Immediate percutaneous transluminal angioplasty reduced the combined occurrence of death and nonfatal reinfarction in patients with acute myocardial infarction
ACP J Club. 1993 July-Aug;119:2. doi:10.7326/ACPJC-1993-119-1-002
Grines CL, Browne KF, Marco J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med. 1993 Mar 11;328:673-9.
To compare the effectiveness of immediate percutaneous transluminal coronary angioplasty (PTCA) with thrombolytic therapy in patients with acute myocardial infarction (MI).
Randomized controlled trial with 6-month follow-up.
11 clinical centers in the United States and 1 in France.
395 patients (mean age 60 y, 73% men) who presented within 12 hours of the onset of MI (ST-segment elevation ≥ 1 mm in ≥ 2 contiguous electrocardiographic [ECG] leads). Exclusion criteria were dementia, complete left bundle-branch block, cardiogenic shock, or a high risk for bleeding.
All patients were initially treated with heparin intravenously (10 000-unit bolus) and aspirin (325 mg). Patients were then randomly allocated to immediate PTCA without previous thrombolytic therapy (n = 195) or to intravenous tissue plasminogen activator (t-PA; 100 mg [or 1.25 mg per kg of body weight for patients weighing < 65 kg] over 3 h) followed by conservative care (n = 200). In both treatment groups, heparin was administered intravenously for 3 to 5 days, and patients were routinely treated with nitroglycerin, aspirin, and diltiazem. The use of β-blockers and intravenous lidocaine was left to the discretion of the attending physician.
Main outcome measures
Death and nonfatal reinfarction (recurrent chest pain lasting > 30 minutes with new ST-segment elevation and either emergency angiographic confirmation of an occluded vessel or recurrent elevation of cardiac enzymes).
Analysis was by intention to treat. 175 patients (90%) assigned to PTCA had angioplasty with a 97% success rate. 5 patients assigned to PTCA died in the hospital compared with 13 in the t-PA group (P = 0.06) (Table). Reinfarction or death in the hospital occurred in more patients in the PTCA group than in the t-PA group (P = 0.02) (Table). Hemorrhagic strokes occurred more frequently in patients who received t-PA (P = 0.05) (Table). Left ventricular ejection fraction assessed by radionuclide ventriculography at rest and during exercise at 6 weeks did not differ between groups.
Immediate percutaneous transluminal coronary angioplasty reduced the combined occurrence of nonfatal reinfarction and death when compared with t-PA therapy in patients with acute myocardial infarction.
Source of funding: Not stated.
For article reprint: Dr. C.L. Grines, Division of Cardiology, William Beaumont Hospital, 3601 West Thirteen Mile Road, Royal Oak, MI 48073-6769, USA. FAX 248-551-5596.
Table. Immediate percutaneous transluminal coronary angioplasy (PTCA) vs intravenous tissue plasminogen activator (t-PA) at 6 months in patients with acute myocardial infarction*
|Outcomes||PTCA||t-PA||RRR (95% CI)||NNT (CI)|
|Deaths||3%||7%||61% (-4 to 85)||Not significant|
|Reinfarction or death||5%||12%||57% (15 to 79)||15 ( 8 to 72)|
|Hemorrhagic stroke||0%||2%||100%||50 (26 to 1676)|
*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
PTCA after thrombolytic therapy results in a high risk for hemorrhage at the access site and frequently results in recurrent occlusion of the infarct-related artery. PTCA has been compared with streptokinase in a small trial and now the larger trials of Grines and colleagues and Zijlstra and colleagues extend these observations, providing clear evidence for the improvement of clinically important outcomes, as well as residual coronary stenosis and left ventricular function.
As clinicians and health care systems attempt to translate the findings into improvements in clinical practice, the following considerations are essential. These studies were done in institutions with the capacity to provide expert PTCA and on-call revascularization surgery on an emergency basis. Only 18% of hospitals in the United States do angioplasty, and a much smaller percentage have facilities of the standard available in these studies. The reduction in hospital stay in the Grines' study was statistically significant, but a 1-day difference is not likely to be economically important, given the increased requirement for cardiac catheterization, PTCA, and bypass surgery. Comparative economic analyses of these approaches, including utilities, have been conducted but data are incomplete and short-term (1).
Hemorrhage was an important cause of morbidity and death in the thrombolytic groups. The rates of these complications were considerably higher than in many recent trials, suggesting that the anticoagulant regimen may have been excessive. Newer dose regimes for t-PA administration may allow higher patency rates and fewer hemorrhages. Ongoing clinical trials are examining modifications of these regimens.
The principal outcome in both trials is a composite of ischemic events. There was random assignment of treatment and blinded ECG and cineangiogram evaluation, although caregivers were not blinded to treatment allocation. An additional concern is the high rate of recurrent ischemic outcomes, PTCA, and bypass surgery in the t-PA group in both trials, in contrast to that in the Thrombolysis in Myocardial Infarction-II trial.
These trials showed a remarkable achievement by participating centers in doing PTCA with a high patency rate, great speed, and a low risk for death and hemorrhage. It is, therefore, likely that centers with a similar capacity for angioplasty by expert operators, within 1 hour of hospital admission with acute MI and with standby revascularization surgery, will be able to achieve clinical outcomes of survival, recurrent ischemia, and hemorrhage that are at least as satisfactory as they are with commonly used regimens of thrombolytic therapy and anticoagulation.
Hence, in a suitably equipped hospital, a patient with a clear contraindication to thrombolytic therapy (recent major surgery, recent trauma, etc.) might be offered primary PTCA as an excellent alternative. Further, a patient with no contraindication to coronary thrombolysis might also benefit from primary PTCA. The benefit found in the present trials, however, was modest and was detected in a setting of relatively high risk for bleeding complications and recurrent ischemia in the comparison population in relation to that observed in previous large clinical trials. Hence, the true benefit may be less than that observed in these 2 studies. A recent meta-analysis provided additional data (2). The economic consequences of offering primary PTCA in appropriately equipped hospitals are incompletely defined.
Many hospitals do not have expert emergency PTCA and bypass surgery available. Therefore, patients arriving with acute MI in these hospitals could not derive the benefits observed in these studies. Before any marked expansion of such facilities could be advocated, more data are required to clarify the comparative benefits in terms of clinically important outcomes using optimal strategies for thrombolytic and adjuvant treatments. Further economic analysis of the 2 approaches are essential to delineate the incremental cost per life-year gained (with appropriate consideration of quality of life). Finally, any redirection of resources to expand this capacity for the management of acute MI will require rigorous assessment of the optimal allocation of a finite resource.
John A. Cairns, MD
McMaster UniversityHamilton, Ontario, Canada
1. Stone GW, Grines CL, Rothbaum D, et al., for the PAMI Trial Investigators. Analysis of the relative costs and effectivenes of primary angioplasty versus tissue-type plasminogen activator: the Primary Angioplasy in Myocardial Infarction (PAMI) trial. J Am Coll Cardiol. 1997;29:901-7.