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Brain & Heart Transforming transthyretin cardiac amyloidosis

(from January 1, 2014, to January 9, 2024). The SANRA decompensations that frequently require hospitalization.
scale was used to assess the quality of narrative review ATTR-CM is often diagnosed at advanced stages.
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articles, and the Jadad scale was utilized for RCTs and Therefore, the ability to substantially lower hospitalization
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non-RCTs. The Joanna Briggs Institute quality appraisal rates represents a significant improvement in disease
checklist was used for case series and case reports, and the management and the quality of life of patients. These
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Newcastle–Ottawa checklist was used for case–control findings are supported by the results of functional
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and cohort studies. Duplicates and irrelevant records were measures, such as the 6-min walk test (6MWT) and Kansas
removed before the quality assessment. Finally, 16 studies City Cardiomyopathy Questionnaire (KCCQ), which
were included in this systematic review. Figure 1 shows the showed remarkable improvements in functional capacity
PRISMA chart summarizing the screening process. and patient-reported quality of life. Patients on tafamidis
Table 2 shows the studies included in this systematic exhibited an 80-m increase in the 6MWT distance and a
review. 13 – 18-point improvement in KCCQ scores, surpassing
the thresholds for clinical relevance. 5,6,8,9,11,22
4. Discussion After the completion of ATTR-ACT, the participants

4.1. Tafamidis in ATTR-CM: Redefining standards of were invited to enroll in an LTE study, which provided
care further insights into the long-term effects of tafamidis.
The results of the LTE study underscored the importance
Tafamidis has revolutionized the management of
ATTR-CM, a rare but increasingly recognized cause of of early intervention and showed that the median survival
HF. Tafamidis, the first Food and Drug Administration- of patients who started treatment with tafamidis at the
approved treatment for ATTR-CM, has redefined the onset of the ATTR-ACT trial and those initially assigned
standard of care by not only extending survival rates but to placebo treatment were 53 and 35 months, respectively.
also remarkably improving the quality of life and functional This reinforces the idea that early tafamidis therapy has
capacity of patients. The drug’s ability to stabilize TTR, substantial survival benefits. Importantly, the LTE study
which prevents misfolding and amyloid deposition, has revealed that a dose of 80 mg led to better survival rates
opened new avenues for tackling this previously intractable than a dose of 20 mg, without increasing the incidence of
disease. This section provides an in-depth examination of adverse effects, thereby highlighting the potential benefits
5,12
the clinical trial data of functional outcomes, subgroup of higher doses. This finding has prompted further
analyses, and dosage effects of tafamidis and its impact discussion on optimizing dosing strategies to maximize
on mortality and hospitalization, thereby illustrating its patient outcomes.
profound role in inhibiting disease progression. 4.3. Reductions in mortality and hospitalization
4.2. Clinical trial data: ATTR-ACT and long-term rates
extension (LTE) studies The profound impact of tafamidis on mortality and
The ATTR-ACT trial is a cornerstone for the approval and hospitalization rates has been consistent across multiple
widespread use of tafamidis in the treatment of ATTR-CM. analyses, which underscores its critical role in treating the
The trial involved 441 patients diagnosed with ATTRwt or wild-type and variant forms of ATTR-CM. Patients with
ATTRv who had New York Heart Association (NYHA) ATTRwt exhibited earlier survival benefits than those with
class I–III HF. This trial has set the benchmark for the ATTRv, likely due to differences in disease progression
efficacy of tafamidis. This was a randomized, double- between the two subtypes. The earlier onset of mortality
blind, placebo-controlled study that evaluated tafamidis at reduction in ATTRwt indicates that patients with this type of
doses of 20 and 80 mg over 30 months. The trial’s primary disease have greater benefits from timely initiation of therapy.
endpoints included all-cause mortality and cardiovascular However, in both subgroups, tafamidis was associated with a
event-related hospitalizations, both of which are critical 30% decrease in all-cause mortality and a 32% reduction in
markers of disease progression in HF. cardiovascular hospitalization rates compared with placebo,
demonstrating its broad efficacy across patient populations. 19
The results were groundbreaking, with tafamidis
showing a 13.4% absolute reduction in all-cause Subgroup analyses in the ATTR-ACT trial also
mortality compared with placebo. This statistical value emphasized the variation in outcomes based on the
is particularly notable considering the traditionally poor severity of HF at baseline. Patients with NYHA class I and
prognosis associated with ATTR-CM. Furthermore, II HF exhibited the greatest survival benefit, underscoring
tafamidis reduced cardiovascular hospitalization rates the importance of treating the disease before it advances to
by 32%. Therefore, it is effective in mitigating acute later stages. Patients with NYHA class III HF also showed

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