Researchers report progress in treating MI

Central among sessions at this year's European Society of Cardiology 2005 Annual Meeting, held in Stockholm, Sweden, were those focused on the pharmacological treatment of myocardial infarction (MI). Noteworthy among those were two meetings looking specifically at the risks of such therapy, one at timing, and a fourth at an attempt to combine therapies already proven to be successful separately.

Interventional cardiologists find that performing a PCI (percutaneous coronary intervention-e.g., stenting) on MI patients is much easier when the infarct-related artery is already open. While primary PCI (direct mechanical intervention in the coronary arteries with balloon catheters and usually stents) has been shown to be superior to fibrinolysis, fibrinolysis has a long record of successfully opening arteries.

Frans Van de Werf, M.D., lead author for the ASSENT-4 PCI trial, asked whether giving a fibrinolytic agent before PCI would improve outcomes. ASSENT-4 PCI included patients with large acute MIs with PCI planned. Half the patients received a bolus of the fibrinolytic tenecteplase (TNK) plus a single dose of unfractionated heparin (UFH) followed by PCI, while the other half received UFH and PCI only. Van de Werf is professor of cardiology, Gasthuisberg University Hospital, Leuven, Belgium.

The similarities ceased at this point. Re-MI, abrupt vessel closure, and need for target vessel revascularization were significantly more common in the TNK + PCI group. Furthermore, 30-day mortality was significantly higher in the TNK + PCI group (P=0.04), and total stroke, intracranial hemorrhage, and ischemic stroke were significantly higher, as well. Nonintracranial bleeding complications also significantly favored PCI alone. Van de Werf concluded that a strategy of routine immediate PCI following full-dose fibrinolytic cannot be recommended at this point.

Damping down platelet activation is another well-established strategy in MI treatment. Earlier clinical trial reporting showed that clopidogrel (Plavix, Sanofi-Aventis) helped open blocked arteries and decreased the odds of a second MI by 31%. Giles Montalescot, M.D., Hôpital Pitié-Salpêtrière, Paris, France, studied 1,863 patients in the CLARITY-TIMI-28 trial who had gone on to PCIs, with prevention of major adverse cardiovascular events as the endpoint.

The trial's sought to determine whether, after initial pharmacologic therapy, preangioplasty treatment with clopidogrel would be superior to clopidogrel initiated at the time of PCI. Patients were randomized to a preangioplasty (two to eight days) 300-mg clopidogrel loading dose followed by 75 mg (daily) or to placebo. Following angioplasty, open-label clopidogrel was given in both groups, per physician recommendation.

Overall, patients receiving clopidogrel pretreatment had a 36% reduction in risk of having a closed infarct-related artery (87% for clopidogrel pretreatment versus 81% with placebo) or death or MI before the angiogram. In addition, they had a 20% reduction in odds of cardiovascular death, MI, or urgent revascularization by 30 days. Also, among the pretreatment PCI patients, risk of cardiovascular death, MI, or stroke was reduced 46%. Montalescot stated that for every 100 patients undergoing PCI, four major cardiovascular events were prevented by clopidogrel pretreatment.

The drive to keep MI patients' arteries open with drugs and devices has led to reduced mortality and morbidity rates in recent decades. Successfully combining drugs, however, entails the opposite risk: excessive bleeding. The main goals of the OASIS-5 trial were to test for noninferiority in efficacy (combined death, MI, and refractory ischemia at nine days) between a newer versus an older low-molecular weight heparin (LMWH) (fondaparinux, Arixtra, GlaxoSmithKline, versus enoxaparin, Lovenox, Aventis), and superiority for the newer agent with regard to safety (bleeding events).