PARIS – Removal of circulating C-reactive protein (CRP) via selective extracorporeal apheresis shows considerable promise as a safe and effective adjunctive therapy for ST-segment elevation MI in an interim analysis of an ongoing, multicenter, German, randomized, proof-of-concept trial, Christoph D. Garlichs, MD, reported at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
In the first 64 of 80 scheduled, randomized ST-segment elevation MI (STEMI) patients participating in the CRP Apheresis in the Acute Myocardial Infarction (CAMI 1) trial, CRP apheresis plus standard European Society of Cardiology guideline-recommended STEMI therapy, including complete coronary revascularization, resulted in a 47% reduction in infarct area by cardiac MRI performed 2-7 days post infarct, compared with standard therapy alone, which is the primary study endpoint, reported Dr. Garlichs, a cardiologist and head of the internal medicine clinic at Deaconess Hospital in Flensburg, Germany.
Cardiac MRI will be repeated in all 80 CAMI 1 participants 12 weeks post-MI, Dr. Garlichs added at a session on outside-the-box technologies in the cardiovascular pipeline.
The theory behind CRP apheresis in the treatment of MI is that high serum levels of CRP during acute cardiac events are a key player in the resultant myocardial damage because CRP activates the complement system, promoting destruction of stressed cardiac myocytes by macrophages. This is CRP as a mediator of myocardial tissue damage, not in the protein’s more familiar role as a systemic inflammation marker reflecting damage to coronary arteries, which is a whole different story.
“If you remove CRP from the system, complement will not be activated and myocardial cells regain viability,” Dr. Garlichs explained.
This has been established in animal studies, with elucidation of the specific mechanisms involved. The same process figures prominently in cerebral damage from stroke, he continued.
The device utilized for CRP apheresis in CAMI 1 is the, produced by Henningsdorf, Germany–based Pentracor and already approved for marketing throughout Europe. The treatment regimen consists of two treatment sessions, each lasting roughly 4 hours. The first begins 24 hours after STEMI symptom onset, the second comes 24 hours later. If the serum CRP is above 30 mg/L a few hours after the second session, a third session is given 24 hours later.
In each session, 6,000 mL of plasma gets filtered via peripheral venous access. CRP levels were reduced by an average of 70%, and there have been no side effects or safety issues to date.
Discussant and entrepreneur, said that if the magnitude of infarct size reduction, as measured by cardiac MRI, holds up in the final results, the device would be approvable for treatment of acute MI based upon Food and Drug Administration criteria.
Dr. Garlichs said that once CAMI 1 is finished, a similar randomized trial in stroke patients is planned.
“But you’ve got to get it approved,” said Dr. Fitzgerald, a cardiologist who has founded and/or been a principal in more than a dozen U.S. medical device start-up companies and serves as director of the Center for Cardiovascular Technology at Stanford (Calif.) University. “You can’t jump to the head until you get the heart approved.”
Towards that goal, he suggested that the investigators focus heavily on STEMI patients who have large anterior MIs, which he called “the tombstones.”
“I don’t care what the therapy is, it doesn’t work unless you look at anterior MIs,” said Dr. Fitzgerald.
As it turns out, Dr. Garlichs said, in fact most of the STEMI patients enrolled in CAMI 1 have had anterior MIs.
Asked if CRP apheresis might have a potential role in the treatment of RA and other autoimmune disorders marked by elevated CRP, Dr. Garlichs said indeed it does. But he noted that, in order to utilize the procedure on a regular long-term basis to treat a chronic disease such as RA as opposed to an acute cardiac or cerebrovascular event, a slew of new clinical trials will be required.
Dr. Garlichs serves as a consultant to Pentracor, which sponsored CAMI 1.