Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Characteristic of Combined Natural Foci of Clonorchiasis, Metagonimiasis and Nanophyetiasis in the Ecosystem of the Amur River and the Risk of Infestation in the Population

The objective of the study was to identify patterns of formation of combined natural foci of clonorchiasis, metagonimiasis and nanophyetiasis in the ecosystem of the Amur River, to analyze their structure, and to determine the risk of infection of the population by the pathogens of these invasions. Materials and methods: Landscape, ecological and malacological methods of studying faunal complexes of floodplain reservoirs were used. The study of fish for contamination with trematode metacercariums was carried out by the compressor method. Results: The studies helped characterize combined natural foci of clonorchiasis, metagonimiasis and nanophyetiasis, which were predetermined subject to the existence of a population of two common hosts in conjunction with the population of the pathogen and the formation of parasitocenosis or parasitocenosis of coinciding parasitic systems of “twin species”. In the floodplain-river ecosystem of the middle and lower reaches of the Amur River there remains the risk of infecting the population with the pathogens of these trematodoses when eating fish of various families caught in the river, its tributaries and floodplain reservoirs. Conclusions: The risk of infestation is attributed to loymopotential of the natural foci of these trematodoses. The areas with the highest risk for the population include the zones of removal of pathogens of clonorchiasis, metagonimiasis, and nanophyetiasis such as riverbeds and fairly large reservoirs permanently associated with rivers.</jats:p

New perspectives on the ecology and evolution of siboglinid tubeworms

Siboglinids are tube-dweling annelids that are important members of deep-sea chemosynthetic communities, which include hydrothermal vents, cold seeps, whale falls and reduced sediments. As adults, they lack a functional digestive system and rely on microbial endosymbionts for their energetic needs. Recent years have seen a revolution in our understanding of these fascinating worms. Molecular systematic methods now place these animals, formerly known as the phyla Pogonophora and Vestimentifera, within the polychaete clade Siboglinidae. Furthermore, an entirely new radiation of siboglinids, Osedax, has just recently been discovered living on whale bones. The unique and intricate evolutionary association of siboglinids with both geology, in the formation of spreading centres and seeps, and biology with the evolution of large whales, offers opportunities for studies of vicariant evolution and the calibration of molecular clocks. Moreover, new advances in our knowledge of siboglinid anatomy coupled with molecular characterization of microbial symbiont communities are revolutionizing our knowledge of host-symbiont relationships in the Metazoa. Despite these advances, considerable debate persists concerning the evolutionary history of siboglinids. Here we review the morphological, molecular, ecological and fossil data in order to address when and how siboglinids evolved. We discuss the role of ecological conditions in the evolution of siboglinids and present possible scenarios of the evolutionary origin of the symbiotic relationships between siboglinids and their endosymbiotic bacteria