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Conventional Heart Failure Therapy in Cardiac ATTR Amyloidosis
Quick Takes
- In an observational study of 2,371 patients with transthyretin cardiac amyloidosis (ATTR-CA), beta-blockers and ACEi/ARBs were used in 55% and 57% of patients at the lowest dose with high rates of discontinuation.
- In propensity-matched analyses, beta-blocker use was associated with survival benefit in those with LVEF ≤40% but ACEi/ARBs were not associated with survival benefit, regardless of LVEF.
- MRAs were used in 39% of patients with lower rates of discontinuation and associated with survival benefit in the overall population and in those with LVEF >40%.
Study Questions:
What is the association between treatment with heart failure (HF) medications and survival in transthyretin cardiac amyloidosis (ATTR-CA)?
Methods:
Patients with ATTR-CA without ATTR-polyneuropathy at the National Amyloidosis Center from 2000–2022 were included. The primary endpoint of interest included mortality within ≤60 months of ATTR-CA diagnosis. Propensity-matched survival analyses were performed for each HF drug class stratified by left ventricular ejection fraction (LVEF).
Results:
A total of 2,371 patients with ATTR-CA were included: 78% with wild-type ATTR-CA and 22% with hereditary ATTR-CA. Mean age was 77 years and 90% were male. Overall, 55% received a beta-blocker (BB), 57% an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin-receptor blocker (ARB) ,and 39% a mineralocorticoid receptor antagonist (MRA). Patients treated with HF medications were more likely to have more severe cardiac disease, diabetes, and atrial fibrillation. The majority of patients treated with BB and ACEi/ARB were on the lowest dose with high rates of discontinuation (22% and 33%, respectively). In contrast, MRA discontinuation was rarer, at 7.5%.
Over a follow-up duration of 28 months, the death rate was 14.9 deaths per 100 patient-years. In a multivariable model including demographics and clinical covariates, only MRA use was associated with a lower mortality risk (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94). Propensity-matched analysis demonstrated a survival benefit with use of BB in ATTR-CA patients with LVEF ≤40% and MRA in ATTR-CA patients with LVEF >40%. There was no benefit noted with ACEi/ARB. The combination of all 3 classes was associated with survival benefit after propensity matching (HR, 0.63; 95% CI, 0.49-0.80).
Conclusions:
In a large observational study of ATTR-CA patients, with propensity matching, use of BB was associated with lower mortality among patients with LVEF ≤40%, and MRA use was associated with lower mortality in the overall population and in those with LVEF >40%.
Perspective:
ATTR-CA remains clinically challenging to treat with only one drug, tafamidis, having a positive endpoint in a clinical trial. There is ambiguity around effectiveness of other standard HF medications in this condition. In this large observational study, over one-half of patients with ATTR-CA received BB and ACEi/ARB, albeit with high rates of discontinuation with the vast majority being on the lowest dose. MRAs were used in about two-thirds of patients and were better tolerated. With several sensitivity analyses performed using propensity matching to best control for confounding factors, MRA use was associated with a survival benefit in the overall population and in ATTR-CA patients with LVEF >40%. BBs were associated with a survival benefit in patients with an LVEF ≤40% with no benefits noted with ACEi/ARBs. However, the combination of all 3 classes reduced the hazard for mortality by 37%. The study remains limited due to its observational design and there being inherent biases in use of these medications and residual confounding.
Clinical Topics: Arrhythmias and Clinical EP, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure
Keywords: Adrenergic beta-Antagonists, Amyloidosis, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Atrial Fibrillation, Diabetes Mellitus, Geriatrics, Heart Failure, Mineralocorticoid Receptor Antagonists, Prealbumin, Secondary Prevention, Stroke Volume, Ventricular Function, Left
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