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Brain & Heart Transforming transthyretin cardiac amyloidosis

tafamidis earlier, the outcomes will be better, particularly future therapies. The success of tafamidis has spurred
in patients with ATTRwt and those with less advanced interest in developing additional treatments that target
HF. 10,20 the underlying pathology of ATTR-CM, including gene-
silencing therapies and other small molecules. As the
4.6. Dosage efficacy: 80 versus 20 mg field continues to evolve, tafamidis will likely remain
4,12
Several studies have explored the question of optimal a cornerstone of therapy, particularly for patients who
dosing, with tafamidis at a dose of 80 mg emerging as a cannot tolerate or do not respond to newer treatments.
more potent option. Damy et al. investigated the efficacy of Furthermore, the experience gained from tafamidis
different tafamidis dosages and found that a dose of 80 mg therapy has provided valuable insights into the importance
provided faster and potentially more robust therapeutic of early diagnosis and intervention in ATTR-CM. The
effects than a dose of 20 mg, particularly in improving notion that tafamidis is most effective when started
functional outcomes such as 6MWT distance and KCCQ early in the disease course emphasizes the need for
scores. Patients receiving a dose of 80 mg exhibited increased awareness and screening, particularly in at-risk
4
improvements as early as 6 months of treatment, whereas populations such as older adults and those with a family
those on the 20 mg dose exhibited similar improvements history of amyloidosis. With earlier diagnosis, tafamidis
after 12 months. and future therapies will have an even greater impact on
Despite these differences in the speed of effect, both patient outcomes. 11,12
doses of tafamidis resulted in significant reductions in
mortality and hospitalization rates, underscoring the 5. Limitations
drug’s overall efficacy across dosage levels. Importantly, This systematic review had certain limitations. First, only
there were no significant safety differences between the two studies published within the past decade were included. In
doses, making both options viable based on patient-specific addition, only full-text articles that were freely accessible
factors and health-care provider recommendations. 4 across various databases were utilized. Articles in languages
other than English were excluded during the screening
4.7. Long-term outcomes and biomarkers process. Previous studies involving participants aged
Beyond immediate clinical outcomes, long-term studies have <18 years were also excluded. Finally, the review focuses
begun exploring the broader impact of tafamidis on disease solely on the efficacy of tafamidis in ATTR-CM, excluding
progression, particularly in terms of biomarkers. Tafamidis data on its use in other subtypes of CA.
has been shown to reduce the levels of N-terminal pro-B-
type natriuretic peptide, a biomarker associated with HF 6. Conclusion
severity and prognosis. In addition, reductions in the levels Tafamidis has fundamentally transformed the treatment
of troponin, another biomarker of cardiac injury, have been landscape for ATTR-CM, thereby offering patients
observed. Therefore, tafamidis may exert cardioprotective several benefits such as reduced mortality, fewer
effects beyond its role in TTR stabilization. Nevertheless, hospitalizations, and enhanced functional capacity.
7
further research should be performed to fully elucidate the Clinical trials such as ATTR-ACT and LTE studies have
mechanisms by which tafamidis affects these biomarkers. demonstrated the efficacy of tafamidis, especially when
However, early data are promising. initiated early in the disease course. Although economic
LTE studies have also provided insights into the challenges remain, the therapeutic benefits of tafamidis
durability of the effects of tafamidis. Patients who remained are undeniable, making it a cornerstone treatment for
on tafamidis after the completion of the ATTR-ACT trial ATTR-CM. The use of tafamidis, the interaction of
continued to experience survival and functional benefits, tafamidis with different drug classes, and the prognosis
with a minimal decline in their quality of life. This long- of patients with ATTR-CM coupled with various
term efficacy underscores the potential of tafamidis as a comorbidities, such as diabetes mellitus, hypertension,
chronic therapy for chronic disease, with the possibility of and chronic renal failure, are some potential topics of
transforming the natural history of ATTR-CM from rapid future research.
decline to stabilization as well as improvement in specific Acknowledgments
cases. 6,11,12
None.
4.8. Tafamidis as a foundation for future therapies
Funding
Tafamidis has undoubtedly revolutionized the treatment
of ATTR-CM. However, it also lays the groundwork for None.

Volume 2 Issue 4 (2024) 8 doi: 10.36922/bh.4250