Pharmacogenetics-guided dalcetrapib therapy after an acute coronary syndrome: the dal-GenE trial

Aims: In a retrospective analysis of dal-Outcomes, the effect of dalcetrapib on cardiovascular events was influenced by an adenylate cyclase type 9 (ADCY9) gene polymorphism. The dal-GenE study was conducted to test this pharmacogenetic hypothesis. Methods and results: dal-GenE was a double-blind trial in patients with an acute coronary syndrome within 1–3 months and the AA genotype at variant rs1967309 in the ADCY9 gene. A total of 6147 patients were randomly assigned to receive dalcetrapib 600 mg or placebo daily. The primary endpoint was the time from randomization to first occurrence of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 39.9 months, the primary endpoint occurred in 292 (9.5%) of 3071 patients in the dalcetrapib group and 327 (10.6%) of 3076 patients in the placebo group [hazard ratio 0.88; 95% confidence interval (CI) 0.75–1.03; P = 0.12]. The hazard ratios for the components of the primary endpoint were 0.79 (95% CI 0.65–0.96) for myocardial infarction, 0.92 (95% CI 0.64–1.33) for stroke, 1.21 (95% CI 0.91–1.60) for death from cardiovascular causes, and 2.33 (95% CI 0.60–9.02) for resuscitated cardiac arrest. In a pre-specified on-treatment sensitivity analysis, the primary endpoint event rate was 7.8% (236/3015) in the dalcetrapib group and 9.3% (282/3031) in the placebo group (hazard ratio 0.83; 95% CI 0.70–0.98). Conclusion: Dalcetrapib did not significantly reduce the risk of occurrence of the primary endpoint of ischaemic cardiovascular events at end of study. A new trial would be needed to test the pharmacogenetic hypothesis that dalcetrapib improves the prognosis of patients with the AA genotype

Pharmacogenetics-guided dalcetrapib therapy after an acute coronary syndrome: the dal-GenE trial.

AimsIn a retrospective analysis of dal-Outcomes, the effect of dalcetrapib on cardiovascular events was influenced by an adenylate cyclase type 9 (ADCY9) gene polymorphism. The dal-GenE study was conducted to test this pharmacogenetic hypothesis.Methods and resultsdal-GenE was a double-blind trial in patients with an acute coronary syndrome within 1-3 months and the AA genotype at variant rs1967309 in the ADCY9 gene. A total of 6147 patients were randomly assigned to receive dalcetrapib 600 mg or placebo daily. The primary endpoint was the time from randomization to first occurrence of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 39.9 months, the primary endpoint occurred in 292 (9.5%) of 3071 patients in the dalcetrapib group and 327 (10.6%) of 3076 patients in the placebo group [hazard ratio 0.88; 95% confidence interval (CI) 0.75-1.03; P = 0.12]. The hazard ratios for the components of the primary endpoint were 0.79 (95% CI 0.65-0.96) for myocardial infarction, 0.92 (95% CI 0.64-1.33) for stroke, 1.21 (95% CI 0.91-1.60) for death from cardiovascular causes, and 2.33 (95% CI 0.60-9.02) for resuscitated cardiac arrest. In a pre-specified on-treatment sensitivity analysis, the primary endpoint event rate was 7.8% (236/3015) in the dalcetrapib group and 9.3% (282/3031) in the placebo group (hazard ratio 0.83; 95% CI 0.70-0.98).ConclusionDalcetrapib did not significantly reduce the risk of occurrence of the primary endpoint of ischaemic cardiovascular events at end of study. A new trial would be needed to test the pharmacogenetic hypothesis that dalcetrapib improves the prognosis of patients with the AA genotype.Clinical trial registrationTrial registration dal-GenE ClinicalTrials.gov Identifier: NCT02525939

Shakespeare and Company Project Dataset: Lending Library Books

All data is related to the Shakespeare and Company bookshop and lending library opened and operated by Sylvia Beach in Paris, 1919–1962.This dataset includes information about approximately 6,000 books and other items with bibliographic data as well as summary information about when the item circulated in the Shakespeare and Company lending library and the number of times an item was borrowed or purchased.The Shakespeare and Company Project has received support from Princeton University’s Center for Digital Humanities; Humanities Council and the David A. Gardner ’69 Magic Project Fund; University Committee on Research in the Humanities and Social Sciences; the Dean’s Innovation Fund for New Ideas in the Humanities; the Bain-Swiggett Fund, Department of English; and the Princeton-Mellon Initiative in Architecture, Urbanism, and the Humanities.1.

Shakespeare and Company Project Dataset: Lending Library Members

All data is related to the Shakespeare and Company bookshop and lending library opened and operated by Sylvia Beach in Paris, 1919–1962.The Shakespeare and Company Project: Lending Library Members dataset includes information about approximately 5,700 members of Sylvia Beach's Shakespeare and Company lending library.Princeton University Center for Digital Humanities, Office of the Dean for Research, Innovation Fund for New Ideas in the Humanities, Humanities Council, David A. Gardner '69 Magic Grants, Office of the Dean of Faculty, and the University Committee on Research in the Humanities and Social Sciences.1.

Shakespeare and Company Project Dataset: Lending Library Members, Books, Events

All data is related to the Shakespeare and Company bookshop and lending library opened and operated by Sylvia Beach in Paris, 1919–1962.The Shakespeare and Company Project makes three datasets available to download in CSV and JSON formats. The datasets provide information about lending library members; the books that circulated in the lending library; and lending library events, including borrows, purchases, memberships, and renewals. The datasets may be used individually or in combination site URLs are consistent identifiers across all three. The DOIs for each dataset are as follows: Members (https://doi.org/10.34770/ht30-g395); Books (https://doi.org/10.34770/g467-3w07); Events (https://doi.org/10.34770/2r93-0t85).The Shakespeare and Company Project has received support from Princeton University’s Center for Digital Humanities; Humanities Council and the David A. Gardner ’69 Magic Project Fund; University Committee on Research in the Humanities and Social Sciences; the Dean’s Innovation Fund for New Ideas in the Humanities; the Bain-Swiggett Fund, Department of English; and the Princeton-Mellon Initiative in Architecture, Urbanism, and the Humanities.1.

Shakespeare and Company Project Dataset: Lending Library Events

All data is related to the Shakespeare and Company bookshop and lending library opened and operated by Sylvia Beach in Paris, 1919–1962.The events dataset includes information about approximately 33,700 lending library events including membership activities such as subscriptions, renewals and reimbursements and book-related activities such as borrowing and purchasing. For events related to lending library cards that are available as digital surrogates, IIIF links are provided.The Shakespeare and Company Project has received support from Princeton University’s Center for Digital Humanities; Humanities Council and the David A. Gardner ’69 Magic Project Fund; University Committee on Research in the Humanities and Social Sciences; the Dean’s Innovation Fund for New Ideas in the Humanities; the Bain-Swiggett Fund, Department of English; and the Princeton-Mellon Initiative in Architecture, Urbanism, and the Humanities.1.