Heart failure & cardiomyopathiesRandomised controlled trial
Effects of Acoramidis on Kidney Function in Transthyretin Amyloid Cardiomyopathy
- Data from randomized phase 2 and phase 3 studies
Authors' conclusion
Acoramidis initiation resulted in an acute dip in eGFR and reductions in both the chronic eGFR slope and urinary albumin-to-creatinine ratio versus placebo without adverse kidney-related events. Acoramidis effects on kidney function may be mediated through direct kidney-protective hemodynamic effects. Importantly, the acute dip in eGFR was associated with a reduced risk of adverse clinical outcomes within the first year.
Study context
- Population
- Patients with transthyretin amyloid cardiomyopathyphase 2 and phase 3 studies · phase 2 49 · phase 3 632
- Comparison
- acoramidis versus placebo
Primary result
As reported in the abstract
acoramidis
8.5
mean dip · SE 0.48 · mL/min per 1.73 m 2
Further findings
| Outcome | Estimate | P value | |
|---|---|---|---|
| Urinary albumin-to-creatinine ratio, placebo-corrected reduction · Day 28 · reduction with acoramidis | placebo-corrected reduction 15.5% (95% CI 0.4%–28.4%) | P = 0.044 | |
| Urinary albumin-to-creatinine ratio, sustained reduction · over time · reduction with acoramidis | reduction 13.7% (95% CI 1.7%–24.2%) | P = 0.026 | |
| −2002040Difference (linear scale) |
| Outcome | hazard ratio (95% CI) | P value | |
|---|---|---|---|
| All-cause mortality or cardiovascular-related hospitalization, subgroups with acute eGFR dips ≥ the median (4.89 mL/min per 1.73 m 2 ) · P interaction=0.043 | 0.42 (0.22–0.78) | P = 0.006 | |
| Cardiovascular-related hospitalization, subgroups with acute eGFR dips ≥ the median · P interaction=0.025 | 0.34 (0.17–0.66) | P = 0.002 | |
| 0.10.31310Hazard ratio (log scale) |
mL/min per 1.73 m 2 per year
| Outcome | acoramidis | placebo | Estimate | P value |
|---|---|---|---|---|
| Chronic eGFR slope · significantly improved with acoramidis | −1.01 | −3.48 | P < 0.001 |
Chronic estimated glomerular filtration rate (eGFR) slope by concomitant tafamidis use
- Concomitant tafamidis use did not influence the chronic eGFR slope in either arm
Outcomes by eGFR dip within placebo arm
- Within the placebo arm, eGFR dips portended worse outcomes
Original publication
Summarised from the published abstract; every number is checked against it