Background: People with diabetes and recent ACS are at higher risk for ischemic CV events and derive greater benefit from intensive lipid-lowering therapy than those without diabetes. Effect of PCSK9 ...inhibition in patients with recent ACS and diabetes is unknown.
Methods: Alirocumab (ALI) is a fully human monoclonal antibody to PCSK9. In ODYSSEY OUTCOMES, 18,924 patients with recent ACS and LDL-C≥70mg/dL on a maximum-tolerated dose of atorvastatin or rosuvastatin were randomly assigned to ALI 75mg or placebo SC every 2 weeks. ALI blindly increased to 150mg or decreased to placebo to achieve an LDL-C of 25-50mg/dL. Primary efficacy endpoint was time to first MACE: CHD death, nonfatal MI, ischemic stroke or hospitalization for unstable angina. This prespecified analysis reports efficacy and safety by baseline glucometabolic status, including new-onset diabetes (NOD).
Results: Table reports incidence of MACE by assigned treatment and baseline glucometabolic status. Overall ALI reduced MACE, without evidence of effect modification by baseline glucometabolic status: a greater absolute risk reduction was observed with ALI in those with diabetes. NOD was not increased with ALI.
Conclusion: Patients with recent ACS and diabetes derived greater absolute benefit from ALI added to maximum-tolerated statin. No increase in NOD was seen with ALI (NCT01663402).CategoryN (% of cohort)ARRHazard ratio (95% CI)PinteractionMACE cumulative incidenceAlirocumab n/N (%)Placebo n/N (%)All subjects18,924 (100)903/9462 (9.5)1052/9462 (11.1)1.60.85 (0.78, 0.93)NADiabetes5444 (28.8)380/2693 (14.1)452/2751 (16.4)2.30.84 (0.74, 0.97)0.98 Prediabetes8246 (43.6)331/4130 (8.0)380/4116 (9.2)1.20.86 (0.74, 1.00)Normoglycemia5234 (27.7)192/2639 (7.3)220/2595 (8.5)1.20.85 (0.70, 1.03)Median follow-up: 34 months. ARR, absolute risk reduction; NA, not applicable.
Disclosure
K.K. Ray: Consultant; Self; Amgen Inc., Sanofi. Research Support; Self; Sanofi. Consultant; Self; The Medicines Company. Research Support; Self; Amgen Inc., Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc., Pfizer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., AstraZeneca, Esperion Therapeutics, Kowa Pharmaceuticals America, Inc.. Research Support; Self; Pfizer Inc.. Consultant; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Merck Sharp & Dohme Corp. H. Colhoun: Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Stock/Shareholder; Self; Bayer AG. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Other Relationship; Self; Eli Lilly and Company. Advisory Panel; Self; Novartis Pharmaceuticals Corporation. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Advisory Panel; Self; Regeneron Pharmaceuticals, Inc.. Speaker's Bureau; Self; Regeneron Pharmaceuticals, Inc.. Other Relationship; Self; Regeneron Pharmaceuticals, Inc.. Research Support; Self; Pfizer Inc., Roche Pharma. Stock/Shareholder; Self; Roche Pharma. Research Support; Self; Sanofi-Aventis. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi. Other Relationship; Self; Sanofi. Research Support; Self; Novo Nordisk Inc. M. Szarek: Consultant; Self; Sanofi, Regeneron Pharmaceuticals, Inc., Baxter, Resverlogix Corp. M. Baccara-Dinet: Employee; Self; Sanofi. D.L. Bhatt: Research Support; Self; Amarin Corporation, Amgen Inc., AstraZeneca, Bristol-Myers Squibb Company, Chiesi USA, Inc., Eisai Inc., Ethicon US, LLC., Forest Laboratories, Inc., Ironwood Pharmaceuticals, Inc., Ischemix, Eli Lilly and Company, Medtronic, Pfizer Inc., Roche Pharma, Sanofi-Aventis, The Medicines Company. Other Relationship; Self; American Heart Association. V. Bittner: Research Support; Self; AstraZeneca, Sanofi, Bayer AG, Esperion Therapeutics, Amgen Inc.. Advisory Panel; Self; Sanofi. Research Support; Self; Dalcor. A.J. Budaj: Other Relationship; Self; Sanofi-Aventis, AstraZeneca, Pfizer Inc., GlaxoSmithKline plc.. Consultant; Self; Bayer AG. Other Relationship; Self; Novartis Pharma K.K., Eisai Co., Ltd.. R. Diaz: None. S.G. Goodman: Research Support; Self; Amgen Inc.. Consultant; Self; Amgen Inc.. Research Support; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; Bayer AG. Consultant; Self; Bayer AG. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Bristol-Myers Squibb Company. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Consultant; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation. Research Support; Self; Pfizer Inc.. Consultant; Self; Pfizer Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc.. Research Support; Self; CSL Behring. C.G. Hanotin: Employee; Self; Sanofi. J. Jukema: Research Support; Self; Sanofi-Aventis, Regeneron Pharmaceuticals, Inc., Amgen Inc. V. Loizeau: Employee; Self; Sanofi. R.D. Lopes: Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH. Other Relationship; Self; Bristol-Myers Squibb Company. Consultant; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; GlaxoSmithKline plc., Medtronic. Consultant; Self; Merck & Co., Inc.. Other Relationship; Self; Pfizer Inc. A. Moryusef: Employee; Self; Sanofi. R. Pordy: Employee; Self; Regeneron Pharmaceuticals, Inc.. A.D. Ristic: None. M. Roe: None. J. Tuñón: Speaker's Bureau; Self; Sanofi-Aventis. Advisory Panel; Self; Sanofi-Aventis. Other Relationship; Self; Sanofi-Aventis. Speaker's Bureau; Self; Amgen Inc. H.D. White: Other Relationship; Self; AstraZeneca, Eli Lilly and Company. Research Support; Self; National Institute for Health and Clinical Excellence. Other Relationship; Self; Omthera Pharmaceuticals, Inc., Pfizer Inc., Eisai Inc.. Research Support; Self; DalCor Pharma UK Inc. Advisory Panel; Self; Sirtex, Actelion Pharmaceuticals US, Inc.. Other Relationship; Self; Luitpold Pharmaceuticals Ltd., CSL Behring, Sanofi-Aventis. G.G. Schwartz: Research Support; Self; Roche Pharma, Sanofi, Resverlogix Corp. P.G. Steg: Consultant; Self; Amarin Corporation, AstraZeneca. Research Support; Self; Bayer AG. Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company. Advisory Panel; Self; Novartis AG. Consultant; Self; Pfizer Inc., Sanofi. Research Support; Self; Sanofi, Servier. Consultant; Self; Novo Nordisk A/S, Regeneron Pharmaceuticals, Inc..
Abstract Aim We examined the effects of adding glargine to metformin–sitagliptin (MS + G) or sitagliptin to metformin–glargine (MG + S) therapy in type 2 diabetic persons uncontrolled after 24-week ...MS or MG dual therapy. Methods Subjects with A1c ≥ 7% on MS or MG treatment were respectively given glargine (0.2 U/kg starting dose) or sitagliptin (100 mg daily) for 12 weeks. The primary endpoint was number of subjects attaining A1c goal defined as < 7%. Results After receiving 24-week MS or MG dual therapy in the original EASIE Study, 42% (104/248) on MS and 68% (152/224) on MG attained A1c < 7% (p < 0.0001). The reduction in A1c was negatively associated with baseline fasting blood glucose (FBG) only in the MG group. Reduction in A1c was not related to baseline postprandial blood glucose (PPBG) in either the MG or MS group. Amongst 194 eligible patients, 57.7% (n = 111) entered the 12-week extension trial MS + G:74/131, 57.3%; MG + S:37/63, 58.7%) with 55 (51.9%) subjects attaining goal MS + G:59.2%; MG + S:37.1% at week 12. The final insulin dosage was similar in both groups MS + G: 0.46 U/kg; MG + S: 0.45 U/kg with a higher rate of hypoglycemia in the MG + S (6.5 events/patient-year) than the MS + G group (3.2 events/patient-year), although neither group had severe hypoglycemia. Conclusion In metformin-treated type 2 diabetes patients, high fasting BG predicted greater A1c reductions with the addition of glargine, but not with sitagliptin. In subjects uncontrolled with 6-month dual therapy of MS or MG, 50% attained A1c < 7% with triple therapy of MS + G or MG + S in 12 weeks. The increased rate of hypoglycemia with MG + S (but not with MS + G) underlines the need to take measures to avoid the hypoglycemia.
Phytoplankton is acknowledged to be a very diverse source of bioactive molecules. These compounds play physiological roles that allow cells to deal with changes of the environmental constrains. For ...example, the diversity of light harvesting pigments allows efficient photosynthesis at different depths in the seawater column. Identically, lipid composition of cell membranes can vary according to environmental factors. This, together with the heterogenous evolutionary origin of taxa, makes the chemical diversity of phytoplankton compounds much larger than in terrestrial plants. This contribution is dedicated to pigments and lipids synthesized within or from plastids/photosynthetic membranes. It starts with a short review of cyanobacteria and microalgae phylogeny. Then the bioactivity of pigments and lipids (anti-oxidant, anti-inflammatory, anti-mutagenic, anti-cancer, anti-obesity, anti-allergic activities, and cardio- neuro-, hepato- and photoprotective effects), alone or in combination, is detailed. To increase the cellular production of bioactive compounds, specific culture conditions may be applied (e.g., high light intensity, nitrogen starvation). Regardless of the progress made in blue biotechnologies, the production of bioactive compounds is still limited. However, some examples of large scale production are given, and perspectives are suggested in the final section.
Fonds pour la formation à la Recherche dans l'Industrie et dans l'Agriculture (Communauté française de Belgique) - FRIA
Associations of tunas and dolphins in the wild are quite frequent events and ...the question arises how predators requiring similar diet in the same habitat share their environmental resources. As isotopic composition of an animal is related to that of its preys, stable isotopes (13C/12C and 15N/14N) analyses were performed in three predator species from the Northeast Atlantic: the striped dolphin, Stenella coeruleoalba, the common dolphin Delphinus delphis, and the albacore tuna, Thunnus alalunga, and compared to their previously described stomach content. Heavy metals (Cd, Zn, Cu and Fe) are mainly transferred through the diet and so, have been determined in the tissues of the animals. Tunas muscles display higher delta15N than in common and striped dolphins (mean: 11.4 0/00 vs. 10.3 0/00 and 10.4 0/00, respectively) which reflects its higher trophic level nutrition. Higher delta13C are found in common (-18.4 0/00) and striped dolphin (-18.10/00) muscles than in albacore tuna (-19.3 0/00) likely in relation with its migratory pattern. The most striking feature is the presence of two levels of cadmium concentrations in the livers of the tunas (32 mg kg-1 dry weight vs. 5 mg kg-1 dry weight). These two groups also differ by their iron concentrations and their delta15N and delta 13C liver values. These results suggest that in the Biscay Bay, tunas occupy two different ecological niches likely based on different squid input in their diet.
Politique Scientifique Fédérale (Belgique) = Belgian Federal Science Policy
Associations of tunas and dolphins in the wild are quite frequent events and the question arises how predators requiring similar diet in the same habitat share their environmental resources. As ...isotopic composition of an animal is related to that of its preys, stable isotopes (13C/12C and 15N/14N) analyses were performed in three predator species from the Northeast Atlantic: the striped dolphin, Stenella coeruleoalba, the common dolphin Delphinus delphis, and the albacore tuna, Thunnus alalunga, and compared to their previously described stomach content. Heavy metals (Cd, Zn, Cu and Fe) are mainly transferred through the diet and so, have been determined in the tissues of the animals. Tunas muscles display higher delta15N than in common and striped dolphins (mean: 11.4 0/00 vs. 10.3 0/00 and 10.4 0/00, respectively) which reflects its higher trophic level nutrition. Higher delta13C are found in common (-18.4 0/00) and striped dolphin (-18.10/00) muscles than in albacore tuna (-19.3 0/00) likely in relation with its migratory pattern. The most striking feature is the presence of two levels of cadmium concentrations in the livers of the tunas (32 mg kg-1 dry weight vs. 5 mg kg-1 dry weight). These two groups also differ by their iron concentrations and their delta15N and delta 13C liver values. These results suggest that in the Biscay Bay, tunas occupy two different ecological niches likely based on different squid input in their diet.
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