The TOPOS study.

Background: We aimed to study the long-term safety and efficacy of oblique venous stents for post-thrombotic syndrome (PTS) with iliac vein compression. Patients and methods: In the multinational, prospective, single-arm TOPOS study, PTS patients scheduled for endovascular therapy with the sinus-Obliquus® stent and optional distal extension with the sinus-Venous® or sinus-XL Flex® stent were enrolled at eight European vascular centres between October 2016 and December 2020. The primary outcome was primary stent patency at 24 months, and secondary outcomes included the clinical course of PTS (Villalta score, revised Venous Clinical Severity Score [rVCSS], Visual Analog Scale [VAS] of pain), quality of life changes (Chronic Venous Insufficiency Quality of Life Questionnaire, CIVIQ-20), and device-related complications. Results: We enrolled 60 patients (mean age 46±15 years, 68% women, 13% active ulcers): 80% required stent extension (70% below the inguinal ligament). The primary patency rate at 24 months was 80.7% (95%CI 68.1-90.0%); it was higher in patients without vs. those with stent extension (90.9% vs. 78.3%, p=.01). Compared to baseline, the Villalta, rVCSS, pain VAS, and CIVIQ-20 decreased by a median of 8 (interquartile range (IQR): 4-11), 5 (IQR: 3-7), 3 (IQR: 2-5), and 17 (IQR: 6-22) points, respectively; p<.001 for all parameters. Overall, 9 events of acute stent occlusion, 4 symptomatic stent stenosis, and 1 pulmonary embolism occurred. We did not observe major bleeding events or contralateral thrombosis. Conclusions: Endovascular treatment with the oblique stent and optional stent extension was safe and resulted in high patency rates at 24 months. The reduction in PTS severity was substantial and persisted over 2-year follow-up.

Mortality rate related to peripheral arterial disease: A retrospective analysis of epidemiological data (years 2008-2019).

BACKGROUND AND AIMS: Peripheral arterial disease (PAD) is one of the most prevalent cardiovascular diseases with more than 230 million people being affected worldwide. As highlighted by the recent European Society of Cardiology guidelines, data on the epidemiology of PAD is urgently needed. METHODS AND RESULTS: We accessed the vital registration data of the Veneto region (Northern Italy, approximately five millions inhabitants) covering the period 2008-2019. We computed annual age-standardized rates for PAD reported as the underlying cause of death (UCOD) or as one of multiple causes of death (MCOD). Age-adjusted odds ratios (OR) served to study the association between PAD and cardiovascular comorbidities. The age-standardized mortality rate for PAD as MCOD slightly declined from 19.6 to 17.8 in men and from 10.8 to 9.1 deaths per 100,000 population-years in women. The age-standardized PAD-specific mortality rate (UCOD) remained stable: 3.1 to 3.7 per 100,000 person-years in women (Average Annual Percent Change 1.3, 95% CI -0.8; 3.4%) and 4.4 to 4.3 per 100,000 person-years (Average Annual Percent Change -0.2, 95% CI -3.6; 3.4%) in men. PAD contributed to 1.6% of all deaths recorded in the region. Ischemic heart disease, diabetes mellitus and neoplasms were the most prevalent UCOD among PAD patients. PAD was associated with diabetes mellitus (OR 3.79, 95%CI 3.55-4.06) and chronic kidney diseases (OR 2.73, 95%CI 2.51-2.97) in men, and with atrial fibrillation (OR 2.26, 95%CI 2.10-2.44) in women. CONCLUSION: PAD remains a substantial cause of death in the general population of this high-income region of Western Europe with marked sex-specific differences.

Coagulation-monitored, dose-adjusted catheter-directed thrombolysis or pharmaco-mechanical thrombus removal in deep vein thrombosis.

Background: Pharmaco-mechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) are therapeutic options for selected patients with acute deep vein thrombosis (DVT) to prevent post-thrombotic syndrome (PTS). Patients and methods: We aimed to describe the clinical characteristics and outcomes of 159 patients with symptomatic iliofemoral DVT undergoing PMT alone, CDT alone, or CDT followed by PMT (bail-out) in the Swiss Venous Stent Registry. The primary outcome was the incidence of peri-interventional major and minor bleeding complications (ISTH criteria). Secondary outcomes included the incidence of PTS and stent patency after 3 years. Results: Mean age was 49±20 years and 58% were women. DVT involved the iliac veins in 99% of patients, whereas 53% had an underlying iliac vein compression. PMT alone was used in 40 patients, CDT alone in 77, and 42 received initial CDT followed by bail-out PMT due to insufficient thrombus clearance. Single-session PMT was the preferred approach in patients with iliac vein compression, patent popliteal vein, and absence of IVC thrombus. Patients treated with PMT alone received a lower r-tPA dose (median 10 mg, IQR 10-10) vs. those treated with CDT (20 mg, IQR 10-30). The rate of peri-interventional major bleeding was 0%, 1%, and 2%, whereas that of minor bleeding was 0%, 1%, and 12%, respectively, all occurring during CDT. After 3 years, PTS occurred in 6%, 9%, and 7% of patients, respectively. The primary stent patency rate was 95%, 88%, and 83%, respectively. Conclusions: The use of PMT and CDT for iliofemoral DVT was overall safe and resulted in high long-term patency and treatment success. Given the less severe presentation of DVT, single-session PMT appeared to be characterized by numerically better primary patency and lower perioperative bleeding event rates than CDT.

A novel management strategy for treatment of pelvic venous disorders utilizing a clinical screening score and non-invasive imaging.

Background: Treatment of pelvic venous disorders (PVD) including pelvic congestion syndrome (PCS) are often delayed due to its varying clinical manifestations. Patients and methods: Patient referral was based on a literature- and personal experience-derived clinical "PCS screening score" (higher score points indicate greater likelihood with a maximum score of 10 points). We studied consecutive women who were (i) referred for vascular assessment and treatment to the University Hospital Zurich (2017-2021), (ii) had a PCS score ≥3 points, (iii) had evidence of obstructive or non-obstructive PVD by duplex sonography or cross-sectional imaging, and (iv) underwent endovascular therapy. The primary outcome was change in symptom severity after endovascular therapy: (i) freedom from symptoms, (ii) improvement with residual symptoms, (iii) no improvement. Results: We included 43 women (mean age 36 years): 81% had previous pregnancy, 19% endometriosis. The median PCS score was 7 (IQR 5-9) points. Chronic lower-abdominal pain was the leading symptom in 86% patients, followed by recurrent leg (9%) and vulvar (5%) varicosities. The main PVD pathologies were ovarian vein insufficiency (61%), internal iliac vein insufficiency (9%), or a combination of both (30%), whereas 42% had a deep venous obstruction of the inferior vena cava, common iliac or left renal veins. Endovascular therapy included ovarian vein embolization (86%), internal iliac vein embolization (9%), and venous stent placement (35%). After a median of 4 (IQR 1-8) months from endovascular treatment, 40 (93%) patients reported improvement of the leading symptom, and 14 (33%) were symptom-free. Complications included re-intervention for stent stenosis (13%, all post-thrombotic), coil-migration into the left renal vein (7%, all retrieved), and transient pelvic sclerotherapy-induced thrombophlebitis (2%). Conclusions: Endovascular therapy following a diagnostic approach, which included a PCS screening tool and non-invasive imaging, appeared to be highly effective and was associated with a low rate of complications.

Prevalent use of high-intensity statin therapy and LDL-C target attainment among PAD patients undergoing angioplasty.

Background: The global burden of peripheral arterial disease (PAD) is substantial. Reducing the major modifiable risk factors for noncommunicable disease, including dyslipidaemia, represents a public health priority. Aim is to evaluate the prevalent adequate use of lipid-lowering therapy (LLT) and low-density lipoprotein cholesterol (LDL-C) attainment among patients with PAD of the lower extremities undergoing percutaneous transluminal angioplasty. Patients and methods: We screened PAD patients treated at the University Hospital Zurich (January 2012-December 2018). We excluded patients <18 years, without classifiable severity of PAD, or with missing LDL-C or medication data. In this cross-sectional study, we studied the prevalent LLT use and LDL-C values in target according to the most recent European guidelines. Available clinical data included demographic information, lipid profile, type and dose of LLT, characteristics of the artery obstruction and angioplasty. Results: A total of 2,148 angioplasties were performed in 956 patients: 614 (64%) were men; the mean age was 70.6 (SD 11.4) years. A total of 608 (64%) had a non-critical PAD (Fontaine stage I-IIb), whereas the remaining had a critical limb ischemia or a diabetic foot syndrome. Their median LDL-C value was 2.00 (Q1-Q3: 1.50-2.60) mmol/L. In accordance to the 2016 and 2019 European Society of Cardiology guidelines, the LDL-C target of 1.8 and 1.4 mmol/L was not reached in 63% (n=599) and in 79% (n=760) of patients, respectively. Only 41% (n=390) of patients were on high-intensity statin therapy. Conclusions: The attainment of LDL-C targets, as recommended by current European guidelines, and the use of high-intensity LLT were unsatisfactory in the majority of PAD patients.

Impact of concomitant popliteal vein thrombosis in patients with acute iliofemoral deep vein thrombosis treated with endovascular early thrombus removal.

Background: Catheter-based thrombus removal (CBTR) reduces the risk of moderate to severe post-thrombotic syndrome (PTS) in patients with acute iliofemoral deep vein thrombosis (IF-DVT). However, the impact of concomitant popliteal DVT on clinical and duplex sonographic outcomes is unknown. Patients and methods: In this post-hoc analysis including the entire cohort of the randomized controlled BERNUTIFUL trial (48 patients), we compared clinical (incidence/severity of PTS assessed by Villalta score and revised venous clinical severity scores, rVCSS), disease-specific quality-of-life (QOL, CIVIQ-20 survey) and duplex sonographic outcomes (patency, reflux, post-thrombotic lesions) at 12 months follow-up between patients with IF-DVT with and without concomitant popliteal DVT treated by CBTR. Results: Overall, 48 IF-DVT patients were included (48% men, median age of 50 years), of whom 17 (35%) presented with popliteal DVT. At baseline, patients with popliteal DVT were older, had a higher body mass index and more important leg swelling. At 12 months, freedom from PTS (93% vs 87%, P=0.17), median total Villalta score (1 vs 1.5; P=0.46), rVCSS (2 vs 1.5, P=0.5) and disease-specific QOL (24 points vs 24 points, P=0.72) were similar between patient with and without popliteal DVT, respectively. Duplex sonographic outcomes were similar, except for more frequent popliteal post-thrombotic lesions and reflux (P=0.02) in patients with popliteal DVT. Conclusions: Relevant clinical outcomes 1 year after successful CBTR were favorable, regardless of the presence or absence of concomitant popliteal DVT. However, post-thrombotic popliteal vein lesions and reflux are more frequent in IF-DVT patients with popliteal involvement. Their impact on long-term outcomes remains to be investigated.

Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial.

Importance: Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown. Objective: To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction. Design, Setting, and Participants: The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrollment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals. Interventions: Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 hours after urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg). Main Outcomes and Measures: Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 non-infarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary end points were changes in near-infrared spectroscopy-derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography-derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52. Results: Among 300 randomized patients (mean [SD] age, 58.5 [9.7] years; 56 [18.7%] women; mean [SD] low-density lipoprotein cholesterol level, 152.4 [33.8] mg/dL), 265 (88.3%) underwent serial IVUS imaging in 537 arteries. At 52 weeks, mean change in percent atheroma volume was -2.13% with alirocumab vs -0.92% with placebo (difference, -1.21% [95% CI, -1.78% to -0.65%], P < .001). Mean change in maximum lipid core burden index within 4 mm was -79.42 with alirocumab vs -37.60 with placebo (difference, -41.24 [95% CI, -70.71 to -11.77]; P = .006). Mean change in minimal fibrous cap thickness was 62.67 µm with alirocumab vs 33.19 µm with placebo (difference, 29.65 µm [95% CI, 11.75-47.55]; P = .001). Adverse events occurred in 70.7% of patients treated with alirocumab vs 72.8% of patients receiving placebo. Conclusions and Relevance: Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy resulted in significantly greater coronary plaque regression in non-infarct-related arteries after 52 weeks. Further research is needed to understand whether alirocumab improves clinical outcomes in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT03067844.

Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study-Rationale and design of the PACMAN-AMI trial.

BACKGROUND: The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown. AIMS: To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI4 mm) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI. METHODS: In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI4 mm, and OCT-derived minimal FCT, will be assessed 52 weeks post randomization. SUMMARY: The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI. CLINICAL TRIAL REGISTRATION: NCT03067844.

Duplex Ultrasound Investigation for the Detection of Obstructed Iliocaval Venous Stents.

OBJECTIVE: Duplex ultrasound (DUS) is used for routine surveillance of stents in iliocaval veins, but direct visualisation is often challenging. Duplex ultrasound criteria for detecting venous stent obstruction (VSO) have not been defined to date. METHODS: A nested case control study of 120 patients (42 ± 17 years, 53% women, mean 2.7 ± 1.8 stents) was performed, and the performance of various duplex parameters for detecting VSO (defined as > 50% lumen diameter reduction or occlusion) was tested, confirmed by biplane venography or intravascular ultrasound (IVUS). Forty patients with VSO (25 with stent occlusion, 15 with >50% in stent stenosis) were matched to 80 control patients by age, gender and index diagnosis who fulfilled the following criteria: (1) ongoing symptom control (Villalta score < 5), (2) good image quality of entire stent segment, (3) spontaneous colour Doppler signal > 50% of lumen in entire stent segment, (4) at least two DUS where the baseline DUS was obtained within 24 h after successful venous intervention. RESULTS: The best test was the combination of peak flow velocity and flow pattern analysis at the stent inlet. A peak flow velocity >10 cm/s and a flow pattern spontaneously modulated by respiration ruled out VSO with a specificity of 93.7% (95% CI 86.0%-97.3%). A peak flow velocity ≤10 cm/s or any Doppler flow pattern other than spontaneously modulated by respiration was 92.1% (95% CI 79.2%-97.3%) sensitive to detect VSO. CONCLUSION: The combination of peak flow velocity and analysis of Doppler flow pattern at the stent inlet is accurate to diagnose or rule out stent occlusion. Indirect criteria should always be combined with direct visualisation of iliocaval stents since those may be less sensitive for detecting stent stenosis.

Venous Thromboembolism and Renal Impairment: Insights from the SWIss Venous ThromboEmbolism Registry (SWIVTER).

Renal impairment (RI) has increased substantially over the last decades. In the absence of data from confirmatory research, real-life data on anticoagulation treatment and clinical outcomes of venous thromboembolism (VTE) in patients with RI are needed. In the SWIss Venous ThromboEmbolism Registry (SWIVTER), 2,062 consecutive patients with objectively confirmed VTE were enrolled. In the present analysis, we compared characteristics, initial and maintenance anticoagulation, and adjusted 90-day clinical outcomes of those with (defined as estimated creatinine clearance < 30 mL/min) and without severe RI. Overall, 240 (12%) patients had severe RI; they were older, and more frequently had chronic and acute comorbidities. VTE severity was similar between patients with and without severe RI. Initial anticoagulation in patients with severe RI was more often performed with unfractionated heparin (44 vs. 24%), and less often with low-molecular-weight heparin (LMWH) (52 vs. 61%) and direct oral anticoagulants (DOACs; 4 vs. 12%). Maintenance anticoagulation in patients with severe RI was more frequently managed with vitamin K antagonists (70 vs. 60%) and less frequently with DOAC (12 vs. 21%). Severe RI was associated with increased risk of 90-day mortality (9.2 vs. 4.2%, hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.41-3.65), but with similar risk of recurrent VTE (3.3 vs. 2.8%, HR: 1.19, 95% CI: 0.57-2.52) and major bleeding (2.1 vs. 2.0%, HR: 1.05, 95% CI: 0.41-2.68). In patients with severe RI, the use of LMWH versus any other treatment was associated with reduced mortality (HR: 0.37; 95% CI: 0.14-0.94; p = 0.036) and similar rate of major bleeding (HR: 0.59, 95% CI: 0.17-2.00; p = 0.39). Acute or chronic comorbidities rather than VTE severity or recurrence may explain increased early mortality in patients with severe RI. The higher rate of VTE recurrence, specifically fatal events, than major bleeding reinforces the need for effective anticoagulation in VTE patients with severe RI.

Cessation of anticoagulation therapy following endovascular thrombus removal and stent placement for acute iliofemoral deep vein thrombosis.

Background: The optimal duration of anticoagulation therapy (AT) following catheter-based therapy of acute iliofemoral deep vein thrombosis (IFDVT) with stent placement is unknown. Theoretically, resolving the underlying obstructive iliac vein lesion by a stent may eliminate the main trigger for recurrence, the post-thrombotic syndrome (PTS), and the need for extended-duration AT. Patients and methods: From 113 patients with acute IFDVT who underwent endovascular thrombus removal and stent placement, we compared patency rates and clinical outcomes between 58 patients on limited-duration AT (3-12 month) and 55 patients on extended-duration AT (> 12 months). Results: Mean follow-up duration was 26 ± 18 (range 3-77) months; it was 24 ± 18 (range 3-69) months after cessation of AT in the limited-duration AT group. In comparison to patients with extended-duration AT, patients with limited-duration AT were younger (38 versus 54 years; p < 0.001), more often female (74 % versus 49 %; p = 0.01), and had less often prior venous thromboembolism (VTE) (9 % versus 35 %; p = 0.001). May-Thurner syndrome was more frequent in the limited-duration AT group (66 % versus 38 %; p = 0.004). Overall, primary and secondary patency rates at 24 months were 80 % (95 % CI, 70-87 %) and 95 % (95 % CI, 88-98 %), respectively, with no difference between the groups. Overall, 17 (15 %) patients developed recurrent VTE, of which 14 (82 %) events were thrombotic stent occlusions, and 13 (76 %) events occurred during AT. In the limited-duration AT group, 98 % patients were free from the PTS at two years with a VTE recurrence rate of 3.5 per 100 patient years after cessation of AT. Conclusions: In selected patients with acute IFDVT and patent venous stent, particularly in younger and otherwise healthy patients with May-Thurner syndrome, it appears to be safe to discontinue AT 3-12 months after endovascular treatment. Clinical Trial Registration: The study is registered on the National Institutes of Health website (ClinicalTrials.gov; identifier NCT02433054).

Effect of Home Blood Pressure Monitoring on Patient's Awareness and Goal Attainment Under Antihypertensive Therapy: The Factors Influencing Results in Anti-HypertenSive Treatment (FIRST) Study.

BACKGROUND/AIMS: Despite availability of a broad spectrum of blood pressure (BP)-lowering drugs many hypertensive patients do not attain BP goals. We aimed to evaluate the influence of home blood pressure monitoring (HBPM) on patient's awareness and attainment of BP goals under antihypertensive treatment with irbesartan alone or in combination with hydro-chlorothiazide. METHODS: In total, 1,268 patients with arterial hypertension were enrolled in the Factors Influencing Results in anti-hypertenSive Treatment (FIRST) study by 348 general practitioners and internal medicine specialists across Switzerland. Patients selected for HBPM received detailed information and training on BP self-management. The study endpoints included patient's awareness and attainment of BP goals, and the efficacy and tolerability of antihypertensive treatment at 3 months. RESULTS: Overall, the mean age was 61±13 years and 616 (49%) were women. The mean systolic/diastolic BP was 161±17/96±11 mmHg, and 239 (19%) patients had diabetes mellitus. 758 (60%) patients were instructed to use HBPM. Both the proportion of patients aware of their BP goals (81% vs. 70%; p< 0.001) and the percentage of patients reaching their BP goal (64% vs. 57%; p=0.028) were higher in those with vs. without HBPM. The mean reduction in systolic/diastolic BP was 23.8/13.2 mmHg. Only 35 (3.0%) patients discontinued antihypertensive therapy. CONCLUSION: In a large Swiss cohort of patients with arterial hypertension, information and training on BP self-measurement and direct involvement of patients by using HBPM led to improvement in BP control. Treatment with irbesartan alone or in combination with hydrochlorothiazide was well tolerated and markedly reduced BP.

[Inhibitors of PCSK9]. / Inhibiteurs de la PCSK9.

Observational data show a consistent association between elevated low density lipoproteins (LDL-C) and cardiovascular disease (CVD). Reduction of LDL-C reduces the risk of CVD as has been shown by many trials. Statins are currently the most effective drugs for lowering LDL-C, but can present side effects which might limit the prescribed dosage and prevent patients from reaching the recommended LDL levels. Although treated with statins important residual cardiovascular event risk remains in patients in primary and secondary prevention for CVD. The discovery of protein convertase subtilisin kexin 9 antibodies is a very promising new hypolipidemic treatment and the aim of this review is to explain their mechanism of action and to discuss safety and efficacy results of some phase III studies.

Les données d'observation montrent une association cohérente entre une élévation des lipoprotéines de basse densité (LDL-C) et les maladies cardiovasculaires (MCV). Les statines sont actuellement les médicaments les plus efficaces pour abaisser le LDL-C, mais elles peuvent présenter des effets secondaires qui pourraient limiter les patients d'atteindre les niveaux de LDL-C recommandés. Bien que traités par les statines, un important risque résiduel d'événement cardiovasculaire reste chez les patients en préventions primaire et secondaire. La découverte des anticorps contre la protéase convertase subtilisine / kexine 9 est un nouveau traitement antilipémique très prometteur et le but de cet examen est d'expliquer leur mécanisme d'action et de discuter les données de sécurité et d'efficacité de quelques études de phase III.

Clinical Outcomes of Venous Thromboembolism in Patients with and without Cancer: The SWIss Venous ThromboEmbolism Registry (SWIVTER).

Background The association between cancer and venous thromboembolism (VTE) in producing adverse clinical outcomes requires further investigation. Methods In the Swiss Venous ThromboEmbolism Registry (SWIVTER), we compared adverse clinical outcomes between 493 patients with cancer-associated VTE and 1,569 VTE patients without cancer, and identified independent predictors of 90-day mortality. Results Among cancer patients, 351 (71%) had active disease at the time of VTE diagnosis and 232 (47%) had metastatic disease. Cancer patients more frequently had asymptomatic VTE (13 vs. 4%; p < 0.001), iliofemoral deep vein thrombosis (42 vs. 32%; p = 0.017), and upper extremity deep vein thrombosis (16 vs. 7%; p < 0.001). Cancer was associated with an increased risk of cumulative 90-day mortality (13.0 vs. 2.2%; hazard ratio [HR], 6.27; 95% confidence interval [CI], 4.13-9.50; p < 0.001), recurrent VTE (4.7 vs. 2.3%; HR, 2.05; 95% CI, 1.21-3.45; p = 0.007), and bleeding requiring medical attention (5.7 vs. 3.3%; HR, 1.80; 95% CI, 1.13-2.86; p = 0.013). Among cancer patients, the strongest factor associated with mortality was metastatic disease (HR, 4.86; 95% CI, 2.68-8.81; p < 0.001), whereas it was pulmonary embolism among noncancer patients (HR, 4.96; 95% CI, 1.50-16.45; p = 0.009). Symptomatic as compared with asymptomatic VTE predicted neither mortality (12.6 vs. 15.9%; HR, 0.76; 95% CI, 0.39-1.49; p = 0.42) nor recurrent VTE (4.7 vs. 4.8%; HR, 0.98; 95% CI, 0.29-3.31; p = 0.98) in cancer patients. Conclusion In SWIVTER, early mortality of cancer-associated VTE was mainly driven by the extent of cancer disease and not by VTE symptoms or severity.

Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy.

BACKGROUND AND AIMS: The effects of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on endothelial function as assessed by flow-mediated dilation (FMD) in patients with acute myocardial infarction (AMI) are unknown. Therefore, we aimed to investigate the effects of the PCSK9 inhibitor alirocumab added to high-intensity statin on FMD, and its association with coronary atherosclerosis in non-infarct related arteries using intracoronary intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT). METHODS: This was a pre-specified substudy among patients recruited at Bern University Hospital, Switzerland, for the randomized-controlled, double-blind, PACMAN-AMI trial, which compared the effects of biweekly alirocumab 150 mg vs. placebo added to rosuvastatin. Brachial artery FMD was measured at 4 and 52 weeks, and intracoronary imaging at baseline and 52 weeks. RESULTS: 139/173 patients completed the substudy. There was no difference in FMD at 52 weeks in the alirocumab (n = 68, 5.44 ± 2.24%) versus placebo (n = 71, 5.45 ± 2.19%) group (difference = -0.21%, 95% CI -0.77 to 0.35, p = 0.47). FMD improved throughout 52 weeks in both groups similarly (p < 0.001). There was a significant association between 4 weeks FMD and baseline plaque burden (IVUS) (n = 139, slope = -1.00, p = 0.006), but not with lipid pool (NIRS) (n = 139, slope = -7.36, p = 0.32), or fibrous cap thickness (OCT) (n = 81, slope = -1.57, p = 0.62). CONCLUSIONS: Among patients with AMI, the addition of alirocumab did not result in further improvement of FMD as compared to 52 weeks secondary preventative medical therapy including high-intensity statin therapy. FMD was significantly associated with coronary plaque burden at baseline, but not with lipid pool or fibrous cap thickness.

Predictors of in-hospital mortality in elderly patients with acute venous thrombo-embolism: the SWIss Venous ThromboEmbolism Registry (SWIVTER).

AIMS: Although acute venous thrombo-embolism (VTE) often afflicts patients with advanced age, the predictors of in-hospital mortality for elderly VTE patients are unknown. METHODS AND RESULTS: Among 1247 consecutive patients with acute VTE from the prospective SWIss Venous ThromboEmbolism Registry (SWIVTER), 644 (52%) were elderly (≥65 years of age). In comparison to younger patients, the elderly more often had pulmonary embolism (PE) (60 vs. 42%; P< 0.001), cancer (30 vs. 20%; P< 0.001), chronic lung disease (14 vs. 8%; P= 0.001), and congestive heart failure (12 vs. 2%; P< 0.001). Elderly VTE patients were more often hospitalized (75 vs. 52%; P< 0.001), and there was no difference in the use of thrombolysis, catheter intervention, or surgical embolectomy between the elderly and younger PE patients (5 vs. 6%; P= 0.54), despite a trend towards a higher rate of massive PE in the elderly (8 vs. 4%; P= 0.07). The overall in-hospital mortality rate was 6.6% in the elderly vs. 3.2% in the younger VTE patients (P= 0.033). Cancer was associated with in-hospital death both in the elderly [hazard ratio (HR) 4.91, 95% confidence interval (CI) 2.32-10.38; P< 0.001] and in the younger patients (HR 4.90, 95% CI 1.37-17.59; P= 0.015); massive PE was a predictor of in-hospital death in the elderly only (HR 3.77, 95% CI 1.63-8.74; P= 0.002). CONCLUSION: Elderly patients had more serious VTE than younger patients, and massive PE was particularly life-threatening in the elderly.

Effect of Alirocumab Added to High-Intensity Statin on Platelet Reactivity and Noncoding RNAs in Patients with AMI: A Substudy of the PACMAN-AMI Trial.

OBJECTIVE: The effect of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. We aimed to explore the effect of alirocumab added to high-intensity statin therapy on P2Y12 reaction unit (PRU) among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). In addition, we assessed circulating platelet-derived noncoding RNAs (microRNAs and YRNAs). METHODS: This was a prespecified, powered, pharmacodynamic substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Patients recruited at Bern University Hospital, receiving DAPT with a potent P2Y12 inhibitor, and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The primary endpoint was PRU at 4 weeks after study drug initiation as assessed by VerifyNow P2Y12 point-of-care assays. RESULTS: Among 139 randomized patients, the majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] in the alirocumab group vs. 69 [94.5%] in the placebo group, p = 0.14). There were no significant differences in the primary endpoint PRU at 4 weeks between groups (12.5 [interquartile range, IQR: 27.0] vs. 19.0 [IQR: 30.0], p = 0.26). Consistent results were observed in 126 patients treated with ticagrelor (13.0 [IQR: 20.0] vs. 18.0 [IQR: 27.0], p = 0.28). Similarly, platelet-derived noncoding RNAs did not significantly differ between groups. CONCLUSION: Among AMI patients receiving DAPT with a potent P2Y12 inhibitor, alirocumab had no significant effect on platelet reactivity as assessed by PRU and platelet-derived noncoding RNAs.

Impact of alirocumab on plaque regression and haemodynamics of non-culprit arteries in patients with acute myocardial infarction: a prespecified substudy of the PACMAN-AMI trial.

BACKGROUND: Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on top of statins leads to plaque regression and stabilisation. The effects of PCSK9 inhibitors on coronary physiology and angiographic diameter stenosis (DS%) are unknown. AIMS: This study aimed to investigate the effects of the PCSK9 inhibitor alirocumab on coronary haemodynamics as assessed by quantitative flow ratio (QFR) and DS% by three-dimensional quantitative coronary angiography (3D-QCA) in non-infarct-related arteries (non-IRA) among acute myocardial infarction (AMI) patients. METHODS: This was a prespecified substudy of the randomised controlled PACMAN-AMI trial, comparing alirocumab versus placebo on top of rosuvastatin. QFR and 3D-QCA were assessed at baseline and 1 year in any non-IRA ≥2.0 mm and 3D-QCA DS% >25%. The prespecified primary endpoint was the number of patients with a mean QFR increase at 1 year, and the secondary endpoint was the change in 3D-QCA DS%. RESULTS: Of 300 enrolled patients, 265 had serial follow-up, of which 193 underwent serial QFR/3D-QCA analysis in 282 non-IRA. At 1 year, QFR increased in 50/94 (53.2%) patients with alirocumab versus 40/99 (40.4%) with placebo (Δ12.8%; odds ratio 1.7, 95% confidence interval [CI]: 0.9 to 3.0; p=0.076). DS% decreased by 1.03±7.28% with alirocumab and increased by 1.70±8.27% with placebo (Δ-2.50%, 95% CI: -4.43 to -0.57; p=0.011). CONCLUSIONS: Treatment of AMI patients with alirocumab versus placebo for 1 year resulted in a significant regression in angiographic DS%, whereas no overall improvement of coronary haemodynamics was observed. CLINICALTRIALS: gov: NCT03067844.

Enoxaparin for outpatients with COVID-19: 90-day results from the randomised, open-label, parallel-group, multinational, phase III OVID trial.

INTRODUCTION: The benefits of early thromboprophylaxis in symptomatic COVID-19 outpatients remain unclear. We present the 90-day results from the randomised, open-label, parallel-group, investigator-initiated, multinational OVID phase III trial. METHODS: Outpatients aged 50 years or older with acute symptomatic COVID-19 were randomised to receive enoxaparin 40 mg for 14 days once daily vs. standard of care (no thromboprophylaxis). The primary outcome was the composite of untoward hospitalisation and all-cause death within 30 days from randomisation. Secondary outcomes included arterial and venous major cardiovascular events, as well as the primary outcome within 90 days from randomisation. The study was prematurely terminated based on statistical criteria after the predefined interim analysis of 30-day data, which has been previously published. In the present analysis, we present the final, 90-day data from OVID and we additionally investigate the impact of thromboprophylaxis on the resolution of symptoms. RESULTS: Of the 472 patients included in the intention-to-treat population, 234 were randomised to receive enoxaparin and 238 no thromboprophylaxis. The median age was 57 (Q1-Q3: 53-62) years and 217 (46 %) were women. The 90-day primary outcome occurred in 11 (4.7 %) patients of the enoxaparin arm and in 11 (4.6 %) controls (adjusted relative risk 1.00; 95 % CI: 0.44-2.25): 3 events per group occurred after day 30. The 90-day incidence of cardiovascular events was 0.9 % in the enoxaparin arm vs. 1.7 % in controls (relative risk 0.51; 95 % CI: 0.09-2.75). Individual symptoms improved progressively within 90 days with no difference between groups. At 90 days, 42 (17.9 %) patients in the enoxaparin arm and 40 (16.8 %) controls had persistent respiratory symptoms. CONCLUSIONS: In adult community patients with COVID-19, early thromboprophylaxis with enoxaparin did not improve the course of COVID-19 neither in terms of hospitalisation and death nor considering COVID-19-related symptoms.

Concomitant Coronary Atheroma Regression and Stabilization in Response to Lipid-Lowering Therapy.

BACKGROUND: The frequency, characteristics, and outcomes of patients treated with high-intensity lipid-lowering therapy and showing concomitant atheroma volume reduction, lipid content reduction, and increase in fibrous cap thickness (ie, triple regression) are unknown. OBJECTIVES: This study was designed to investigate rates, determinants, and prognostic implications of triple regression in patients presenting with acute myocardial infarction and treated with high-intensity lipid-lowering therapy. METHODS: The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients with Acute Myocardial Infarction) trial used serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography to compare the effects of alirocumab vs placebo in patients receiving high-intensity statin therapy. Triple regression was defined by the combined presence of percentage of atheroma volume reduction, maximum lipid core burden index within 4 mm reduction, and minimal fibrous cap thickness increase. Clinical outcomes at 1-year follow-up were assessed. RESULTS: Overall, 84 patients (31.7%) showed triple regression (40.8% in the alirocumab group vs 23.0% in the placebo group; P = 0.002). On-treatment low-density lipoprotein cholesterol levels were lower in patients with vs without triple regression (between-group difference: -27.1 mg/dL; 95% CI: -37.7 to -16.6 mg/dL; P < 0.001). Triple regression was independently predicted by alirocumab treatment (OR: 2.83; 95% CI: 1.57-5.16; P = 0.001) and a higher baseline maximum lipid core burden index within 4 mm (OR: 1.03; 95% CI: 1.01-1.06; P = 0.013). The composite clinical endpoint of death, myocardial infarction, and ischemia-driven revascularization occurred less frequently in patients with vs without triple regression (8.3% vs 18.2%; P = 0.04). CONCLUSIONS: Triple regression occurred in one-third of patients with acute myocardial infarction who were receiving high-intensity lipid-lowering therapy and was associated with alirocumab treatment, higher baseline lipid content, and reduced cardiovascular events. (Vascular Effects of Alirocumab in Acute MI-Patients [PACMAN-AMI]; NCT03067844).