Open Artery Hypothesis Revisited

ABSTRACT & COMMENTARY

Synopsis: Late angioplasty post initial anteroseptal Q-wave MI reduces left ventricular volumes and decreases subsequent cardiac events.

Source: Horie H, et al. Circulation 1998;98:2377-2382.

Late reperfusion after myocardial infarction (MI) has been associated with improved survival in observational studies, but many believe a randomized trial is necessary to prove the open artery hypothesis. Thus, Horie and associates from Japan conducted a randomized trial to assess the effects of late reperfusion post-MI by angioplasty on long-term clinical outcomes. Patients with first acute Q-wave anteroseptal MI more than 24 hours from symptom onset and total occlusion of the culprit artery were recruited if they were younger than 80 and had no confounding co-morbidities. Of the 101 consecutive patients admitted, 83 met these criteria and formed the study group. They were randomized in the catheterization laboratory to angioplasty or medical therapy (no thrombolysis). Mean time to reperfusion after symptom onset was eight days in the angioplasty group, and all but three patients were successfully reperfused (93%). At six months, all underwent repeat catheterization. Among the angioplasty patients, two had reoccluded and 12 restenosed, but all 14 had successful reperfusion procedures. Among the medical patients, five had spontaneously reperfused. Left ventricular angiography showed no difference in the two treatment groups at six months in ejection fraction, but left ventricular volumes were significantly smaller in the angioplasty group. Cardiac death occurred in one patient in the angioplasty group and four patients in the medical group (P = 0.06) and other cardiac events were significantly lower in the angioplasty group (3 vs 14; P < 0.001). Horie et al conclude that late angioplasty post-initial anteroseptal Q-wave MI reduces left ventricular volumes and decreases subsequent cardiac events.

Comment by Michael H. Crawford, MD

This paper was published in Circulation because it is the first randomized trial of the open artery hypothesis, not because it is a great study. Remember, the first three rules of scientific publishing are priority, priority, and priority. That is not to say that this is a bad study; it is just limited in scope and underpowered to show a survival benefit alone. In order to reduce confounding variables and thereby keep the study population low, they studied patients with first anteroseptal MIs and totally occluded arteries who presented more than 24 hours after symptoms. Revascularization was accomplished 1-42 days post-MI with a higher success rate initially (93%) and at six months (94%), compared to prior observational studies of more diverse populations. In this select group, cardiac events over five years were clearly reduced beginning at about 10 months post-MI and there was a strong trend (P = 0.06) toward reduced mortality. These data clearly support previous reports of an association between an open infarct artery and improved outcomes and fly in the face of those that would restrict post Q-wave MI catheterization based upon a lack of evidence supporting its benefit.

The mechanism of this benefit is not evident from the study, but the reduction in left ventricular volumes (systolic and diastolic) is interesting, especially since ejection fraction was not altered by angioplasty. Perhaps there is a reduction of remodeling that reduces left ventricular wall stress and prevents arrhythmias or improves diastolic function. There are no data to support the former (i.e., Holter Monitor) but most of the deaths in the medical group were due to heart failure despite an average ejection fraction of 50% in this group. Abrogation of residual peri-infarction ischemia that otherwise would have led to a heart failure death cannot be excluded since no tests for ischemia were reported. We also do not know if vessel patency was maintained after six months. Finally, the use of stents and platelet glycoprotein 11b/111a inhibitors could enhance the results in the angioplasty group. Clearly, the walls are cracking around the guards at the post-MI catheterization gates and the cracks are due to the increasing weight of evidence.