Elena-Mihaela Cordeanu

A critical appraisal of the guidelines from France, the UK, Europe and the USA for the management of hypertension in adults

Hypertension is the leading cause of death in developed countries; its management is the subject of guidelines that are regularly reviewed and updated. However, the guidelines from France, the UK, Europe and the USA differ. Some recommendations are graded, whereas others are not. All recommendations emphasize the role of alternative methods for clinical measurement of blood pressure, such as ambulatory blood pressure measurement (ABPM) or self-measurement. The UK guideline recommends that the diagnosis of hypertension should be established by ABPM. The USA guideline recommends a target of ≤ 150/90 mmHg for patients aged >60 years. The French guideline recommends that the target blood pressure remains at <140/90 mmHg, with <150 mmHg for patients aged >80 years. Systolic blood pressure between 130 and 139 mmHg and diastolic blood pressure <90 mmHg are recommended for diabetic patients and those with chronic kidney disease. The French Society of Hypertension (SFHTA) guideline is unique in recommending a dedicated consultation to announce the diagnosis to the patient. In the French and European guidelines, diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor blockers (ARBs) remain indicated as first-line therapy for hypertension; if the target blood pressure is not achieved, they recommend combining two active substances. The UK guideline recommends ACE inhibitors or ARBs as first-line therapy for patients aged <55 years; calcium antagonists are advised for patients aged >55 years and for black patients. The USA guideline advises treating non-black patients, including those with diabetes, with thiazides, calcium antagonists, ACE inhibitors or ARBs; for black patients, including those with diabetes, it recommends thiazide and calcium antagonists.

Rivaroxaban versus standard anticoagulation for symptomatic venous thromboembolism (REMOTEV observational study): Analysis of 6-month outcomes

BACKGROUND This study aimed to provide safety and efficacy data of rivaroxaban in routine patient care in a non-selected symptomatic venous thromboembolism (VTE) population. METHODS AND RESULTS REMOTEV is a prospective, non-interventional study of patients with acute symptomatic VTE, treated with oral rivaroxaban, VKA or parenteral heparin/fondaparinux alone for at least 3months and who are followed up for 6months. From Nov. 2013 to July 2015, 499 consecutive patients were retained for baseline analysis and 445 for safety analysis. The mean age was 65.1years, 7.6% had previously known active cancer, 18.6% had creatinine clearance 30≤CrCl<60mL/min, and 87.8% had pulmonary embolism with or without deep venous thrombosis. The major and clinically relevant bleeding rate was 5.4% (15/280) in the rivaroxaban group, 9.4%/(9/96) in the VKA group and 7.2% (5/69) in the heparin/fondaparinux group. The recurrent VTE rate was 1.4% (4/280) in the rivaroxaban group, 3.1% (3/96) in the VKA group and 11.6% (8/69) in the heparin/fondaparinux group. In the propensity score-adjusted samples, major and clinically relevant non-major bleeding (HR 0.37 [95% CI, 0.15 to 0.93], p<0.05), all-cause death (HR 0.21 [95% CI, 0.06 to 0.66], p<0.01) and the composite of recurrent VTE, major and clinically relevant non-major bleeding and all-cause mortality (HR 0.35 [95% CI, 0.17 to 0.71], p<0.01), were significantly lower in the rivaroxaban group compared to the VKA group. CONCLUSION In REMOTEV 6-month outcomes are consistent with the findings of the phase 3 randomized trials and post-marketing data, with low rates of major bleeding and symptomatic recurrent VTE.

Statins and prevention of venous thromboembolism: Myth or reality?

The pleiotropic effects of statins, beyond their cholesterol-lowering properties, are much debated. In primary prevention, several observational cohort and case-control studies appear to show that statins reduce the incidence of venous thromboembolism by about 30%. In a single randomized placebo-controlled clinical trial (JUPITER), which included 17,000 patients, rosuvastatin 20mg/day reduced the risk of venous thromboembolism by 43%. However, these patients were at low risk of venous thromboembolism, and the frequency of the event was, in principle, low. In secondary prevention, several observational studies and post-hoc analyses of randomized clinical trials have suggested that statins may prevent recurrence of venous thromboembolism. However, none of these studies had enough scientific weight to form the basis of a recommendation to use statins for secondary prevention. The putative preventive effect of statins appears to be independent of plasma cholesterol concentration and could be a pharmacological property of the statin class, although a dose-effect relationship has not been demonstrated. The mechanism through which statins might prevent venous thrombosis is thought to involve their anti-inflammatory and antioxidant effects or perhaps a more specific action, by blocking the degradation of antithrombotic proteins. A mechanism involving the action of statins on interactions between risk factors for atherosclerosis and venous thromboembolism is supported by some studies, but not all. In the absence of firm evidence, statins cannot currently be recommended for primary or secondary prevention of venous thromboembolism.

Increased risk and severity of unprovoked venous thromboembolism with clustering cardiovascular risk factors for atherosclerosis: Results of the REMOTEV registry

BACKGROUND The role of cardiovascular risk factors (CVRF) for atherosclerosis in venous thromboembolic disease (VTE) is controversial. The aim of this study was to evaluate the impact of CVRF and their cumulative effects on the occurrence of unprovoked VTE, severity, recurrence and survival. METHODS AND RESULTS This is a prospective cohort from the REMOTEV registry including all consecutively hospitalized patients for acute symptomatic VTE. From November 2013 to December 2016, 515 patients with 6months follow-up (FU) were selected for the analysis. Events were classified as unprovoked or provoked VTE. In univariate analysis, hypertension (OR 1.44, [95% CI 1.01-2.06]), diabetes (OR 2.07, [95% CI: 1.25-3.55]) and age (OR 1.94, [95% CI: 1.31-2.88]) were significantly associated with the risk of unprovoked VTE. After adjustment, diabetes (OR 1.82, [95% CI: 1.07-3.18]) and age (OR 1.79, [95% CI: 1.15-2.8]) remained associated with the risk of unprovoked VTE. The proportion of unprovoked VTE increased significantly with the number of CVRF adjusted for thrombophilia (1 CVRF: OR 3 [95% CI: 1.44-6.52]) 2 CVRF: OR 4.33 [95% CI: 2.07-9.49] and ≥3 CVRF: OR 4.58 [95% CI: 2.27-9.7]). The severity of pulmonary embolism was significantly associated with CVRF clustering. There were more VTE recurrences and deaths during the 6months of FU with cumulative CVRF. CONCLUSION The risks of unprovoked VTE and PE severity are associated with clustering CVRF. The role of cumulative CVRF predominates rather than the specific burden of each of the CVRF in the risk of VTE occurrence.

Stroke revealing celiac disease associated with multiple arterial thrombotic locations.

La Presse Medicale - In Press.Proof corrected by the author Available online since mercredi 15 avril 2015

Incidence and risk factors of venous thromboembolism: Peculiarities in psychiatric institutions

INTRODUCTION The objectives of this study were to assess the incidence and risk factors for venous thromboembolism (VTE) in a population of patients hospitalized in a psychiatric setting. MATERIAL AND METHODS Episodes of VTE occurring in patients hospitalized at the Erstein Hospital (France), specialized in psychiatry, were retrospectively identified from a computerized database. The clinical, somatic, psychiatric and therapeutic characteristics of each patient were analyzed in comparison with a control population composed of patients of similar age and sex, hospitalized during the same period in a psychiatric setting but who did not suffer from VTE. RESULTS Between January 2012 and October 2015, 12,320 patients were hospitalized. Forty-one patients experienced an episode of VTE, giving an incidence of 47.8per1000patient-years (3.32 cases per 1000 patients). Restriction of mobility (restraint or confinement), somatic clinical profile, psychiatric diagnosis or psychotropic treatment were not associated with an increased risk of VTE. The event occurred within the first 48h of hospitalization for 31.7% of patients, and within the first week for 56.1%. Time to onset for the occurrence of VTE between admission and the end of the first week was significantly associated with acute decompensation of a chronic psychiatric pathology (p=0.003). CONCLUSION The incidence of VTE in a psychiatric setting is high. Acute decompensation of a chronic psychiatric pathology is associated with a risk of VTE.

Real-life practices of chronic thromboembolic pulmonary hypertension screening: Results from the REMOTEV observational study

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but curable complication of pulmonary embolism (PE) associated with its severity. CTEPH is defined by a mean pulmonary artery pressure (mPAP) 25 mm Hg and a pulmonary capillary wedge pressure (PCWP) <15 mm Hg measured by right heart catheterization (RHC), in the presence of perfusional defects on a ventilation/perfusion (V/Q) scan performed at least 3 months after acute PE. In case of suggestive symptoms, transthoracic echocardiography (TTE) is the first-line procedure allowing the assessment of a probability of CTEPH (low, intermediate and high) according to peak tricuspid regurgitation velocity (TRv) and additional

Prise en charge actualisée de l’hypertension artérielle de l’adulte

L’hypertension arterielle (HTA) beneficie de recommandations sans cesse renouvelees a l’aune des essais cliniques les plus recents. Les sujets ayant fait l’objet d’une reevaluation de l’HTA sont : les modalites du diagnostic – et singulierement la methode de mesure de la pression arterielle (PA) –, les niveaux tensionnels cibles et, consequemment, les objectifs tensionnels et les strategies therapeutiques. La mesure clinique de la PA au cabinet medical est insuffisante, car elle est contaminee par l’« effet blouse blanche » qui ne permet pas de statuer sur le niveau tensionnel exact du patient. Automesures et mesure ambulatoire de la PA (MAPA) sont des alternatives indispensables au diagnostic et au suivi. L’objectif tensionnel optimal a atteindre chez l’hypertendu fait l’objet d’un debat sans cesse renouvele. Les recommandations nord-americaines du Eighth Joint National Committee (JNC-8), publiees en 2014, pronaient des objectifs moins drastiques chez les patients âges de plus de 60 ans. Cependant, l’essai Sprint montrait que maintenir une PA systolique (PAS) < 120 mmHg avait un plus grand impact sur la mortalite et la survenue de complications cardiovasculaires et renales qu’une PAS < 140 mmHg. En matiere therapeutique, le protocole ACD, des recommandations anglaises du National Institute for Health and Clinical Excellence (NICE), proches des recommandations nord-americaines, s’imposent par leur simplicite. Il est ainsi recommande de commencer le traitement par un bloqueur du systeme renine-angiotensine (A) chez les patients de moins 55 ans ; chez les patients de plus de 55 ans et les Noirs, il est recommande de debuter le traitement par un inhibiteur calcique de type dihydropyridine de longue duree d’action (C). En cas de non-obtention de l’objectif tensionnel, il est recommande de combiner A et C. En troisieme intention, il est recommande d’ajouter un diuretique thiazidique (D). Enfin, la non-obtention de l’objectif tensionnel apres quatre a six semaines definit la resistance au traitement et justifie de solliciter l’avis du specialiste et, le cas echeant, d’ajouter 25 a 50 mg de spironolactone au traitement avec surveillance de la kaliemie.

Rifampicin reverses nicardipine effect inducing uncontrolled essential hypertension

Dihydropyridine calcium‐channel blockers are a known substrate for the cytochrome P450 isoform 3A4. Rifampicin, an antitubercular agent, is one of the most potent inducers of hepatic and intestinal CYP3A4 thus increasing dihydropyridine metabolism. We report a case of a 67‐year‐old hypertensive female treated with a four‐drug antihypertensive regimen including a dihydropyridine (nicardipine 50 mg bid), who was admitted for septic arthritis of the knee requiring antibiotic treatment with teicoplanin 400 mg od and rifampicin 600 mg bid. Six days after rifampicin initiation, she presented with Posterior Reversible Encephalopathy Syndrome due to uncontrolled hypertension. We hypothesized that disequilibrium of previously controlled hypertension was partially due to nicardipine ineffectiveness. Plasma nicardipine concentration was assessed through high‐performance liquid chromatography 5 hours after coadministration of the two drugs and proved undetectable.

Place of non-vitamin K antagonist oral anticoagulants in anticoagulant–antiplatelet combinations in peripheral artery disease

Non-vitamin K antagonist oral anticoagulants are becoming increasingly important in the prophylaxis and treatment of thrombosis in atrial fibrillation and venous thromboembolism. Antiplatelets are widely prescribed in the primary and secondary prevention of cardiac and vascular diseases. There are potentially numerous situations where anticoagulants and antiplatelets may be combined; these combinations have been explored in coronary artery disease, and some have been included in updated recommendations. Is it legitimate to transpose these recommendations to the management of peripheral artery disease? The specific characteristics of the treated vessels, the stents used, the respective frequencies of stent thrombosis and its effect on the target organ are probably different, and explain why opinions differ. However, because of a lack of evidence, empirical behaviours are being established without scientific validation. This review of the literature details the situations in which combinations of an anticoagulant and an antiplatelet have been explored in peripheral artery disease. We discuss the issue of antithrombotic combinations in stable peripheral artery disease and for vascular or endovascular surgery.