Head-to-Head Trials of Etripamil (Cardamyst)
No head-to-head trials directly comparing etripamil to other standard SVT treatments (such as adenosine, verapamil, or diltiazem) have been published; all available evidence consists of placebo-controlled trials. 1, 2, 3, 4
Available Evidence for Etripamil
The current evidence base for etripamil consists exclusively of placebo-controlled randomized trials, not active comparator studies:
Placebo-Controlled Trial Data
The RAPID study (NODE-301) demonstrated that 64% of patients treated with etripamil 70 mg intranasal spray converted to sinus rhythm within 30 minutes, compared to 31% with placebo, with a median time to conversion of 17 minutes versus 53 minutes. 2
A 2025 meta-analysis of four randomized controlled trials (540 patients total) showed etripamil achieved higher conversion rates than placebo at 15 minutes (RR 1.84), 30 minutes (RR 1.80), and 60 minutes (RR 1.24). 1
The NODE-302 open-label extension study followed 169 patients over a median of 232 days, with 60.2% probability of conversion within 30 minutes (median time 15.5 minutes) among 188 positively adjudicated PSVT episodes. 3
The NODE-303 study enrolled 1,116 patients who self-treated 1,054 perceived PSVT episodes without prior test dosing, achieving 70.5% conversion to sinus rhythm by 60 minutes (median time 18.3 minutes). 4
Why No Head-to-Head Trials Exist
The absence of active comparator trials reflects the unique positioning of etripamil as a self-administered, non-parenteral therapy for outpatient use, whereas standard treatments (adenosine, IV verapamil, IV diltiazem) require medical supervision and intravenous access. 5
Traditional SVT treatments are administered in emergency departments or supervised medical settings, making direct comparison methodologically challenging. 6
Etripamil's development focused on demonstrating superiority over placebo for unsupervised home use, a different clinical scenario than hospital-based IV therapies. 2, 5
Clinical Context
Standard guideline-recommended acute treatments for hemodynamically stable SVT include IV beta blockers, diltiazem, or verapamil, which are moderately effective in terminating focal AT or slowing ventricular rate in approximately 30-50% of patients. 6
For AVNRT specifically, oral verapamil (360-480 mg/day) and beta blockers have demonstrated efficacy in reducing episode frequency and duration in small randomized trials. 6
Catheter ablation remains the definitive first-line treatment with 94-98% success rates for patients with recurrent symptomatic SVT. 7, 8
Safety Profile Comparison
While direct comparative safety data are unavailable, etripamil's adverse events were predominantly mild-to-moderate nasal symptoms (nasal discomfort 14-30%, nasal congestion 14%, rhinorrhea 12-13%, epistaxis 7.4%) with no serious cardiac safety events within 24 hours of administration. 1, 3, 4
- This contrasts with IV calcium channel blockers and beta blockers, which carry risks of hypotension and bradycardia requiring close monitoring during administration. 6
Clinical Implications
The lack of head-to-head trials means clinicians cannot directly compare etripamil's efficacy to IV adenosine or calcium channel blockers. However, the consistent placebo-controlled data suggest etripamil fills a distinct niche for patient self-management rather than replacing supervised acute care interventions. 5, 4