(Circulation. 2000;102:147.)
© 2000 American Heart Association, Inc.
Editorials |
Acute and Delayed Benefits of ß-Blockers During Coronary Intervention
True, True and Unrelated
From the Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, Va.
Correspondence to George W. Vetrovec, MD, 1200 E. Broad Street, W6N-Room 607, PO Box 980036, Richmond, VA 23219. E-mail gvetrove{at}hsc.vcu.edu
Key Words: Editorials • creatine kinase • ß-blockers • angioplasty
The early outcomes after coronary intervention have improved remarkably, particularly in the stent era. Patients previously at risk for acute closure and possibly urgent bypass surgery now go home the next day. The risk of bypass surgery is likewise markedly reduced. Nonetheless, subgroups of patients remain at increased risk for adverse outcomes, both short-term and over subsequent follow-up. Predictors of adverse outcome include slow or no reflow, side branch occlusion, diffuse multivessel disease, and preprocedure thrombotic or unstable lesions, as determined by angiography and clinical history. Furthermore, the risk of embolic complications seems to increase with the use of nonballoon devices.1
Importantly, the risk of short-term and late adverse outcomes seems partially related to the presence and extent of the release of creatine kinase (CK)-MB2 or other markers3 after the intervention. However, many of the patients at increased risk on the basis of CK-MB release were previously defined as successes because of the lack of a recognized, acute, in-laboratory event with no electrocardiographic changes. Although initially controversial, the importance of CK-MB release in terms of short-term and late outcome is now convincing.4 5 6 7 8 Overall, there seems to be an up to 30% risk of increased CK-MB release after a "successful" coronary intervention,2 particularly in complex interventional procedures, often involving nonballoon devices.9
Coincident with the data regarding CK-MB release, the use of IIb/IIIa platelet antagonists has evolved with evidence that use of these agents reduces the risk of CK-MB elevation and, in the case of abciximab, is associated with an improved late outcome, especially after coronary intervention.6
In this issue of Circulation, Sharma et al10 address an important question relating to the possibility of further improving interventional outcome using preprocedure ß-blocker therapy. In a prospective, nonrandomized trial of 1675 consecutive patients undergoing coronary intervention, short-term and intermediate outcomes were compared for patients who received peri-interventional ß-blocker treatment (38.4% of population) and those who did not. The incidence of CK-MB elevation was significantly lower in the subgroup of patients receiving ß-blockers (13.2% versus 2.2%). By multivariant analysis, the use of prior ß-blocker therapy seemed to be the only independent factor for the reduced CK-MB release. Furthermore, the intermediate outcome for patients on ß-blocker therapy revealed a lower late mortality compared with those patients not on ß-blockers, although this difference did not seem to be related to the early reduction in CK-MB release.
In this study, there was a relatively high use of devices, with 25% of patients having rotational atherectomy alone and an additional 31% having combined rotational atherectomy and stent placement. Interestingly, in high-risk patients, such as those with multivessel disease, vein graft lesions, and American College of Cardiology/American Heart Association type C lesions, the ß-blocker subset had an overall lower CK-MB release. The fact that the late outcome seemed to be unrelated to CK-MB release suggests different operative mechanisms for these cardioprotective benefits.
The authors postulate that the benefits of ß-blockers in lower acute CK release are secondary to a reduction in heart rate and blood pressure, thus lowering myocardial oxygen consumption in the setting of microvascular ischemia and providing local protection. Although this explanation may be sufficient, it is also possible that because the rise in CK-MB was greatest in patients with diffuse disease, other factors could affect the result. ß-blockers may further reduce arterial sheer force by decreasing the systolic rate of blood pressure rise, which in an already instrumented artery may be another factor reducing microemboli and, thus, CK release.
A second possible explanation is a ß-blocker–abciximab interaction. In this particular trial, the only IIb/IIIa described is abciximab, which was previously demonstrated to improve late outcome.11 Although the overall use of abciximab was not significantly different in the ß-blocker and no ß-blocker patients, it is noteworthy that patients in the "high risk" subgroups noted above (who were perhaps more likely to receive abciximab) had the greatest reduction in CK release. Further support for this suggestion is provided by the Platelet Receptor inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and symptoms (PRISM-PLUS) study.12 In this study, which used tirofiban for unstable patients both with and without coronary intervention, the use of ß-blockers provided significant additional benefits in both absolute and relative risk reductions. Sharma and colleagues7 do not break out the relative comparative efficacy of abciximab versus a ß-blocker, but additive effects are an intriguing and possibly favorable interaction that may occur with IIb/IIIa agents.
The late benefit of pre- and periprocedure ß-blocker treatment is important. The fact that ß-blockers improve late outcome separate from CK release may well relate to the favorable post–myocardial infarction characteristics of ß-blockers.13 14 15 16 Gottlieb et al14 showed that ß-blocker use was associated with an improved outcome in Medicare-aged patients undergoing coronary intervention and/or experiencing non–Q-wave myocardial infarctions. Thus, the intermediate benefits seen by Sharma et al10 are not unexpected. However, these data may also suggest that ß-blockers have favorable effects in patients with a small CK-MB rise and an otherwise open artery.
The original ß-blocker trials, such as the ß-Blocker Heart Attack Trial (BHAT),13 demonstrated the greatest benefit in patients with larger myocardial infarctions and higher risk profiles. However, this trial was performed before the routine recanalization of coronary vessels during infarction, and whether ß-blockers provide peri-infarction benefits in patients with an open artery after infarction (and often with a limited extent of infarction secondary to acute recanalization) has been a consistent question. The intermediate benefits reported by Sharma et al10 for ß-blocker treatment, despite the fact that many of the infarctions were small on the basis of CK-MB release and most often associated with an open artery, continue to support the aggressive use of ß-blocker therapy during acute myocardial infarction, even in the area of acute revascularization.
I have 2 notes of caution. First, Sharma et al10 do report that a trend toward greater slow flow and coronary spasm was associated with ß-blocker use. Although this may not be a significant clinical problem given the protective effects of ß-blockers, it is also possible that the concomitant use of other drugs, such as nitrates or even calcium-channel blocking agents, to maximize vasodilatation in conjunction with the protective effects of ß-blockers may be very favorable. Maximum drug effect could possibly be obtained with cocktails including ß-blockers, nitrates, calcium-channel blocking agents, IIb-IIIa antagonists, and low-molecular-weight heparin, and they may provide the best overall short-term and late outcomes. Finally, although the study by Sharma et al10 was prospective, it was not randomized; thus, the possibility of unrecognized bias exists. For the moment, however, this trial provides the most definitive information to date suggesting a benefit of ß-blockers. It certainly supports the need for randomized clinical data relating to drug therapy before and after coronary intervention to optimize short-term and late clinical results.
Footnotes
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
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