Effectiveness of statins for secondary prevention in elderly patients after acute myocardial infarction: an evaluation of class effect

Background

Clinical trials have shown the benefits of statins after acute myocardial infarction (AMI). However, it is unclear whether different statins exert a similar effect in reducing the incidence of recurrent AMI and death when used in clinical practice.

Methods

We conducted a retrospective cohort study (1997–2002) to compare 5 statins using data from medical administrative databases in 3 provinces (Quebec, Ontario and British Columbia). We included patients aged 65 years and over who were discharged alive after their first AMI-related hospital stay and who began statin treatment within 90 days after discharge. The primary end point was the combined outcome of recurrent AMI or death from any cause. The secondary end point was death from any cause. Adjusted hazard ratios (HRs) for each statin compared with atorvastatin as the reference drug were estimated using Cox proportional hazards regression analysis.

Results

A total of 18 637 patients were prescribed atorvastatin (n = 6420), pravastatin (n = 4480), simvastatin (n = 5518), lovastatin (n = 1736) or fluvastatin (n = 483). Users of different statins showed similar baseline characteristics and patterns of statin use. The adjusted HRs (and 95% confidence intervals) for the combined outcome of AMI or death showed that each statin had similar effects when compared with atorvastatin: pravastatin 1.00 (0.90–1.11), simvastatin 1.01 (0.91– 1.12), lovastatin 1.09 (0.95–1.24) and fluvastatin 1.01 (0.80– 1.27). The results did not change when death alone was the end point, nor did they change after adjustment for initial daily dose or after censoring of patients who switched or stopped the initial statin treatment.

Interpretation

Our results suggest that, under current usage, statins are equally effective for secocondary prevention in elderly patients after AMI.Randomized controlled trials (RCTs) have shown that the use of statins after acute myocardial infarction (AMI) are effective in reducing the incidence of both fatal and nonfatal cardiovascular events.^{1,2,3,4,5,6,7,8} Although these trials have significantly influenced post-AMI treatment,^9,10,11,12 it remains unclear whether all statins are equally effective in preventing recurrent AMI and death. Drugs in the same class are generally thought to be therapeutically equivalent because of similar mechanisms of action (class effect).^13,14,15 However, in the absence of comparative data, this assumption requires evaluation. Statins differ in multiple characteristics, including liver and renal metabolism, half-life, effect on other serum lipid components, bioavailability and potency.^16,17,18,19 These differences could potentially influence the extent to which the drugs are beneficial. Despite limited evidence in support of a differential benefit of statins for secondary prevention, preferential prescribing already occurs in practice and cannot be fully explained by the existing evidence or guidelines.²⁰ Comparative data of statins are thus required to inform health care decision-making.A number of RCTs have directly compared statins using surrogate end points, such as lipid reduction,^21,22,23 markers of hemostasis and inflammation^24,25,26 or reduction in number of atherotic plaques.²⁷ However, the extent to which these results can be extrapolated to clinically relevant outcomes remains to be established. The newly released PROVE IT– TIMI 22 trial²⁸ was the first trial to compare 2 statins for cardiovascular prevention. The study showed that atorvastatin used at a maximal dose of 80 mg (intensive therapy) was better than pravastatin at a dose of 40 mg (standard therapy) in decreasing the incidence of cardiovascular events and procedures. The study was, however, conducted to show the benefit associated with increased treatment intensity. It did not compare the drugs by milligram-equivalent doses or by cholesterol-lowering equivalent doses. Moreover, no difference was detected when death alone or the combined outcome of death or AMI was evaluated. Other than the PROVE IT–TIMI 22 trial, few data are currently available from RCTs that compare statins for cardiovascular prevention.²⁹We conducted a population-based study to examine the relative effectiveness of different statins for long-term secondary prevention after AMI. We used retrospective cohorts of elderly patients prescribed statins after AMI in 3 provinces. Five statins were studied: atorvastatin, pravastatin, simvastatin, lovastatin and fluvastatin. The newest statin, rosuvastatin, was not available during the study period and was not considered in this study.     

Influence of Polymer Aggregation and Liquid Immiscibility on Morphology Tuning by Varying Composition in PffBT4T‐2DT/Nonfullerene Organic Solar Cells

The temperature‐dependent aggregation behavior of PffBT4T polymers used in organic solar cells plays a critical role in the formation of a favorable morphology in fullerene‐based devices. However, there is little investigation into the impact of donor/acceptor ratio on morphology tuning, especially for nonfullerene acceptors (NFAs). Herein, the influence of composition on morphology is reported for blends of PffBT4T‐2DT with two NFAs, O‐IDTBR and O‐IDFBR. The monotectic phase behavior inferred from differential scanning calorimetry provides qualitative insight into the interplay between solid–liquid and liquid–liquid demixing. Transient absorption spectroscopy suggests that geminate recombination dominates charge decay and that the decay rate is insensitive to composition, corroborated by negligible changes in open‐circuit voltage. Exciton lifetimes are also insensitive to composition, which is attributed to the signal being dominated by acceptor excitons which are formed and decay in domains of similar size and purity irrespective of composition. A hierarchical morphology is observed, where the composition dependence of size scales and scattering intensity from resonant soft X‐ray scattering (R‐SoXS) is dominated by variations in volume fractions of polymer/polymer‐rich domains. Results suggest an optimal morphology where polymer crystallite size and connectivity are balanced, ensuring a high probability of hole extraction via such domains.     

FAT1 cadherin is multiply phosphorylated on its ectodomain but phosphorylation is not catalysed by the four-jointed homologue

The interaction between the Drosophila cadherins fat and dachsous is regulated by phosphorylation of their respective ectodomains, a process catalysed by the atypical kinase four-jointed. Given that many signalling functions are conserved between Drosophila and vertebrate Fat cadherins, we sought to determine whether ectodomain phosphorylation is conserved in FAT1 cadherin, and also whether FJX1, the vertebrate orthologue of four-jointed, was involved in such phosphorylation events. Potential Fj consensus phosphorylation motifs were identified in FAT1 and biochemical experiments revealed the presence of phosphoserine and phosphothreonine residues in its extracellular domain. However, silencing FJX1 did not influence the levels of FAT1 ectodomain phosphorylation, indicating that other mechanisms are likely responsible.     

Conquering the cytokine storm in COVID-19-induced ARDS using placenta-derived decidua stromal cells

Acute respiratory distress syndrome (ARDS) is the most common cause of death in COVID-19 patients. The cytokine storm is the main driver of the severity and magnitude of ARDS. Placenta-derived decidua stromal cells (DSCs) have a stronger immunosuppressive effect than other sources of mesenchymal stromal cells. Safety and efficacy study included 10 patients with a median age of 50 (range 14–68) years with COVID-19-induced ARDS. DSCs were administered 1–2 times at a dose of 1 × 10⁶/kg. End points were safety and efficacy by survival, oxygenation and effects on levels of cytokines. Oxygenation levels increased from a median of 80.5% (range 69–88) to 95% (range 78–99) (p = 0.012), and pulmonary infiltrates disappeared in all patients. Levels of IL-6 decreased from a median of 69.3 (range 35.0–253.4) to 11 (range 4.0–38.3) pg/ml (p = 0.018), and CRP decreased from 69 (range 5–169) to 6 (range 2–31) mg/ml (p = 0.028). Two patients died, one of a myocardial infarction and the other of multiple organ failure, diagnosed before the DSC therapy. The other patients recovered and left the intensive care unit (ICU) within a median of 6 (range 3–12) days. DSC therapy is safe and capable of improving oxygenation, decreasing inflammatory cytokine level and clearing pulmonary infiltrates in patients with COVID-19.     

The stability evaluation of mesenchymal stem cells differentiation toward endothelial cells by chemical and mechanical stimulation

Adipose-derived mesenchymal stem cells (ADSCs) are adult multipotent cells able to differentiate into several cell lineages. Vascular endothelial growth factor (VEGF) and the shear stress associated with blood flow are considered as the most important chemical and mechanical cues that play major roles in endothelial differentiation. However, the stability of endothelial-specific gene expression has not been completely addressed yet. ADSCs in passage 3 were cultured inside the tubular silicon tubes and then exposed to VEGF or shear stress produced in a perfusion bioreactor. To investigate the differentiation, the expression levels of Flk-1, von Willebrand factor (vWF), and vascular endothelial-cadherin (VE-cadherin) were studied using Real-Time PCR. For studying the endothelial differentiation stability, mRNA levels of the genes were evaluated in certain time intervals after completion of the tests so as to determine whether the expression level of each gene in different time points was stable and remained constant or not. Application of VEGF and shear stress caused an elevation in endothelial cells’ specific genes. Although there are some changes following the days after application of mechanical and chemical stimuli, the gene expression results depicted significantly higher gene expression between sequential chemically and mechanically incited groups. In conclusion, stress alone can be a differentiating factor, by itself. Our results verified the efficient stable differentiation ability of the chemical and mechanical factors.     

Production of Soluble and Functional Anti-TNF-α Fab' Fragment in Cytoplasm of E. coli: Investigating the Effect of Process Conditions on Cellular Biomass and Protein Yield Using Response Surface Methodology

The Protein Journal - With the increasing dominance of monoclonal antibodies (mAbs) in the biopharmaceutical industry and smaller antibody fragments bringing notable advantages over full-length...     

Identification of follicular vitellogenesis stage by monitoring of plasma calcium and estradiol-17β concentrations in the cultured Caspian brown trout, Salmo trutta caspius Kessler, 1877

To identify a simple indicator for detection of follicular vitellogenesis stage of cultured Caspian brown trout, the changes of plasma calcium and estradiol-17β along with ovarian histology were investigated over a reproductive cycle. For this purpose, the blood and gonad samples were taken monthly over a six months period. According to results, the concentrations of plasma calcium increased significantly during October and November but then declined steadily until the end of experiment. Estradiol-17β concentrations were low throughout the experiment, a clear peak was observed in October. Histological observations showed that all examined females were in vitellogenesis when the peak of plasma calcium and estradiol-17β were observed. Also, significant positive relationship was found between plasma calcium and estradiol. The good fitness of plasma calcium and estradiol-17β peak with histological observations suggests that plasma calcium could be a good and simple indicator for detection of follicular vitellogenesis stage in the cultured Caspian brown trout.     

Effect of Prepartum Supplementation of Selenium and Vitamin E on Serum Se, IgG Concentrations and Colostrum of Heifers and on Hematology, Passive Immunity and Se Status of Their Offspring

Forty heifers at the late stage of gestation were randomly assigned into five groups. Heifers were balanced for age, weight, and time of calving in each group. Four and 2?weeks before expected time of calving, the heifers were injected with 0?ml (C), 10?ml (T1), 20?ml (T2), 30?ml (T3), and 40?ml (T4) Se and VE supplements, respectively. Each milliliter of the supplement contained of 0.5?mg Se as sodium selenite and 50?IU of dl-alpha-tocopheryl acetate. Blood samples were collected from the heifers 4?weeks before expected calving and at calving day and from the calves at birth and 7?days of age. The serum Se and immunoglobulin G (IgG) concentrations, white blood cell and differential leukocyte counts were measured. The Se concentrations in the sera of the heifers before the injections of Se and VE supplements were the same among the groups (P?>?0.05), but after calving were significantly increased in the treated heifers (P??0.05). The white blood cell counts were higher in calves of heifers in groups T3 and T4 compared with the control group at 7?days of age (P?相似文献   

Molecular Characterization of Monochloroacetate-Degrading Arthrobacter sp. Strain D2 Isolated from Universiti Teknologi Malaysia Agricultural Area

Arthrobacter sp. strains D2 and D3 and Labrys sp. strain D1 capable of degrading 20 mM monochloroacetic acid (MCA) were isolated from soil contaminated with herbicides and pesticides. All three isolates were able to grow on MCA as the sole source of carbon and energy with concomitant chloride ion release in the growth medium (19 mM). Strains D2 and D3 (cells doubling time 7 ± 0.3 h) grew four times faster than D1 (26 ± 0.1 h). Strain D2 was then further investigated and could also grow in 10 mM of monobromoacetic acid (MBA), 2,2-dichloropropionic acid (2,2DCP), d,l-2-chloropropionic acid (D,L2CP), l-2-chloropropionic acid (L-2CP), d-2-chloropropionic acid (D-2CP), and glycolate as the sole sources of carbon and energy. Dehalogenase gene amplification using group I primers revealed a 410-bp polymerase chain reaction (PCR) product, but there was none using group II primers. The partial amino acid sequence analysis of group I DehD2 dehalogenase showed at least 32% identity to the corresponding regions of DehE, DhlIV, DehI, and D,L-DEX, with key amino acid residues Ser188, Ala187, and Asp189. These amino acid residues were involved in substrate binding and catalysis and were conserved in the partial amino acid sequence.     

Investigation of effects of newly synthesized Pt(II) complex against human serum albumin and leukemia cell line of K562

The biological evaluation of a new synthesized Pt(II)-complex, 2,2'-bipyridin Butylglycinato Pt(II) nitrate, an anti-tumor component, was studied at different temperatures by fluorescence and far UV circular dichroism (CD) spectroscopic methods. Human serum albumin (HSA) and human tumor cell line K562 were as targets. The Pt(II)-complex has a strong ability to quench the intrinsic fluorescence of HSA. Binding and thermodynamic parameters of the interaction were calculated by fluorescence quenching method. Far-UV-CD results showed that Pt(II)-complex induced increasing in content of α helical structure of the protein and stabilized it. The 50% cytotoxic concentration (Cc(50)) of complex was determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay at different incubation times. Also, fluorescence staining with DAPI (4,6-diamidino-2-phenylindole) revealed some typical nuclear changes, which are characteristic of apoptosis. Above results suggest that Pt (II) complex is a promising anti-proliferative agent and should execute its biological effects by inducing apoptosis.