Clinical Experience With the Use of Doxycycline and Ursodeoxycholic Acid for the Treatment of Transthyretin Cardiac Amyloidosis

J Card Fail. 2019 Mar;25(3):147-153. doi: 10.1016/j.cardfail.2019.01.006. Epub 2019 Jan 18.

Abstract

Background: The tolerability and utility of combination doxycycline and ursodeoxycholic acid (ursodiol) amyloid fibril disruption therapy for transthyretin cardiac amyloidosis (ATTR CA) in clinical practice is poorly described.

Methods and results: We report the clinical experience of 53 ATTR CA patients treated with doxycycline and ursodiol. Six patients (11%) did not tolerate the therapy owing to dermatologic and gastrointestinal effects. Of those remaining, the median follow-up was 22 months (range 8-30), mean age was 71 ± 11years, 41 (87%) were male, and 42 (89%) had wild-type and 5 (11%) mutant ATTR. Five patients (11%) died during follow-up. There was no significant change in New York Heart Association (NYHA) functional class, cardiac biomarkers, or echocardiographic parameters during follow-up. Left ventricular (LV) global longitudinal systolic strain (GLS) improved in 16 patients (38%) (-12 ± 4% to -17 ± 4%; P < .01). Patients whose LV GLS improved were significantly younger and had lower NYHA functional class, troponin-T, N-terminal pro-B-type natriuretic peptide (BNP), and baseline LV GLS levels compared with those whose LV GLS did not improve. Troponin-T improved in follow-up for patients whose LV GLS improved (35 ± 21 to 20 ± 14 ng/L; P = .06).

Conclusions: Doxycycline and ursodiol therapy for treatment of ATTR CA was tolerable and was associated with stabilized markers of disease progression. LV GLS improved in patients with less advanced disease.

Keywords: Transthyretin cardiac amyloidosis; doxycycline; efficacy; tolerability; ursodiol.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid / antagonists & inhibitors
  • Amyloid / metabolism
  • Amyloidosis / drug therapy*
  • Amyloidosis / metabolism
  • Anti-Bacterial Agents / administration & dosage
  • Cholagogues and Choleretics / administration & dosage
  • Cohort Studies
  • Doxycycline / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Heart Diseases / drug therapy*
  • Heart Diseases / metabolism
  • Humans
  • Male
  • Middle Aged
  • Prealbumin* / metabolism
  • Treatment Outcome
  • Ursodeoxycholic Acid / administration & dosage*

Substances

  • Amyloid
  • Anti-Bacterial Agents
  • Cholagogues and Choleretics
  • Prealbumin
  • TTR protein, human
  • Ursodeoxycholic Acid
  • Doxycycline