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Gene transfer does not improve recurrent heart failure-related hospitalization

Roshini Claire Anthony
28 Sep 2015

Gene transfer therapy to correct an enzyme abnormality did not improve the rate of recurrent hospitalization due to heart failure or terminal events in patients with moderate to severe heart failure, the CUPID 2* study showed.

The CUPID 1** study suggested that adeno-associated virus (AAV1) and sarcoplasmic reticulum CA2+ ATPase (SERCA2a) were associated with a reduction in recurrent heart failure and improved certain measures of cardiac function and patient well-being. The CUPID 2 study was designed to confirm the safety and efficacy of percutaneous intra-coronary administration of AAV1/SERCA2a in patients with moderate to severe heart failure and reduced ejection fraction.

Patients aged 18-80 from 67 investigative sites in the USA, Europe and Israel were randomized to receive either one dose of AAV1/SERCA2a (n=121) or a placebo (n=122). At follow-up (median 17.5 months), treatment with AAV1/SERCA2a failed to improve the rate of recurrent events, with 104 recorded events in the AAV1/SERCA2a group compared to 128 in placebo (hazard ratio [HR], 0.93; 95% CI, 0.53-1.65, p=0.81). AAV1/SERCA2a also did not improve time to first terminal event with 36 and 29 terminal events recorded in the AAV1/SERCA2a and placebo groups, respectively (HR, 1.27; 95% CI, 0.72-2.24, p=0.40). [ESC Congress 2015, presentation 7165]

AAV1/SERCA2a also demonstrated no impact on secondary endpoints such as New York Heart Association (NYHA) Functional Classification, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score or N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, nor were there any safety issues.

“Overall, there were no differences in cardiovascular related-death between the two treatment groups... nor was there any significant difference for any of the critical endpoints that one would look at in a heart failure population between the two treatment groups,” said Dr. Barry Greenberg, principal investigator and director of the Advanced Heart Failure Treatment Program at University of California, San Diego, in La Jolla, California, US.

“While the results of CUPID 2 were disappointing, it does represent an important building block for gene transfer for the treatment of heart failure and raises a number of questions that need to be addressed. A fundamental question is whether or not gene transfer to improve the deficit in SERCA2a is adequate to improve clinical events in heart failure patients. In other words, does the data from the experimental animal studies translate to the complex milieu of patients with advanced heart failure? In order to answer that question, we must ask... was there adequate drug delivery to cardiac myocytes?” Greenberg said. “It is the hope of the CUPID investigators that by presenting this data, this will stimulate further interest and debate and future research will prove gene therapy to be useful in patients with heart failure.”

*CUPID 2: Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease Phase 2b

**CUPID 1: Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease

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Most Read Articles
Roshini Claire Anthony, 28 Sep 2015

Individuals with chronic ischaemic heart disease (IHD) and a small left ventricle and thick myocardium demonstrated higher levels of cardiac remodelling as opposed to those with a large ventricle and thin myocardium, contrary to the prevailing understanding, according to the DOPPLER-CIP study. 

18 Aug 2016
Chronic kidney disease (CKD), regardless of the stage, appears to have no direct effect on cardiovascular mortality within 180 days and 2 years from digoxin treatment initiation in treatment-naïve patients with non-valvular atrial fibrillation (AF), a Danish cohort study suggests.
2 days ago
The presence of target organ damage (TOD) in hypertension is more likely to result in blood pressure (BP) elevation, independently of the type of measurement (office or ambulatory, central or peripheral), according to a recent study. Central BP, even monitored during 24 hours, is not better correlated with TOD than peripheral BP.
09 Nov 2016
Ischaemic conditioning has no overall effect on the mortality risk in people undergoing invasive procedures, and its possible effects on stroke and acute kidney injury remain unknown given methodological concerns and low event rates, according to a systematic review and meta-analysis.