Influence of Vutrisiran on Systolic Blood Pressure in ATTR-CM: HELIOS-B
A Sheikh, B Claggett, I Kulac, P Y Jay, M Fontana, J D Gillmore, S D SolomonAbstract
Background
Transthyretin amyloid cardiomyopathy (ATTR-CM) is frequently associated with low systolic blood pressure (SBP) due to restrictive physiology and autonomic dysfunction, which may reflect more advanced myocardial involvement. Vutrisiran reduces morbidity and mortality in ATTR-CM, but its influence on SBP is unknown.
Purpose
To assess the association between baseline SBP and outcomes, and the influence of Vutrisiran on SBP in patients with ATTR-CM.
Methods
In this post-hoc analysis of HELIOS-B, patients were stratified into clinically meaningful baseline SBP groups. Baseline characteristics and clinical outcomes were compared across SBP categories. Longitudinal SBP was analysed using a linear mixed-effects model with covariate adjustment to estimate the adjusted mean difference in SBP between treatment groups across follow-up. Hypotension during follow-up (SBP <100 mmHg or hypotension-related adverse events) was evaluated as a safety outcome, and its association with the primary composite endpoint of all-cause mortality and recurrent cardiovascular events was assessed using a time-varying Cox model.
Results
Among 654 participants, lower baseline SBP was associated with a more advanced disease phenotype, including higher NT-proBNP (2132 for SBP <120 vs 1759 ng/L for SBP ≥130) and lower LVEF (53% for SBP<120 vs 59% for SBP ≥130). There was a significant inverse correlation between SBP and NT-proBNP (p<0.001). SBP declined in both groups over time, but the decline was significantly less in those treated with Vutrisiran (adjusted coefficient +2.4 mmHg, 95% CI +1.0 to +3.7 mmHg; p=0.001, Figure 1). Vutrisiran reduced the primary composite endpoint regardless of baseline SBP (p-interaction =0.34). Hypotension during follow-up was associated with increased risk of the primary composite outcome (HR 1.29, p=0.043). The frequency of hypotension and related adverse events was similar in both treatment arms.
Conclusion
Lower SBP identifies a high-risk phenotype in ATTR-CM. Vutrisiran significantly attenuated the decline in systolic blood pressure, with treatment benefit regardless of baseline SBP.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.