Acute coronary syndrome (ACS) survivors have heightened risk for subsequent cardiovascular events. All baseline characteristics collected in both the Dal-Outcomes and Dal-GenE trials were considered a Show more
Acute coronary syndrome (ACS) survivors have heightened risk for subsequent cardiovascular events. All baseline characteristics collected in both the Dal-Outcomes and Dal-GenE trials were considered as potential risk markers. A prediction index for subsequent fatal and non-fatal myocardial infarction (MI) following ACS was developed using Cox proportional hazards modeling on data from Dal-Outcomes placebo patients (n=7086). This prediction index was then applied in all Dal-GenE participants (n=5989) to determine whether the reduction in MI observed with dalcetrapib (versus placebo) in patients with the AA genotype at rs1967309 in the ADCY9 gene remained significant, independent of the other markers integrated into the prediction index. Of the 36 baseline variables considered as potential risk markers, 18 contributed to the prediction index with a Harrell's C-index of 0.72 (95% CI, 0.69-0.75) in Dal-Outcomes placebo patients. Prior history of coronary events, LDL-C, blood pressure, A1c, hs-CRP, smoking and age were contributors. The prediction index was strongly predictive when applied to the 5989 AA genotype patients from Dal-GenE, with a HR for MI of 1.92 (95%CI: 1.78-2.08) for each SD increase in score. When adjusting for the prediction index, the HR for dalcetrapib versus placebo was 0.77 (95% CI, 0.63-0.94) in Dal-GenE. Despite guideline directed therapy following ACS, history of prior coronary events and on-treatment LDL-C, A1c, hs-CRP and blood pressure remain determinants of future MI. In the Dal-GenE AA genotype patients, dalcetrapib reduced the rate of MI, independently of those variables. The Dal-GenE 2 trial is designed to confirm this pharmacogenetic hypothesis. Show less
Type 2 diabetes presents significant public health challenges. The gut microbiome has emerged as a potential factor influencing glucose metabolism. We performed a randomized, double-blind, single-cent Show more
Type 2 diabetes presents significant public health challenges. The gut microbiome has emerged as a potential factor influencing glucose metabolism. We performed a randomized, double-blind, single-center trial involving patients with type 2 diabetes and glycated hemoglobin (HbA1c) concentration of 7 % or greater. Patients were randomly assigned to receive 100 billion colony-forming units (CFUs) of probiotic supplementation daily or placebo. The primary efficacy endpoint was the change in HbA1c from baseline to 12 weeks, and secondary endpoints included lipid and inflammatory markers. A total of 130 patients were included. HbA1c was 7.63 ± 0.54 % at baseline and 7.63 ± 0.63 % at 12 weeks in the probiotic group and 7.71 ± 0.74 % and 7.81 ± 0.84 % in the placebo group (p = 0.29 between treatment groups). There were also no significant differences between treatment groups in plasma glucose (p = 0.60) and insulin (p = 0.41), as well as in LDL-cholesterol (p = 0.90) and triglycerides (p = 0.32). The adjusted geometric mean percent change (95 % confidence interval) in high-sensitivity C-reactive protein was 1.59 % (-15.71, 22.44) in the probiotic group and -1.37 % (-18.04, 18.70) in the placebo group (p = 0.82). Gastrointestinal adverse events occurred in 38.5 % and 46.2 % of patients in the probiotic group and placebo group respectively (p = 0.48). Probiotic supplementation for 12 weeks did not improve glycemic control, lipid or inflammatory markers in patients with type 2 diabetes. Further research is needed to determine the potential benefits and underlying mechanisms of probiotics in subsets of patients. gov Identifier no. NCT03239366. Show less