Role of Clinical Presentation

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strategy compared with the conservative strategy (5-year incidence, 19.9% vs. 24.5; P = .009).14

The benefit from the invasive strategy compared with the conservative strategy is not uniform across the spectrum of acute coronary syndromes. The major, more recent clinical studies, FRISC-2, TACTICS-TIMI 18, and RITA-3,15-17 consistently show that the benefit from the invasive strategy is linked to various markers of risk, whereas patients without these risk markers may be treated according to the same principles as patients with stable angina. The risk factors that could be established in previous studies include elevated myocardial marker proteins, dynamic ST-segment changes, ongoing myocardial ischemia, hemodynamic instability, and diabetes mellitus.18

This concept of routine invasive strategy was recently challenged by the ICTUS trial.19 The ICTUS trial accepted the need for coronary revascularization in most patients but challenged troponin levels as the sole criterion for revascularization. The ICTUS trial randomized 1200 patients to a routine invasive versus a selective invasive strategy. To be included, patients had to have unstable angina with elevated cardiac troponin levels. During 1-year follow-up, 54% of the patients in the selective invasive arm and 76% of the patients in the routine invasive arm underwent coronary revascularization. It is noteworthy that the rate of coronary revascular-ization in the conservative arm of ICTUS was as high as in the invasive arm of RITA-3. During 1-year follow-up, the primary end point of ICTUS (death, MI, and hospital readmission for unplanned coronary revascularization) was not significantly different between the two treatment arms. Secondary analyses, however, revealed a significant increase of MIs in the invasive arm (15% vs. 10%), which could be attributed to an early hazard of the intervention. The ICTUS trial is consistent with other previous trials that suggested that there is a need for revascu-larization in the majority of patients presenting with high-risk acute coronary syndromes. As a new aspect, ICTUS suggests that there may be an optimal rate of coronary revascularization, above which the potential benefit from revascularization is reversed by peri-interventional complications. It appears that in low-risk patients the long-term benefit from revas-cularization cannot compensate for the incidence of peri-interventional complications. In this respect, ICTUS challenges the elevation of myocardial marker proteins as the only criterion for recommending revascularization. Using a Bayesian approach to the analysis of all available or published studies on treatment strategies in acute coronary syndromes, including ICTUS, it can be demonstrated that there is a more than 94% probability that the invasive approach will yield a benefit with respect to death and MI and a 75% probability that this benefit will be a least 5% (Fig. 6-2).11

In summary, the majority of patients with high-risk acute coronary syndromes benefit from coronary revascularization with respect to death and MI. The results of RITA-3 and FRISC II even suggest a

Probability of benefit with invasive strategy (%)

Probability of benefit with invasive strategy (%)

Figure 6-2. Bayesian analysis of trials comparing conservative versus invasive strategy in acute coronary syndromes with respect to death and myocardial infarction during 6- to 12-month follow-up. The curves show the probability of a benefit with the invasive strategy, of the extent specified, based on sequential analysis of the trials in chronologic order. The dotted horizontal line represents the boundary for conventional statistical significance. (From Neumann FJ, Kastrati A, Schwarzer G: New aspects in the treatment of acute coronary syndromes without ST-elevation: ICTUS and ISAR-COOL in perspective. Eur Heart J Suppl 2007;9: A4—A10.)

Figure 6-2. Bayesian analysis of trials comparing conservative versus invasive strategy in acute coronary syndromes with respect to death and myocardial infarction during 6- to 12-month follow-up. The curves show the probability of a benefit with the invasive strategy, of the extent specified, based on sequential analysis of the trials in chronologic order. The dotted horizontal line represents the boundary for conventional statistical significance. (From Neumann FJ, Kastrati A, Schwarzer G: New aspects in the treatment of acute coronary syndromes without ST-elevation: ICTUS and ISAR-COOL in perspective. Eur Heart J Suppl 2007;9: A4—A10.)

long-term survival benefit with prudent use of coronary revascularization.

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