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The TRUE-AHF study investigated the effects of ularitide on cardiovascular mortality in patients with acute heart failure. 2157 patients were randomised in a double-blind design to receive a continuous intravenous infusion of either ularitide (15 µg/kg/min) or matching placebo for 48 hours in addition to accepted therapy. Treatment started a median 6 hours after the initial clinical evaluation. 236 patients (21.7%) in the ularitide group and 225 patients (21.0%) in the placebo group died from cardiovascular causes during a median 15 months’ follow-up. In the intention-to-treat analysis, there was no significant between-group difference with respect to the initial 48-hour clinical course. There are no treatments that have been shown to improve outcomes in patients with acute decompensated heart failure (ADHF). The initial study with serelaxin suggested a mortality benefit, but the larger RELAX-AHF -2 study was not able to reproduce those results and the drug is not being taken forward. Similarly, ularitide was shown to have favourable haemodynamic effects in patients with ADHF in this study, but no improvement in outcomes, so I suspect it will go the same way as serelaxin and that little, if any, study will be done on it in this area in the future.
This cost-effectiveness analysis of data from the ARISTOTLE trial evaluated the value of substituting apixaban for warfarin in patients with AF. 3417 US patients were enrolled in ARISTOTLE. After 2 years of anticoagulation therapy, US health care costs (excluding the study drug) of patients treated with apixaban and warfarin did not differ significantly. Life expectancy (modelled from ARISTOTLE outcomes) was significantly longer with apixaban than with warfarin (7.94 vs 7.54 quality-adjusted life years [QALYs]). The incremental cost of achieving these benefits was within accepted US norms. Results were generally consistent when model assumptions were varied. The direct oral anticoagulants (DOACs) are increasingly being used as an alternative to warfarin for stroke prevention in nonvalvular AF but these drugs are much more expensive, so cost effectiveness has always been an issue. Modelling used in this paper is concordant with the results of the ARISTOTLE study, where there was a significant decrease in all- cause mortality, and showed that in the US medical system there was an acceptable cost per QALY saved. The cost effectiveness of the DOACs in the Australian context has not been published but this was taken into account by the Pharmaceutical Benefits Advisory Committee when considering the submissions for Pharmaceutical Benefits Scheme reimbursement, and presumably was acceptable given that they have been approved.