PRESERVATION I: Bioabsorbable Cardiac Matrix Does Not Benefit STEMI Patients
LONDON, England—Use of a novel bioabsorbable cardiac matrix (BCM) in STEMI patients with large infarcts is safe but does not prevent LV remodeling or other adverse outcomes, according to results presented September 1, 2015, at the European Society of Cardiology Congress.
The BCM, dubbed IK-5001 (Bellerophon Therapeutics; Hampton, NJ), is a combination of sodium alginate and calcium gluconate that turns into a flexible hydrogel in the presence of free calcium. The gel replaces the degraded extracellular matrix, which results in reduced wall stress and a thicker scar. In animal models, the BCM, which dissolves in 4 to 6 weeks, provided mechanical support and prevented remodeling during the healing period.
For PRESERVATION I, Uwe Zeymer, MD, of Institut für Herzinfarktforschung (Ludwigshafen, Germany), and colleagues enrolled 303 STEMI patients with large infarcts (defined by peak cardiac markers, clinical presentation, and imaging) between April 2014 and December 2014 at 64 centers in 9 countries. The patients were randomized to receive a 4 mL intracoronary injection of BCM (n = 201) or saline (n = 102) between 2 and 5 days after the infarction as long as they had achieved TIMI 3 flow. The deployment was performed via a dedicated catheter proximal to the stent of the infarct-related artery.
Baseline characteristics were largely similar in both groups, although patients in the BCM group tended to have larger infarcts associated with higher NT-pro-BNP levels.
At 6 months, there was an increase in LV end-diastolic volume index (LVEDVI; primary endpoint), with no difference between the groups (difference of 3.8 mL/m2; 95% CI -0.5 to 8.0). The same held true at 12 months. Additionally, the BCM arm did not have a significant advantage for any of the secondary outcomes at 6 months; however, there was a trend toward a greater increase in the 6-minute walk test (table 1).
There was no difference in the composite endpoint of cardiovascular death, acute MI, revascularization, stent thrombosis, arrhythmia, or myocardial rupture between the treatment groups (P = .5).
Repeat catheterization was done in 22% of patients, but there were no differences between BCM and saline within 24 hours with respect to ischemia and arrhythmia. Five occlusions occurred in the BCM group compared with 1 among saline controls.
Not the End of BCM
The large size of the infarcts included in PRESERVATION I likely explain the discrepant findings compared with the animal models, Dr. Zeymer said. “This might have prevented the BCM to go into the infarct myocardium,” he suggested, adding that future studies should look at different patient populations and potentially deploy the BCM earlier. It might also be studied in combination therapies with stem cells.
Discussing the study, Marc Claeys, MD, of the University of Antwerp (Antwerp, Belgium), explained that “the adverse remodeling process is complex and seems to be triggered by a couple of pathways such as neurohumoral activation, inflammation, and apoptosis. You might have the perception that with timely reperfusion [in STEMI]… the issue of remodeling is almost solved [but] reality shows you that even today the risk of adverse remodeling is present in up to 40% of our STEMI patients, as was shown by the CIRCUS trial. So there’s a clear need to achieve reverse remodeling.”
Although the primary endpoint of the study was not met, it proves the safety of the procedure, Dr. Claeys said. He suggested the following 3 reasons for the negative results:
- The concentration of the artificial matrix might have been too low to increase scar thickness
- Matrix fixation and absorption rate in humans is unknown
- Only relying on mechanical support might not be enough to obtain reverse remodeling without more active regeneration of myocardium
“This is not the end of the study. This could be the beginning,” he concluded.
Zeymer U. PRESERVATION I: bioabsorbable cardiac matrix for the prevention of remodeling of the ventricle after large ST-segment elevation myocardial infarction. Presented at: European Society of Cardiology Congress; September 1, 2015; London, England.
- PRESERVATION I was sponsored by Bellerophon.
- Dr. Zeymer reports receiving honoraria.
- Dr. Claeys reports holding stocks in, receiving consulting and royalty fees from, or owning a healthcare company.