Pharmacists Have a Crucial Role Helping Patients With ATTR-CM Navigate Treatment With Tafamidis

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a potentially fatal disease that impacts the heart when clumps of amyloid are deposited in heart tissue, impacting its ability to function properly. There are 2 types of ATTR-CM: hereditary ATTR-CM—including a variant of the transthyretin gene—and wild-type ATTR-CM, without the transthyretin gene. Although ATTR-CM is a rapidly progressive—and ultimately fatal—disease that is estimated to affect about 150,000 people in the US and over 300,000 people worldwide, it is often underdiagnosed in patients. Risk factors for hereditary ATTR-CM include having a family member who has the disease or heart failure and being aged 50 and older, Black, and/or male.^1,2

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Symptoms—which can begin anywhere from 20 to 80 years of age depending on the type of ATTR-CM—can vary and are sometimes subtle, often causing the disease to be misdiagnosed because of the symptoms’ similarities to heart failure and hypertrophic cardiomyopathy. Common symptoms can include fatigue; leg, ankle, or abdominal swelling; arrhythmia; and shortness of breath with activity.^1,2

Tafamidis in the Treatment of ATTR-CM

Initially approved in 2019³, tafamidis (Vyndamax; Pfizer) is a selective transthyretin (TTR) kinetic stabilizer that binds to thyroxine-binding sites on TTR tetramers, which prevents dissociation into monomers, or the breakdown into amyloid deposits that damage the heart in ATTR-CM. Tafamidis offers a targeted approach by directly addressing the protein’s instability, whereas other treatments address upstream causes.

“[Tafamidis] was compared to placebo and reduced all-cause mortality by 30% and [cardiovascular] hospitalizations by 32% over 30 months. Compared to diflunisal—[which is less potent than tafamidis and may have more adverse events (AEs)]—it was superior in slowing cardiac progression, such as reduced wall thickness increase and ejection fraction decline,” Jennifer Goldman, PharmD, CDCES, BC-ADM, FCCP, professor of pharmacy practice and clinical pharmacist, Massachusetts College of Pharmacy and Health Sciences, Boston, explained in a written Q&A with Pharmacy Times^®. “Unlike symptomatic heart failure treatments, tafamidis targets the underlying pathology.”

Additionally, tafamidis stands out compared with other TTR stabilizers that are used off-label and require monitoring for renal and gastrointestinal AEs. Goldman emphasized that the field of ATTR-CM is continuing to evolve, with several new therapies under investigation, including RNA interference, gene editing, and monoclonal antibodies.

The Pharmacist’s Role Counseling Patients Tafamidis Therapy

Pharmacists can help patients navigate treatment with tafamidis by explaining how the medication works while also overseeing the process to ensure patients are adhering to or taking their medication properly. Additionally, pharmacists are also vital in identifying financial assistance programs or navigating specialty pharmacies or mail-order services.¹

Goldman also emphasized several key counseling points that pharmacists should be aware of when helping patients with tafamidis treatment, including the following: the importance of adhering to once-daily dosing, administered around the same time each day either with or without food; swallowing the capsules whole; not doubling the dose if a dose is missed; being aware of mild gastrointestinal AEs; contraindications in patients who are pregnant; advising patients to avoid breastfeeding while receiving treatment; and discussing potential drug interactions with certain breast cancer resistance protein substrates that may require dose adjustments, such as methotrexate and rosuvastatin.

“Pharmacists should counsel patients that this agent will slow further progression, but will not reverse existing amyloid deposits. Initiating tafamidis early leads to better outcomes,” said Goldman. “[Because] insurance and cost barriers can be difficult for patients, pharmacists can help patients navigate copayment programs and the prior authorization process.”

Ongoing Research and Further Evaluation of ATTR-CM and Tafamidis

As far as ongoing research, the extended efficacy and safety of tafamidis is undergoing evaluation in the long-term extension (NCT02791230)⁴ to the phase 3 ATTR-ACT trial (NCT01994889)⁵. In addition to efficacy and safety, the investigators aim to provide valuable information on functional capacity and survival in this open-label extension.⁴

“There are also studies looking at real-world data to assess long-term outcomes in a broader patient population. Research is being conducted on the impact tafamidis has on specific subgroups, such as patients 80 years [of age] and older. There has been promising early data on the combination of vutrisiriran with tafamidis targeting an additive survival benefit (which was demonstrated in HELIOS-B [NCT04153149])⁶. Research [could also] investigate tafamidis’ potential in other forms of heart failure or as a preventative measure in asymptomatic patients who carry the TTR mutations with early signs of amyloid deposition,” Goldman said in the Q&A.

REFERENCES

1. Gallagher A. Pharmacists Can Increase Access to Care for Patients With ATTR-CM. Pharmacy Times. November 27, 2023. Accessed June 30, 2025. https://www.pharmacytimes.com/view/pharmacists-can-increase-access-to-care-for-patients-with-attr-cm

2. McGovern G. FDA Approves Vutrisiran to Reduce Cardiovascular Death, Hospitalizations in Patients With ATTR-CM. Pharmacy Times. March 21, 2025. Accessed June 30, 2025. https://www.pharmacytimes.com/view/fda-approves-vutrisiran-to-reduce-cardiovascular-death-hospitalizations-in-patients-with-attr-cm

3. Pfizer. U.S. FDA Approves VYNDAQEL® and VYNDAMAX™ for Use in Patients with Transthyretin Amyloid Cardiomyopathy, a Rare and Fatal Disease. News release. May 6, 2019. Accessed June 30, 2025. https://www.pfizer.com/news/press-release/press-release-detail/u_s_fda_approves_vyndaqel_and_vyndamax_for_use_in_patients_with_transthyretin_amyloid_cardiomyopathy_a_rare_and_fatal_disease

4. Long-Term Safety of Tafamidis in Subjects With Transthyretin Cardiomyopathy. ClinicalTrials.gov identifier: NCT02791230. Updated February 3, 2025. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT02791230

5. Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy (ATTR-ACT). ClinicalTrials.gov identifier: NCT01994889. Updated April 24, 2019. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT01994889

6. HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy. ClincialTrials.gov identifier: NCT04153149. Updated May 13, 2025. Accessed March 21, 2025. https://clinicaltrials.gov/study/NCT04153149