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Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM.

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Title: Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM.
Authors: Dobner, Stephan1,2 (AUTHOR) sara.zarro@usz.ch, Zarro, Sara1 (AUTHOR) fabian.wieser@ik.me, Wieser, Fabian1 (AUTHOR) mohammad.kassar@insel.ch, Kassar, Mohammad1 (AUTHOR) bashir.alaour@kcl.ac.uk, Alaour, Bashir1,3 (AUTHOR) sebastian.wiedemann@hin.ch, Wiedemann, Sebastian1 (AUTHOR) adam.bakula@insel.ch, Bakula, Adam1 (AUTHOR) stefan.stortecky@insel.ch, Caobelli, Federico4 (AUTHOR) federico.caobelli@insel.ch, Stortecky, Stefan1 (AUTHOR) christoph.graeni@insel.ch, Gräni, Christoph1 (AUTHOR) lukas.hunziker@insel.ch, Hunziker, Lukas1 (AUTHOR) benni.bernhard@web.de, Bernhard, Benedikt1 (AUTHOR)
Source: Journal of Clinical Medicine. Sep2024, Vol. 13 Issue 17, p5291. 15p.
Subject Terms: *CARDIAC amyloidosis, *REGULATORY approval, *TRANSTHYRETIN, *MORTALITY, *DISEASE progression, *HEART failure
Abstract: Highlights:  What is known? Tafamidis, a transthyretin stabilizer, reduces cardiovascular morbidity and mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).  What is new? Availability of tafamidis increases diagnostic efficacy reducing time-to-diagnosis and time-to-therapy initiation. Timely diagnosis and availability of therapy allow therapy initiation and optimization of supportive therapies at earlier disease stages and translate into improved clinical outcomes by reducing heart failure hospitalizations and all-cause mortality.  What is next? Future studies are needed to examine whether faster initiation of TTR-targeting therapies improves long-term morbidity and mortality and to identify which patients benefit most from early therapy. Background: Tafamidis reduces cardiovascular morbidity and mortality in transthyretin amyloid cardiomyopathy (ATTR-CM), yet availability and access to therapy vary. Objective: To determine how availability and access to tafamidis impact time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in ATTR-CM. Methods: 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. Results: 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%, p = 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; p = 0.018; TAPSE 17.3 ± 4.7 to 15.7 ± 3.9 mm, p = 0.008), it remained unchanged in IA patients (S'-velocity 9.6 ± 2.6 to 9.4 ± 2.3 cm/s; p = 0.83; TAPSE 15.6 ± 4.2 to 16.3 ± 3.1 mm, p = 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, p < 0.001) and improved MACE-free survival (HR = 0.51; 95%CI: 0.26–1.00; p = 0.051). Timely diagnosis (<12-months) prolonged MACE-free survival (HR = 0.424; 95%CI: 0.22–0.81; p = 0.004), and reduced HFH (HR = 0.40; 95%CI: 0.19–0.81); p = 0.011) and all-cause mortality (HR = 0.29; 95%CI: 0.11–0.74); p = 0.009). Conclusions: Availability of tafamidis improves diagnostic efficacy in ATTR-CM patients. Timely diagnosis and initiation of therapy reduces adverse cardiovascular events. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Clinical Medicine is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM.
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  Data: &lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Dobner%2C+Stephan%22&quot;&gt;Dobner, Stephan&lt;/searchLink&gt;&lt;relatesTo&gt;1,2&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; sara.zarro@usz.ch&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Zarro%2C+Sara%22&quot;&gt;Zarro, Sara&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; fabian.wieser@ik.me&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Wieser%2C+Fabian%22&quot;&gt;Wieser, Fabian&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; mohammad.kassar@insel.ch&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Kassar%2C+Mohammad%22&quot;&gt;Kassar, Mohammad&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; bashir.alaour@kcl.ac.uk&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Alaour%2C+Bashir%22&quot;&gt;Alaour, Bashir&lt;/searchLink&gt;&lt;relatesTo&gt;1,3&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; sebastian.wiedemann@hin.ch&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Wiedemann%2C+Sebastian%22&quot;&gt;Wiedemann, Sebastian&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; adam.bakula@insel.ch&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Bakula%2C+Adam%22&quot;&gt;Bakula, Adam&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; stefan.stortecky@insel.ch&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Caobelli%2C+Federico%22&quot;&gt;Caobelli, Federico&lt;/searchLink&gt;&lt;relatesTo&gt;4&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; federico.caobelli@insel.ch&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Stortecky%2C+Stefan%22&quot;&gt;Stortecky, Stefan&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; christoph.graeni@insel.ch&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Gr&#228;ni%2C+Christoph%22&quot;&gt;Gr&#228;ni, Christoph&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; lukas.hunziker@insel.ch&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Hunziker%2C+Lukas%22&quot;&gt;Hunziker, Lukas&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; benni.bernhard@web.de&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Bernhard%2C+Benedikt%22&quot;&gt;Bernhard, Benedikt&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22Journal+of+Clinical+Medicine%22&quot;&gt;Journal of Clinical Medicine&lt;/searchLink&gt;. Sep2024, Vol. 13 Issue 17, p5291. 15p.
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  Data: *&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22CARDIAC+amyloidosis%22&quot;&gt;CARDIAC amyloidosis&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22REGULATORY+approval%22&quot;&gt;REGULATORY approval&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22TRANSTHYRETIN%22&quot;&gt;TRANSTHYRETIN&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22MORTALITY%22&quot;&gt;MORTALITY&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22DISEASE+progression%22&quot;&gt;DISEASE progression&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22HEART+failure%22&quot;&gt;HEART failure&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Highlights:  What is known? Tafamidis, a transthyretin stabilizer, reduces cardiovascular morbidity and mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).  What is new? Availability of tafamidis increases diagnostic efficacy reducing time-to-diagnosis and time-to-therapy initiation. Timely diagnosis and availability of therapy allow therapy initiation and optimization of supportive therapies at earlier disease stages and translate into improved clinical outcomes by reducing heart failure hospitalizations and all-cause mortality.  What is next? Future studies are needed to examine whether faster initiation of TTR-targeting therapies improves long-term morbidity and mortality and to identify which patients benefit most from early therapy. Background: Tafamidis reduces cardiovascular morbidity and mortality in transthyretin amyloid cardiomyopathy (ATTR-CM), yet availability and access to therapy vary. Objective: To determine how availability and access to tafamidis impact time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in ATTR-CM. Methods: 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. Results: 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%, p = 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&#39;-velocity 10.0 &#177; 2.2 to 9.2 &#177; 2.2 cm/s; p = 0.018; TAPSE 17.3 &#177; 4.7 to 15.7 &#177; 3.9 mm, p = 0.008), it remained unchanged in IA patients (S&#39;-velocity 9.6 &#177; 2.6 to 9.4 &#177; 2.3 cm/s; p = 0.83; TAPSE 15.6 &#177; 4.2 to 16.3 &#177; 3.1 mm, p = 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, p &lt; 0.001) and improved MACE-free survival (HR = 0.51; 95%CI: 0.26–1.00; p = 0.051). Timely diagnosis (&lt;12-months) prolonged MACE-free survival (HR = 0.424; 95%CI: 0.22–0.81; p = 0.004), and reduced HFH (HR = 0.40; 95%CI: 0.19–0.81); p = 0.011) and all-cause mortality (HR = 0.29; 95%CI: 0.11–0.74); p = 0.009). Conclusions: Availability of tafamidis improves diagnostic efficacy in ATTR-CM patients. Timely diagnosis and initiation of therapy reduces adverse cardiovascular events. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: &lt;i&gt;Copyright of Journal of Clinical Medicine is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder&#39;s express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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        Value: 10.3390/jcm13175291
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        Text: English
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      – SubjectFull: CARDIAC amyloidosis
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      – SubjectFull: REGULATORY approval
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              Text: Sep2024
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