Calcium antagonists are associated with reduced mortality after cardiac surgery: A propensity analysis

Wijeysundera DN, Beattie WS, Rao V, Ivanov J, Karkouti K. J Thorac Cardiovasc Surg 2004;127:755-762.

Reviewer: Mark A. Chaney, MD
Associate Professor
University of Chicago

Abstract: Previous observational studies have questioned the effectiveness of perioperative calcium channel blockers yet have failed to correct for selection biases. These investigators performed a prospective observational cohort study using a propensity score technique for risk adjustment in order to evaluate the effects of calcium channel blockers on cardiac surgical mortality. Six thousand, six hundred, nineteen patients undergoing nontransplant cardiac surgery at a single institution were studied. Propensity scores for calcium channel blocker use were constructed for the entire sample and for the subgroup (5,222 patients) that underwent coronary artery bypass grafting. Calcium channel blocker adjusted odds ratio for in-hospital mortality after cardiac surgery was determined by using multiple logistic regression and propensity matched-pairs analyses. A subgroup analysis was performed for patients who underwent coronary artery bypass grafting. Calcium channel blocker adjusted odds ratio for mortality was determined by using propensity score matched-pairs analyses. Calcium channel blockers were associated with significantly reduced cardiac surgical mortality after adjustment with both multiple logistic regression (p=0.028) and propensity score matched-pairs analyses (p=0.042). Calcium channel blockers were also associated with reduced mortality (p=0.044) among patients who underwent coronary artery bypass grafting. These investigators conclude that, after adjustment for baseline differences, calcium channel blockers were associated with significantly reduced mortality after cardiac surgery. This benefit also extended to the subgroup that underwent coronary artery bypass grafting. Thus, a large randomized controlled clinical trial evaluating use of perioperative calcium channel blockers seems warranted.

Comments: Calcium channel blockers have multiple potentially beneficial physiologic effects which improve balance between myocardial oxygen supply and demand (negative chronotropy, negative inotropy, decreased afterload, coronary vasodilation). Other potential clinical benefits include decreased postoperative tachyarrhythmias, including atrial fibrillation. However, previous studies are contradictory whether or not perioperative use of calcium channel blockers is truly beneficial, for a wide variety of reasons (suboptimal study design, selection bias, inadequate risk adjustment, inadequate power, etc.) These investigators undertook a prospective observational cohort study aiming to determine effects of calcium channel blockers on in-hospital mortality following cardiac surgery while adjusting for selection biases with propensity score techniques. They demonstrated that calcium channel blockers were associated with reduced mortality and free of major side effects. While these drugs are negative chronotropes, negative inotropes, and platelet inhibitors, they found no evidence that they increased the incidence of related postoperative complications. Furthermore, the benefits of calcium channel blockers appeared to be consistent, regardless of whether patients were or were not receiving beta-blockers preoperatively. These results contradict prior observational studies and support a recent meta-analysis. Why do these discrepancies exist? Possible reasons are succinctly summarized in the two accompanying Editorials "Perioperative calcium-channel blockade in cardiac surgery: The good, the bad, and the issues" (J Thorac Cardiovasc Surg127:622-624, 2004) and "Calcium antagonists and good results: Association or causation?" (J Thorac Cardiovasc Surg 127:625-626, 2004). On one hand, this is a large, well-designed observational clinical study that relied on a robust clinical information system to address the question being asked and demonstrated a relatively large (roughly 50%) reduction in mortality, implying that these results could save many lives. On the other hand, this study did not differentiate between the different classes of calcium channel blockers and, despite propensity score analysis, association does not prove causality. While the benefits of perioperative use of calcium channel blockers remain potential, the results of this investigation (along with others) justify the need for prospectively investigating perioperative calcium channel blocker use among cardiac surgical patients. For perspective, at one time, preoperative aspirin and beta-blockers were relative contraindications to surgical intervention, whereas at present time, compelling data documents the benefits of perioperative therapy of both. Will calcium channel blockers go down the same path? Time, and properly designed prospective investigations, will tell.

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Table of Contents:

• President's Message
• Journal Supplement to Disappear


• Literature Reviews
  • Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial
  • Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs
  • Calcium antagonists are associated with reduced mortality after cardiac surgery: A propensity analysis
  • One-year coronary bypass graft patency: A randomized comparison between off-pump and on-pump surgery angiographic results of the PRAGUE-4 Trial
  • Tissue Doppler Echocardiography


• Drug and Innovation Reviews
  • Angiotensin modulation and cerebroprotection
  • Lung volume reduction

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