ORLANDO, FL — Injections of calcium-alginate gel beads (Algisyl, LoneStar Heart) into the left ventricular endocardium of patients with advanced heart failure led to improved exercise capacity, symptoms, and NYHA clinical status a year later compared with standard medical therapy alone in the AUGMENT HF trial[1].
However, these are early days. "I think it is important to emphasize that this is a provisional trial," Dr Douglas L Mann (Washington University School of Medicine, St Louis, MO) cautioned, presenting these findings at a press briefing prior to a late-breaking clinical-trial session at the American Heart Association (AHA) 2015 Scientific Sessions. The study was published online in the European Journal of Heart Failure the same day.
Dr Douglas Mann
This was a small trial with no sham procedure, and the hydrogel beads were implanted via an open thoracotomy, which is invasive in these very sick patients, Mann pointed out. There were also more deaths in the Algisyl group (nine, 22.5%) than in the control group (four, 10.5%), although the trial was not powered for mortality.
Nevertheless, these 1-year data build on promising 6-month results, which were presented at last year's AHA meeting and were recently published[2]. The procedure received CE approval in Europe in 2014, and the US Food and Drug Administration recently gave the company investigational device exemption (IDE) for a premarket approval (PMA) study, which will enroll 240 patients, Mann announced.
"Overall, I think this is an important step in terms of extending our understanding of this intervention," assigned discussant Dr Adrian F Hernandez (Duke Clinical Research Institute, Durham, NC) told the press. Although unanswered questions remain, this study showed that "the effects of peak VO2 were durable and actually perhaps augmented [from 6 months to 12 months], and [it also provided] some additional information regarding the long-term safety. Finally, [it showed that this treatment] can be feasible . . . and addresses an important need in severe heart failure."
New Way to Mend a Failing Heart?
Algisyl is an inert hydrogel derived from brown marine algae that is injected into the mid LV wall, where it remains as a permanent scaffold "that's intended to reduce LV-wall stress and prevent or reverse the progression of HF," Mann explained.
AUGMENT HF, a multicenter, open-label trial of Algisyl vs usual care in patients with advanced heart failure in Australia and Europe, met its primary 6-month efficacy end point, and it has prespecified 12-, 18-, and 24-month secondary safety and efficacy end points.
To shore up the left ventricle, surgeons perform a limited thoracotomy and then inject 12 to 15 beads of Algisyl gel in the mid LV wall, in a procedure that takes about 80 minutes, Mann said.
A total of 73 patients were randomized and treated in AUMENT HF. At 12 months, 13 patients had died and two patients did not have complete data, leaving 58 patients for the current analysis.
These patients had a mean age of 62.3 years; slightly more than half had ischemic HF (57.7%), and the rest had nonischemic HF (42.3%).
The three longer-term efficacy outcomes continued to show significant improvement compared with placebo.
The 12-month change in VO2max from baseline was 2.10 mL/kg/min higher in the treated group than in the control group (95% CI 0.96–3.24, P<0.001). This surpassed the 1.24 mL/kg/min improvement in VO2max compared with the control group that was seen at 6 months.
The 12-month median 6-minute walk distance was 101 m greater in the treated group than in the control group (P<0.001).
Last, patients in the Algisyl-treated group had a greater improvement in NYHA functional class. At 12 months, of the 26 Algisyl-treated patients, 85% were class 2 or class 1 (14 patients and eight patients, respectively), and the rest were class 3 (four patients). In contrast, of the 32 patients in the control group, only 25% (eight patients) were class 2, and 75% (24 patients) were class 3.
Patients in the treated group were three times more likely to have an adverse event, but the incidence of serious adverse events was similar in both groups.
However, compared with patients in the control group, patients in the treated group had substantially lower rates of worsening heart failure (34.2% vs 15.0%) or sustained ventricular arrhythmias (13.2% vs 2.5%).
The upcoming larger trial will have the same end points as AUGMENT HF, said Mann. "Also around the corner is an endovascular approach . . . to implant the beads percutaneously, which I think will be a significant advance," he added.
Cardiologists Are Cautiously Hopeful
Asked to weigh in, three cardiologists told heartwire from Medscape that they were hopeful but were waiting for more hard outcomes in a larger trial.
"The take-home is that this is a challenging [end-stage] population of patients and we need novel approaches," said AHA spokesperson Lori J Mosca (Columbia University, New York, NY). "These early results are very promising, but we have to keep in mind this is invasive, and the mortality data really need to be looked at very closely as we move forward in trials."
"I hope that the work on this will continue, because I think that the early results are very favorable," AHA spokesperson Dr Sidney C Smith Jr (University of North Carolina at Chapel Hill) echoed. The researchers need to follow up on the observation of increased mortality in Algisyl-treated patients, which might be due to chance since the numbers were small in this trial, he added. "Although this is clearly preliminary research, it is "not the kind of thing where I say 'this needs to be shut down,' " he said. "I'm impressed."
Press briefing moderator Dr Raymond J Gibbons (Mayo Clinic, Rochester, MN) said, "I think that any of these trials, when they meet their end point at the first round, the logical next step is larger numbers and more data to confirm the results and give a better handle on safety."
Mann is on the scientific advisory board for LoneStar Heart. Disclosures for the coauthors are listed in the article. Hernandez receives research support from Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Genentech, Janssen, Merck, Novartis, and Portola and honoraria from Amgen, AstraZeneca, Merck, Janssen, and Novartis. Gibbons is a consultant for Lantheus Medical Imaging, Astellas Pharmaceuticals, Stealth Peptides, and Mobility (Lenovo).
Heartwire from Medscape © 2015
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Cite this: AUGMENT HF: Functional Gains With LV Gel Scaffold Durable at 1 Year - Medscape - Nov 18, 2015.
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