Literature Review |

Top Ten List in Myocardial Infarction* FREE TO VIEW

Steven M. Hollenberg, MD, FCCP
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*From the Sections of Cardiology and Critical Care Medicine, Rush Medical College, Chicago, IL.

Correspondence to: Steven M. Hollenberg, MD, FCCP, 1725 W. Harrison St, Suite 407, Chicago, IL 60612; e-mail: shollenb@rush.edu

Chest. 2000;118(5):1477-1479. doi:10.1378/chest.118.5.1477
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Abbreviation: MI = myocardial infarction

1. Goldberg RJ, Yarzebske J, Lessard D, et al. A two-decades (1975 to 1995) long experience in the incidence, in-hospital and long-term case-fatality rates of acute myocardial infarction: a community-wide perspective. J Am Coll Cardiol 1999; 33:1533–1539

The Worcester Heart Attack Study has followed up 5,270 residents of a metropolitan area since 1975. In this report examining incidence and mortality of acute myocardial infarction (MI) over a 20-year period, both age-adjusted incidence rates and risk-adjusted mortality rates were declining. These results suggest that primary and secondary prevention strategies are having a beneficial effect, but there is clearly room for improvement.

2. Grines CL, Cox DA, Stone GW, et al. Coronary angioplasty with or without stent implantation for acute myocardial infarction: Stent Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med 1999; 341:1949–1954

Primary angioplasty has been shown to be as effective as thrombolysis for patients with MI and is clearly preferred in some situations: patients with contraindications to thrombolytic therapy and those with cardiogenic shock (vide infra). The Stent Primary Angioplasty in Myocardial Infarction Study compared primary angioplasty with implantation of a heparin-coated stent, and showed improved angiographic outcomes and improvement in the combined outcome of death, reinfarction, stroke, and target-vessel revascularization (12.6% vs 20.1%; p = 0.02). Of note, however, all of this improvement was due to decreased target-vessel revascularization with stenting (7.7% vs 17.0%); 6-month mortality rates with stenting were actually slightly (but not significantly) higher (4.2% vs 2.6%; p = 0.27). Further refinement of stenting techniques and improved adjunctive antithrombotic regiments may result in improvements in hard outcomes after primary angioplasty, but this will need to be demonstrated in future trials. Why improved angiographic outcomes did not translate into a mortality benefit will require further investigation.

3. Ross AM, Coyne KS, Reiner JS, et al. A randomized trial comparing primary angioplasty with a strategy of short-acting thrombolysis and immediate planned rescue angioplasty in acute myocardial infarction: the PACT trial. J Am Coll Cardiol 1999; 34:1954–1962

Antman EM, Giugliano RP, Gibson CM, et al. Abciximab facilitates the rate and extent of thrombolysis: results of the Thrombolysis in Myocardial Infarction (TIMI) 14 trial. Circulation 1999; 99:2720–2732

The primary goal of reperfusion therapy for acute MI is rapid, complete, and sustained restoration of blood flow in the infarct-related artery. These two pilot studies tested new strategies in reperfusion for MI. The PACT (Plasminogen-activator Angioplasty Compatibility Trial) showed that a strategy of giving half-dose tissue plasminogen activator before proceeding to the catheterization laboratory for primary angioplasty was safe and resulted in increased arterial patency on arrival to the catheterization laboratory. The TIMI 14 trial found that a combination of platelet glycoprotein IIb/IIIa inhibition using abciximab with reduced-dose tissue plasminogen activator increased patency of the infarct artery at 90 min without appreciably increasing hemorrhagic combinations. Data with respect to clinical outcomes using these promising strategies are expected soon.

4. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock: SHOCK Investigators; should we emergently revascularize occluded coronaries for cardiogenic shock? N Engl J Med 1999; 341:625–634

Ryan, T. Early revascularization in cardiogenic shock: a positive view of a negative trial [editorial]. N Engl J Med 1999; 341:687–688

The SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial is a landmark study that randomized patients with cardiogenic shock to optimal medical management, including intra-aortic balloon pump and thrombolytic therapy, or to cardiac catheterization with revascularization using angioplasty or bypass surgery. The trial enrolled 302 patients, and showed a 30-day mortality of 46.7% in patients treated with early intervention and 56.0% in patients treated with initial medical stabilization; this did not reach statistical significance. At 6 months, the absolute risk reduction was significant at 12.8% (50.3% vs 63.1%). In patients < 75 years old, mortality at both 30 days (41.4% vs 56.8%; p < 0.01) and 6 months (53.1% vs 75.0%; p < 0.01) was improved significantly. The control group in this study (medical management) had a lower mortality than in prior studies; this may reflect the aggressive use of thrombolytic therapy and balloon pumping in these control subjects. Due to this improved survival in the control group, the study was underpowered to detect the primary end point (30-day mortality). The improved survival with revascularization at 6 months and in patients < 75 years old argues strongly for the superiority of a strategy of early revascularization in most patients with cardiogenic shock.

5. Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 11B trial. Circulation 1999; 100:1593–1601

Antman EM, Cohen M, Radley D, et al. Assessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarction: TIMI 11B-ESSENCE meta-analysis. Circulation 1999; 100:1602–1608

Anticoagulation with heparin is an important component of primary therapy for patients with unstable coronary syndromes without ST-segment elevation (unstable angina and non-Q-wave MI), but its anticoagulant effect can be unpredictable. Low-molecular-weight heparins have longer half-lives and produce a more predictable response. The TIMI 11B trial compared a 3-day infusion of unfractionated heparin to enoxaparin in patients with unstable angina/non-Q-wave MI, and found a significant reduction in the combined end point of death, MI, or urgent revascularization at 8 days and at 42 days (12.4% vs 14.5%, 17.3% vs 19.7%; both p < 0.05). When analyzed in combination with the similar ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events) trial using enoxaparin,1 enoxaparin produced a reduction of 20% in the harder end point of death and MI.

6. Invasive compared with noninvasive treatment in unstable coronary-artery disease: FRISC II prospective randomized multicentre study; FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Lancet 1999; 354:708–715

The FRISC II trial randomized patients with unstable coronary syndromes in a 2 × 2 factorial design to dalteparin (a low-molecular-weight heparin) or unfractionated heparin and to an early invasive strategy (early catheterization with revascularization if appropriate) or a noninvasive strategy catheterization (only for refractory symptoms). No significant effect of dalteparin was seen in the composite end point of death, MI, or need for revascularization at 3 months. Death or MI at 6 months was lower with the invasive strategy (9.4% vs 12.1%; p = 0.03). This study supports the use of an early interventional strategy, especially in patients with high-risk features (older age, rest pain, ECG abnormalities, elevated troponin T).

7. Buxton AE, Lee, KL, Fisher, JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease: Multicenter Unstained Tachycardia Trial Investigators. N Engl J Med 1999; 341:1882–1890

Patients with left ventricular dysfunction after MI are at risk for sudden arrhythmic death. The MUSTT (Multicenter UnSustained Tachycardia trial) randomized 704 patients with coronary artery disease, ejection fraction < 40%, and nonsustained ventricular tachycardia to antiarrhythmic therapy guided by electrophysiologic study or no antiarrhythmic therapy. Although the primary end point, cardiac arrest or sudden arrhythmic death at 5 years, was lower among the treatment group (25% vs 32%; p = 0.04), the most important finding of the study was that the reduction in this end point was almost entirely attributable to the use of implantable defibrillators (9% with defibrillators vs 37%; p < 0.001).

8. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342:145–153

While entry into this trial was not restricted to patients who had sustained MI, its importance merits mention in this forum. A total of 9,297 high-risk patients (age > 55 years, with a history of coronary artery disease, stroke, peripheral vascular disease or diabetes, and one other cardiovascular risk factor) were randomized to placebo or ramipril group and followed up for 5 years. Treatment with ramipril reduced overall mortality (10.4% vs 12.2%; p = 0.005), cardiovascular death (6.1% vs 8.1%; p < 0.001), MI (9.9% vs 12.3%; p < 0.001), and stroke (3.4% vs 4.9%; p < 0.001). Angiotensin-converting enzyme inhibitors were known to decrease mortality in patients with ejection fraction < 40% after MI. This study supports use of ramipril in all patients after MI.

9. Dupuis J, Tardif JC, Cernacek P, et al. Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes: the RECIFE (reduction of cholesterol in ischemia and function of the endothelium) trial. Circulation 1999; 99:3227–3233

Cholesterol-lowering agents reduce mortality and recurrent events after MI, but the mechanism by which they do so is unclear. The effects are too rapid to be explained by reduction in atherosclerotic burden. This trial used brachial artery ultrasound to demonstrate improved endothelial function in patients randomized to receive pravastatin after MI or unstable angina. This may be an important mechanism by which statins reduce cardiac events, and the study lends support to initiation of cholesterol-lowering therapy during the index hospitalization for MI.

10. de Lorgeril M, Salen P, Martin JL, et al. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 1999; 99:779–785

Epidemiologic data support the benefits of a Mediterranean diet in reducing cardiac risk. The Lyon Diet Heart Study was a carefully conducted trial randomizing patients to a Mediterranean-type diet or a prudent Western-type diet after an MI. The results were striking: a 65% reduction in cardiac death or MI at 5 years. This risk reduction occurred without differences in total or low-density lipoprotein cholesterol levels between the groups. This study suggests that relatively simple dietary changes may have dramatic effects in high-risk patients.

Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med, 1997; 337:447–452.




Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med, 1997; 337:447–452.
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