Patisiran may reduce the risk of outpatient heart failure in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), according to an analysis of clinical trial data recently published in the Journal of the American College of Cardiology.
A randomized multicenter clinical trial called APOLLO-B evaluated the efficacy of patisiran, a drug that degrades transthyretin messenger RNA to prevent the accumulation of misfolded protein in patients with ATTR-CM.
What is ATTR-CM?
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a rare progressive disease of the heart muscle that leads to congestive heart failure. It occurs when the transthyretin protein produced by the liver is unstable. Symptoms include fatigue; shortness of breath; irregular heart rate or palpitations; swelling of the legs, ankles and stomach; brain fog; wheezing; and dizziness. It often goes underdiagnosed because of a lack of awareness and knowledge of the disease. There is currently no cure for ATTR-CM.
The study sought to assess worsening outpatient heart failure (HF) as a prognostic indicator for ATTR-CM and the efficacy of patisiran in reducing the risk of worsening HF based on data from the APOLLO-B study.
Read more about ATTR-CM therapies
“Outpatient worsening HF, characterized by initiation or intensification of oral loop diuretics, is emerging as a clinically meaningful event in the trajectory of patients with ATTR-CM,” the authors said.
The study included 360 patients, 181 of whom received patisiran and 179 of whom received a placebo during the one-year double-blind portion of the trial. Of these individuals, 334 participated in the open-label extension and received patisiran.
During the study period, 157 (43.7%) individuals had at least one occurrence of outpatient worsening HF. Additionally, 47 participants (13.1%) died during the study period.
The results revealed an association between worsening HF and all-cause mortality and cardiovascular events. This association was not affected by whether a participant was receiving tafamidis.
During the double-blind phase of the study, 21% of patients receiving patisiran experienced worsening HF, compared to 28.1% of those receiving a placebo. Individuals who initially received patisiran had a reduced risk of worsening HF during both the double-blind period and the open-label extension.
When worsening HF was included in the definition of a clinical event, the number of individuals experiencing an event increased by 52%, from 141 to 215.
“The inclusion of outpatient worsening HF in an expanded composite endpoint in
future clinical trials of patients with ATTR-CM may effectively reduce sample size requirements, the duration of follow-up time required to accrue the target number of events, and related study costs by capturing clinically significant events early on in the disease trajectory of patients with ATTR-CM,” the study said.
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