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J Thorac Cardiovasc Surg 2008;136:1100-1101
© 2008 The American Association for Thoracic Surgery

Letter to the Editor

Statins with equivalent lipid-lowering capacity exhibit differential effects on atrial fibrillation after cardiac surgery

Antonios Kourliouros, MRCS, Neil Roberts, MRCS, Marjan Jahangiri, FRCS

Department of Cardiothoracic Surgery, St George's Hospital, London, UK

To the Editor:

We read with interest the study by Lertsburapa and colleagues1Go highlighting the beneficial effects of preoperative statin therapy on atrial fibrillation (AF) after cardiac surgery. This nested cohort analysis constituted part of the Atrial Fibrillation Suppression Trials I, II, and III, which evaluated the effects of oral amiodarone, atrial septal pacing and preservation of aortic fat pad on AF after cardiac surgery. A total of 555 patients were studied. Postoperative AF occurred in 27.8% of the patients receiving statins versus. 36.6% not receiving statins, demonstrating a statistically significant reduction in postoperative AF in response to statin therapy.

In an attempt to correct for the confounding effects of such variables as age, preoperative AF, and valve surgery, Lertsburapa and colleagues1Go performed a stepwise multivariate regression analysis, which confirmed the beneficial impact of statin treatment on postoperative AF. However, it is well-established that in nonrandomised comparative studies, multivariate analysis alone may not be sufficient to adjust for treatment-selection bias and other balancing methods will have to be employed.2Go

Lertsburapa and colleagues1Go suggest a dose-dependent effect of statins on postoperative AF. Atorvastatin ≥40 mg or equivalent doses conferred the greatest effect when compared with no statins. Atorvastatin ≥20 mg but <40 mg, and <20 mg equivalents also conferred an incremental reduction in AF, albeit not statistically significant. Statin types were converted into atorvastatin equivalents based on their lipid-lowering properties as previously evaluated by efficacy comparison trials.3Go The division of statin doses to high, intermediate and low is conventionally based on their lipid-lowering efficacy, but it is now well-established that statins exhibit ‘pleiotropic’ properties. Lertsburapa and colleagues have used this arbitrary division by creating dose-equivalents, which may have influenced the accuracy of their results.

Our group has recently examined the effect of varying doses of statins on postoperative AF in 623 patients undergoing cardiac surgery.4Go We concur with Lertsburapa and colleagues that statins significantly reduce AF and that this effect is dose-related. However, following propensity score analysis, we identified that the antifibrillatory effect of statins did not match their lipid-lowering capacity. More specifically, simvastatin 20 mg, which is an atorvastatin 10 mg equivalent based on lipid-lowering efficacy, demonstrated a statistically significant effect on postoperative AF when compared to no statins (OR 2.32, 95%CI 1.30-4.11), whereas atorvastatin 10 mg had no impact on AF (OR 1.05, 95%CI 0.55-1.99). In addition, the beneficial effect of simvastatin 40 mg (OR 3.89, 95%CI 2.03-7.45), which is an atorvastatin 20 mg equivalent, was significantly more pronounced than the effect conferred by atorvastatin 20 mg (OR 1.99, 95%CI 1.00-3.94) or atorvastatin 40 mg (OR 2.76, 95%CI 1.24-6.15) when compared to no statins.

In conclusion, there is enough evidence to support the antiarrhythmic role of statins through mechanisms independent of their lipid-lowering activity, such as modulation of inflammatory response and atrial structural remodeling.5Go However, we suggest that since there is an indication of differential effect of equivalent statin doses, appropriate methodological measures need to be in place when assessing outcomes beyond their lipid-lowering capacity.

References

  1. Lertsburapa K, White CM, Kluger J, Faheem O, Hammond J, Coleman CI. Preoperative statins for the prevention of atrial fibrillation after cardiothoracic surgery. J Thorac Cardiovasc Surg 2008;135:405-411.[Abstract/Free Full Text]
  2. Blackstone EH. Comparing apples and oranges. J Thorac Cardiovasc Surg 2002;123:8-15.[Free Full Text]
  3. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses. Am J Cardiol 2003;92:152-160.[Medline]
  4. Kourliouros A, De Souza A, Roberts N, Marciniak A, Tsiouris A, Valencia O, et al. Dose-related effect of statins on atrial fibrillation after cardiac surgery. Ann Thorac Surg 2008;85:1515-1520.[Abstract/Free Full Text]
  5. Liu T, Li L, Korantzopoulos P, Liu E, Li G. Statin use and development of atrial fibrillation: A systematic review and meta-analysis of randomized clinical trials and observational studies. Int J Cardiol 2008;126:160-170.[Medline]



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