs had increased risk of recurrent thromboembolic events and recurrent VTE alone compared with those on VKAs (hazard ratio (HR) = 3.98, 95% confidence interval (CI): 1.54–10.28, p = 0.004 and HR = 3.69, 95% CI: 1.27–10.68, p = 0.016, respectively) with no differences between rivaroxaban and apixaban or single- or double-positive and triple-positive APS. Thromboembolism on DOACs was associated with older age (median 52 versus 42 years, p = 0.008) and higher global APS score (median 13 versus 8.5, p = 0.013). Patients on DOACs had increased risk of major bleeding or CRNMB (HR = 3.63, 95% CI: 1.53–8.63, p = 0.003), but rates of gastrointestinal bleeds (HR = 3.36, 95% CI: 0.70–16.16, p = 0.13) and major bleeds or CRNMB other than heavy menstrual bleeding (HR = 2.45, 95% CI: 0.62–9.69, p = 0.2) were similar in both treatment groups. Conclusion During long-term follow-up of real-life APS patients, DOACs are less effective and less safe as VKAs in the prevention of thromboembolism.

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Sugar-sweetened beverages, vascular risk factors and events: a systematic literature review

Public Health Nutrition ◽

10.1017/s1368980014002122 ◽

2014 ◽

Vol 18 (7) ◽

pp. 1145-1154 ◽

Cited By ~ 22

Author(s):

Amelie Keller ◽

Berit L Heitmann ◽

Nanna Olsen

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Blood Sugar ◽

Blood Lipid ◽

Vascular Risk Factors ◽

Current Evidence ◽

Vascular Risk ◽

Vascular Events ◽

Sugar Sweetened Beverages ◽

Sweetened Beverages

AbstractObjectiveA high intake of sugar-sweetened beverages (SSB) has been linked to weight gain, obesity and type 2 diabetes; however, the influence on CVD risk remains unclear. Therefore, our objective was to summarize current evidence for an association between SSB consumption and cardiovascular risk factors and events.DesignThe article search was performed in August 2013. Two independent researchers performed the article search and selection, data extraction and quality assessment. Eligible studies reported the intake of SSB and one of the following outcomes: change in blood pressure, blood lipid or blood sugar, or CVD events such as stroke or myocardial infarction. Only intervention and longitudinal studies were included.SubjectsOnly studies in adults (aged 18+ years old) were considered.ResultsTwo of four prospective studies found clear direct associations between SSB consumption and CHD, while two of three studies, including both men and women, found direct associations between SSB consumption and stroke; however, the association was significant among women only. All included studies examining vascular risk factors found direct associations between SSB consumption and change in blood pressure, blood lipid or blood sugar.ConclusionsThe reviewed studies generally showed that SSB intake was related to vascular risk factors, whereas associations with vascular events were less consistent. Due to a limited number of published papers, especially regarding vascular events, the strength of the evidence is still limited and hence more studies are needed before firm conclusions can be made.

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Primary Thromboprophylaxis in Patients with Malignancies: Daily Practice Recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO), the Society of Thrombosis and Hemostasis Research (GTH), and the Austrian Society of Hematology and Oncology (ÖGHO)

Cancers ◽

10.3390/cancers13122905 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2905

Author(s):

Martin Kirschner ◽

Nicole do Ó Hartmann ◽

Stefani Parmentier ◽

Christina Hart ◽

Larissa Henze ◽

...

Keyword(s):

Risk Factors ◽

Cancer Patients ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Working Party ◽

Major Surgery ◽

Thrombotic Risk ◽

Indwelling Catheters ◽

Increased Risk

Patients with cancer, both hematologic and solid malignancies, are at increased risk for thrombosis and thromboembolism. In addition to general risk factors such as immobility and major surgery, shared by non-cancer patients, cancer patients are exposed to specific thrombotic risk factors. These include, among other factors, cancer-induced hypercoagulation, and chemotherapy-mediated endothelial dysfunction as well as tumor-cell-derived microparticles. After an episode of thrombosis in a cancer patient, secondary thromboprophylaxis to prevent recurrent thromboembolism has long been established and is typically continued as long as the cancer is active or actively treated. On the other hand, primary prophylaxis, even though firmly established in hospitalized cancer patients, has only recently been studied in ambulatory patients. This recent change is mostly due to the emergence of direct oral anticoagulants (DOACs). DOACs have a shorter half-life than vitamin K antagonists (VKA), and they overcome the need for parenteral application, the latter of which is associated with low-molecular-weight heparins (LMWH) and can be difficult for the patient to endure in the long term. Here, first, we discuss the clinical trials of primary thromboprophylaxis in the population of cancer patients in general, including the use of VKA, LMWH, and DOACs, and the potential drug interactions with pre-existing medications that need to be taken into account. Second, we focus on special situations in cancer patients where primary prophylactic anticoagulation should be considered, including myeloma, major surgery, indwelling catheters, or immobilization, concomitant diseases such as renal insufficiency, liver disease, or thrombophilia, as well as situations with a high bleeding risk, particularly thrombocytopenia, and specific drugs that may require primary thromboprophylaxis. We provide a novel algorithm intended to aid specialists but also family practitioners and nurses who care for cancer patients in the decision process of primary thromboprophylaxis in the individual patient.

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Age in relation to comorbidity and outcome in patients with high-risk TIA or minor ischemic stroke: A Swedish national observational study

European Stroke Journal ◽

10.1177/2396987320975980 ◽

2020 ◽

pp. 239698732097598

Author(s):

Oskar Fasth ◽

Eva Lesén ◽

Peter Appelros ◽

Bahman Farahmand ◽

Jonatan Hedberg ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

High Risk ◽

Observational Study ◽

Vascular Risk Factors ◽

Stroke Severity ◽

Vascular Risk ◽

Vascular Events ◽

Risk Of Death ◽

Minor Ischemic Stroke

Introduction Recent trials report positive results for preventing vascular events with dual antiplatelet therapy (DAPT) in patients with high-risk TIA or minor ischemic stroke. We aimed to investigate this population regarding influence of age on vascular risk factors, hospital stay and mortality. Patients and methods Data on patients aged 40–100 years with TIA or ischemic stroke in the Swedish Stroke Register during 2012–13 were linked with national registers. To identify patients with high-risk TIA (ABCD2 ≥6) or minor ischemic stroke (NIHSS ≤5) eligible for DAPT, we excluded patients with atrial fibrillation, anticoagulant use, prior major bleeding, or unknown stroke severity. Findings We identified 10,053 potential DAPT-candidates (mean age 72.6 years, 45.2% female, 16.4% with TIA). With advancing age, most vascular risk factors increased. Antiplatelet treatment increased from 31.9% before the event to 95.5% after discharge. Within 1 year following index event, the proportion of patients with ≥1 re-admission increased with age (29.2% in 40–64 year-olds; 47.2% in 85–100 year-olds). All-cause death per 100 person-years was 6.9 (95% CI 6.4–7.4) within 1 year, and highest in the first 30 days (15.2; 95% CI 12.8–18.2). For each year of increased age, the risk of death increased with 3.5% (p = 0.128) in patients 40–64 years and with 11.8% (p < 0.001) in those ≥85 years. Conclusions While in theory representing a subset of patients with mild injury, our observational study highlights substantial use of health-care resources and high mortality rates among patients with high-risk TIA or minor ischemic stroke assumed eligible for DAPT.

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Is there a role for low-dose DOACs as prophylaxis?

Hematology ◽

10.1182/hematology.2019000026 ◽

2019 ◽

Vol 2019 (1) ◽

pp. 187-193 ◽

Cited By ~ 1

Author(s):

Alexander T. Cohen ◽

Beverley J. Hunt

Keyword(s):

Secondary Prevention ◽

Low Dose ◽

Standard Dose ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Secondary Prophylaxis ◽

Medical Patients ◽

Vascular Events

Abstract The direct oral anticoagulants (DOACs) have transformed the management of thrombotic disorders. Large clinical trials have demonstrated that DOACs can replace vitamin K antagonists (VKAs) in the 2 existing major indications for anticoagulation: the prevention of stroke in atrial fibrillation and the acute treatment and secondary prevention of venous thromboembolism (VTE); this literature is widely known. In this article, we will concentrate on the less well-discussed benefits of the use of DOACs—using low doses as primary and secondary prophylaxis in both venous and arterial thromboprophylaxis. The attractiveness of using a low-dose DOAC is that the bleeding risk seems to be slightly lower than with the standard dose and significantly lower than with VKAs so that they can be used safely for long periods, where previously, VKAs had risk/benefit ratios that did not permit this. We discuss in detail the extended use of low-dose DOACs in secondary VTE prevention. We also cover the utility of low-dose DOACs in the evolving fields of prevention of hospital-associated VTE in acutely ill medical patients, after total hip and knee replacement, and in cancer patients. To complete the indications, we briefly discuss the role of low-dose DOACs in the secondary prevention of arterial vascular events.

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Abstract 91: Small Perivascular Spaces as Vascular Risk Factors

Stroke ◽

10.1161/str.47.suppl_1.91 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Jose Gutierrez ◽

Chuanhui Dong ◽

Sandino Cespedes ◽

Tatjana Rundek ◽

Ralph Sacco ◽

...

Keyword(s):

Risk Factors ◽

Population Based ◽

Vascular Risk Factors ◽

Vascular Event ◽

Perivascular Spaces ◽

Vascular Risk ◽

Vascular Events ◽

High Burden ◽

Lacunar Infarcts ◽

Vascular Death

Introduction: Small perivascular spaces (SPVS) are gaining momentum as imaging biomarkers of cerebrovascular health. Hypothesis: SPVS confer vascular risks and the coexistence of SPVS with lacunar infarcts (LI) heightens these risks. Methods: Stroke-free participants in the population-based Northern Manhattan Study were followed for incident stroke (ischemic and hemorrhagic), MI, all death, vascular death, and any vascular event. Lesions with diameter of 3 mm or less and absence of FLAIR rim were classified as SPVS on a semi-quantitative scale (range 0 to 28). We defined “high SPVS burden” as the upper quintile and compared the rate of vascular events in this group to individuals in the lower 4 quintiles combined. LI were defined as lesions greater than 3 mm with associated FLAIR rim, round shape, and typical location. Cox models were used to calculate risks of outcomes after adjusting for confounders. Results: This analysis includes 1208 NOMAS participants (40% male, 65% Hispanic; mean age 71 ± 9 years at time of MRI) followed a mean of 6 ± 2 years. SPVS were present in 91% of the sample (median SPVS scale score 5). Compared to participants with a lesser burden of SPVS, participants with a high SPVS burden had a higher incidence rate per 1000 person-years of death (48 vs 34), vascular death (20 vs 11), ischemic stroke (12 vs 7) and any vascular event (37 vs 24). After adjusting for demographics and vascular risk factors, participants with a high burden of SPVS had a higher risk of death (HR 1.35, 1.00-1.78), vascular death (HR 1.55, 0.96-2.51), any stroke (HR 1.53, 0.91-2.57), MI (HR 1.29, 0.69-2.41), and any vascular event (HR 1.50, 1.07-2.11). The presence of lacunar infarcts was an effect modifier such that those with LI and a high SPVS burden had a greater risk of vascular death (B=0.63, P=0.03), any stroke (B=0.72, P=0.03) and any vascular event (B=0.54, P=0.02) compared to those without LI. Conclusions: In this multi-ethnic, population-based study, participants with a high burden of SPVS had increased incidence rates of vascular events. Furthermore, the joint presence of SPVS and LI heighten the risk of vascular death, any stroke and any vascular event. The presence of SPVS may help select subjects for randomized trials to assess intervention strategies.

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Stroke Prevention by Anticoagulants in Daily Practice Depending on Atrial Fibrillation Pattern and Clinical Risk Factors

Stroke ◽

10.1161/strokeaha.120.032704 ◽

2021 ◽

Author(s):

Lamiae Grimaldi-Bensouda ◽

Jean-Yves Le Heuzey ◽

Jean Ferrières ◽

Didier Leys ◽

Jean-Marc Davy ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Vitamin K ◽

Oral Anticoagulant ◽

Hemorrhagic Stroke ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Clinical Risk Factors ◽

Direct Oral Anticoagulant

Background and Purpose: The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns. Methods: A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors. Results: In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50–0.98) for dabigatran, 0.68 (95% CI, 0.53–0.86) for rivaroxaban, and 0.73 (95% CI, 0.52–1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14–0.68), 0.64 (95% CI, 0.39–1.06), and 0.70 (95% CI, 0.33–1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients. Conclusions: Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.

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Management of vascular risk factors and co-morbidities in secondary stroke prevention

ESC CardioMed ◽

10.1093/med/9780198784906.003.0232 ◽

2018 ◽

pp. 971-975

Author(s):

Martin O’Donnell ◽

Cliona Small

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Risk Factor ◽

Ischaemic Stroke ◽

Stroke Prevention ◽

Alcohol Intake ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Vascular Events ◽

Lifestyle Risk

Medical approaches to reducing the risk of recurrent stroke following ischaemic stroke or transient ischaemic attack, and other major vascular events, involves a targeted modification of vascular risk factors, including lifestyle factors (e.g. physical inactivity, smoking, and diet), hypertension, and hyperlipidaemia and glycaemic control. The INTERSTROKE study reported that ten potentially modifiable vascular risk factors were associated with about 90% of the population attributable risk for stroke. Modification of lifestyle risk factors remains a cornerstone of stroke prevention, and includes promoting increased physical activity, smoking cessation, adopting healthier dietary patterns, weight reduction in those who are overweight/obese, and avoiding high alcohol intake (and heavy episode alcohol intake). All patients with blood pressure levels greater than or equal to 140/90 mmHg should be treated with antihypertensive therapy (although some suggest a lower threshold in patients with non-cardioembolic stroke), with a recent trial suggesting that patients with small vessel ischaemic stroke may benefit from lowering blood pressure to less than 130/90 mmHg. Statin therapy in patients with elevated low-density lipoprotein is associated with a reduction in major vascular events after ischaemic stroke, with a more aggressive strategy adopted in patients with ischaemic stroke due to large vessel atherosclerosis. While sleep apnoea is a risk factor for stroke, treatment with continuous positive airway pressure did not reduce the risk of stroke in a recent, large clinical trial. The optimal approach to achieve high rates of vascular risk factor targets following stroke has not been identified, but evaluations of community-based interventions are ongoing.

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