Editor's Choice - Revascularisation for Peripheral Artery Disease in France: Implications for the Implementation of VOYAGER-PAD.

OBJECTIVE: The VOYAGER-PAD trial demonstrated the interest in dual pathway inhibition (DPI) (low dose rivaroxaban plus aspirin) to reduce limb and cardiovascular events after revascularisation for peripheral artery disease (PAD), but its applicability in clinical practice has not yet been assessed. This study aimed to assess the number of patients revascularised in France for PAD and to estimate the proportion of those matching the VOYAGER-PAD trial selection criteria. A secondary objective was to examine the prognosis of revascularised patients in a real world setting. METHODS: This observational retrospective study was conducted on the national hospital discharge database and included all patients with PAD who underwent lower extremity revascularisation for PAD (without lower extremity revascularisation in the two years prior to inclusion) from 1 January 2016 to 31 December 2019. Available VOYAGER-PAD selection criteria were then applied to the study population. RESULTS: In total, 180 870 patients were included (mean age 72.0 ± 12.2 years, 30.9% female), with approximately 45 000 patients revascularised annually. Among them, 90 379 (50.0%) matched the VOYAGER-PAD trial criteria (VOYAGER-PAD eligible subgroup; mean age 69.8 ± 12.1 years, 29.5% female). In the study population and the VOYAGER-PAD eligible subgroup, 33.9% and 26.6% of patients had diabetes, 28.1% and 19.9% had chronic coronary artery disease, and 14.6% and 5.7% had renal failure, respectively. Overall, 73.1% of study patients were treated by an endovascular approach (75.5% in the VOYAGER-PAD eligible subgroup). In patients with more than one year of follow up, 45.4% of study patients and 36.0% of the VOYAGER-PAD eligible subgroup experienced a limb or cardiovascular event. The median time until the first event and in hospital death was 4.8 months and 7.8 months, respectively (6.7 months and 12.9 months in the VOYAGER-PAD eligible subgroup). CONCLUSION: The burden of PAD for revascularisation and secondary events is considerable. One half of revascularised patients in France are eligible for DPI therapy. Those patients are younger, with fewer comorbidities, and better outcomes.

Soluble endothelial protein C receptor (sEPCR) levels and venous thromboembolism in carriers of two dysfunctional protein C variants.

The role of the A3 haplotype and soluble endothelial protein C receptor (sEPCR) plasma levels in predisposing the carriers of two peculiar dysfunctional protein C (PC) variants (PC Arg-1-->Cys and PC Arg-1-->Leu, also known as PC Padua(2) and PC Padua(3), respectively) to venous thromboembolism (VTE) has been evaluated. The levels of sEPCR have been assessed in family members during 6 years of follow-up and correlated to the presence of the A3 haplotype. Individuals who carried both a dysfunctional PC and the A3 haplotype and presenting with high levels of sEPCR experienced severe VTE at young age. The increased plasma levels of sEPCR were not related to excessive thrombin generation. Carriers of the A3 haplotype showed levels of sEPCR above 135 ng/ml (80th percentile of the distribution in healthy subjects), which remained elevated during the follow-up. In non-carriers of the A3 haplotype, sEPCR levels remained persistently around 100 ng/ml or lower. In conclusion, we have observed that elevated sEPCR plasma levels and the concomitant presence of the A3 haplotype of EPCR gene are associated with severe thrombotic manifestations in carriers of two dysfunctional PC variants. Whether high plasma levels of sEPCR and/or the presence of the A3 haplotype increase the risk of thrombosis in carriers of other PC defects or thrombophilic conditions remains to be clarified.

Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study.

To assess the clinical significance of lupus anticoagulants (LAs) and antiphospholipid antibodies (aPLs) toward thrombosis and abortions, we measured them in 112 patients whose samples were available at enrollment in the warfarin in the antiphospholipid syndrome (WAPS) study. Enzyme-linked immunosorbent assay (ELISA) and coagulation test values in the highest and lowest tertiles were compared. When considered separately, IgG antibodies to beta2-glycoprotein I (abeta2GPI) and prothrombin (aPT) were associated with anamnestic arterial and venous thrombosis, respectively, and those to annexin AV (aAnAV) with abortions. IgM antibodies to protein S and the lupus ratio of the dilute prothrombin time were associated with prospective thrombosis. No other association for IgM antibodies was seen. LA-positive patients who carried abeta2GPI antibodies were at risk of anamnestic arterial and total thrombosis and aPT antibodies to that of anamnestic venous and total thrombosis. LA-positive patients who carried IgG abeta2GPI and aAnAV antibodies were at risk for both anamnestic abortion and prospective thrombosis. Overall, these data support the inclusion of abeta2GPI antibodies in and suggest the removal of anticardiolipin antibodies from the laboratory criteria of the antiphospholipid syndrome. They also suggest that the measurement of aPT and aAnAV antibodies is useful in some selected situations and that there is little role for IgM antibody detection.