Summary

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• This summary is based on the review of 13 systematic review(s)/meta-analysis(es). ^[1-13]
• Tafamidis has been shown to significantly reduce cardiovascular mortality (Odds Ratio 0.58; 95% Confidence Interval: [0.41-0.83], P=0.003) and all-cause mortality (OR 0.45; 95% CI: [0.32-0.64], P≤0.00001) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), particularly when initiated at earlier stages.
• In the ATTR-ACT trial, tafamidis demonstrated stability in echocardiographic findings, cardiac biomarkers, and electrocardiogram (ECG) in patients with transthyretin cardiomyopathy, indicating its effectiveness in managing disease progression.
• Subgroup analysis indicated no significant deterioration in left ventricular ejection fraction (LVEF) in patients with wild-type ATTR after tafamidis treatment. Wild-type ATTR patients exhibited higher survival rates compared to those with hereditary ATTR after adjusting for confounders.
• Comparative analyses revealed that patisiran and vutrisiran provided significant improvements in neuropathy, quality of life, and cardiac function in patients with ATTRv amyloidosis, with vutrisiran showing superiority over tafamidis in indirect treatment comparisons.
• Tafamidis was generally well-tolerated, with predominantly mild to moderate adverse events reported across various studies, indicating a favorable safety profile.
• No significant differences were observed in the number of participants who died, dropped out due to adverse events, or experienced at least one severe adverse event compared to placebo in studies evaluating tafamidis.
• Inotersen was associated with a slight increase in mortality and the occurrence of severe adverse events compared to placebo, while patisiran exhibited a lower risk of severe adverse events.
• Studies included both hereditary (ATTRv) and wild-type (ATTRwt) transthyretin amyloidosis patients. Subgroup analyses showed no significant differences in outcomes such as extracellular volume (ECV) change and left ventricular ejection fraction deterioration. Wild-type ATTR patients were older and predominantly male compared to hereditary ATTR patients, and tafamidis demonstrated higher survival rates in wild-type ATTR after adjusting for confounders.