Patient Perspectives on Transthyretin Amyloid Cardiomyopathy (ATTR-CM) Treatment Attributes

Abstract

Introduction

Transthyretin amyloid cardiomyopathy (ATTR-CM), a progressive disease characterized by the accumulation of misfolded transthyretin amyloid proteins in the myocardium, often leads to heart failure. The experiences and treatment priorities of individuals living with ATTR-CM have not been evaluated in depth.

Methods

This multinational patient advisory board qualitatively explored patients’ experiences with ATTR-CM and their preferences for the attributes of current and emerging treatments for heart failure caused by ATTR-CM. In a pre-advisory board survey, participants answered benefit–risk scaling questions to gauge the importance of treatment side effects, treatment benefits, and modes of administration. The results of the survey were then discussed during the advisory board.

Results

Of the 13 participants who completed the survey (two in Australia, two in Canada, one in Switzerland, four in the United Kingdom, and four in the United States), 11 participated in the advisory board discussion and two in follow-up discussions. The survey results and advisory board discussion revealed tiredness and fatigue to be the most bothersome and injection site pain to be the least bothersome of the side effects evaluated. Lowering the risk of death was the most important and being able to easily take a bath or a shower was the least important of the treatment benefits evaluated. On average, once-daily oral administration was the most preferred mode of administration tested, over twice-daily oral administration, subcutaneous injection, and infusion, although participants’ preferences were heterogeneous. Although the length of life was important, quality of life was also important to participants: they especially valued spending time doing the activities they enjoyed and prioritized these activities over basic functioning and self-care routines.

Conclusions

Individuals living with ATTR-CM have heterogeneous preferences. As the ATTR-CM treatment landscape expands to include treatments with distinct attributes, patients and care teams should participate in shared decision-making to prioritize patients’ preferences and goals.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40119-026-00452-w.

Plain Language Summary

Researchers conducted a multinational study in November 2024 to understand what patients with the heart condition called cardiac amyloidosis related to transthyretin (TTR) thought were the most important from a set of potential medication features. Thirteen patients completed a survey and later joined a discussion about their priorities. Participants answered questions that allowed the researchers to calculate the importance of different potential medication benefits, side effects, and ways they take their medicine. The options for how to take medicine were as a pill once daily; as pills twice daily; as an injection in the clinic every 3 months; as an injection every month (self-administered or in the clinic); and as an infusion at the hospital every 3 months. Individual patients had different priorities when thinking about the features of a medicine for cardiac amyloidosis. When thinking about benefits, patients in general were most concerned with a medicine’s ability to increase their chance of living longer. Their least concern was making it easier to bathe or take a shower. When considering side effects, tiredness was the most concerning, whereas pain from an injection was the least concern. Patients preferred to take their medicine as a pill over a monthly injection or a quarterly infusion. Patients also value a treatment that fits easily into daily life, allowing them to continue doing the things they enjoy most. As more treatments for cardiac amyloidosis become available, patients and care teams should work together to make shared treatment decisions and incorporate patient preferences wherever possible.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40119-026-00452-w.

Key Summary Points

Why carry out this study?

Available and emerging ATTR-CM treatments have different benefit–risk profiles and vary in mode of administration, Patients living with ATTR-CM experience a heterogeneous disease course, and individualized treatment decisions that consider a patient’s unique preferences and goals for therapy are important.

This multinational patient advisory board, which included a pre-advisory board survey, sought to explore patients’ preferences for the attributes of current and emerging treatments for heart failure caused by transthyretin amyloid cardiomyopathy (ATTR-CM).

What was learned from this study?

Among 13 participants in 5 countries (Australia, Canada, Switzerland, United Kingdom, and United States) who took the pre-advisory board survey, tiredness or fatigue was the most bothersome side effect in a medication to treat heart failure, and injection site pain was the least bothersome. Lowering the risk of death was the most important and being able to easily take a bath or a shower was the least important of the treatment benefits evaluated. Once-daily oral administration generally was the preferred mode of administration, over twice-daily oral administration, subcutaneous injection, and infusion, although participants’ preferences were heterogeneous, and some prioritized minimizing pill burden. Quality of life was also important to participants, and they prioritized spending time doing the activities they enjoyed over basic functioning and self-care routines.

Study findings highlight the diverse priorities and preferences of people living with ATTR-CM and emphasize the importance of ensuring that patients have access to treatments that are tailored to their circumstances, preferences, and treatment goals.

Introduction

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a serious and progressive disease characterized by the accumulation of misfolded transthyretin amyloid proteins in the myocardium [1]. Of the two subtypes of ATTR-CM, the more common is wild type, which occurs without genetic mutations, is thought to be age related, and manifests in individuals older than 60 years primarily as cardiomyopathy [2, 3]. Variant ATTR-CM, characterized by inherited transthyretin gene mutations, occurs more commonly in relatively younger individuals and is associated with higher all-cause mortality than wild-type ATTR-CM [1, 2, 4]. Individuals with ATTR-CM commonly present with signs and symptoms of congestive heart failure, atrial fibrillation, and heart conduction disturbances, and they may experience coexisting aortic stenosis [3, 5]. Symptoms associated with ATTR-CM, including fatigue, dyspnea, edema, peripheral neuropathy, and dizziness, limit daily activities and functioning [6]. These symptoms are of uncertain etiology and are nonspecific, making differential diagnosis challenging. ATTR-CM is underdiagnosed, and misdiagnosis and diagnostic delays are common [3].

Although there is currently no cure for ATTR-CM, existing and emerging treatment options have led to significant reductions in mortality and cardiovascular-related hospitalizations and slower declines in patient-centered outcomes [7, 8]. The ATTR-CM treatment landscape is evolving rapidly, and at the time of writing, available disease-modifying therapies for ATTR-CM included transthyretin silencer therapies, which suppress transthyretin protein synthesis, and transthyretin stabilizers, which bind to transthyretin and prevent the formation of amyloid fibrils [2, 3]. The small interfering RNA transthyretin silencer agents, patisiran, administered intravenously every 3 weeks, and vutrisiran, administered subcutaneously in the clinic every 3 months, are also indicated for polyneuropathy associated with variant ATTR [9, 10].

Similarly indicated for polyneuropathy associated with variant ATTR is the antisense oligonucleotide transthyretin knockdown agent eplontersen, which is administered subcutaneously [11]. Vutrisiran was recently approved, and eplontersen is under investigation for use in ATTR-CM [3]. The transthyretin stabilizers are indicated for both variant and wild-type ATTR-CM and are administered orally: tafamidis as one pill once daily and acoramidis as two pills twice daily [12, 13]. Diflunisal is a twice-daily oral nonsteroidal anti-inflammatory agent that stabilizes transthyretin and is used off-label to treat ATTR [3]. The numerous available and emerging ATTR-CM treatments carry different benefit–risk profiles and vary in mode of administration. To date, no head-to-head trials of ATTR-CM therapies have been conducted. Furthermore, because individuals living with ATTR-CM experience a heterogeneous disease course, individualized treatment decisions that incorporate a patient’s unique preferences and goals for therapy are important [14].

With the emergence of novel ATTR-CM therapies, it is important for healthcare professionals to understand patients’ preferences for treatment attributes and their priorities regarding living with ATTR-CM. The aim of this study was to explore patients’ experiences with ATTR-CM and to understand which features of current and emerging ATTR-CM treatments are most important and why. Patients’ priorities were sought through a multinational patient advisory board and pre-advisory board survey, an approach previously employed to elicit discussions around relative importance and prioritization of treatment features to patients and involve them in decision-making [15].

Methods

Overview

Participants were recruited in the United States (US), Canada, Switzerland, the United Kingdom (UK), and Australia through local amyloid patient advocacy groups and were selected to foster diversity, to the extent possible, with respect to ATTR-CM subtype (variant/hereditary vs. wild-type), nationality, gender, and race. Eligible participants were aged 18 years or older, had a self-reported confirmed diagnosis of ATTR-CM, were receiving treatment for ATTR-CM, and were comfortable speaking and reading English. Advisory board members were contracted for their participation in this study and provided consent by entering into the contract. The sponsor of the study was disclosed during the advisory board discussion.

Before participating in the patient advisory board, participants completed an online survey, the results of which informed the development of the advisory board discussion guide. The pre-advisory board survey included questions about participants’ sociodemographic characteristics, their experiences with diagnosis and monitoring of ATTR-CM, their health perceptions, and exploratory questions related to their preferences for attributes of treatments for heart failure associated with ATTR-CM. The survey instrument was reviewed by patient advocacy advisors from Hereditary Amyloidosis Canada and Cardiomyopathy UK before it was administered to the participants. All survey questions and attribute descriptions were presented in patient-friendly language. Participation in the survey and advisory board was voluntary, and participants signed an agreement that included informed consent before completing the survey. Salus IRB reviewed the study materials for the confirmatory survey and provided an exemption from full review on June 2, 2025 (study ID 23528).

Pre-Advisory Board Survey

The pre-advisory board survey began with questions about participants’ experiences with diagnosis, disease monitoring, symptoms, and treatments for ATTR-CM. The survey then presented exploratory object-case benefit–risk scaling (BWS) questions to elicit preliminary preference estimates for attributes related to ATTR-CM treatments, including treatment side effects, treatment benefits, and mode of administration [16], for later discussion in the advisory board (Fig. 1A–C). BWS can be employed as a values clarification method to assess priorities for treatment attributes at the individual level and thus is a suitable method to elicit quantitative preference estimates with small respondent samples. In this case, individuals with ATTR-CM were asked to choose what they viewed as best and worst (or most or least important) among a set of features related to ATTR-CM. The features were split into three topics (Table 1):

• Side effects of treatment (e.g., tiredness, nausea)

• Benefits of treatment (e.g., lowering the risk of death, reducing the need for a heart transplant)

• Ways that a treatment could be taken (e.g., injections, pills)

Fig. 1.

Example benefit–risk scaling questions for A treatment side effects, B treatment benefits, and C mode of administration. IV intravenous

Table 1.

Items included in the benefit–risk scaling exercises

Topic	Side effects of treatment	Benefits of treatment	Mode of administration
Best–worst wording	Best: least bothersome Worst: most bothersome	Best: most important Worst: least important	Best: least bothersome Worst: most bothersome
Items per BWS question	▪ Tiredness and lack of energy because of treatment ▪ Injection pain ▪ Soreness, swelling, or redness after your injection ▪ Joint pain or stiffness because of treatment ▪ Feeling dizzy or lightheaded ▪ Trouble seeing in darker settings or at night ▪ Feeling sick ▪ Diarrhea	▪ Lower your chance of dying because of heart failure ▪ Reduce the need for a heart transplant or heart device ▪ Prevent heart-related hospital admissions ▪ Being able to easily take a bath or shower by yourself ▪ Being able to easily walk 1 block (100 m) on level ground ▪ Being able to easily walk up steps ▪ Being able to easily travel to visit friends outside your home ▪ Being able to easily do the things you enjoy ▪ Being able to easily do tasks in your home ▪ Being able to sleep without sitting or being propped up with pillows ▪ Waking in the morning without having swelling in the feet, ankles, or legs	▪ 1 pill taken at home, once per day ▪ 2 pills taken at home, 1 pill twice per day ▪ Injection under the skin at a clinic once every 3 months ▪ Injection under the skin either at home or a clinic once every month ▪ IV infusion at a hospital once every 3 months

BWS benefit–risk scaling, IV intravenous

Participants were shown the items in a choice set for each topic and were asked to select which item was most or least important or most or least bothersome. For each topic, participants answered between 6 and 12 choice sets, which were determined by an experimental design with desirable statistical properties (e.g., showing each item as often as another) [17]. The results from the survey were then used in the advisory board to prompt discussion among the advisory board participants about what aspects of treatment were most important to participants and why.

Advisory Board

Participants took part in the advisory board virtually on November 11, 2024, and the advisory board lasted for approximately 2 h. To facilitate discussion and allow time for in-depth discussions, participants were split into two breakout groups for a 50-min portion of the advisory board, which focused on participants’ preferences regarding treatment side effects and treatment benefits. The advisory board discussions, plus a later conversation with two participants, one of whom was unable to participate in the advisory board and one of whom had technical issues during the advisory board, were recorded and transcribed, with participant consent, using Microsoft Teams functionality.

Two authors (BH, JC) facilitated the advisory board following a semi-structured discussion guide, which was informed by the results of the exploratory BWS analysis. The focus of the advisory board discussion was on understanding the drivers of participants’ treatment choices. There were four main topics of discussion:

• Side effects of treatment

• Benefits of treatment

• Mode of administration

• Other diagnostic, monitoring, and health perceptions

The discussion of side effects, treatment benefits, or modes of administration explored why the items associated with these topics were ranked relatively higher and lower in the exploratory BWS. The discussion time focused on priority topics (i.e., items at the extremes of the BWS and/or items where preferences were heterogeneous) and the most prominent themes apparent in the preliminary preference estimates.

Statistical and Qualitative Analyses

The exploratory BWS data were analyzed using hierarchical Bayes models in Qualtrics to produce sample-average estimates of preference for each BWS item and individual-level estimates to illustrate the degree of heterogeneity. The Bayesian model used the polar choices (i.e., most and least) to estimate a lower-level model that estimated individual preferences and a model that estimated sample-level preferences until the estimates converged. The primary outcome of the model was the individual BWS scores, which were the basis for the sample-level average BWS scores [17]. Descriptive statistics were used to summarize data collected in the survey.

From the automated transcriptions of the advisory board discussions, analyses were conducted to identify meaningful patterns and themes in the qualitative data. As the focus was on preference for treatment, the qualitative analysis focused on drivers of preference and reasons why choices were made in the exploratory BWS tasks. Quotes were extracted from the transcripts to support the interpretation of the exploratory BWS survey findings. Qualitative findings were discussed iteratively with the study team to ensure that the generated themes and patterns were well developed and comprehensive.

Confirmatory Survey

A confirmatory survey explored preferences for the same features of current and emerging treatments that were discussed in the advisory board among a larger sample of individuals living with ATTR-CM in Australia, Belgium, Canada, Spain, the UK, and the US. Appendix A (Supplementary Material) describes the survey design, analyses, and respondent characteristics for the confirmatory survey in detail. The confirmatory survey was conducted to evaluate the consistency of the study findings in a larger population of people with heart failure resulting from ATTR-CM. The items in the pre-advisory board survey and the confirmatory survey were identical, with one exception: the mode of administration item reflecting oral administration multiple times daily was presented as one pill twice per day in the pre-advisory board survey and as two pills twice per day in the confirmatory study. This change was made to reflect new information regarding available treatment options that emerged between the time the pre-advisory board survey was administered and the time the confirmatory survey was administered.

Results

Participant Characteristics

A total of 13 adults living with ATTR-CM were identified to participate through local patient advocacy groups and completed the survey: two participants in Australia, two in Canada, one in Switzerland, four in the UK, and four in the US. The mean age of the participants was 73 years (Table 2). Most participants were men (77%), were retired (85%), and had a regular care partner (85%); 38% had a university degree and 38% had a postgraduate degree (38%). Nearly two-thirds of participants (62%) had wild-type ATTR-CM, and 38% had variant/hereditary ATTR-CM; all patients were receiving therapy for ATTR. The median time since diagnosis was 4 years. Nearly half of respondents (46%) had experienced mild heart failure symptoms, and 39% had experienced moderate heart failure symptoms in the week preceding the survey. Of those who completed the survey, 11 participated in a group advisory board and two participated in follow-up discussions.

Table 2.

Participants’ demographic and clinical characteristics

Characteristic	N = 13
Mean (SD) age, years	72.8 (6.1)
Sex, n (%)
Female	3 (23.1%)
Male	10 (76.9%)
Country of residence, n (%)
Australia	2 (15.4%)
Canada	2 (15.4%)
Switzerland	1 (7.7%)
UK	4 (30.8%)
US	4 (30.8%)
Has a regular care partner, n (%)
Yes	11 (84.6%)
No	2 (15.4%)
Employment status, n (%)
Retired	8 (61.5%)
Retired due to medical conditions	3 (23.1%)
Employed part-time	1 (7.7%)
Other	1 (7.7%)
Educational attainment, n (%)
Postgraduate degree	5 (38.5%)
University degree	5 (38.5%)
Some university but no degree	1 (7.7%)
High school, secondary school, or equivalent	2 (15.4%)
ATTR-CM subtype, n (%)
Variant/hereditary type	5 (38.5%)
Wild type	8 (61.5%)
Severity of heart failure symptoms in past week, n (%)
None	2 (15.4%)
Mild	6 (46.2%)
Moderate	5 (38.5%)
Severe	0 (0.0%)
Median time since diagnosis	4 years
Comedications, n (%)
Diuretic	8 (61.5%)
Beta blocker	5 (38.5%)
Blood thinner	7 (53.8%)
SGLT2 inhibitor	4 (30.8%)
Other treatments	4 (30.8%)

ATTR-CM transthyretin amyloid cardiomyopathy, SD standard deviation, SGLT2 sodium-glucose cotransporter 2, UK United Kingdom, US United States

Patient Preferences

The results of the exploratory BWS exercises that were conducted in the pre-advisory board survey are presented in Fig. 2 (treatment side effects), Fig. 3 (treatment benefits), and Fig. 4 (mode of administration). Illustrative quotations from the advisory board discussions are presented in Tables 3, 4, 5, and 6.

Fig. 2.

Results of the best–worst scaling exercise in the pre-advisory board survey: Treatment side effects. Note: Each bar presents the unscaled average BWS score of each item across all respondents. BWS scores represent the relative preference for each item

Fig. 3.

Results of the best–worst scaling exercise in the pre-advisory board survey: Treatment benefits. Note: Each bar presents the unscaled average BWS score of each item across all respondents. BWS scores represent the relative preference for each item

Fig. 4.

Results of the best–worst scaling exercise in the pre-advisory board survey: Mode of administration. IV intravenous. Note: Each bar presents the unscaled average BWS score of each item across all respondents. BWS scores represent the relative preference for each item

Table 3.

Participant quotations: Treatment side effects

Topic and item	Participant quotations
Tiredness and lack of energy	“I’d like to point out that it’s actually more than tiredness and lack of energy…in my experience, it’s a deep-seated fatigue. It’s not really just tiredness.” (female patient, UK [Northern Ireland]) “You know, I’ve done a lot of things like take gummies and supplements to help boost up your energy. Smoothies. I’ve done a lot of things, but when you get to that point where you’re feeling that fatigue and tiredness, it seems like nothing seems to help at all.” (female patient, US) “It’s just [being] unable to do a lot of things which I used to take for granted and just crept in gradually.” (male patient, UK)
Injection pain	“I think you get to a point that you have a cannula inserted in your arm so frequently, so to speak, that I think that you just become completely accustomed to…and that’s just something you live with…so that’s why I don’t see injection pain as an important issue for me.” (male patient, Australia) “Every time someone says to me, oh, you have an injection, my legs go a bit wobbly.” (male patient, UK)
Trouble seeing in darker settings	“I found it [seeing in darker settings] really troublesome. I’m 64. I live alone. I don’t have anybody to drive for me and not being able to drive in the dark, you know, especially in our winters here in the UK and Ireland. So, I can’t drive in the early morning. I have to check when the sun’s going to be coming up and similarly. I’m sort of stuck at home from about half 4 or 5 in the evening…so I find it incredibly restrictive.” (female patient, UK [Northern Ireland]) “I guess why I’ve rated this one very highly [seeing in darker settings] was the consequences of this sort of difficulty, that if you’re driving, obviously. And fail to see some obstruction or whatever the consequences of that are pretty severe, and similarly, even making one’s way around the house at night. If you miss seeing an object. The consequences of that too can be quite severe. Falls and broken hips or whatever.” (male patient, Australia)

UK United Kingdom, US United States

Table 4.

Participant quotations: Treatment benefits

Topic and item	Participant quotations
Lowering the chance of death	“I think one of the things that influenced me in this part of the survey was the harsh reality in coming to terms with that, that be it as part of treatment or aging or whatever. That we’re slowing down, and it’s therefore more difficult to take part and enjoy group activities, you know, if you’re going on a day excursion somewhere with a group. Those that you know don’t have the condition and don’t have side effects of treatment, etc., can do a hell of a lot more than people who do. I find that is a thing you have to learn to live with.” (male patient, Australia) “I think some of these [side effects] is because you know the other ones of life and death situations where the other ones you can get people to help you or things to help you with. Other stuff like putting your shoes on or bending down or walking. You can go with other people to help you, but I think it’s, you know, it is very difficult, and I think also as you live with this disease, it becomes the norm, doesn’t it? So, you’ve kind of forget what it was really like to be a normal person. And it’s only when you see other people that you think, oh, I should be doing that. But I can’t do that.” (male patient, UK)
Being able to easily do the things you enjoy	“So I like to, you know, I used to do a lot of backpacking, being outdoors, work out at the gym every day…now I huff and puff…I was hoping that, you know, somehow there would be some medication that would allow me to get back to where I was before.” (female patient, US) “Purpose. Purpose is very important and that would fall under doing the things I enjoy…if you don’t have a purpose in life, well then, why are you living?” (male patient, Canada) “I’ve had trouble spending as much time gardening. I love gardening and I couldn’t spend a full day doing it as I used to. It also meant I couldn’t walk up hills, therefore, the ability to play 18 holes of golf was…had…gone…so in similar ways amyloidosis has affected my ability to do those things and enjoy.” (male patient, Australia)
Reducing swelling and edema	“The only time that I have swollen in my feet is when I first was diagnosed with this. I ended up in an emergency room because I didn’t know what the heck was wrong with me and you know right away they saw that my ankles and legs were swollen so they gave me some medication to drain the water out of my body…the other thing is my cardiologist told me to stay active. You know, to exercise every day. If I could. And that seems to have helped.” (female patient, US) “Exercise is very, very important, even though it’s just simple exercises that make a huge difference. So, I do that every day and also I’ve started to go to armchair yoga as well, which is very good. You know, all those things keep you active and able to do the normal things that everybody else would do during the day.” (male patient, UK)
Easily taking a bath or shower and doing tasks in the home	“For taking a bath and that stuff, I guess you can get, in my mind, you can get assistance with that caregiver or even somebody that comes in. That can help you with that versus actually having to go to the hospital, maybe possibly having surgery for me is more terrifying. So, I just kind of simplified it that way.” (female patient, US) “I understand it’s very hard for me to stand at the sink, cook, put away dishes, anything like that. From getting clothes in and out of the dryer where I feel like I’m gonna fall in the dryer. I have a caregiver. I will admit to that.” (female patient, US)

UK United Kingdom, US United States

Table 5.

Participant quotations: Mode of administration

Topic and item	Participant quotations
How treatments are taken	“So yeah, the ‘every 12 weeks injection at home’ is incredibly convenient. But a pill where I would have autonomy over my treatment would be very welcome.” (female patient, UK [Northern Ireland]) “Certainly, the preferable way of treatment is via pills rather than scheduled infusions or injections or whatever that latter option. For me to get to a place where that treatment can be given is quite extreme in the sense that it requires two steps of public transport. Walking from the station down to the treatment center and all that takes time. It needs to be scheduled in.” (male patient, Australia)
Pill burden and pill size	“I’m already on enough. You know, you get blood thinners, you get cholesterol. You get this that whatever…plus, I do some supplement regime. I’ll take a pen any day or an IVIG any day, whether it’s sub-Q or whether it’s IVIG, as long as I have good veins.” (female patient, US) “I take quite a few pills and I think you can get pill overload. On top of also you taking vitamins and everything and you know you get people recommending certain things to you [that you] think is going to help. I certainly have [to] have a limit because I just get, I just can’t take any more. It’s just one of those things…you just have too many to take and it’s just mind-blowing really.” (male patient, UK) “Going from 1 pill to 2, I also have gastroparesis. So, a lot of my food stays in my stomach for like 50% of the time, and then I’m also taking other medications to manage the other symptoms that I’m having besides the cardiac issue. So, to add another pill, it means that I would have to like switch some of my supplements to maybe liquid, and that’s not so easy to do based on taste and what time and you’re taking it and trying to find a good supplement company. So that’s for me, that’s where it’s troublesome.” (female patient, UK [Northern Ireland]) “So, taking 1 pill per day. That’s not a problem. I mean, I’ll 100%, I’ll remember that, but sometimes during the course of the day, you know, I’ll just forget, and you know, that’s happened in the past where I’ve just forgotten to take the pill at the end of the day, so it’s just a matter of, you know, my memory to be able to keep it, keep it going.” (female patient, US) “I would like to just say that the coating of the tablet would make a difference. You know, there are some tablets are really dry and they can stick and then others are more sort of have a smoother coating on them. I’m not sure what the technical term is or like a gelatin capsule I can swallow much more easily, but the dryer tablets are a problem.” (female patient, UK [Northern Ireland])
Infusions	“When I was getting the treatment with the IV again 3 h, 4 h every 3 weeks. I had trouble with the premeds. My body didn’t really like those and also, I had very small veins, so it was difficult for the nurse to find a good vein to use…it was a very physical tasking on my body.” (female patient, US) “It takes 30 to 45 min to drive to get from my house to the hospital. And as I said earlier, it takes up most of the day and you, I think the other important thing that I think someone else raised is that it, as we’re retirees, we are trying to do some travel and have holidays. Trying to program that monthly infusion amongst all that does require some effort.” (male patient, Australia) “It would take me a few days to recover and then I was getting insomnia for 2 to 3 nights also after. Which was difficult to deal with. So that’s why, you know pill is perfect versus infusion for me.” (female patient, US)
Convenience	“I leave home at 7:30 in the morning or 7:45 to be at the hospital by 8:30. And then there are all sorts of preliminaries before the infusion takes place. So I may not leave the hospital until about 3:30 in the afternoon, so you know it’s manageable, but it is something people would need to be aware of that. This time and other elements that need to be taken into account.” (male patient, Australia)

UK United Kingdom, US United States

Table 6.

Participant quotations: Diagnosis and monitoring

Topic and item	Participant quotations
Diagnosis	“For me, I, you know, I first experienced it because I had gurgling sounds while I was lying in bed and apparently my lungs had filled up with water so I went to emergency and they told me I had heart failure, which shocked the hell out of me…I’m pretty sure I had this going on in my body for a number of years, but my word, it started to really show up. It was probably a year before I went to emergency and I did start to feel, you know, some of the symptoms which became more exaggerated later.” (female patient, US) “Symptoms were similar to bucous [sic] symptoms. I started with a with a bad cough and my ankles swollen. Just cough for no reason at all and got worse and worse and worse, and shortness of breath…the doctor told me because of the climate I live in, I [should] just drive to get a humidifier and that, so that didn’t work. I had to go to the emergency…and the doctor said, oh, you got, did anybody ever tell you that you have a serious heart problem?” (male patient, Canada)
Monitoring	“I monitored myself as what I can do in the garden, like cutting the lawn and you know, some years, you know, previous years it only took me half an hour. Now it takes me an hour because you have to sit down in between things and it’s during the daily activities that you kind of know get slower to do or more difficult and it’s very important…you can tell you know in yourself what you monitor on your daily activities.” (male patient, UK) “I see my hematologist once a quarter and my cardiologist once every 6 months. For hematologist, I have blood tests, the troponin tests. Kept a spreadsheet. Ever since I’ve been diagnosed with recording those key parameters.” (male patient, Australia)

UK United Kingdom, US United States

Treatment Side Effects

Important themes related to patients’ perspectives on side effects associated with ATTR-CM therapy were discussed in the advisory board, with a particular focus on three side effects on which the respondents had extensive feedback (Table 3):

• Tiredness or lack of energy

• Injection pain

• Trouble seeing in darker settings

Patients, on average, considered tiredness and lack of energy to be highly bothersome, selecting this as the most bothersome side effect 65.4% of the time that it appeared in the pre-advisory board survey. In the advisory board discussion, participants expressed that tiredness affected how they were able to enjoy their lives and experience the activities they enjoyed. They also pointed out that tiredness was different from fatigue. Although tiredness can improve with sleep, fatigue can be unremitting. Tiredness, lack of energy, and fatigue were profoundly bothersome to participants and impeded how they experienced their lives. Participants conveyed that it was challenging for them to distinguish between tiredness or fatigue associated with treatment from tiredness or fatigue associated with ATTR-CM itself. Participants discussed their strategies to manage tiredness (e.g., use of supplements) but noted that little helped with this feeling. Participants also explained that their fatigue had worsened as their disease progressed, and their expectations about their present and future energy levels were diminished as a result.

Advisory board participants generally noted that injection pain and redness or soreness after injections were relatively less bothersome than other side effects, and this side effect was ranked as the least bothersome, on average, in the pre-advisory board survey. Most participants explained that injection pain was not bothersome because it had become routine: injections were normal, and the pain associated with injections, compared with other aspects of their treatment and disease (such as feeling dizzy or tired), was not a source of worry or impairment in their daily lives. Tiredness and fatigue had a much greater impact than injection pain or injection reactions on participants’ sense of self and ability to live their lives. One participant, however, offered a different perspective, finding injections to be more bothersome than most other participants. This participant had undergone many injections, both for ATTR-CM and for a previous organ transplant, and injections were still worrisome. This qualitative insight emphasizes how patients’ preferences vary based on individual experiences both with ATTR-CM and other health conditions.

Trouble seeing in darker settings, in general, was relatively not as bothersome as other side effects, but patients’ perspectives on this side effect were diverse. The advisory board discussion revealed that trouble seeing in darker settings was not of great concern for some participants who had adapted to this side effect or had support from a care partner in managing it. However, trouble seeing in darker settings particularly affected some participants and, for one participant without a care partner and living alone, it was particularly challenging, again illustrating how ATTR-CM and its treatment affect individual patients differently.

In addition to the diverse patient perspectives captured during the advisory board discussion, individual-level variability for some side effects was observed in the pre-advisory board survey results. Substantial heterogeneity was observed for the following side effects:

• Injection site pain

• Soreness or swelling after an injection

• Trouble seeing in darker settings at night

• Tiredness and lack of energy

Heterogeneity was most pronounced for injection pain and for trouble seeing in darker settings at night (Figure B1, Supplemental Appendix).

Treatment Benefits

The advisory board discussion focused on the treatment benefits that patients identified as most important in the pre-advisory board survey, on average (Table 4):

• Lowering the risk of death (selected as the most important treatment benefit 60% of the time it was shown in the pre-advisory board survey)

• Lowering the need for a heart transplant or device

• Being able to easily do enjoyable things

Lowering the risk of death was important to participants because they wanted to continue living, feeling they had purpose, and enjoying the activities that were most important to them (sports, hobbies, and being with family). The daily impacts of disease and treatment, such as tasks in the home, showering, and sleeping sitting up, were not as important to participants as the sense of living life to the fullest. Participants spoke of learning to tolerate the symptoms of ATTR-CM, such as swelling, and were able to use support aids for their daily activities.

Although participants were asked specifically to share their views on “lowering your chance of dying,” participants reframed this concept to being able to live to do the things they enjoyed doing and wanting to be alive for these moments. Accepting the condition and living well with it also came up in discussions around death and dying. Central themes in the advisory board discussions were coming to terms with illness and treatment, life being different than before, and finding a way to live with the condition in a new way, through treatment and adapting life to ATTR-CM and treatment.

When asked in the advisory board to expand on why being able to do activities they enjoyed was so important, participants offered that they sometimes felt restricted in being able to do the activities they did before having ATTR-CM because of the disease symptoms (primarily feeling tired and out of breath). They emphasized that they wanted to feel normal, to have purpose, and to continue doing the things they liked to do the most. Although advisory board participants had worked to adapt to their illness, the feeling of being different and unable to participate in the activities they enjoyed was challenging. Therefore, the treatment benefit of being able to easily do things they enjoyed was important. Being able to continue spending time outside, being active, engaging in hobbies, and spending time with family were meaningful to participants; thus, having a treatment that allowed participants to maintain the activities they enjoyed was ranked highly in the exploratory BWS exercise in the pre-advisory board survey and was an important theme in the advisory board discussions.

Participants then discussed the nuances of their experiences with other treatment benefits that had been evaluated in the advisory board survey. For example, among most participants, reducing swelling and edema was relatively not very important because they had found ways to manage these effects through exercise and physical therapy. Similarly, taking a bath or shower and doing tasks in the home were not as important to participants as some of the other treatment benefits (e.g., lowering the risk of death) discussed. Of note, having a caregiver—as 85% of participants did—was a key factor for participants who considered daily tasks to be of relatively lower importance.

The pre-advisory board survey results showed variability in relative importance scores between participants for most benefits (e.g., waking in the morning without swelling in the feet, ankles, or legs). The extent of variability differed across items, and greater variability was found in the assessment of benefit items than had been observed in the assessment of side effect items (Figure B2).

Mode of Administration

Participants’ comments in the advisory board provided insight into their preferences regarding mode of administration (Table 5). Pills taken once daily were perceived by most participants to be the least bothersome way of taking a treatment, due to convenience, independence, autonomy, and the need to travel less. Side effects of infusions were also described as difficult to manage, making infusions a less preferred mode. Diversity in patients’ preferences regarding mode of administration was observed in the pre-advisory board survey and explored further in the advisory board discussion.

The advisory board discussion surfaced numerous reasons why some participants considered once-daily oral treatment to be the least bothersome way of taking a treatment. These participants preferred to avoid the challenge of traveling to a treatment center for injections or infusions. They appreciated the increased independence oral treatment affords and preferred to avoid having illness-related appointments interrupt their lives. Pills allowed these participants to feel autonomous and organize their lives in a way that did not center on their illness. Some advisory board participants also valued a lower frequency of administration for oral treatment. When asked whether pill size was important, participants generally agreed it was and that smaller pills were preferred to larger pills. One participant commented that the coating of the pill was also important. For one participant, avoidance of pills was important because of the feeling of “pill burden” and, for another, a gastrointestinal condition made taking additional pills more bothersome.

The advisory board discussion revealed that infusions were particularly challenging for participants. The time involved in receiving an infusion relative to the shorter time required for an injection was important, as was the premedication impact. Participants further noted that steroids taken at the same time as infusions interfered with sleep, overall making pills (or injections) less burdensome than infusions. Although the travel time may be less for an infusion every 3 months, compared with a once-monthly injection, participants still generally preferred to avoid infusions. Participants also discussed treatment convenience. Some participants needed to travel to receive treatment, which had an impact on their day and their wider schedules. Participants went through the steps needed to take their hospital- or clinic-based treatment, but noted the travel, traffic, and time impacts these had on their lives.

The discussion in the advisory board generally confirmed the rankings revealed in the exploratory BWS results from the pre-advisory board survey. The three least bothersome of the five ways of taking treatment, in order, were:

• Oral administration once daily

• Oral administration twice daily (one capsule twice daily)

• An injection under the skin at a hospital once every 3 months

The 2 most bothersome ways of taking treatment, in order, were:

• Intravenous (IV) infusion at the clinic once every 3 months

• Injection under the skin

Of note, although monthly injections occur more frequently, they were, on average, considered less bothersome than IV infusions every 3 months. The greatest individual-level variability was observed injection item and the once-daily oral treatment item (Figure B3).B3).

Experiences with Diagnosis and Monitoring

The final discussion topic during the advisory board focused on patients’ experiences with diagnosis and monitoring (Table 6). Some participants discussed openly the challenges of receiving a diagnosis and adjusting to rapid life changes, signifying a change in the way participants were able to live their lives after diagnosis. Others described a prolonged sense that something was wrong before obtaining a formal diagnosis. Finally, participants reflected on past and current strategies for monitoring their disease. Some participants prioritized keeping detailed records of their health, using spreadsheets to track test results and queries, whereas others found a physical self check-in, whether incidentally when undertaking normal activities or an intentional exercise to monitor their health specifically (e.g., running on the treadmill), to be the most useful way of understanding their health state and disease progression.

Confirmatory Survey

In total, 169 patients with ATTR-CM participated in the confirmatory survey. Respondents were from Australia (n = 66), UK (n = 36), Spain (n = 26), Belgium (n = 20), Canada (n = 15), and the US (n = 6). The mean age was 67 years (SD, 11.8 years), and a majority of respondents were male (n = 111) and had wild-type ATTR-CM (n = 105). About 42% of the sample had less than a 4-year college degree (n = 63). Most respondents (95%) had taken or were currently taking a medication for ATTR-CM.

Results of the BWS in the confirmatory survey were broadly consistent with the results from the advisory board (Appendix A). Of the treatment side effects evaluated, tiredness and lack of energy was the most bothersome side effect and injection pain was the least bothersome side effect among both the confirmatory survey respondents and the advisory board participants. Similarly, lowering the risk of death was the most important treatment benefit to both confirmatory survey respondents and advisory board participants. Being able to easily take a bath or shower by yourself was the least important benefit to advisory board participants and ranked second-to-last in importance by confirmatory survey participants (with being able to easily travel to visit friends outside the home as the only benefit ranked as less important). With respect to mode of administration, both confirmatory survey respondents and advisory board participants considered a daily pill the least bothersome means of taking a treatment and infusion the most bothersome.

Discussion

This multinational study is the first to have explored preferences for features of current and emerging cardiac amyloidosis treatments. On average, tiredness and a lack of energy were ranked as the most bothersome of the side effects considered in the pre-advisory board survey. These findings were confirmed in the advisory board discussions, during which patients reported feeling an overwhelming lack of energy, often exacerbated by treatments that left them feeling more fatigued. Whether tiredness and fatigue are attributable to ATTR-CM or to its treatments may be difficult for patients and their care teams to discern; nonetheless, results of this study reinforce that fatigue is an important dimension of patients’ experiences living with ATTR-CM.

Among the range of treatment benefits that were discussed in the advisory board, lowering the risk of death and patients being able to easily do the things they enjoy were among the most important benefits, and easily taking a bath or a shower was the least important. Patients emphasized the importance of longevity and being able to engage in the activities they enjoy (e.g., spending time with family and participating in hobbies). Relative to longevity and engaging in meaningful activities, basic functioning and self-care routines were less important to participants.

With respect to mode of administration, once-daily oral administration on average was the least burdensome mode of administration, as reflected both in the advisory board discussion and in the pre-advisory board exploratory BWS exercise. The preference for once-daily oral administration (the option selected as least bothersome 87.1% of the time when shown in the survey) was preferred to a twice-daily administration, likely due to patients’ aversion to increased pill burden. Although not a preferred mode of administration, both the advisory board discussion and the pre-advisory board survey results suggested patients who would tolerate injectable treatment and preferred injections over infusions. Infusions were the least preferred administration mode, with patients citing the time involved in travel to the infusion center and the infusion appointment itself, caregiver impacts, and the disruptions of steroid treatments given with infusions as inconveniences.

The advisory board discussions and exploratory BWS results revealed considerable heterogeneity at the individual level for some side effects (e.g., injection pain and trouble seeing in darker settings at night), treatment benefits (e.g., avoidance of swelling), and mode of administration items (e.g., once-daily oral vs. monthly injectable treatment), driven by the patients’ circumstances and previous experiences. In general, greater variability was observed across items related to treatment benefit and to mode of administration than to side effects. Some participants expressed a preference to avoid pill burden altogether, and others required more information on the size and shape of the pill, the burden associated with traveling to a clinic for an injection or infusion, and the need for concomitant medication such as steroids. Nuances in patient perceptions of administration emphasize the importance of treatment decisions that reflect patient preferences regarding mode and frequency of administration, especially because medication delivery differentiates many of the approved and emerging therapies in ATTR-CM.

Findings from the advisory board discussions highlight that previous experience with treatment, the patient’s age, having a caregiver (or not), having comorbidities (e.g., gastrointestinal conditions) and associated additional treatments, and life stage were all important factors in participants’ decision-making. Notably, most participants (85%) had regular care partners to support them and may have had less need for independence than individuals without this form of social support. The involvement of a care partner may have influenced patients’ heterogeneous perspectives on the importance of trouble seeing in darker settings at night and on the burden of different modes of administration, as well as the relatively lower importance of basic self-care items. It is possible that patients with lower independence or greater reliance on support with daily tasks or treatment management may be especially cautious about increased administration burden or side effects. Thus, patients’ independence, their existing support, and current treatment burdens should factor into shared treatment decisions between patients and care teams.

Patients’ adaptation to their diagnosis and the impacts of ATTR-CM emerged as an important theme in the advisory board discussions. The day-to-day impacts of disease and treatment (such as tasks in the home, showering, and sleeping sitting up) were not as important as the feeling of living life to the fullest. Participants spoke of learning to live with side effects such as swelling and were able to use support aids in their day-to-day activities to help them. In this way, participants adapted to the day-to-day impacts of ATTR-CM and treatment, prioritizing instead living to do the things they enjoyed. Furthermore, participants’ accounts of their experiences with ATTR-CM diagnosis and health monitoring strategies highlight their individual approaches to managing their condition and understanding their potential disease progression. Some participants described keeping detailed records of their health status and tracking clinical encounters in spreadsheets, reflecting that the advisory board participants represent a highly engaged and motivated sample.

The confirmatory survey results generally mirrored the insights from the advisory board and pre-advisory board survey about the side effects, benefits, and administration aspects of ATTR-CM treatments that are most important to patients. The most bothersome side effects (tiredness and lack of energy) and least bothersome (injection pain) were identical in both the pre-advisory board and confirmatory surveys. Lowering the risk of death was the most important treatment benefit and being able to easily take a bath or shower by yourself was among the least important benefits in both elicitations. Even though infusion was the most bothersome and daily oral administration the least bothersome mode of administration in both surveys, twice-daily oral administration (two pills twice per day) was more bothersome to the confirmatory survey respondents than was twice-daily oral administration (one pill twice per day) to the advisory board participants.

Although the most and least important side effects, benefits, and administration aspects generally aligned between the advisory board participants and confirmatory survey respondents, some differences in ordering were observed between the samples in the features that were of moderate importance. These subtle distinctions in preferences may be driven by regional differences or differences in clinical characteristics between the samples but do not suggest any meaningful differences in preferences between the samples. Thus, results of the confirmatory survey support that the key findings from the advisory board are consistent with a broader sample of individuals living with ATTR-CM.

The ATTR-CM treatment landscape is evolving rapidly. Although not all available ATTR-CM therapies may be appropriate or available to every patient, patients do have an expanded range of treatment options to consider. Thus, individualized ATTR-CM treatment decisions will require increasingly nuanced discussions among patients, care partners, and healthcare professionals. Patients come from diverse backgrounds and have unique experiences and priorities. Findings from the qualitative component of this work suggest that factors such as caregiver support, distance from a treatment center, and daily pill burden may influence treatment preferences. Factors not explored in this study, such as treatment availability, ease of access, cost, and reimbursement pathways, are also likely drivers of patients’ treatment decisions. It is important that care teams and patients collaboratively make treatment decisions informed by individual patient preferences. In particular, whether the features of novel and emerging therapies for ATTR-CM may be beneficial to an individual patient will be an important factor in making shared and informed treatment decisions.

Although no theoretic framework exists to measure the alignment of preferences and adherence [18], evidence suggests that treatment adherence correlates with patient preferences in populations living with chronic disease [19]. Moreover, real-world evidence suggests that patients living with ATTR-CM are generally adherent to and persist with treatment regimens for cardiomyopathy [20–22]. Because patients may be more likely to adhere to treatments that align with their preferences, ensuring that treatment decisions reflect the outcomes and modes of administration patients value may help support adherence and ultimately improve clinical outcomes.

Even though no previously published studies have evaluated patient preferences for the attributes of ATTR-CM therapies, previous preference research has evaluated the treatment preferences of patients with heart failure of other origin [23, 24]. Whereas the results of preference studies cannot be compared directly because study findings are specific to the disease and treatment context, the respondent population, and the study design, some broad similarities in preference tendencies emerge across these studies. Similar to the findings of our study in patients with ATTR-CM, Trinkley et al. [23] found that patients with heart failure with reduced ejection fraction valued quality of life and longevity: in this mixed-methods study of 13 participants, these features were prioritized over the other treatment attributes evaluated, including tolerability and convenience. Similarly, MacDonald and colleagues’ [24] scoping review of six preference studies in heart failure found that mortality risk was consistently the most important or second most important attribute in studies in which it was evaluated. Symptom improvement and hospitalization risk also tended to be highly ranked in the reviewed studies, whereas pill burden and tolerability were of lower or inconsistent importance. These similarities suggest that the preferences of people with ATTR-CM may be similar to the preferences of people with heart failure of any origin.

Limitations of this study are noted. First, patients with heart failure caused by other conditions may exhibit different preferences than those of individuals with ATTR-CM; this study did not evaluate preferences associated with heart failure of a different origin or any other health condition. As with all voluntary survey and interview studies, the results are subject to potential selection bias. The sample size of 13 participants was small and highly educated, with three-quarters having a university degree or higher; however, the confirmatory survey had a more diverse educational background. Study participants lived in different countries with differing healthcare systems. Therefore, participants’ experiences with treatment and ATTR-CM care may vary regionally and in terms of access to treatment and care. Although the results may not be generalizable to the broader ATTR-CM population, the confirmatory survey showed that ATTR-CM treatment preferences and priorities were generally consistent in a larger sample. Patient preferences for only a subset of ATTR-CM treatment features were explored. Finally, in each BWS question, all but the included items were held equal, and responses may not be reflective of real-world choices. For example, respondents’ preferences for mode of administration may not reflect a mode that is available for their individual regimen.

Conclusions

Individuals living with ATTR-CM prioritize living longer and being able to spend time doing the things they enjoy and value treatments that allow them the independence and time for these activities. Findings from this patient advisory board study highlight the diverse circumstances, priorities, and preferences of people living with ATTR-CM and emphasize the importance of ensuring that patients have access to treatments that are tailored to their circumstances, preferences, and future goals. As the ATTR-CM treatment landscape evolves to include additional disease-modifying therapies, it is crucial for care teams to have shared decision-making conversations to understand patients’ needs and priorities and their preferences for differentiating features (such as mode and/or frequency of administration). Such conversations will ensure that treatment decisions align with patients’ goals and values.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Nisith Kumar, Joshua Coulter, Alexandra Haddad-Angulo, Louis Baig, Haechung Chung, Sanjana Mahalakshmi Chandrasekar, Caroline Vass, Jayne Galinsky, Anne Marie Carr, Katharine McIntosh, and Brett Hauber each made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This study and the development of this manuscript were sponsored by Pfizer Inc. The journal’s Rapid Service Fee was funded by Pfizer Inc.

Data Availability

To protect participants’ privacy, study data will not be shared.

Declarations

Conflict of Interest

Nisith Kumar, Joshua Coulter, Alexandra Haddad-Angulo, Louis Baig, Haechung Chung, Sanjana Mahalakshmi Chandrasekasr, and Brett Hauber are employees and own stock in Pfizer Inc., the funder of this study. Caroline Vass is an employee of RTI Health Solutions, an independent nonprofit research organization, which was retained by Pfizer to contribute to the research thatis the subject of this manuscript. Jayne Galinsky was an employee of RTI Health Solutions at the time of the study and is currently affiliated with Glasgow Caledonian University. Katharine McIntosh is an employee of Cardiomyopathy UK, which has received research funding from Pfizer Inc. Anne-Marie Carr has nothing to disclose.

Ethical Approval

Salus IRB reviewed the study materials for the confirmatory survey and provided an exemption from full review on June 2, 2025 (study ID 23528).