3 Key Takeaways
Plain English Summary- 01Core Finding
Echocardiograms were performed at baseline and weeks 61, 97, and 140.
- 02Study Evidence
Tested in a randomized controlled trial (1432 patients) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
What This Means for You
Among patients with TTR amyloidosis with cardiomyopathy, eplontersen modestly attenuated deterioration in prognostically important measures of LV systolic, diastolic and right ventricular function, primarily among patients not receiving stabilizers at baseline. These findings complement the clinical findings of CARDIO-TTRansform and suggest that TTR silencing may attenuate progression of cardiac dysfunction in TTR amyloidosis with cardiomyopathy.
The Discovery
In CARDIO-TTRansform, the TTR (transthyretin) silencer eplontersen did not significantly reduce the primary end point of cardiovascular death and recurrent cardiovascular events in patients with TTR amyloidosis with cardiomyopathy, although treatment effects varied by baseline TTR stabilizer use. Whether eplontersen favorably affects cardiac structure and function is unknown.
CARDIO-TTRansform randomized 1432 patients with TTR amyloidosis with cardiomyopathy to eplontersen (45 mg) subcutaneously every 4 weeks or placebo (inactive comparison treatment). Echocardiograms were performed at baseline and weeks 61, 97, and 140. Associations of baseline echocardiographic measures with all-cause mortality and the primary end point were evaluated using Cox and semiparametric proportional rates models. Between-group differences at week 140 were analyzed with mixed models for repeated measures.
Among 1426 participants with baseline echocardiograms (mean age, 76±7 years, 91% men, 85% wild type, 57% receiving stabilizers), baseline measures of left ventricular systolic function (LV ejection fraction, global longitudinal strain, stroke volume, myocardial contraction fraction), diastolic function (E wave deceleration time, septal e', average E/e'), and right ventricular function and hemodynamics were independently associated with all-cause mortality or the primary end point. At week 140 (echocardiograms available in 554 patients in the eplontersen group and 506 in the placebo group), eplontersen attenuated increases in mean LV wall thickness (least-squares mean [LSM] difference, -0.24 mm [95% CI, -0.48 to -0.01]) and declines in LV stroke volume (LSM difference, 1.88 mL [95% CI, 0.07-3.69]), myocardial contraction fraction (LSM difference, 0.88% [95% CI, 0.25-1.57]), average E/e' (LSM difference, -0.71 [95% CI, -1.36 to -0.07]), and right ventricular outflow tract velocity-time integral (LSM difference, 0.42 [95% CI, 0.00-0.85]) versus placebo (inactive comparison treatment) in the overall cohort. Beneficial effects were driven almost exclusively by patients not receiving stabilizers at baseline. No significant treatment effects were observed in patients receiving stabilizers.
How It Works, Simply
This cardiology research focuses on cardiovascular hemodynamic & lipid pathway modulation. Researchers evaluated it using a randomized controlled trial (1432 patients) at the randomized clinical trial stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Echocardiograms were performed at baseline and weeks 61, 97, and 140.
- 02Study Evidence
Tested in a randomized controlled trial (1432 patients) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (1432 patients) · Randomized Clinical Trial
Biological Pathway & Modality
Cardiovascular hemodynamic & lipid pathway modulation
Intervention: Effects of Eplontersen on Cardiac Structure and Function in Patients With
Experimental Findings & Endpoints
In CARDIO-TTRansform, the TTR (transthyretin) silencer eplontersen did not significantly reduce the primary end point of cardiovascular death and recurrent cardiovascular events in patients with TTR amyloidosis with cardiomyopathy, although treatment effects varied by baseline TTR stabilizer use.
Whether eplontersen favorably affects cardiac structure and function is unknown.
CARDIO-TTRansform randomized 1432 patients with TTR amyloidosis with cardiomyopathy to eplontersen (45 mg) subcutaneously every 4 weeks or placebo. Echocardiograms were performed at baseline and weeks 61, 97, and 140.
Associations of baseline echocardiographic measures with all-cause mortality and the primary end point were evaluated using Cox and semiparametric proportional rates models. Between-group differences at week 140 were analyzed with mixed models for repeated measures.
Among 1426 participants with baseline echocardiograms (mean age, 76±7 years, 91% men, 85% wild type, 57% receiving stabilizers), baseline measures of left ventricular systolic function (LV ejection fraction, global longitudinal strain, stroke volume, myocardial contraction fraction), diastolic function (E wave deceleration time, septal e', average E/e'), and right ventricular function and hemodynamics were independently associated with all-cause mortality or the primary end point. At week 140 (echocardiograms available in 554 patients in the eplontersen group and 506 in the placebo group), eplontersen attenuated increases in mean LV wall thickness (least-squares mean [LSM] difference, -0.24 mm [95% CI, -0.48 to -0.01]) and declines in LV stroke volume (LSM difference, 1.88 mL [95% CI, 0.07-3.69]), myocardial contraction fraction (LSM difference, 0.88% [95% CI, 0.25-1.57]), average E/e' (LSM difference, -0.71 [95% CI, -1.36 to -0.07]), and right ventricular outflow tract velocity-time integral (LSM difference, 0.42 [95% CI, 0.00-0.85]) versus placebo in the overall cohort.
Beneficial effects were driven almost exclusively by patients not receiving stabilizers at baseline. No significant treatment effects were observed in patients receiving stabilizers.
Clinical Translation & Practice Context
Among patients with TTR amyloidosis with cardiomyopathy, eplontersen modestly attenuated deterioration in prognostically important measures of LV systolic, diastolic and right ventricular function, primarily among patients not receiving stabilizers at baseline.
These findings complement the clinical findings of CARDIO-TTRansform and suggest that TTR silencing may attenuate progression of cardiac dysfunction in TTR amyloidosis with cardiomyopathy.
The Bottom Line · Clinical Pearl
“Among patients with TTR amyloidosis with cardiomyopathy, eplontersen modestly attenuated deterioration in prognostically important measures of LV systolic, diastolic and right ventricular function, primarily among patients not receiving stabilizers at baseline. These findings complement the clinical findings of CARDIO-TTRansform and suggest that TTR silencing may attenuate progression of cardiac dysfunction in TTR amyloidosis with cardiomyopathy.”
Published in Circulation · Current Stage: Randomized Clinical Trial
