The Big Heart Disease Lie

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Coronary heart disease is the single largest cause of morbidity and mortality in the United States. Each year, approx 1.1 million people in the United States will suffer an acute myocardial infarction (MI)—650,000 of these will be first attacks and 450,000 will be recurrent. Nearly 500,000 will result in death, half dying before reaching a hospital (1,2).

Mortality from acute Mi has been dramatically reduced through successful myocar-dial reperfusion strategies with thrombolytics or primary percutaneous transluminal coronary angioplasty (PTCA). The 6.3% mortality in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) I trial is approximately half the mortality for patients with acute MI reported in the immediate prethrombolytic era (3). Early achievement of reperfusion of the infarct-related artery is directly related to reduced mortality and morbidity—through myocardial salvage and reduction of the degree of left ventricular dysfunction (4).

The issue of time to treatment with these artery-opening therapies has been of great interest, in particular since the advent of thrombolytic therapy. There is clear evidence from both the original animal work and extensive clinical trials with all agents supporting a time-dependent relationship between early reperfusion and outcome (5). The time benefit curve is very steep, with maximum benefit accruing to those patients who are

From: Contemporary Cardiology: Management of Acute Coronary Syndromes, Second Edition Edited by: C. P. Cannon © Humana Press Inc., Totowa, NJ

Fig. 1. Absolute 35-d mortality reduction vs treatment delay. Small closed dots, information from trials included in the FTT analysis; open dots, information from additional trials; small squares, data beyond scale of XY cross—the linear (34.7-1.6X) and nonlinear (19.4-0.6 X + 29.3 x — 1) regression lines are fitted within these data and weighted by the inverse of the variance of the absolute benefit for each data point; black squares, average effects in six time to treatment groups (area of squares inversely proportional to the variance of absolute benefits). Reproduced with permission from Boerma et al. The Lancet 1996;348:771-775.


Fig. 2. Myocardial Infarction, Triage, and Intervention (MITI) Trial: 30-d mortality benefits.


Fig. 2. Myocardial Infarction, Triage, and Intervention (MITI) Trial: 30-d mortality benefits.

reperfused within the first 1 to 2 h after symptomatic occlusion. Analysis of clinical trials provides evidence that equates 1 h of delay in reperfusion to an increase in absolute mortality by approx 1%, or 10 lives per 1000, and this is a linear relationship in the first 4-6 h following symptom onset (5,6) (Fig. 1). Also, the classic Myocardial Infarction, Triage, and Intervention (MITI) trial, examining prehospital vs hospital-initiated throm-bolysis, found that all patients who received this treatment, within 70 min of symptom onset, experienced a 30-d mortality rate of only 1.2% compared to 8.7% for those treated 70 min or more. Similarly, infarct size was 4.9% for those treated within 70 min vs 11.2% for those treated thereafter (7) (Fig. 2). Given the clear cut relationship between delay and mortality, a 30-min delay will result in 5 lives lost per 1000, and a 1-h delay results in 10 lives lost per 1000 (5,6). Therefore, it is imperative that time be considered as much of an adjunct to the treatment of patients with acute MI, as proposed by Cannon et al., as drugs that have been shown to have efficacy in reducing mortality (8).

Unfortunately, the full potential of reperfusion and other therapies is not realized by patients who need these treatments, because many patients do not reach the hospital on time to benefit from them. Approximately one in five patients with acute MI present to the hospital within 1 h of symptom onset, whereas slightly less than one-quarter of patients delay seeking care by 6 or more hours, with no change in these distributions over time (9). The National Registry of Acute Myocardial Infarction-2 analysis of data on 272,651 patients showed that only 31% were eligible for reperfusion therapy. Of these eligible patients, 41% were considered ineligible because symptoms of acute MI were present for more than 6 h prior to diagnosis (10).

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