No effect of low-dose carperitide on mortality or hospitalisation in acute HF

In patients with acute heart failure (HF), low-dose carperitid did not reduce long-term mortality or HF hospitalisation when combined with standard treatment in the Japanese LASCAR-AHF study. Since enrolment was terminated prematurely, the study was underpowered, and the results were deemed inconclusive.

In HF, natriuretic peptides (NPs) are risk markers as well as adaptive protective factors. Direct treatment of HF patients with the NPs nesiritide and ularitide in respective randomised trials yielded neutral results [1,2]. Carperitide is an intravenous (IV) formulation of human atrial NP that promotes vasodilation and natriuresis. Several observational studies have indicated that the use of IV carperitide is significantly associated with a higher risk of in-hospital death in patients with acute HF [3,4]. However, at low doses, carperitide may enhance decongestion and improve outcomes in patients with acute HF. Dr Toshiyuki Nagai (Hokkaido University, Japan) explained that the LASCAR-AHF trial was designed to test the hypothesis that adding low-dose IV carperitide to standard diuretic therapy reduces long-term adverse events in patients with acute HF [5].

Key inclusion criteria of LASCAR-AHF included ages ≥20 to <85 years; ≥1 symptom of HF (i.e. dyspnoea, orthopnoea, or oedema); ≥1 sign of HF (i.e. rales, oedema, ascites, or chest radiographic sign of HF); systolic blood pressure ≥100 mmHg; and enrolment within 6 hours of presentation. The study's primary endpoint was first occurrence of all-cause death or HF hospitalisation in the 2 years following randomisation. Participants (n=247) were randomised to carperitide 0.02 μg/kg/min plus standard treatment (n=122) or standard treatment alone (n=125) for 72 hours.

There was no significant difference in the primary endpoint between the groups (see Table).

Table: Primary endpoint of all-cause death or HF hospitalisation [5]



CV, cardiovascular; HF, heart failure.

Similarly, no significant difference was observed in patient-reported dyspnoea. The visual analogue scale area under the curve was 528 (95% CI 36–1,350) and 630 (95% CI 120–1,800) in the carperitide and the control group, respectively, with no significant between-group difference (-81.2; 95% CI -328 to 165).

Prof. Nagai pointed out several limitations of this study: patient enrolment was lengthy (576 months) and was exceptionally slow, which is why it was prematurely halted. As a result, the number of enrolled participants was much smaller than that in the original design; and the clinical event rate was lower than expected. Lastly, during the enrolment period, the treatment guidelines for HF changed with the inclusion of sacubitril-valsartan and SGLT2 inhibitors.

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   1. O‘Connor CM, et al. N Engl J Med 2011;365:32–43.
   2. Packer M, et al. N Engl J Med 2017;376:1956–64.
   3. Mizuno A, et al. Int J Cardiol. 2017;241:243–8.
   4. Nagai T, et al. Int J Cardiol. 2019; 280: 104–9.
   5. Nagai T, et al. Low-dose administration of carperitide for acute heart failure. Late-breaking clinical trials: medical therapy, Heart Failure 2024, 11–14 May, Lisbon, Portugal.atrial N

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Posted on 16 July 202416 July 2024