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J Thorac Cardiovasc Surg 2004;127:622-624
© 2004 The American Association for Thoracic Surgery
Editorial |
a Departments of Surgery and Physiology, LSU Health Sciences Center, New Orleans, La, USA
Received for publication October 29, 2003; accepted for publication November 3, 2003.
* Address for reprints: T. Bruce Ferguson, Jr, MD, LSU Cardiovascular Outcomes Research Group, 3535 Bienville St, Suite E-325, New Orleans, LA 70119, USA
tbruceferg732{at}pol.net
| See related articles on page 625 and 755.
|
For years, cardiothoracic surgeons have focused on care factors that affect outcomes. These efforts have directly resulted in documented declines in mortality and morbidity from major cardiac surgical interventions with time, despite an increase in severity of the risk profile of patients coming to surgical intervention.1-3
Part of this focus has been to recognize pharmacologic agents that could affect outcomes, mostly in an adverse manner. At one time, preoperative aspirin, ß-blocker, and clopidogrel therapies were relative contraindications to surgical intervention. Now most patients undergoing coronary artery bypass grafting (CABG) are on aspirin therapy before the operation, there are compelling data documenting the benefits of preoperative ß-blocker therapy4 and perioperative aspirin therapy5,6 in patients undergoing CABG, and many surgeons administer clopidogrel before off-pump CABG.
This reversal in our thinking about ß-blockers4 and to some extent aspirin6 therapy was inspired by large, multicenter observational studies rather than randomized clinical trials. These observational studies have provided scientific data to reevaluate previous practices in light of newer information. By using sufficiently large patient populations, controlling for such confounding factors as site and provider effects, and using statistical techniques such as propensity score analyses, important information has been obtained that has improved the quality of care. In the case of ß-blocker therapy, these findings challenged surgical providers to change not only their own practice but also the practice of their referring cardiologists.7
In this issue of the Journal, Wijeysundera and colleagues8 have done just such a reevaluation of the role of calcium-channel blockers (CCBs) as preoperative pharmacologic therapy in patients undergoing cardiac surgery. Through the years, CCBs have been investigated in cardiac surgery as cardioplegia additives,9,10 as antiarrhythmic agents,11 and as additives to ameliorate vasospasm in radial artery grafts.12 Wijeysundera and colleagues8 raise the question of whether CCBs might convey a mortality and morbidity benefit in patients undergoing cardiac surgery. The primary pharmacologic effects of CCBs addressed here are the antianginal and potentially myoprotective effect of CCBs in patients undergoing the stress of surgical intervention.13 This important study is of interest because it highlights both the good and the bad related to calcium-channel blockade.
The good
On the "good" side of the ledger, this is a well-designed observational clinical study that relies on a robust clinical information system to address the question being asked. The scientific analysis uses appropriate techniques in the careful evaluation of these observational data. Wijeysundera and colleagues8 have asked an important clinical question about a class of cardiovascular drugs that most cardiac surgeons have not thought much about during the past 5 years. And finally, the study and its presentation highlight both the importance of these carefully analyzed observational studies and the limitations in their interpretation. Clearly, this study suggests that further investigation of the role of preoperative CCBs is warranted.
This was a single-center study, and therefore, as Wijeysundera and colleagues8 point out, site confounding cannot be ruled out as possibly contributing to the results. For example, the risk-adjusted mortality for the CABG subset was somewhat lower than national US data4; this could be due to a lower risk study population at this site, differences in the risk models, or other indeterminate factors that are specific to the study institution.
The bad
On the "bad" side of the ledger related to calcium-channel blockade, it is important to recognize that this study could not differentiate between different classes of CCBs. The adverse cardiovascular effects of short-acting, dihydropyridine calcium antagonists are well-documented.14,15 This is a potentially important confounding issue in light of the relatively diverse negative inotropic effects, conduction system effects, and coronary vascular resistance effects of the different subtypes of these drugs.11,13
Table 1 in the article of Wijeysundera and colleagues8 shows that the percentage of patients in this study receiving both CCBs and ß-blocker therapy was significantly higher than that of those receiving ß-blocker therapy but not CCBs. This illustrates an additional difficulty with interpretation of the study, that of separating preoperative ß-blocker therapy effects on outcomes from CCB effects on outcomes. This study confirms previous studies4,16 documenting the benefit of preoperative ß-blocker therapy (Table 3 in the Wijeysundera and colleagues8 article). While the Society of Thoracic Surgeons database analysis4 did not address CCB use, the study of Weightman and coworkers16 did not document CCBs to be of benefit, in contrast to the study of Wijeysundera and colleagues.8 However, preoperative therapy with CCBs does appear not to lessen a survival benefit in patients receiving both drugs. In addition, CCBs may provide some independent benefit (overall data set P value .42, as stated in Table 4 of the Wijeysundera and colleagues8 article, and CABG subset P value .44, as stated in Table 6 of the Wijeysundera and colleagues8 article), although this question can only ultimately be answered by a prospective trial.
Furthermore, although the study indicates that CCBs did not significantly increase morbidity, the odds ratios for major morbidity outcomes were 1.00 or greater for 8 of 10 morbidities assessed. Clearly, these results from this robust analysis should be confirmed.
The issues
The use of CCBs in ischemic heart disease has become more focused during the past 5 years, in part through the recognition that some CCBs can be harmful in certain subsets of patients.13 In addition, the effectiveness of combination therapies for angina control and prevention of myocardial infarction has been shown,13 and efforts to improve the use of ß-blockers in ischemic heart disease patients have been more successful.17,18 There was a substantial decline in patients presenting for surgery receiving CCBs in this study population, presumably reflecting a decline in the use of these drugs by the referring cardiologists. Unlike the situation with preoperative ß-blocker therapy, if the suggested benefit of CCB therapy in surgical patients is confirmed, a reversal of this trend on the part of the cardiology community would be necessary to realize this benefit in the surgical population.
One important finding from the study is the suggestion that CCBs may be of benefit in patients undergoing valve and combined valve and coronary procedures. Because the benefit of preoperative ß-blocker therapy has only been demonstrated for patients, undergoing CABG, the conclusion that a prospective investigation is warranted is timely and fully supportable.
The current American College of Cardiology and American Heart Association guidelines for management of patients with chronic stable angina recommend that long-acting CCBs be used in combination with ß-blocker therapy when initial treatment with ß-blockers is not successful or as a substitute for ß-blocker therapy when initial treatment leads to unacceptable side effects.13 Perhaps these recommendations can provide some structure for identifying patients in whom preoperative CCB therapy would be potentially beneficial in surgical revascularization and possibly other cardiac procedures.
Wijeysundera and colleagues8 have readdressed an important issue in cardiac surgery in their article. Without such observational analyses, the ability of the cardiac surgical community to successfully propose randomized trials, particularly pharmacologic trials, has been limited. Studies such as this create the opportunity to partner with the pharmaceutical industry to address the impact of preoperative medications on short-term outcomes. Perhaps more importantly, the cardiac surgical community needs to address the impacts of perioperative and postoperative pharmacologic therapies on long-term surgical outcomes.19,20 Through these efforts, cardiac surgeons and their care teams can positively influence both short-term outcomes and the long-term benefits of our surgical interventions. In turn, these efforts will greatly facilitate the placement of these surgical interventions, and their efficacy and appropriateness evaluations, into the larger context of chronic disease processes.
References
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