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Therapeutics

Aggressive therapy was ineffective for unstable angina and non-Q-wave MI

ACP J Club. 1994 Sept-Oct;121:43. doi:10.7326/ACPJC-1994-121-2-043

Related Content in the Archives
Conservative management was more effective than invasive management in acute non-Q-wave MI


Source Citation

The TIMI IIIB Investigators. Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction. Circulation. 1994 Apr;89:1545-56.


Abstract

Objective

To determine the effects of thrombolytic therapy and early invasive strategy in patients with unstable angina (UA) or non-Q-wave myocardial infarction (MI).

Design

2 × 2 factorial design randomized controlled trial of 6 weeks' duration.

Setting

31 medical centers in North America.

Patients

1473 patients (mean age 59 y, 66% men) with chest pain at rest that lasted ≥ 5 minutes but ≤ 6 hours within 24 hours of enrollment and accompanied by evidence of ischemic heart disease confirmed by electrocardiogram, coronary arteriogram, or positive exercise thallium scintigram. Exclusion criteria were a treatable cause of UA, MI within 21 days, coronary arteriography within 30 days, percutaneous transluminal coronary angioplasty within 6 months, coronary artery bypass grafting, pulmonary edema, systolic arterial pressure > 180 mm Hg or diastolic pressure > 100 mm Hg, contraindication to thrombolytic therapy or heparin, left bundle-branch block, coexisting severe illness, receipt of oral anticoagulants, or potential of being or becoming pregnant. Follow-up was 95%.

Intervention

Patients were randomly assigned to tissue plasminogen activator (tPA), 0.8 mg/kg (maximum 80 mg) (n = 729), or placebo (n = 744) and an early invasive strategy (cardiac catheterization, left ventricular angiography, and coronary arteriography) 18 to 48 hours after randomization (n = 740) or an early conservative strategy (cardiac catheterization and angiography) done only after failure of initial therapy (n = 733). All patients received conventional medical therapy for UA (β-blocker, calcium antagonist, and long-acting nitrate) plus heparin and aspirin.

Main outcome measures

For the tPA and placebo comparison, unfavorable outcomes included death, MI, or failure of initial therapy. For the invasive and conservative strategy comparison, unfavorable outcomes included death, MI, or positive exercise tolerance test (ETT).

Main results

The patients receiving tPA did not differ for death, MI, or failure of initial therapy when compared with those receiving placebo (P > 0.2) (Table). The occurrence of MI was higher in patients receiving tPA than in patients receiving placebo (7.4% vs 4.9%, P = 0.04). For early invasive compared with early conservative strategy, the groups did not differ for death, MI, or positive ETT (P > 0.2) (Table). Early invasive strategy resulted in shorter initial hospitalization and rehospitalization rates (P ≤ 0.01).

Conclusions

The addition of thrombolytic therapy to conventional medical therapy did not provide clinical benefit to patients with unstable angina or non-Q-wave MI. An early invasive strategy did not affect patient outcome.

Source of funding: National Heart, Blood, and Lung Institute; Core Laboratories; Data Coordinating Center.

For article reprint: Dr. E. Braunwald, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. FAX 617-278-0023.


Table. tPA vs placebo and early invasive vs early conservative strategy for unstable angina and non-Q-wave myocardial infarction (MI)*

Outcomes at 6 wk TPA Placebo RRR (95% CI) NNT
Death, MI, or failure of initial therapy 54.2% 55.5% 2.4% (-7 to 11) Not significant
Early invasive strategy Early conservative strategy
Death, MI, or positive exercise tolerance test 16.2% 18.1% 10.6% (-12 to 29) Not significant

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

Since the publication of TIMI IIIB comparing invasive with conservative strategies in patients with unstable angina and non-Q-wave MI, the VANQWISH trial of patients with exclusively non-Q-wave MI has been published and reviewed (1). In essence, these studies taken together fail to show a benefit for an invasive approach.

Despite these findings, interventional cardiology is a booming business, at least in the United States. The VANQWISH trial appears to have generated a large body of criticism and its findings are largely ignored, even in university centers. Beyond the cardiology division ledger sheet, reasons for the discrepancy between the data and the approach may include the fact that invasive strategies have consistently shown superior control of symptoms in stable angina (2, 3), are excellent tools for risk stratification, and may provide better outcomes in patients with acute MI compared with thrombolysis (4). Perhaps more compelling, but probably not measurable, is the pressure to shorten hospital stays, which can be readily accomplished by an early trip to the catheter lab, although with an unclear effect on overall costs. Further, the technical improvement in outcome and safety with stenting and intense platelet inhibition have lowered thresholds for doing percutaneous transluminal coronary angioplasty in such previously avoided high-risk patients as the elderly and those with renal failure, so proponents of catheter revascularization argue that trial results are not contemporary.

The issue is not how our practice should be influenced by these trials (a conservative strategy is justified, as is an interventional one), but why some trials are ignored while others are embraced. In the case of revascularization for unstable coronary disease, the reasons are complex and not just economic.

Steven Borzak, Md
Henry Ford HospitalDetroit, Michigan, USA


References

1. Boden WE, O'Rourke RA, Crawford MH, et al., for the Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial Investigators. Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. N Engl J Med. 1998;338:1785-92.

2. Rogers WJ, Bourassa MG, Andrews TC, et al., for the ACIP Investigators. Asymptomatic Cardiac Ischemia Pilot (ACIP) Study: outcome at 1 year for patients with asymptomatic cardiac ischemia randomized to medical therapy or revascularization. J Am Coll Cardiol. 1995;26:594-605.

3. RITA-2 Trial Participants. Coronary angioplasty versus medical therapy for angina: the second Randomised Intervention Treatment of Angina (RITA-2) trial. Lancet. 1997;350:461-8.

4. Weaver WD, Simes RJ, Betriu A, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review. JAMA. 1997;278:2093-8.