Page 47 - BH-2-4

Brain & Heart Transforming transthyretin cardiac amyloidosis

Table 2. (Continued)
Author(s) Year of Type of study Population (sample size and Major findings
publication median age)
Maurer et al. 12 2018 RCT 441 patients (median age: Compared with patients receiving placebo, tafamidis
76 years); 307 on tafamidis was associated with lower all-cause mortality, reduced
(212 males and 95 females), cardiovascular hospitalization rates, slower functional decline,
134 on placebo (90 males and and improved quality of life in patients with ATTR-CM.
44 females) Follow-up duration: 30 months.
Griffin et al. 6 2021 Review article N/A Over the past few decades, research has revealed the
mechanisms underlying amyloidogenesis. This led to the
development of successful treatments for various classes of
amyloidosis.
Abbreviations: FDA: Food and drug administration; RCT: Randomized controlled trial; N/A: Not applicable; ATTR-CM: Transthyretin amyloid
cardiomyopathy; TTR: Transthyretin; ATTRv: variant ATTR; ATTRwt: wild-type ATTR; NYHA: New York Heart Association; CA: Cardiac
amyloidosis.
Beyond mortality, the impact of tafamidis on a progressive and often fatal disease such as ATTR-CM, is
cardiovascular hospitalizations cannot be overstated. HF substantial, and therapies that can enhance the quality of
decompensations, often requiring hospitalization, not only life of patients should be prioritized alongside those that
cause patient distress but also have significant prognostic extend survival.
implications. The 32% reduction in hospitalization rates Further studies have supported these findings. In a
observed in tafamidis-treated patients translates to a lower study by Ruberg et al., tafamidis was associated with a 32%
burden on health-care systems and improved patient reduction in cardiovascular hospitalizations and a 13.4%
experiences. Cardiovascular hospitalizations are often reduction in all-cause mortality, thereby further supporting
accompanied with significant morbidity, and reducing the improvements in survival and functional outcomes.
their frequency with tafamidis can remarkably improve Moreover, the study revealed reductions in the levels of
the survival and quality of life in this patient population. N-terminal pro-B-type natriuretic peptide, a biomarker of
4.4. Functional and quality-of-life improvements HF severity. Based on this finding, tafamidis may stabilize,
if not reverse, the clinical decline often observed in
Although extending survival is a paramount goal, ATTR-CM. Similarly, Wang et al. conducted a systematic
9
improving functional capacity and quality of life are equally review and meta-analysis and confirmed that tafamidis not
essential in managing a chronic, debilitating disease such only improved survival but also reduced hospitalization
as ATTR-CM. Tafamidis has consistently shown the ability rates and enhanced other clinical endpoints, indicating its
to not only inhibit disease progression but also enhance therapeutic role in ATTR-CM. 10
the day-to-day experiences of patients. In the ATTR-ACT
trial, the functional capacity – as measured using the 4.5. Subgroup analyses of ATTRwt versus ATTRv and
6MWT – and quality of life – assessed using the KCCQ differences in NYHA classifications
– of tafamidis-treated patients improved significantly Subgroup analyses from the ATTR-ACT trial have
12
compared with those of placebo-treated patients. These provided valuable insights into the differential effects of
benefits are far from trivial, as the 80-m increase in the tafamidis across various patient populations. Tafamidis
6MWT distance and the 13 – 18-point rise in KCCQ demonstrated similar reductions in all-cause mortality in
scores underscore the tangible benefits of therapy, enabling patients with ATTRwt and ATTRv. However, those with
patients to perform activities of daily living with greater ATTRwt showed earlier survival benefits. This finding
ease and comfort. 9 suggests that early intervention may be particularly
The importance of these findings lies in not only important for this patient group, considering the rapid
numerical improvements but also the thresholds for clinical progression often observed in ATTRwt.
relevance. Both the 6MWT and KCCQ have established In terms of NYHA class, patients with NYHA class I
cutoffs that indicate a meaningful improvement, and and II HF showed the most significant survival benefits
tafamidis consistently exceeded these thresholds. These from tafamidis therapy. Patients with NYHA class III HF
results imply that patients not only lived longer but also experienced reductions in mortality rates. However,
also lived better, with improved physical functions and the magnitude of the benefit was somewhat limited. These
emotional well-being. The emotional toll of HF, particularly subgroup analyses indicate that if the disease is treated with

Volume 2 Issue 4 (2024) 7 doi: 10.36922/bh.4250