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Hot Line 5: ATTRibute-CM, ARREST and ADVENT

27 Aug 2023

Sunday morning’s Hot Line 5 session described a new treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), assessed the value of transferring resuscitated cardiac arrest patients to cardiac arrest centres, and compared pulsed field ablation (PFA) with conventional ablation for the treatment of paroxysmal atrial fibrillation (AF).

Following the success of the ATTR-ACT trial of tafamidis in ATTR-CM, the double-blind phase 3 ATTRibute-CM trial evaluated the novel transthyretin stabiliser, acoramidis. In total, 632 patients with wild-type or variant symptomatic ATTR-CM were randomised (2:1) to oral acoramidis 800 mg twice daily or placebo for 30 months. The primary endpoint was a hierarchical analysis by the Finklestein-Schoenfeld method of all-cause mortality, CV-related hospitalisation, NT-proBNP and 6-minute walk distance at 30 months. Secondary endpoints included the components of the primary endpoint, Kansas City Cardiomyopathy Questionnaire overall summary score and serum transthyretin levels.

Summing up, presenter Professor Julian Gillmore (Royal Free London NHS Foundation Trust - London, UK) says, “Despite the challenges imposed by the COVID-19 pandemic, we were able to enrol patients largely from countries without access to tafamidis, such as the UK. The trial showed that in patients with ATTR-CM, acoramidis was consistently associated with clinical benefits as reflected in the primary hierarchical analysis, with 58% of the win ratio ties broken by all-cause mortality and CV-related hospitalisations, and an overall win ratio of 1.8 that was highly statistically significant. The positive treatment effect was consistent across components of the primary endpoint, amongst key clinical subgroups, and across key secondary endpoints. Acoramidis was more effective in preserving both functional capacity and quality of life, and increased circulating transthyretin levels, compared with placebo. Acoramidis has the potential to be an effective and safe alternative to tafamidis for the treatment of ATTR-CM.”

The next presentation, by Doctor Tiffany Patterson (Guy's and St Thomas' NHS Trust Hospitals - London, UK), described the ARREST trial, which investigated whether expedited transfer of resuscitated patients with out-of-hospital cardiac arrest to a cardiac arrest centre reduces mortality compared with delivery to the closest emergency department. The trial also examined whether there was any difference in neurological outcomes between the two strategies.

Across 862 enrolled patients, the primary outcome of 30-day all-cause mortality occurred in 63% of patients in both groups, with no significant difference in 3-month all-cause mortality or neurological outcomes. Dr. Patterson concludes, “Cardiac arrest centres are heavily resourced hospitals. If delivering these patients to such centres to receive multiple interventions does not improve overall survival, then these resources are better allocated elsewhere. Furthermore, if cardiac arrest patients are not taken to such hospitals, this frees up space for other emergency work – including trauma, ST-elevation myocardial infarction and acute aortic dissection – that requires high-dependency beds and the specialist input provided by these centres.”

Professor Vivek Reddy (Icahn School of Medicine at Mount Sinai - New York, USA) ended the session by revealing results from ADVENT, the first randomised controlled trial comparing PFA to conventional ablation. The study enrolled 687 patients with drug-resistant, symptomatic paroxysmal AF at 30 sites in the US. One to three roll-in patients were permitted at each site to ensure experience using the PFA catheter. The remaining 607 patients were randomised (1:1) to PFA or conventional thermal ablation.

The primary efficacy endpoint was the success rate, defined as acute success and chronic success (1-year freedom from recurrent atrial arrhythmias, antiarrhythmic drug use, and cardioversion or repeat ablation). The success rate of 73.3% with PFA versus 71.3% with thermal ablation met prespecified criteria for non-inferiority. Non-inferiority was also demonstrated with the primary safety endpoint composite of 7-day serious adverse events related to use of an ablation catheter or the procedure itself, as well as pulmonary vein stenosis or oesophageal fistula occurring at any time during the 12-month follow up (PFA: 2.1%; thermal group: 1.5%). Prof. Reddy points out that although PFA was as effective and safe as conventional thermal ablation and was associated with faster procedure times, there was more X-ray exposure with PFA.