Supportive Care to Manage Cardiovascular Complications

In principle, the same general treatment recommendations apply to patients with symptomatic CA as for patients with HF due to other causes—but, notably, most of the well-recognized anti-HF drugs may be harmful to amyloidosis patients [1,3]
Responsive Image
Overview of CA Treatment by Stage of HF [2]
Responsive Image
Patients with ATTRwt amyloidosis generally have the disease clinically isolated to the heart [4], but see also supportive care for other organ systems potentially impacted by amyloidoses
Notes: ACCF = American College of Cardiology Foundation; A-fib = atrial fibrillation; ACEI = angiotensin converting enzyme inhibitor; AHA = American Heart Association; ARB = angiotensin receptor blockers; BB = β-blocker; CA = cardiac amyloidosis; HF = heart failure; HFpEF = heart failure with preserved ejection fraction; ICD = implantable cardiac defibrillator; SCD = Sudden cardiac death

Notes: * Pacemaker Implantation: Many ATTR‐CA patients are facing at high risk of conduction system disorders requiring cardiac pacing for symptomatic atrioventricular block or bradycardia, and its indication follows current standard guidelines. However, there are no guidelines for the indication or optimal timing of prophylactic pacemaker implantation for asymptomatic ATTR‐CA patients. Although cardiac pacing can be helpful in symptomatic relief, there are no significant beneficial effects on patient survival. Moreover, ventricular dyssynchrony or lead‐induced tricuspid regurgitation caused by right ventricular pacing might have deleterious impacts on haemodynamics.​

Notes: ** Common causes of death in patients with cardiac amyloidosis are a (rapidly) progressive heart failure and sudden cardiac death. While some studies have documented a high incidence of ventricular arrhythmias and have even shown a prognostic significance for the occurrence of ventricular couplets or nsVTs, other studies indicate a greater significance of bradycardic arrhythmias (especially higher grade AV blockages or electromechanical decoupling) as triggering factors for decompensation or sudden cardiac death. A causally obvious benefit of pacemaker or ICD therapy (e.g., in the form of a reduction in mortality or SCD risk) has so far not been observed in larger studies. However, it needs to be considered that in individual cases and smaller studies, convincing evidence of the benefit of ICD therapy in patients with cardiac amyloidosis has been provided. In the American guidelines updated in 2017, these recommendations were withdrawn; instead, only an individual decision is recommended. Recently published recommendations from the Heart Rhythm Society (HRS) suggest ICD implantation in patients with AL amyloidosis in case of nsVTs and an expected survival of > 1 year (IIb/C)—but do not separately address patients with ATTR amyloidosis.3

Deep Dive
Patients with ATTRwt amyloidosis generally have the disease clinically isolated to the heart [4], but see also supportive care for other organ systems potentially impacted by amyloidoses
Go to Deep Dive
  1. Yamamoto H, Yokochi T. Transthyretin cardiac amyloidosis: an update on diagnosis and treatment. ESC Heart Fail. 2019;6(6):1128-1139. doi:10.1002/ehf2.12518
  2. Kitaoka H, et al. JCS 2020 guideline on diagnosis and treatment of cardiac amyloidosis. Circ J. 2020. 84(9), 1610-1671.
  3. Yilmaz, A., Bauersachs, J., Bengel, F. et al. Diagnosis and treatment of cardiac amyloidosis: position statement of the German Cardiac Society (DGK). Clin Res Cardiol 110, 479–506 (2021).
  4. Fontana M. Mar. 23, 2021. Amyloid cardiomyopathy: Treatment and prognosis. UptoDate.

Quantitative Survey

japan Responsive Image
Not All Patients Receive Disease-Modifying Txs
Enigmatically, accurate diagnosis was not consistently associated with appropriate and satisfactory treatment—many patients only find the therapeutic interventions they need at specialized centers [2]
Drs. of institutions NOT approved for Vyndaqel
< Past 1 year >
At institutions where Vyndaqel is NOT approved, < ¼ reached a definitive diagnosis [1]
Responsive Image
Of the < ¼ able to be diagnosed, 77% of wild-type continued to be treated at the
unapproved institution* without referral after definitive diagnosis[1]
Responsive Image
Deep Dive
HCPs of unapproved institutions—thoughts on clinical environment
Go to Deep Dive
Tx for patients Dx’d at unapproved institution (n=37)
Responsive Image
Treatments were mostly “symptomatic therapies for cardiac dysfunctions” [1]
And of those who remained at an unapproved institution* for treatment, only 16% were reported to be doing causal therapies for amyloidosis
Copyrightⓒ INTAGE Healthcare Inc. All Rights Reserved.

* = unapproved for Vyndaqel
Patients Seen in Past Year
Approved Vyndaqel prescribers reported seeing an average of ~3 ATTRwt-CM patients in the past year, with most being new patients
Nos. of ATTR-CM patients seen (past 1 year)(N = 39 HCPs)
Responsive Image
Responsive Image
Source: ALXN: Acceptance of ALXN2060 for ATTR-CM (Quantitative Survey). October 28, 2021.​
Copyrightⓒ INTAGE Healthcare Inc. All Rights Reserved.
Treatment of ATTR-CM Patients
Among approved prescribers, using Vyndaqel as causal therapy against amyloidosis was the most popular treatment option for ATTRwt patients (79%)
Responsive Image
Responsive Image
Source: ALXN: Acceptance of ALXN2060 for ATTR-CM (Quantitative Survey). October 28, 2021; ^see Speaker Notes for additional information​
Copyrightⓒ INTAGE Healthcare Inc. All Rights Reserved.
Notes: * Vyndaqel ROA and frequency: 80 mg orally once-daily, taken as four 20 mg capsules, or VYNDAMAX 61 mg orally once-daily, taken as a single capsule. VYNDAMAX was developed for patient convenience; VYNDAQEL and VYNDAMAX are not substitutable on a per milligram basis.
  1. ALXN: Acceptance of ALXN2060 for ATTR-CM (Quantitative Survey). October 28, 2021. 02_210823_ATTR-CM quantitative research.
  2. Rintell, D., Heath, D., Braga Mendendez, F. et al. Patient and family experience with transthyretin amyloid cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN) amyloidosis: results of two focus groups. Orphanet J Rare Dis 16, 70 (2021).


Future Disease-Modifying ATTR Treatments

Emerging treatments in ATTR amyloidosis: agents in development
Responsive Image
Notes: ASO = antisense oligonucleotide; siRNA = small inhibitory RNA; SQ = subcutaneous; TUDCA = tauroursodeoxycholic acid
ALXN: Acoramidis ​for the Treatment of ATTR-CM: Training Deck. November 22, 2021. 34_Acoradmidis Training Deck_22Nov21 FINAL. Citing:
  1. Vutrisiran fact sheet: an investigational RNAi therapeutic for ATTR amyloidosis. Accessed August 31, 2021.
  2. Adams D, et al. Neurology 2021;96(15 suppl):1234.
  3. Alnylam presents positive results from HELIOS-A phase 3 study of investigational vutrisiran. Accessed August 31, 2021.
  4. Coelho T, et al. Neurol Ther. 2021;10(1):375-389.
  5. Penchala SC, et al. Proc Natl Acad USA. 2013;10:9992-9997.
  6. Ruberg FL, et al. J Am Coll Cardiol. 2019;73:2872-2891.
  7. Michalon A, et al. Nat Commun. 2021;12:3142.
  8. Cardoso I, et al. J Transl Med. 2010;8:74.
  9. Sekijima Y, et al. Orphanet J Rare Dis. 2018;13:6.

Acoramidis Competitive Assessment

Responsive Image
*tafamidis, diflunisal, tolcapone
**Also referred to as TTR knockdown agents
***Preliminary assumption
Deep Dive
Competitor Trial Listings
Go to Deep Dive
  1. Transthyretin Amyloidosis Overview. October 1, 2021. 06_ATTR Overview - Oct 2021.