Aficamten retains upper hand over metoprolol for oHCM in subanalysis

Results from a subanalysis of the MAPLE-HCM* trial presented at ESC 2026 continue to support the superiority of aficamten over metoprolol in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) irrespective of beta-blocker (BB) use at screening and prior standard-of-care (SoC) status.

Compared with metoprolol, aficamten improved peak oxygen uptake at week 24 irrespective of BB use (with BB: least-squares mean [LSM] difference, 1.9 mL/kg/min; without BB: LSM difference, 3.1 mL/kg/min) and among those who did not receive any SoC therapy for at least 12 months before screening (no SoC; LSM difference, 4.1 mL/kg/min; p<0.001 for all).

According to presenting author Dr Fernando Dominguez from Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain, these results contradict the hypothesis that this population may have been enriched with BB-resistant patients because the treatment effect was consistent across the three subgroups.

The week-24 changes in KCCQ-CSS** also favoured aficamten over metoprolol regardless of pretrial treatment (with BB: difference, 6.5; p=0.019; without BB: difference, 7.6; p=0.06; no SoC: difference, 5.3; p=0.782), as did the improvement of ≥1 NYHA*** Functional Class (with BB: difference, 26.7; p=0.003; without BB: difference, 19.1; p=0.160; no SoC: difference, 30.2; p=0.151).

“[Although] some of the differences did not achieve statistical significance, we must bear in mind that these are relatively small subgroups,” noted Dominguez.

Pretrial therapy also did not influence the mean changes in Valsalva LVOT-G^# (with BB: –46.1 vs –6.9 mm Hg; p<0.001; without BB: –26.6 vs 3.2 mm Hg; p<0.001; no SoC: –32.8 vs –1.2 mm Hg; p=0.068) with aficamten vs metoprolol. The same held true for the geometric mean changes in NT-proBNP^## (with BB: –75 percent vs 41 percent; without BB: –68 percent vs 45 percent; no SoC: –75 percent vs 53 percent; p<0.001 for all).

The safety profile of aficamten was comparable to that of metoprolol irrespective of previous treatment status. “Serious adverse events (AEs) were uncommon, and AEs resulting in treatment interruption were very infrequent,” said Dominguez. Of note, one aficamten recipient in the subgroup with BB use had an LVEF^### <50 percent.

An early Tx alternative

In MAPLE-HCM, 175 adults with recently diagnosed or treatment-naïve oHCM or chronic oHCM on SoC were randomized 1:1 to aficamten 5–20 mg daily or metoprolol 50–200 mg daily for 24 weeks. Of these, 123 (mean age 58.6 years, 54.5 percent men) received BB therapy at screening, 52 (mean age 55.7 years, 67.3 percent men) did not, and 22 (mean age 55 years, 68.2 percent men) did not receive SoC for at least 12 months before screening.

Of note, participants in the no-BB and no-SoC groups overlapped, as all patients in the latter group were also included in the former.

In the primary analysis, aficamten was superior to metoprolol in this patient setting, with no LVOT-G improvement observed with metoprolol. [N Engl J Med 2025;393:949-960] Another study reinforced these results, showing that aficamten was effective across all evaluated doses, whereas metoprolol was not. [Masri, A, et al, ESC-HF 2026]

However, whether the inclusion of predominantly BB-resistant patients influenced the results against detection of BB impact remained an outstanding question, noted Dominguez and colleagues.

“[This subanalysis] suggests that there is no confounding by selective enrolment of BB-resistant patients. [Hence,] aficamten may be considered as an early treatment option for patients with symptomatic oHCM independent of prior SoC history,” he concluded.