Dobner Stephan, Zarro Sara, Wieser Fabian, Kassar Mohammad, Alaour Bashir, Wiedemann Sebastian, Bakula Adam, Caobelli Federico, Stortecky Stefan, Gräni Christoph, Hunziker Lukas, Bernhard Benedikt
Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
3rd Medical Department of Cardiology and Intensive Care Medicine, Clinic Ottakring (Former Wilhelminenhospital), 1160 Vienna, Austria.
J Clin Med. 2024 Sep 6;13(17):5291. doi: 10.3390/jcm13175291.
: Tafamidis reduces cardiovascular morbidity and mortality in transthyretin amyloid cardiomyopathy (ATTR-CM), yet availability and access to therapy vary. : To determine how availability and access to tafamidis impact time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in ATTR-CM. : Ninety-one consecutive ATTR-CM (~97% wt-TTR) patients diagnosed between June 2019 and June 2021 were evaluated for tafamidis. Access to therapy was regulated by compassionate use [n(CU) = 42] prior to, and insurance [n(IA) = 49] after regulatory approval. : Tafamidis was started in 37/42 (88.1%), and 39/49 (79.6%) patients, respectively. At diagnosis, ATTR-CM disease stage (≤stage 2: 88.2% vs. 90.9%, = 0.92) was similar between groups. Timely access (after tafamidis approval) reduced the median time from first presentation to diagnosis from 6.2 (IQR: 1.3-28.9) to 2.4 (0.7-21.7) months, and from first presentation to therapy from 24.4 (10.7-46.8) to 11.8 (6.4-32.4) months. While RV function significantly worsened between diagnosis and therapy initiation in CU patients diagnosed before tafamidis approval (S'-velocity 10.0 ± 2.2 to 9.2 ± 2.2 cm/s; = 0.018; TAPSE 17.3 ± 4.7 to 15.7 ± 3.9 mm, = 0.008), it remained unchanged in IA patients (S'-velocity 9.6 ± 2.6 to 9.4 ± 2.3 cm/s; = 0.83; TAPSE 15.6 ± 4.2 to 16.3 ± 3.1 mm, = 0.45). After a median follow-up of 42.3 and 24.9 months in CU and IA patients, respectively, timely availability was associated with a reduction in annual heart failure hospitalizations (0.40 vs. 0.16 per patient, < 0.001) and improved MACE-free survival (HR = 0.51; 95%CI: 0.26-1.00; = 0.051). Timely diagnosis (<12-months) prolonged MACE-free survival (HR = 0.424; 95%CI: 0.22-0.81; = 0.004), and reduced HFH (HR = 0.40; 95%CI: 0.19-0.81); = 0.011) and all-cause mortality (HR = 0.29; 95%CI: 0.11-0.74); = 0.009). : Availability of tafamidis improves diagnostic efficacy in ATTR-CM patients. Timely diagnosis and initiation of therapy reduces adverse cardiovascular events.
塔法米迪斯可降低转甲状腺素蛋白淀粉样心肌病（ATTR-CM）患者的心血管发病率和死亡率，但药物的可及性和治疗获取情况存在差异。
为确定塔法米迪斯的可及性和治疗获取情况如何影响ATTR-CM患者的诊断时间、治疗时间及心血管结局。
对2019年6月至2021年6月期间连续诊断的91例ATTR-CM患者（约97%为野生型转甲状腺素蛋白）进行了塔法米迪斯评估。在监管批准之前，通过同情用药[ n（CU）=42]来控制治疗获取情况，批准之后则通过保险[ n（IA）=49]来控制。
分别有37/42（88.1%）和39/49（79.6%）的患者开始使用塔法米迪斯。诊断时，两组之间的ATTR-CM疾病阶段（≤2期：88.2%对90.9%，P = 0.92）相似。及时获取（塔法米迪斯批准之后）使从首次就诊到诊断的中位时间从6.2（四分位间距：1.3 - 28.9）个月缩短至2.4（0.7 - 21.7）个月，从首次就诊到治疗的时间从24.4（10.7 - 46.8）个月缩短至11.8（6.4 - 32.4）个月。在塔法米迪斯批准之前诊断的同情用药组患者中，右心室功能在诊断和开始治疗之间显著恶化（S'速度从10.0±2.2降至9.2±2.2 cm/s；P = 0.018；三尖瓣环平面收缩期位移从17.3±4.7降至15.7±3.9 mm，P = 0.008），而在保险组患者中保持不变（S'速度从9.6±2.6降至9.4±2.3 cm/s；P = 0.83；三尖瓣环平面收缩期位移从15.6±4.2升至16.3±3.1 mm，P = 0.45）。同情用药组和保险组患者分别经过4 . 23个月和24.9个月的中位随访后，及时可及性与年度心力衰竭住院率降低相关（每位患者0.40对0.16，P<0.001）以及无主要不良心血管事件生存率提高相关（风险比=0.51；95%置信区间：0.26 - 1.00；P = 0.051）。及时诊断（<12个月）可延长无主要不良心血管事件生存率（风险比=0.424；95%置信区间：0.22 - 0.81；P = 0.004），并降低心力衰竭住院率（风险比=0.40；95%置信区间：0.19 - 0.81；P = 0.011）和全因死亡率（风险比=0.29；95%置信区间：0.11 - 0.74；P = 0.009）。
塔法米迪斯的可及性提高了ATTR-CM患者的诊断效率。及时诊断和开始治疗可减少不良心血管事件。
