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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.

Canadian guidelines suggest using a positive, empowering, comprehensive, and safe approach to provide sexual health education (SHE). However, when they do so, decision-makers and educators often favour sexual risk prevention [...]

Objective: To identify potentially modifiable risk factors related to prolonged cardiovascular pharmacological support after weaning from cardiopulmonary bypass (CPB). Methods: This is a secondary analysis of two prospective cohort study in a specialized cardiac surgery institution in adult patients undergoing cardiac surgery with the use of CPB between August 2016 and July 2017. Prolonged cardiovascular pharmacological support was defined by the need for at least one vasopressor or one inotropic agent 24 hours after separation from CPB. Risk factors were identified among baseline characteristics and peri-operative events through multivariable logistic regression. Results: A total of 247 patients were included and 98 (39.7%) developed prolonged pharmacological support. In multivariable analysis, left ventricular ejection fraction ≤ 30% (OR 9.52, 95% confidence interval (CI) 1.14; 79.25), elevated systolic pulmonary artery pressure (sPAP) > 30 and ≤ 55 mmHg (moderate) (OR 2.52, CI 1.15; 5.52) and sPAP > 55 mmHg (severe) (OR 8.12, CI 2.54; 26.03), as well as cumulative fluid balance in the first 24 hours after surgery (OR 1.76, CI 1.32; 2.33) were independently associated with the development of prolonged pharmacological support. Conclusions: Prolonged cardiovascular pharmacological support is frequent after cardiac surgery on CPB. Severe LV systolic dysfunction, preoperative pulmonary hypertension and postoperative fluid overload are risk factors. Further studies are required to explore if those risk factors could be modified or not. [ABSTRACT FROM AUTHOR]