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- Calderone, Dario, et al.
(författare)
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Efficacy and Safety of Aspirin for Primary Cardiovascular Risk Prevention in Younger and Older Age : An Updated Systematic Review and Meta-analysis of 178,310 Subjects from 21 Randomized Studies.
- 2022
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Ingår i: Thrombosis and haemostasis. - : Georg Thieme Verlag KG. - 2567-689X .- 0340-6245. ; 122:03, s. 445-455
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The efficacy and safety of aspirin for primary cardiovascular disease (CVD) prevention is controversial. The aim of this study was to investigate the efficacy and safety of aspirin in subjects with no overt CVD, with a focus on age as a treatment modifier.METHODS AND RESULTS: Randomized trials comparing aspirin use versus no aspirin use or placebo were included. The primary efficacy outcome was all-cause death. The primary safety outcome was major bleeding. Secondary ischemic and bleeding outcomes were explored. Subgroup analyses were conducted to investigate the consistency of the effect sizes in studies including younger and older individuals, using a cut-off of 65 years. A total of 21 randomized trials including 173,810 individuals at a mean follow-up of 5.3 years were included. Compared with control, aspirin did not reduce significantly the risk of all-cause death (risk ratio: 0.96; 95% confidence interval: 0.92-1.00, p = 0.057). Major adverse cardiovascular events were significantly reduced by 11%, paralleled by significant reductions in myocardial infarction and transient ischemic attack. Major bleeding, intracranial hemorrhage, and gastrointestinal bleeding were significantly increased by aspirin. There was a significant age interaction for death (p for interaction = 0.007), with aspirin showing a statistically significant 7% relative benefit on all-cause death in studies including younger patients.CONCLUSION: The use of aspirin in subjects with no overt CVD was associated with a neutral effect on all-cause death and a modest lower risk of major cardiovascular events at the price of an increased risk in major bleeding. The benefit of aspirin might be more pronounced in younger individuals.
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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Laudani, Claudio, et al.
(författare)
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Short Duration of DAPT Versus De-Escalation After Percutaneous Coronary Intervention for Acute Coronary Syndromes
- 2022
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Ingår i: JACC. - : Elsevier BV. - 1936-8798 .- 1876-7605. ; 15:3, s. 268-277
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to compare short dual antiplatelet therapy (DAPT) and de-escalation in a network meta-analysis using standard DAPT as common comparator.BACKGROUND: In patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), shortening DAPT and de-escalating to a lower potency regimen mitigate bleeding risk. These strategies have never been randomly compared.METHODS: Randomized trials of DAPT modulation strategies in patients with ACS undergoing PCI were identified. All cause death was the primary outcome. Secondary outcomes included net adverse cardiovascular events (NACE), major adverse cardiovascular events, and their components. Frequentist and Bayesian network meta-analyses were conducted. Treatments were ranked on the basis of posterior probability. Sensitivity analyses were performed to explore sources of heterogeneity.RESULTS: Twenty-nine studies encompassing 50,602 patients were included. The transitivity assumption was fulfilled. In the frequentist indirect comparison, the risk ratio (RR) for all-cause death was 0.98 (95% CI: 0.68-1.43). De-escalation reduced the risk for NACE (RR: 0.87; 95% CI: 0.70-0.94) and increased major bleeding (RR: 1.54; 95% CI: 1.07-2.21). These results were consistent in the Bayesian meta-analysis. De-escalation displayed a >95% probability to rank first for NACE, myocardial infarction, stroke, stent thrombosis, and minor bleeding, while short DAPT ranked first for major bleeding. These findings were consistent in node-split and multiple sensitivity analyses.CONCLUSIONS: In patients with ACS undergoing PCI, there was no difference in all-cause death between short DAPT and de-escalation. De-escalation reduced the risk for NACE, while short DAPT decreased major bleeding. These data characterize 2 contemporary strategies to personalize DAPT on the basis of treatment objectives and risk profile.
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