New drug aids heart surgery

For over 20 years, angioplasty – formally known as percutaneous transluminal coronary angioplasty (PTCA) – has provided people suffering from coronary artery disease (CAD) with a comparatively non invasive alternative to open heart surgery. It’s a very effective procedure, repeated some 25,000 times a year in Canadian hospitals, but it’s not perfect: Perhaps as many as 30 per cent of patients who have the operation suffer a recurrence of arterial narrowing, known as restenosis, within six months of the initial procedure.

To thwart this complication, scientists have come up with a new class of agents known as GPIIb/IIIa inhibitors. The first to be approved for clinical use in Canada is a chemical mouthful called abciximab, more easily pronounced by its brand name, ReoPro. ReoPro’s designed to block the IIb/IIIa (two b, three a) receptor, or binding site, on the surface of platelets, the blood cells responsible for initiating clotting. Block the receptor, and the platelets can’t clump together; in effect, ReoPro makes them too slippery to clot.

Dr. Eric Cohen is an interventional cardiologist and director of the Cardiac Catheterization Laboratory at the Sunnybrook Health Scies Centre in Toronto. He and his colleagues took part in a series of multicentre trials designed to evaluate ReoPro’s effectiveness in preventing complications following angioplasty – trials that were halted in midstream when it became apparent the drug was so effective it wouldn’t have been ethical to continue giving a placebo to patients in the control group.

“Obviously we’re excited about this new technology,” Cohen says. “It extends the usefulness of the [angioplasty] procedure, and allows us to do it with what we perceive to be more safety. And this is the first of what’s going to be a number of drugs that work on this same IIb/IIIa receptor, so I think over the next few years, we’re going to see lots of developments in this area of cardiology.”

In an angioplasty procedure, a thin tube called a guiding catheter is inserted (typically) into the femoral artery in the groin, where the vessel is fairly large and close to the surface. It’s threaded straight up the abdominal aorta, around the arch of the aorta and into the heart until it “finds” the opening of the coronary artery. The procedure is done under x ray, with blood vessels outlined in dye so the physician can follow the catheter to where the vessel walls are clogged and narrowed with a buildup of fatty deposits known as plaque. Once it’s reached the deadly narrows, the guiding catheter becomes a pipeline for a second catheter, this one tipped with an inflatable balloon that’s used to compress the plaque and widen the artery.

Sometimes the artery recloses after an angioplasty, often in the first hours or days afterward, usually because of a blood clot. “When we put the balloon in and stretch the artery,” Cohen explains, “it’s doing a bit of damage – controlled damage, but still damage to the lining cells of the artery.

“The body has a pretty elaborate system for responding to damage and trying to heal. It perceives any tearing in the inner layer of the artery wall as needing patching, and that sets in process the clot formation, of which the platelets clumping together is the first step. Sometimes that process goes too far, and a clot forms that can block the artery altogether — and that’s dangerous because it can cause a heart attack. This is the one of the major areas where ReoPro can help prevent that.”

Restenosis can also happen months after the operation, again because of scar tissue forming in the artery. Unfortunately, it’s difficult to predict which patients will undergo late renarrowing; it’s easier to predict which patients are likely candidates for early complications, “but even that’s somewhat limited,” Cohen says. Administering ReoPro “reduces the chance of this early blockage right across the board, in everybody. Since we’re not that good at figuring out who’s at risk for it, it makes the drug attractive to everyone.”

In fact, ReoPro (which is given in conjunction with heparin), showed a roughly equal beneficial effect in both men and women, and only a slightly lower benefit in people over as against under 65.

“You wouldn’t give this to patients who are actively bleeding,” Cohen says. “On the other hand, you have a very hard time doing an angioplasty on those kind of patients, because you can’t give them heparin, to thin the blood so it doesn’t form clots during or immediately after an operation.” Previous use of ReoPro isn’t an absolute contraindication, but using it again isn’t recommended – at the moment, at least. The drug acts as an antibody to the platelet receptor, but about six per cent of people who take it develop antibodies to the antibody – in other words, to ReoPro. “If those people receive the drug again, first of all, it may not work,” Cohen points out, “because it may be attacked by their antibodies to the drug. But they can also have reactions. Not so much allergic reactions, but it can make their platelet count go down quite dramatically.”

The danger there, of course, is you might not have enough platelets in your blood to form a clot if you do need to stem the tide, in case of a cut, say. Apart from that, the antibody doesn’t seem to have any adverse effect, because it appears to be specific to ReoPro. Catheterization labs across Canada have been using ReoPro in varying degrees for almost a year, the rate of use reflecting an economic reality: ReoPro’s expensive — about $1,650 for one time use.

Given that 25,000 angioplasties are done in Canada each year – a number that’s steadily rising – the drug could have a fairly hefty economic impact. However, ongoing American analysis may eventually demonstrate that ReoPro reduces complications enough to offset the added cost of the drug. More important, ReoPro may make it possible for someone not perceived as a potential candidate for surgery to have an angioplasty.

“That’s one of the areas where we’ve felt the impact in our practice,” Cohen says. “We believe it’s allowed us to extend the indications of the procedure, particularly to some patients at very high risk. They’re still high risk, even with the drug, but it diminishes the risk sufficiently that we feel we can go ahead with the procedure.”

And that’s the real bottom line.