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

ReX: Extrapolating Relational Data in a Representative Way

International audienceGenerating synthetic data is useful in multiple application areas (e.g., database testing, software testing). Nevertheless, existing synthetic data generators generally lack the necessary mechanism to produce realistic data, unless a complex set of inputs are given from the user, such as the characteristics of the desired data. An automated and efficient technique is needed for generating realistic data. In this paper, we propose ReX, a novel extrapolation system targeting relational databases that aims to produce a representative extrapolated database given an original one and a natural scaling rate. Furthermore, we evaluate our system in comparison with an existing realistic scaling method, UpSizeR, by measuring the representativeness of the extrapolated database to the original one, the accuracy for approximate query answering, the database size, and their performance. Results show that our solution significantly outperforms the compared method for all considered dimensions

Composite Key Generation on a Shared-Nothing Architecture

Generating synthetic data sets is integral to benchmarking, debugging, and simulating future scenarios. As data sets become larger, real data characteristics thereby become necessary for the success of new algorithms. Recently introduced software systems allow for synthetic data generation that is truly parallel. These systems use fast pseudorandom number generators and can handle complex schemas and uniqueness constraints on single attributes. Uniqueness is essential for forming keys, which identify single entries in a database instance. The uniqueness property is usually guaranteed by sampling from a uniform distribution and adjusting the sample size to the output size of the table such that there are no collisions. However, when it comes to real composite keys, where only the combination of the key attribute has the uniqueness property, a different strategy needs to be employed. In this paper, we present a novel approach on how to generate composite keys within a parallel data generation framework. We compute a joint probability distribution that incorporates the distributions of the key attributes and use the unique sequence positions of entries to address distinct values in the key domain

COCOA: A synthetic data generator for testing anonymization techniques

Conducting extensive testing of anonymization techniques is critical to assess their robustness and identify the scenarios where they are most suitable. However, the access to real microdata is highly restricted and the one that is publicly-available is usually anonymized or aggregated; hence, reducing its value for testing purposes. In this paper, we present a framework (COCOA) for the generation of realistic synthetic microdata that allows to de ne multi-attribute relationships in order to preserve the functional dependencies of the data. We prove how COCOA is useful to strengthen the testing of anonymization techniques by broadening the number and diversity of the test scenarios. Results also show how COCOA is practical to generate large datasets