P-182: 24-hour ambulatory blood-pressure effects of valsartan + hydrochlorothiazide combinations compared with amlodipine in hypertensive patients at increased cardiovascular risk

In a randomised, double-blind trial, the effects on 24-hr ABP of the combination valsartan 160 mg od and hydrochlorothiazide (HCTZ) 25 or 12.5 mg during 24 weeks of therapy were compared with the effects of amlodipine 10 mg monotherapy (group A10) in 474 stage-II hypertensive patients with additional cardiovascular risk factors. After a two-week single-blind placebo run-in period, patients were randomised to receive valsartan 160 mg od or amlodipine 5 mg od. At Week 4, HCTZ 12.5 mg (group V160/HCTZ12.5) and 25 mg (group V160/HCTZ25) were added to the valsartan groups and in the A10 patients the amlodipine dose was force-titrated to 10 mg od. All treatments reduced BP as well as night-time and daytime BP levels from baseline. 24-hr SBP was reduced by 15.9 ±1.0 mmHg (least-squares mean change ±SE), 19.3 ±1.0 mmHg and 16.1 ±1.1 mmHg in the V160/HCTZ12.5, V160/HCTZ25 and A10 groups, respectively and 24-hr DBP was reduced by 9.3 ±0.6 mmHg, 11.4 ±0.6 mmHg and 9.6 ±0.7 mmHg in the three groups. The differences between the V160/HCTZ25 group and the A10 group were significant (p<0.05) for the changes in 24-hr systolic BP as well as for changes in daytime systolic BP and night-time diastolic BP. Control rates defined as ABPM ≤130/80 mmHg were: 48.4%, 60.8% and 50.9% in the V160/HCTZ12.5, V160/25 and A10 groups, respectively; the differences between the V160/HCTZ25 group and the other two treatment groups were significant at p<0.05. (See Figure) In conclusion, the fixed-dose combination of valsartan 160 mg + HCTZ 25 mg od is an attractive therapeutic option measured on the effects on 24-hr ABPM, night-time and daytime BP reduction and control rates in hypertensive patients at additional cardiovascular ris

Risk factors and management of pasireotide-associated hyperglycemia in acromegaly

Pasireotide, a multireceptor-targeted somatostatin analog with highest affinity for somatostatin receptor subtype (SST) 5, has demonstrated superior efficacy over the SST2-preferential somatostatin analogs octreotide and lanreotide. The safety profile is similar to those of octreotide and lanreotide, except for a higher frequency and degree of hyperglycemia. This analysis investigated baseline characteristics and occurrence and management of hyperglycemia during pasireotide treatment in patients with acromegaly treated in two prospective clinical studies, SOM230C2305 (C2305) and SOM230C2402 (C2402; PAOLA)

Clinical profile and prognostic significance of natriuretic peptide trajectory following hospitalization for worsening chronic heart failure: findings from the ASTRONAUT trial

International audienceAIMS:The purpose of this study was to determine the prognostic significance and associated clinical profile of early post-discharge N-terminal pro-B-type natriuretic peptide (NT-proBNP) trajectory among patients hospitalized for worsening chronic heart failure (HHF).METHODS AND RESULTS:This post-hoc analysis of the Aliskiren Trial in Acute Heart Failure Outcomes (ASTRONAUT) included 1351 HHF patients with ejection fraction (EF) ≤40%, elevated B-type natriuretic peptide ≥400 pg/mL or NT-proBNP ≥1600 pg/mL at admission, and available NT-proBNP measurements (from a central core laboratory) at baseline (median 5 days after admission) and 1-month follow-up. The co-primary endpoints were all-cause mortality and cardiovascular mortality or HHF within 12 months. Median follow-up was 11.3 months. Patients with decreasing post-discharge NT-proBNP trajectory tended to be younger and have non-ischaemic HF aetiology. The presence of baseline atrial fibrillation was associated with high NT-proBNP at 1 month (i.e. above the median), regardless of the baseline value. After adjustment for patient characteristics and 1-month NT-proBNP level, every twofold increase in continuous NT-proBNP change from baseline to 1 month was predictive of increased cardiovascular mortality or HHF (hazard ratio 1.14; 95% confidence interval 1.02-1.26), but not all-cause mortality (hazard ratio 0.95; 95% confidence interval 0.81-1.11).CONCLUSION:In this cohort of HHF patients with reduced EF, early post-discharge NT-proBNP trajectory was associated with a distinct clinical profile and carried independent prognostic value after adjustment for patient characteristics and absolute NT-proBNP level. Future prospective study of serial NT-proBNP measurement during the hospital and early post-discharge periods is warranted to validate these findings and evaluate post-discharge NT-proBNP trajectory as a therapeutic target

Risk factors and management of pasireotide-associated hyperglycemia in acromegaly

International audiencePasireotide, a multireceptor-targeted somatostatin analog with highest affinity for somatostatin receptor subtype (SST) 5, has demonstrated superior efficacy over the SST 2 -preferential somatostatin analogs octreotide and lanreotide. The safety profile is similar to those of octreotide and lanreotide, except for a higher frequency and degree of hyperglycemia. This analysis investigated baseline characteristics and occurrence and management of hyperglycemia during pasireotide treatment in patients with acromegaly treated in two prospective clinical studies, SOM230C2305 (C2305) and SOM230C2402 (C2402; PAOLA). One hundred and seventy-eight patients naïve to medical therapy at baseline (C2305) and 125 uncontrolled on first-generation somatostatin analogs at baseline (C2402) received long-acting pasireotide in these studies. Of patients treated with pasireotide in studies C2305 and C2402, respectively, 75.3 (134/178) and 65.6% (82/125) developed hyperglycemia or experienced worsening of existing hyperglycemia. Occurrence of hyperglycemia during pasireotide treatment was less frequent in patients with lower age (<40 years, C2402; <30 years, C2305), normal glucose tolerance, and no history of hypertension or dyslipidemia at baseline. Thirteen (4%) patients discontinued pasireotide because of hyperglycemia-related adverse events. Metformin alone or in combination with other oral antidiabetic medications controlled elevations in glucose levels in most pasireotide-treated patients; 78% of C2305 patients and 73 (pasireotide 40 mg) and 60% (pasireotide 60 mg) of C2402 patients achieved the ADA/EASD goal of HbA 1c <7% (<53 mmol/mol) at the end of the core phase. Not all patients develop hyperglycemia, and it is reversible upon pasireotide withdrawal. Close monitoring, patient education and prompt action remain key elements in addressing hyperglycemia during pasireotide treatment

Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to minimize outcomes in patients with heart failure (ATMOSPHERE)study

&lt;p&gt;&lt;b&gt;Aims&lt;/b&gt; The renin–angiotensin–aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS ‘escape'. Direct renin inhibitors (DRIs) have been developed that decrease PRA and thus may provide a greater RAAS blockade. Aliskiren is the first orally active DRI. Plasma levels of B-type natriuretic peptide (BNP) have been observed to be reduced with aliskiren compared with placebo. The aim of the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II–IV symptoms, and elevated plasma levels of BNP.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods&lt;/b&gt; Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril monotherapy, or the combination. The primary endpoints of ATMOSPHERE are (i) whether the aliskiren/enalapril combination is superior to enalapril monotherapy in delaying time to first occurrence of cardiovascular death or HF hospitalization and (ii) whether aliskiren monotherapy is superior or at least non-inferior to enalapril monotherapy on this endpoint.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Perspective&lt;/b&gt; The ATMOSPHERE study will definitively determine the role of a DRI strategy additional to or as an alternative to conventional RAAS blockade in patients with chronic systolic HF.&lt;/p&gt

Marine Waste Utilization as a Source of Functional and Health Compounds

Consumer demand for convenience has led to large quantities of seafood being value-added processed before marketing, resulting in large amounts of marine by-products being generated by processing industries. Several bioconversion processes have been proposed to transform some of these by-products. In addition to their relatively low value conventional use as animal feed and fertilizers, several investigations have been reported that have demonstrated the potential to add value to viscera, heads, skins, fins, trimmings, and crab and shrimp shells by extraction of lipids, bioactive peptides, enzymes, and other functional proteins and chitin that can be used in food and pharmaceutical applications. This chapter is focused on reviewing the opportunities for utilization of these marine by-products. The chapter discusses the various products and bioactive compounds that can be obtained from seafood waste and describes various methods that can be used to produce these products with the aim of highlighting opportunities to add value to these marine waste streams. © 2018 Elsevier Inc.info:eu-repo/semantics/publishe