Patients with antiphospholipid syndrome and a first venous or arterial thrombotic event: clinical characteristics, antibody profiles and estimate of the risk of recurrence.

OBJECTIVES: Thrombosis in antiphospholipid syndrome (APS) involves in most cases the venous circulation. Why in some patients thrombotic APS affects the arterial circulation and in particular cerebral circulation is unknown. In previous studies, both patient characteristics and antiphospholipid antibody types and titers have been associated with arterial thrombosis. Aim of this study was to compare the clinical characteristics and laboratory findings of venous and arterial thrombotic APS from a large series of patients. METHODS: Data were retrieved from the Start 2 antiphospholipid, a multicenter prospective register of long-term collected data from Thrombosis Centers in Italy. RESULTS: Of 167 patients with thrombotic APS, 114 (68 %) had a venous and 53 (32 %) had an arterial event as first clinical manifestation. Several clinical characteristics and risk factors were different among groups in univariate analysis. Using logistic regression analysis, reduced creatinine clearance and hyperlipidemia were independent variable for the occurrence of arterial APS. Notably, no difference in antiphospholipid antibody profiles and aß2-Glycoprotein I levels were found between groups. A higher adjusted global antiphospholipid syndrome score (aGAPSS) was found in arterial group indicating a possible high recurrence rate in arterial APS. CONCLUSIONS: These data have pathophysiological and clinical implication since associated conditions might predispose patients to arterial rather than venous events and call to a close monitoring and treatment of arterial APS due to their increased tendency to recurrence.

Inappropriate Underdosing of Direct Oral Anticoagulants in Atrial Fibrillation Patients: Results from the START2-AF Registry.

Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. We aimed to describe the prevalence of inappropriate DOACs dose prescription in the START2-AF Registry, the outcomes according to the appropriateness of the dosage, and the factors associated with inappropriate dose prescription. Methods: Patients' demographics and clinical data were prospectively collected as electronic files in an anonymous form on the website of the START2-Registry; DOACs dosage was determined to be appropriate when prescribed according to the European Heart Rhythm Association Guidelines. Results: We included 5943 NVAF patients on DOACs; 2572 (46.3%) were female patients. The standard dose (SD) was prescribed to 56.9% of patients and the low dose (LD) was prescribed to 43.1% of patients; 38.9% of all NVAF patients received an inappropriate LD DOAC and 0.3% received inappropriate SD. Patients treated with LD DOAC had a significantly higher rate of all bleedings (RR 1.5; 95% CI 1.2-2.0), major bleedings (RR 1.8; 95% CI 1.3-1.7), and mortality (RR 2.8; 95% CI 1.9-4.1) with respect to patients treated with SD DOAC. No difference was found among patients treated with appropriate and inappropriate LD regarding bleeding, thrombotic, and mortality rates. Age, body weight <60 kg, and renal failure were significantly associated with inappropriate LD DOAC prescription. Conclusions: Inappropriate LD DOACs in NVAF patients is not associated with a reduction in bleeding risk, nor with an increased thrombotic risk. Instead, it is associated with higher mortality rate, suggesting that, in clinical practice, underdosing is preferred for patients at particularly high risk for adverse events.

Machine learning approach for prediction of outcomes in anticoagulated patients with atrial fibrillation.

BACKGROUND: The accuracy of available prediction tools for clinical outcomes in patients with atrial fibrillation (AF) remains modest. Machine Learning (ML) has been used to predict outcomes in the AF population, but not in a population entirely on anticoagulant therapy. METHODS AND AIMS: Different supervised ML models were applied to predict all-cause death, cardiovascular (CV) death, major bleeding and stroke in anticoagulated patients with AF, processing data from the multicenter START-2 Register. RESULTS: 11078 AF patients (male n = 6029, 54.3%) were enrolled with a median follow-up period of 1.5 years [IQR 1.0-2.6]. Patients on Vitamin K Antagonists (VKA) were 5135 (46.4%) and 5943 (53.6%) were on Direct Oral Anticoagulants (DOAC). Using Multi-Gate Mixture of Experts, a cross-validated AUC of 0.779 ± 0.016 and 0.745 ± 0.022 were obtained, respectively, for the prediction of all-cause death and CV-death in the overall population. The best ML model outperformed CHA2DSVA2SC and HAS-BLED for all-cause death prediction (p < 0.001 for both). When compared to HAS-BLED, Gradient Boosting improved major bleeding prediction in DOACs patients (0.711 vs. 0.586, p < 0.001). A very low number of events during follow-up (52) resulted in a suboptimal ischemic stroke prediction (best AUC of 0.606 ± 0.117 in overall population). Body mass index, age, renal function, platelet count and hemoglobin levels resulted the most important variables for ML prediction. CONCLUSIONS: In AF patients, ML models showed good discriminative ability to predict all-cause death, regardless of the type of anticoagulation strategy, and major bleeding on DOAC therapy, outperforming CHA2DS2VASC and the HAS-BLED scores for risk prediction in these populations.

Long-Term Outcomes in Two-Year Follow-Up after Primary Treatment in Patients with a Prior Venous Thromboembolic Event: A Prospective, Observational, Real-Life Study.

BACKGROUND: Patients with acute venous thromboembolism (VTE) need anticoagulation (AC) therapy for at least 3/6 months (primary treatment); after that period, they should receive a decision on the duration of therapy. METHODS: This study examined the complications occurring during two years of follow-up (FU) in patients with a first VTE who were recruited in 20 clinical centers and had discontinued or prolonged AC. They were included in the START2-POST-VTE prospective observational study. RESULTS: A total of 720 patients (53.5% males) who, after the completion of primary treatment, had received the decision to continue (n = 281, 39%; 76.1% with a DOAC) or discontinue (n = 439, 61%) AC were followed up for 2 years (total FU = 1318 years). The decision to prolong or suspend AC was made in similar proportions in patients with unprovoked or provoked index events. Courses of sulodexide treatment or Aspirin (100 mg daily) were prescribed to 20.3% and 4.5%, respectively, of the patients who discontinued AC. The bleeding rate was significantly higher in patients who extended AC (1.6% pt/y) than in those who stopped AC (0.1% pt/y; p = 0.001) and was higher in patients using standard-dose DOACs (3.1% pt/y) than in those using reduced-dose DOACs (0.4% pt/y). The recurrent VTE rates were similar between the two groups (2.2% pt/y during AC vs. 3% pt/y off AC). CONCLUSION: Physicians' decisions about AC duration were independent of the unprovoked/provoked nature of the index event. The bleeding rate was higher in patients who continued AC using standard-dose DOACs. Surprisingly, the rate of thrombotic recurrence was not different between those who continued or discontinued AC. Randomized studies comparing different procedures to decide on the duration of AC after a first VTE are needed.

Thrombotic events associated with low baseline direct oral anticoagulant levels in atrial fibrillation: the MAS study.

ABSTRACT: Although effective and safe, treatment with direct oral anticoagulants (DOAC) in atrial fibrillation (AF) is still associated with thrombotic complications. Whether the measurement of DOAC levels may improve treatment efficacy is an open issue. We carried out the observational, prospective, multicenter Measure and See (MAS) study. Blood was collected 15 to 30 days after starting DOAC treatment in patients with AF who were followed-up for 1 year. Plasma samples were centralized for DOAC level measurement. Patients' DOAC levels were converted into drug/dosage standardized values to allow a pooled analysis in a time-dependent, competitive-risk model. The measured values were transformed into standardized values (representing the distance of each value from the overall mean) by subtracting the DOAC-specific mean value from the original values and dividing by the standard deviation. Trough and peak DOAC levels were assessed in 1657 and 1303 patients, respectively. In total, 21 thrombotic complications were recorded during 1606 years of follow-up (incidence of 1.31% of patients per year). Of 21 thrombotic events, 17 occurred in patients whose standardized activity levels were below the mean of each DOAC (0); the incidence was the highest (4.82% of patients per year) in patients whose standardized values were in the lowest class (-1.00 or less). Early measurement of DOAC levels in patients with AF allowed us to identify most of the patients who, having low baseline DOAC levels, subsequently developed thrombotic complications. Further studies are warranted to assess whether thrombotic complications may be reduced by measuring baseline DOAC levels and modifying treatment when indicated. This trial was registered at www.ClinicalTrials.gov as #NCT03803579.

Renin-angiotensin-aldosterone system inhibitors and mortality risk in elderly patients with atrial fibrillation. Insights from the nationwide START registry.

BACKGROUND: Arterial hypertension is the most common cardiovascular comorbidity in atrial fibrillation (AF). Few studies investigated management strategies of hypertension in AF. MATERIALS AND METHODS: We included 5769 AF patients on oral anticoagulants from the nationwide ongoing Italian START registry. We investigated the prescription of antihypertensive drugs and mortality risk. Subgroup analyses according to sex and major cardiovascular comorbidities were performed. RESULTS: Mean age was 80.8 years, 46.1% were women; 80.3% of patients were hypertensive. Furosemide (30.1%) was the most frequent diuretic followed by hydrochlorothiazide (15.4%) and potassium canrenoate (7.9%). 61.1% received ß-blockers: 34.2% bisoprolol, 6.2% atenolol. Additionally, 36.9% were on angiotensin converting enzyme inhibitors (ACE-I): ramipril (20.9%), enalapril (5.3%) and perindopril (2.8%); 31.7% were on angiotensin receptors blockers (ARBs): valsartan (7.6%) and irbesartan (6.4%). Amlodipine and lercanidipine were prescribed in 14.0% and 2.3%, respectively. ACE-I (p < 0.001), α-blockers (p = 0.020) and Dihydropyridines calcium channel blockers (p = 0.004) were more common in men, while ARBs (p = 0.008), thiazide diuretics (p < 0.001) and ß-blockers (p < 0.001) in women. During 22.61 ± 17.1 months, 512 patients died. Multivariable Cox regression analysis showed that ACE-I (Hazard ratio [HR] 0.758, 95% Confidence Interval [95%CI] 0.612-0.940, p = 0.012) and ARBs (HR 0.623, 95%CI 0.487-0.796, p < 0.001) inversely associated with mortality. ACE-I/ARBs inversely associated with mortality in both sexes and in patients with diabetes. This associastion was evident for ACE-I in patients with previous cardiovascular disease, and for ARBs in HF. CONCLUSION: A lower mortality risk was found in AF patients on ACE-I/ARBs. Different prescription patterns of antihypertensive drugs between men and women do exist.

Statins under-treatment and mortality in patients with atrial fibrillation. Insights from the nationwide START registry.

BACKGROUND AND AIMS: Statins are mainstream drugs for cardiovascular (CV) prevention, but under-prescription is an important clinical challenge. Data on the use of single statins and on the rate of under-prescription in atrial fibrillation (AF) are lacking. We evaluated the association of statin underuse with mortality risk in a large AF cohort. METHODS AND RESULTS: As many as 5477 patients from the Italian nationwide START registry were included. The prevalence of different statins was reported and the association of under prescription with all-cause and CV mortality investigated. Mean age was 80.2 years, and 46.4% were women. Among 2899 patients with a clinical indication to statin, only 1578 (54.4%) were on treatment. In a mean follow-up of 22.5 ± 17.1 months, 491 (4.7%/year) deaths occurred (106 CV deaths, 1.0%/year). Atorvastatin and Simvastatin were inversely associated with all-cause (HR 0.692, 95% CI 0.519-0.923, p = 0.012 and HR 0.598, 95% CI 0.428-0.836, p = 0.003, respectively) and CV death (HR 0.372, 95% CI 0.178-0.776, p = 0.008 and HR 0.306, 95% CI 0.123-0.758, p = 0.010, respectively). The 1321 untreated patients were older, more frequently women and with a higher prevalence of diabetes, previous cerebrovascular disease, peripheral artery disease compared to those on treatment. Statin undertreatment was associated with higher risk of all-cause (HR 1.400, 95% CI 1.078-1.819, p = 0.012) and CV death (HR 2.057, 95% CI 1.188-3.561, p = 0.010). CONCLUSIONS: AF patients with an indication to statins but left untreated show a high risk of all-cause and CV mortality. Implementation of statin prescription in the AF population can help reducing the residual mortality risk.

DOACs use in extreme body-weighted patients: results from the prospective START-register.

BACKGROUND: Direct oral anticoagulants (DOACs) are widely used for the treatment of venous thromboembolism (VTE) and for stroke prevention in atrial fibrillation (AF). However, evidence in obese and underweight patients is limited. We assessed the safety and effectiveness of DOACs and vitamin K antagonists (VKAs) in patients ≥ 120 kg or ≤ 50 kg enrolled in an observational prospective cohort study, the START-Register. METHODS: Adult patients started on anticoagulant therapy were followed up for a median of 1.5 years (IQR 0.6-2.8). Primary efficacy outcome was the occurrence of VTE recurrence, stroke and systemic embolism. Primary safety outcome was major bleeding (MB). RESULTS: 10,080 AF and VTE patients were enrolled between March 2011 and June 2021, 295 patients weighted ≤ 50 kg and 82 patients ≥ 120 kg. Obese patients were significantly younger than underweight patients. Rates of thrombotic events were low and similar between DOACs and VKAs in underweight patients (1 event on DOACs therapy [0.9% 95% CI 0.11-5.39] and 2 on VKAs [1.1% 95% CI 0.01-47.68]) and in overweight patients (0 events on DOACs, 1 on VKAs [1.6%, 95% CI 0.11-5.79]. Two MB events occurred on DOACs (1.9%, 95% CI 0.38-6.00) and 3 on VKAs (1.6%, 95% CI 0.04-22.06) in the underweight group; 1 MB on DOACs (5.3% 95% CI 0.33-16.68) and 2 on VKAs (3.3%, 95% CI 0.02-130.77) in the overweight group. CONCLUSIONS: DOACs seem to be effective and safe also for the treatment of patients with extreme body weights, both underweight and overweight. Further prospective studies are needed to support these findings.

Venous Thromboembolism in Women of Childbearing Age: Insights from the START Registry.

BACKGROUND: Women of childbearing age are exposed to venous thromboembolic risk mainly for pregnancy and use of oral contraceptives. The impact of risk factors (RF) on venous thromboembolism (VTE) in these circumstances is still unclear. AIM: In the context of START registry, we aimed to investigate the weight of a series of RF on the occurrence of pregnancy- or combined oral contraceptive (COC)-associated VTE. MATERIALS AND METHODS: We selected all women included in the START for VTE occurred between 18-42 years and compared those with a first or recurrent pregnancy/postpartum- (group A) or COC-VTE (group B) with those who had VTE outside these circumstances (group C). Final analysis included a cohort of 532 women. Follow-up data showed that there were no significant differences between the groups in terms of thrombotic and haemorrhagic complications. As for pregnancy-associated VTE, the overall outcome was good in terms of both maternal and fetal prognosis. RESULTS: In a binary model of logistic regression, correcting for potential confounders, VTE family history conferred a significant and independent higher risk of COC-VTE compared with group C. Similarly, comparison between group A and C documented that family history significantly affected the risk of pregnancy-associated VTE. VTE in the group C was significantly associated with older age. Lastly, smoke was a significant risk factor for pregnancy/postpartum VTE when group A and group B were compared. CONCLUSION: Present data suggest that in the setting of fertile women, family history of VTE has a greater role in predicting COC- and pregnancy/postpartum- VTE than outside these circumstances.

Venous thromboembolism secondary to hospitalization for COVID-19: patient management and long-term outcomes.

Background: Venous thromboembolism (VTE) is a complication of COVID-19 in hospitalized patients. Little information is available on long-term outcomes of VTE in this population. Objectives: We aimed to compare the characteristics, management strategies, and long-term clinical outcomes between patients with COVID-19-associated VTE and patients with VTE provoked by hospitalization for other acute medical illnesses. Methods: This is an observational cohort study, with a prospective cohort of 278 patients with COVID-19-associated VTE enrolled between 2020 and 2021 and a comparison cohort of 300 patients without COVID-19 enrolled in the ongoing START2-Register between 2018 and 2020. Exclusion criteria included age <18 years, other indications to anticoagulant treatment, active cancer, recent (<3 months) major surgery, trauma, pregnancy, and participation in interventional studies. All patients were followed up for a minimum of 12 months after treatment discontinuation. Primary end point was the occurrence of venous and arterial thrombotic events. Results: Patients with VTE secondary to COVID-19 had more frequent pulmonary embolism without deep vein thrombosis than controls (83.1% vs 46.2%, P <.001), lower prevalence of chronic inflammatory disease (1.4% and 16.3%, P <.001), and history of VTE (5.0% and 19.0%, P <.001). The median duration of anticoagulant treatment (194 and 225 days, P = 0.9) and the proportion of patients who discontinued anticoagulation (78.0% and 75.0%, P = 0.4) were similar between the 2 groups. Thrombotic event rates after discontinuation were 1.5 and 2.6 per 100 patient-years, respectively (P = 0.4). Conclusion: The risk of recurrent thrombotic events in patients with COVID-19-associated VTE is low and similar to the risk observed in patients with VTE secondary to hospitalization for other medical diseases.

Thromboembolic Complications in COVID-19 Patients Hospitalized in Italian Ordinary Wards: Data from the Multicenter Observational START-COVID Register.

Background Coronavirus disease 2019 (COVID-19) infection causes acute respiratory insufficiency with severe interstitial pneumonia and extrapulmonary complications; in particular, it may predispose to thromboembolic disease. The reported incidence of thromboembolic complications varies from 5 to 30% of cases. Aim We conducted a multicenter, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe the clinical characteristics of patients at admission and bleeding and thrombotic events occurring during the hospital stay. Results The number of hospitalized patients included in the START-COVID-19 Register was 1,135, and the number of hospitalized patients in ordinary wards included in the study was 1,091, with 653 (59.9%) being males and 71 years (interquartile range 59-82 years) being the median age. During the observation, two (0.2%) patients had acute coronary syndrome episodes and one patient (0.1%) had an ischemic stroke; no other arterial thrombotic events were recorded. Fifty-nine patients had symptomatic venous thromboembolism (VTE) (5.4%) events, 18 (30.5%) deep vein thrombosis (DVT), 39 (66.1%) pulmonary embolism (PE), and 2 (3.4%) DVT+PE. Among patients with DVT, eight (44.4%) were isolated distal DVT and two cases were jugular thrombosis. Among patients with PE, seven (17.9%) events were limited to subsegmental arteries. No fatal PE was recorded. Major bleeding events occurred in nine (1.2%) patients and clinically relevant nonmajor bleeding events in nine (1.2%) patients. All bleeding events occurred among patients receiving thromboprophylaxis, more frequently when treated with subtherapeutic or therapeutic dosages. Conclusion Our findings confirm that patients admitted to ordinary wards for COVID-19 infection are at high risk for thromboembolic events. VTE recorded among these patients is mainly isolated PE, suggesting a peculiar characteristic of VTE in these patients.

D-dimer and reduced-dose apixaban for extended treatment after unprovoked venous thromboembolism: the Apidulcis study.

D-dimer assay is used to stratify patients with unprovoked venous thromboembolism (VTE) for the risk of recurrence. However, this approach was never evaluated since direct oral anticoagulants are available. With this multicenter, prospective cohort study, we aimed to assess the value of an algorithm incorporating serial D-dimer testing and administration of reduced-dose apixaban (2.5 mg twice daily) only to patients with a positive test. A total of 732 outpatients aged 18 to 74 years, anticoagulated for ≥12 months after a first unprovoked VTE, were included. Patients underwent D-dimer testing with commercial assays and preestablished cutoffs. If the baseline D-dimer during anticoagulation was negative, anticoagulation was stopped and testing repeated after 15, 30, and 60 days. Patients with serially negative results (286 [39.1%]) were left without anticoagulation. At the first positive result, the remaining 446 patients (60.9%) were given apixaban for 18 months. All patients underwent follow-up planned for 18 months. The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% confidence interval [CI], 4.5-11.2), including symptomatic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) recurrence, death for VTE, and major bleeding occurring in patients off anticoagulation vs that in those receiving apixaban (1.1%; 95% CI, 0.4-2.6; adjusted hazard ratio [HR], 8.2; 95% CI, 3.2-25.3). In conclusion, in patients anticoagulated for ≥1 year after a first unprovoked VTE, the decision to further extend anticoagulation should not be based on D-dimer testing. The results confirmed the high efficacy and safety of reduced-dose apixaban against recurrences. This trial was registered at www.clinicaltrials.gov as #NCT03678506.

Clinical Phenotypes of Atrial Fibrillation and Mortality Risk-A Cluster Analysis from the Nationwide Italian START Registry.

Patients with atrial fibrillation (AF) still experience a high mortality rate despite optimal antithrombotic treatment. We aimed to identify clinical phenotypes of patients to stratify mortality risk in AF. Cluster analysis was performed on 5171 AF patients from the nationwide START registry. The risk of all-cause mortality in each cluster was analyzed. We identified four clusters. Cluster 1 was composed of the youngest patients, with low comorbidities; Cluster 2 of patients with low cardiovascular risk factors and high prevalence of cancer; Cluster 3 of men with diabetes and coronary disease and peripheral artery disease; Cluster 4 included the oldest patients, mainly women, with previous cerebrovascular events. During 9857 person-years of observation, 386 deaths (3.92%/year) occurred. Mortality rates increased across clusters: 0.42%/year (cluster 1, reference group), 2.12%/year (cluster 2, adjusted hazard ratio (aHR) 3.306, 95% confidence interval (CI) 1.204−9.077, p = 0.020), 4.41%/year (cluster 3, aHR 6.702, 95%CI 2.433−18.461, p < 0.001), and 8.71%/year (cluster 4, aHR 8.927, 95%CI 3.238−24.605, p < 0.001). We identified four clusters of AF patients with progressive mortality risk. The use of clinical phenotypes may help identify patients at a higher risk of mortality.

Bleeding and mortality risk in patients implanted with mechanical prosthetic heart valves with and without thrombocytopenia. Insights from the nationwide PLECTRUM registry.

Previous studies showed that mechanical prosthetic heart valve (MPHV) patients may develop thrombocytopenia, but its association with clinical outcomes has not been investigated. We enrolled 1,663 patients with available platelet count from the multicenter nationwide retrospective PLECTRUM registry to investigate the association of thrombocytopenia with all-cause mortality and major bleeding (MB) in patients implanted with MPHV. Thrombocytopenia was defined by platelet count <150 × 109/L. Overall, 44.9% of patients were women and the mean age was 56.7 years. At baseline, 184 (11.1%) patients had thrombocytopenia. Patients with thrombocytopenia were more frequently men and elderly. Platelet count showed an age-dependent decline in men but not in women. We found an increased risk of death in patients with age ≥ 65 years, with a low anticoagulation quality, concomitant arterial hypertension, heart failure, a higher INR range, or with thrombocytopenia (OR 1.739, 95%CI 1.048-2.886, p = .032). At multivariable logistic regression, patients with age ≥65 years, concomitant AF and thrombocytopenia (OR 1.907, 95%CI 1.219-2.983, p = .005) had an increased risk of MBs. In MPHV patients, thrombocytopenia is associated with an increased risk of death and MB. There is a growing need for a sex- and age-specific threshold to define platelet count in adult patients.

Low in-hospital mortality rate in patients with COVID-19 receiving thromboprophylaxis: data from the multicentre observational START-COVID Register.

COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease, and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years.

Prevalence and clinical implications of eligibility criteria for prolonged dual antithrombotic therapy in patients with PEGASUS and COMPASS phenotypes: Insights from the START-ANTIPLATELET registry.

AIM: To analyze the prevalence and clinical implications of the eligibility criteria for prolonged dual antithrombotic therapy with ticagrelor 60 mg twice daily and/or rivaroxaban 2.5 mg twice daily in a contemporary real-world ACS registry. METHODS: Patients from the START-ANTIPLATELET registry (NCT02219984) were stratified according to the eligibility criteria of the PEGASUS and COMPASS studies to investigate the proportion of patients eligible for prolonged dual antithrombotic therapy at discharge and after 1-year of DAPT. Net adverse clinical events (NACE), defined as all-cause death, myocardial infarction, stroke, and major bleeding, at 1 year were also evaluated and compared among groups. RESULTS: 1844 were considered for the analysis at baseline. Out of 849 event-free patients continually receiving dual antiplatelet therapy for at least 1 year, 577 (68%) and 583 (68.7%) met at least one eligibility criterion for ticagrelor and rivaroxaban, respectively. In the PEGASUS-like patients, age was the most common criterion (71% of cases). The presence ≥2 cardiovascular risk factors was the most common eligibility criterion in the COMPASS-like patients (80.8%). At 1-year follow-up, 211 (11.4%) and 119 (6.5%) patients experienced NACE and MACE, respectively. The incidence of NACEs was higher in the PEGASUS-only group (15.4% vs. 8.4%; p = 0.008) and numerically higher in the COMPASS-only group (10.9% vs. 8.4%; p = 0.299). CONCLUSIONS: In a contemporary real-world ACS cohort, approximately two-thirds of patients that complete 1-year DAPT met the eligibility criteria for ticagrelor 60 mg twice daily or rivaroxaban 2.5 mg twice daily, showing a higher risk of NACEs.

Management and Outcomes of Isolated Distal Deep Vein Thromboses: A Questionable Trend toward Long-Lasting Anticoagulation Treatment. Results from the START-Register.

Background Isolated distal deep vein thromboses (IDDVT) are frequently diagnosed; however, their natural history and real risk of complications are still uncertain. Though treatment is still not well standardized, international guidelines recommend no more than 3 months of anticoagulation therapy. We investigated how Italian clinicians treat IDDVT patients in their real life in our country. Methods Baseline characteristics and clinical history of the patients enrolled in the prospective, observational, multicenter START-Register for a first IDDVT or proximal DVT (PDVT) were analyzed. Results Overall, 412 IDDVT patients were significantly younger, with better renal function, and more frequent major transient risk factors, when compared with 1,173 PDVT patients. The anticoagulation duration was >180 days in 52.7% of IDDVT patients (70.7% in PDVT). During treatment, bleeding occurred in 5.6 and 2.8% patient-years in IDDVT and PDVT, respectively ( p = 0082). Bleeding was more frequent in IDDVT than PDVT patients treated with warfarin (6.8 vs. 3.2 patient-years, p = 0.0228, respectively). Thrombotic complications occurred in 1.1 and 2.4% patient-years in IDDVT and PDVT patients, respectively. Analyzing together the two groups, 66.1% of bleeds and 86.1% thrombotic complications occurred after 90 days anticoagulation treatment. Conclusion The large majority of IDDVT patients received anticoagulation for more than 3 months. Most bleeding and thrombotic complications occurred after the first 90 days of anticoagulation therapy. These results indicate that an extended anticoagulation beyond 90 days in IDDVT patients is associated with increased risk of complications. Whether an extended treatment may lower recurrences after anticoagulation withdrawal should be assessed by specifically designed studies.

Comparison of Anticoagulation Quality between Acenocoumarol and Warfarin in Patients with Mechanical Prosthetic Heart Valves: Insights from the Nationwide PLECTRUM Study.

Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, p = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, p < 0.001). A higher prevalence of TiTR (<60%, <65%, or <70%) was found in acenocoumarol users than in warfarin ones (p < 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin.

Sex-based difference in anticoagulated patients with mechanical prosthetic heart valves and long-term mortality risk.

BACKGROUND: Vitamin K antagonists (VKAs) reduce thromboembolism in patients with mechanical prosthetic heart valves (MPHV). It is unclear whether a sex-based difference in MPHV patients regarding valve site, anticoagulation quality, and mortality risk does exist. METHODS: We analysed 2111 MPHV patients from the nationwide PLECTRUM study promoted by the Italian Federation of Anticoagulation Clinics (FCSA). We analysed the site of MPHV, anticoagulation quality, as assessed by the time in therapeutic range (TiTR), and mortality risk in women and men. RESULTS: The mean age of the patients was 56.8 ± 12.3 years. Women were older with a lower prevalence of ischemic heart disease and smoking habit and a higher prevalence of atrial fibrillation at baseline. Aortic MPHV was more frequent in men (74.7% vs 43.3%, P < .001), whereas mitral (41.1% vs 17.6%, P < .001) and mitro-aortic (15.6% vs 7.7%, P < .001) MPVH in women. The association between female sex and mitral/mitro-aortic site remained at multivariable logistic regression analysis (Odds Ratio 3.623, 95% Confidence Interval [CI] 2.947-4.455, P < .001). Regarding anticoagulation quality, women showed lower mean TiTR (63.0 ± 19.4 vs 57.5 ± 19.2, P < .001), and a higher proportion of TiTR < 60% (54.9% vs 43.3%, P < .001). During a mean follow-up of 123 months (21 665 pt-years), 152 deaths occurred (0.7%/year); 83 in the aortic (0.63%/year) and 69 in the mitral/mitro-aortic (0.81%/year) group. At multivariable Cox proportional hazard regression analysis, female sex was not associated with mortality (HR 0.953, 95%CI 0.678 1.340, P = .783). CONCLUSIONS: Female sex is independently associated with mitral/mitro-aortic MPHV. Despite a lower TiTR in women, mortality risk did not differ between the two groups.