This novel model suggests that combining EPA with statin therapy for secondary prevention of cardiovascular disease in the US may be a cost-saving and more compelling intervention than statin monotherapy.

Managing dyslipidemia can be challenging in patients with statin intolerance. We describe the lipid effects of icosapent ethyl 4 g/day (high-purity prescription omega-3 eicosapentaenoic acid) in two coronary artery disease patients with statin intolerance who were self-treating with fish oil dietary supplements. After initiating icosapent ethyl, improvements were noted in the first and second patients, respectively, in total cholesterol (-12%; -21%), LDL cholesterol (-3%; -24%), triglycerides (-34%; -16%), non-HDL cholesterol (-12%; -22%), the omega-3 index (+42%; +8%) and eicosapentaenoic acid levels (+275%; +138%). Icosapent ethyl was well tolerated with no adverse events reported. These cases demonstrated favorable lipid effects with prescription icosapent ethyl treatment that may help optimize the care of high-risk coronary artery disease patients with statin intolerance.

Background: Cardiovascular disease (CVD) is responsible for one in every four deaths in the United States as well as direct and indirect costs exceeding $100 billion. Each year in the US, 210,000 heart attacks and 185,000 strokes occur among patients who have previously experienced one. Given the substantial burden of CVD, a novel model was developed to explore the cost-effectiveness of a prescription EPA only omega-3 intervention among secondary prevention populations in the US. Methods: The framework and initial clinical data source for model input was the published Japanese EPA Lipid Intervention Study (JELIS) secondary prevention strata, which included major coronary and stroke endpoints. Two US-focused base case scenarios were developed based on published data: a standard and an aggressive scenario, with the aggressive scenario assuming a highly effective intervention. Costs and utilities were derived from published studies in the US, or the wholesale acquisition cost (WAC), in the case of prescription costs. The initial utility value assigned to this secondary prevention population was 0.78, with unique decrements for each event. Expert opinion was used when clinical assumptions were required for unreported data points. The model takes the perspective of a US, commercial, third-party payer. Costs are presented in 2014 US$. The model extends for 5 years and applies a discount rate of 3% to costs and benefits. Sensitivity analyses are presented to understand the influence of various parameters on outcomes. Results: Under the base case assumptions for the standard US scenario, EPA plus statins compared to statins alone was associated with cost savings (average 5-year costs $29,393 vs. $30,587 per person for EPA plus statins vs statins monotherapy, respectively) and improved utilities (average 3.61 vs. 3.56 respectively), denoting that the strategy of combining EPA with statin therapy exceeds accepted thresholds for cost-effectiveness when compared to statin monotherapy. The aggressive scenario was even more favorable for the combined strategy; being more cost-effective than statin monotherapy, with five-year savings ($29,707 vs. $38,793) and more utilities accrued (3.61 vs 3.50). The results of this model were found to be robust during sensitivity analyses exploring alternative scenarios, with consistent findings of cost-effectiveness or cost savings in the standard and aggressive US scenarios. Conclusions: This novel model suggests that combining EPA with statin therapy for secondary prevention of cardiovascular disease in the United States may be cost-saving and appears to be a more compelling intervention than statin monotherapy. The framework of this model provides a starting point for development of microsimulation models as more data become available.

BackgroundDiagnosis of CDI includes fecal detection of a C. difficile toxigenic strain (TS) or free toxins (FT). TS detection does not distinguish infection from colonization. Guidelines recommend an FT test be part of diagnostic algorithms. Here we report outcome differences, based on diagnostic method at enrollment, from a Phase 2 clinical trial of RDZ, a novel CDI antibiotic designed to treat CDI and reduce recurrence of CDI (rCDI).MethodsThis double-blind study randomized 100 patients 1:1 to 10 days RDZ 200 mg BID or vancomycin (VAN) 125 mg QID treatment. Subjects were enrolled with CDI symptoms and a positive diagnostic result (FT or TS). Baseline (BL) stool samples were assessed for the presence of FT. All subjects entered the intent to treat (ITT) population; those subjects positive for FT entered a modified ITT (mITT), the primary analysis population. Primary endpoint was sustained clinical response (SCR) defined as cure at end of therapy and no rCDI for the next 30 days. rCDI was defined as CDI symptoms, a positive diagnostic test and need for therapy; a sensitivity analysis considered positive FT rCDI cases. BL fecal concentrations of lactoferrin and calprotectin were determined by enzyme immunoassay.ResultsOf 100 subjects enrolled, 69 (36 RDZ: 33 VAN) were FT positive at BL. RDZ compared with VAN recipients had improved SCR rates via reduced rCDI. Absolute differences in SCR between RDZ and VAN (prespecified 90% CI) for MITT (FT positive) and ITT subjects were 24.3% (3.1, 39.1) and 14.0% (−1.8, 28.8), respectively. Absolute SCR differences between the MITT and ITT subjects from the sensitivity analysis were 26.2% (4.6, 40.6) and 14.3% (−1.7, 29.1). Median BL calprotectin and lactoferrin levels (µg/mL) were significantly higher for FT positive subjects at 1,002 and 87, than for FT negative subjects at 53 and 4, respectively.ConclusionRDZ showed improved SCR in comparison with VAN. Treatment differences were greater in MITT subjects. Lower SCR improvement in RDZ ITT subjects is likely due to enrollment of some colonized rather than infected subjects; this explanation is supported by higher calprotectin and lactoferrin levels in FT-positive samples. These data demonstrate the importance of FT testing in-line with CDI guideline recommendations.Disclosures R. Vickers, Summit Therapeutics: Employee, Salary and Stock options. S. Chowdhury, Summit Therapeutics: Employee, Salary and Stock options. M. Wilcox, Summit Therapeutics: Consultant, Research Contractor and Scientific. Advisor, Consulting fee, Research grant and Research support.

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