TOPLINE:
Compared with placebo, the drug tafamidis (Pfizer) reduces decline in left ventricular (LV) systolic and diastolic function, suggests post hoc analysis of a randomized trial of patients with transthyretin amyloid cardiomyopathy (ATTR-CM).
METHODOLOGY:
- The study was a post hoc analysis of the multicenter, phase 3 Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), which showed tafamidis, a transthyretin kinetic stabilizer, significantly reduced mortality and cardiovascular-related hospitalizations in patients with ATTR-CM, a progressive hereditary disease caused by the deposition of transthyretin amyloid fibrils in the myocardium.
- The 436 mostly White male patients included in ATTR-ACT, mean age about 74 years, all with a history of heart failure and nearly half with reduced LV ejection fraction (LVEF), were randomized to receive once-daily oral tafamidis 80 mg, tafamidis 20 mg, or matching placebo for 30 months.
- At baseline and at 6, 18, and 30 months, researchers collected echocardiographic measures for both LV systolic parameters (LV stroke volume [SV], LV global longitudinal strain [LVGLS]) and LV diastolic indices (ratio of early mitral inflow velocity to septal and lateral early diastolic mitral annular velocity [E/e′]).
- The study compared the effect of tafamidis 80 mg, the approved dose for ATTR-CM, with placebo on these measures of cardiac function, which have been identified as prognostic factors for mortality in ATTR-CM.
- Researchers also compared changes between groups in regional measures of LV longitudinal, circumferential, and radial strain and left atrial diameter from baseline to month 30.
TAKEAWAY:
- There was less decline in cardiac function among patients taking the active drug; the least squares mean differences among those receiving tafamidis vs placebo were 7.02 mL (95% CI, 2.55-11.49; P = .002) for LVSV; −1.02% (95% CI, −1.73 to −0.31; P = .005) for LVGLS; −3.11 (95% CI, −5.50 to −0.72; P = .01) for septal E/e′; and −2.35 (95% CI, −4.01 to −0.69; P = .006) for lateral E/e′, with changes in LVEF following a similar pattern although the group difference did not reach statistical significance (P = .13).
- Analyses of changes in regional measures of strain showed less decline with tafamidis in midseptal and basal-lateral LV longitudinal strain, mid and apical LV circumferential strain, and mid and apical LV radial strain, but no differences in left atrial diameter.
- Baseline LVEF did not affect the efficacy benefit of tafamidis in terms of mortality, cardiovascular-related hospitalizations, or changes in echocardiographic measures (LVSV, LVGLS, and lateral and septal E/e′).
IN PRACTICE:
"Our findings provide additional insight into the clinical benefit of tafamidis for patients with ATTR-CM and emphasize the importance of early intervention," the authors conclude, adding that the high proportion of ATTR-ACT patients with reduced LVEF "suggests that ATTR-CM should be considered as a possible diagnosis in all patients with heart failure, regardless of LVEF."
SOURCE:
The study was carried out by Sanjiv J. Shah, MD, Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, and colleagues. It was published online on November 15, 2023 in JAMA Cardiology.
LIMITATIONS:
Analyses were post hoc and not predefined. Longitudinal analyses included patients receiving only tafamidis 80 mg and not tafamidis 20 mg, which precludes the generalization of the results to the lower dose. The study lacked more detailed indices of left atrial size and function beyond the left atrial diameter measurement available in ATTR-ACT.
DISCLOSURES:
The study was sponsored by Pfizer. Shah reported grants from Pfizer and personal fees from Pfizer during the conduct of the study, as well as personal fees from Intellia, Novo Nordisk, Ionis, AstraZeneca, and Eidos outside the submitted work; see paper for disclosures of the other authors.
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