Tafamidis in Transthyretin Amyloid Cardiomyopathy Effects on Transthyretin Stabilization and Clinical Outcomes

被引:96
|
作者
Maurer, Mathew S. [1 ]
Grogan, Donna R. [2 ]
Judge, Daniel P. [3 ]
Mundayat, Rajiv [5 ]
Packman, Jeff [2 ]
Lombardo, Ilise [4 ]
Quyyumi, Arshed A. [6 ]
Aarts, Janske [4 ]
Falk, Rodney H. [7 ]
机构
[1] Columbia Univ, Med Ctr, New York Presbyterian Hosp, CCRLE, New York, NY 10034 USA
[2] Pfizer Inc, FoldRx Pharmaceut, Drug Dev Dept, Cambridge, MA USA
[3] Johns Hopkins Univ, Ctr Inherited Heart Dis, Dept Med Cardiol, Baltimore, MD USA
[4] Pfizer Inc, GMD, New York, NY USA
[5] Pfizer Inc, Global Innovat Pharma Stat, New York, NY USA
[6] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA
[7] Harvard Univ, Sch Med, Harvard Vanguard Med Associates, Dept Cardiol, Boston, MA USA
关键词
amyloid; cardiomyopathies; clinical trial; heart failure; AFRICAN-AMERICANS; SYSTEMIC AMYLOIDOSIS; HEART; V122I; TRANSPLANTATION; MORTALITY; SAFETY;
D O I
10.1161/CIRCHEARTFAILURE.113.000890
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Transthyretin (TTR) amyloidosis is a progressive systemic disorder caused by misfolded TTR monomers that cumulatively deposit in the heart and systemically as amyloid. Methods and Results This phase 2 open-label trial evaluated the stabilization of TTR tetramers using 20 mg of tafamidis daily at week 6 (primary end point), month 6, and month 12, as well as safety of tafamidis treatment and efficacy with respect to progression of TTR amyloid cardiomyopathy. Thirty-one wild-type patients (median age, 76.7 years; 93.5% men) with a median disease duration of 55.6 months and mild to moderate heart failure (96.8%; New York Heart Association, classes I-II) were enrolled. Thirty of 31 patients (96.8%) achieved TTR stabilization after 6 weeks and 25 of 28 patients (89.3%) after 12 months. After 12 months of treatment, 3 patients discontinued prematurely, 2 patients died, 7 patients were hospitalized because of cardiovascular events, 20 of 28 patients demonstrated preserved New York Heart Association classification status, but 15 of 31 (48.4%) patients had clinical progression (eg, admission for cardiac failure, atrial fibrillation, and syncope). N-terminal prohormone brain natriuretic peptide levels did not increase significantly over time, troponin I and troponin T increased moderately, and no consistent clinically relevant changes were seen in echocardiographic cardiac assessments. Tafamidis treatment was generally well tolerated although 7 of 31 patients had bouts of diarrhea. Conclusions Tafamidis treatment effectively achieved and maintained TTR stabilization and was well tolerated. The absence of significant changes in most biochemical and echocardiographic parameters suggests that further evaluation of tafamidis in TTR amyloid cardiomyopathy is warranted. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00694161.
引用
收藏
页码:519 / 526
页数:8
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