Systematic Review: Comparing Routine and Selective Invasive Strategies for the Acute Coronary Syndrome

In their systematic review, Qayyum and colleagues report that there is no mortality benefit or reduction in nonfatal myocardial infarction from an early invasive strategy compared with conservative management for patients with non-ST elevation acute coronary syndromes. (1) We have conducted two prior systematic reviews on this topic, and have demonstrated a significant improvement in mortality and non-fatal myocardial infarction in the same population, over a mean follow-up of 2 years. (2,3) Specifically, on analysis of 7 trials with 8,375 patients, we had noted that the incidence of all-cause mortality was 4.9% in the early invasive group, compared with 6.5% in the conservative group (risk ratio [RR]=0.75, 95% confidence interval [CI] 0.63 to 0.90, p=0.001), and the incidence of nonfatal myocardial infarction was 7.6% in the invasive group, versus 9.1% in the conservative group (RR=0.83, 95% CI 0.72 to 0.96, p=0.012). (2) Men and troponin positive patients were especially benefited. (3)

The main reason for this discrepancy stems from the fact that three of the trials included in the authors' meta-analysis (VANQWISH, MATE and TIMI-3B) were conducted before the current era of glycoprotein IIb/IIIa inhibitors and coronary stents, and hence do not reflect current standards of care. Both glycoprotein IIb/IIIa inhibitors and stents have been shown to significantly increase event-free survival in patients with acute coronary syndromes, with the former even associated with a significant survival advantage. (4,5) Moreover, as the authors note, a significant proportion of patients in VANQWISH and TIMI-3B also received fibrinolytics, which is no longer considered first-line therapy for acute coronary syndromes when percutaneous coronary intervention is easily available. (1) In fact, in our meta-analysis, we had noted a non- significant increase in mortality (RR, 1.31; 95% CI, 0.98 to 1.75) at 6 to 12 months when these three trials were considered separately. (2)

We are reminded again that it is critically important that systematic reviews reflect current practice. In doing so, we strongly believe that the current body of evidence demonstrates a mortality benefit and hence supports early invasive therapy compared with conservative management in patients with non-ST elevation acute coronary syndromes.

References:

1. Qayyum R, Khalid MR, Adomaityte J, Papadakos SP, Messineo FC. Systematic review: comparing routine and selective invasive strategies for the acute coronary syndrome. Ann Intern Med. 2008; 148: 186-96.

2. Bavry AA, Kumbhani DJ, Rassi AN, Bhatt DL, Askari AT. Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of contemporary randomized clinical trials. J Am Coll Cardiol. 2006; 48: 1319 -25.

3. Bavry AA, Kumbhani DJ, Quiroz R, Ramchandani SR, Kenchaiah S, Antman EM. Invasive therapy along with glycoprotein IIb/IIIa inhibitors and intracoronary stents improves survival in non-ST-segment elevation acute coronary syndromes: a meta-analysis and review of the literature. Am J Cardiol. 2004; 93: 830-5.

4. Karvouni E, Katritsis DG, Ioannidis JP. Intravenous glycoprotein IIb/IIIa receptor antagonists reduce mortality after percutaneous coronary interventions. J Am Coll Cardiol. 2003; 41: 26-32.

5. Biondi-Zoccai GG, Abbate A, Agostoni P, Burzotta F, Lotrionte M, et al. Long-term benefits of an early invasive management in acute coronary syndromes depend on intracoronary stenting and aggressive antiplatelet treatment: a metaregression. Am Heart J. 2005; 149: 504-511.

Conflict of Interest:

None declared

The discrepancy between our results and the two meta-analysis (2, 3) cited by Dr. Kumbhani is not due to inclusion of older trials but rather differences in study inclusion criteria. The two meta-analyses by Dr. Kumbhani and his group included ISAR-COOL trial (4). We excluded ISAR-COOL trial as it did not compare routine invasive with selective invasive strategy; instead, it compared 3-5 days of antithrombotic treatment with less than 6-hour treatment before coronary intervention. As almost all patients in this trial underwent angiography within 5 days of randomization, this trial does not have a selective invasive strategy arm and, in our view, should not be included in a comparative systematic review of the two strategies.

Dr. Kumbhani contends that only those trials should be included in the systematic review that performed coronary intervention according to current standards of care. One can extend this contention and argue that only those trials should be included in systematic review that met current standards of care for both coronary intervention and pharmacological therapy. This will leave only one trial, ICTUS (5), in the systematic review as it used both glycoprotein IIb/IIIa and coronary stents and had more than 90% of patients on statins. This trial, that provided currently accepted standard of care to enrolled patients, found a significant benefit of selective invasive strategy over routine invasive strategy.

References

1. Qayyum R, Khalid MR, Adomaityte J, Papadakos SP, Messineo FC. Systematic review: comparing routine and selective invasive strategies for the acute coronary syndrome. Ann Intern Med. 2008;148(3):186-96.

2. Bavry AA, Kumbhani DJ, Quiroz R, Ramchandani SR, Kenchaiah S, Antman EM. Invasive therapy along with glycoprotein IIb/IIIa inhibitors and intracoronary stents improves survival in non-ST-segment elevation acute coronary syndromes: a meta-analysis and review of the literature. Am J Cardiol. 2004;93(7):830-5.

3. Bavry AA, Kumbhani DJ, Rassi AN, Bhatt DL, Askari AT. Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of contemporary randomized clinical trials. J Am Coll Cardiol. 2006;48(7):1319-25.

4. Neumann FJ, Kastrati A, Pogatsa-Murray G, et al. Evaluation of prolonged antithrombotic pretreatment ("cooling-off" strategy) before intervention in patients with unstable coronary syndromes: a randomized controlled trial. JAMA. 2003;290(12):1593-9.

5. Hirsch A, Windhausen F, Tijssen JG, Verheugt FW, Cornel JH, de Winter RJ. Long-term outcome after an early invasive versus selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome and elevated cardiac troponin T (the ICTUS trial): a follow-up study. Lancet. 2007;369(9564):827-35.

Conflict of Interest:

None declared