Correspondence

Fluvastatin in Patients Undergoing Vascular Surgery

N Engl J Med 2009; 361:2186-2188November 26, 2009

Article

To the Editor:

The results of the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography III (DECREASE III) study (Current Controlled Trials number, ISRCTN83738615) reported on by Schouten et al. (Sept. 3 issue)1 should be interpreted carefully. The reduction of cardiac complications observed in the fluvastatin group cannot be generalized to all patients undergoing vascular surgery. Indeed, inclusion criteria required at least 51 points on a prespecified risk index. This requirement excluded 356 patients from the study. In addition, 798 patients who were already receiving statins were excluded; this was probably an initial response to the guidelines on perioperative evaluation from the American College of Cardiology and the American Heart Association which recommended the use of these drugs.2 These guidelines were published after the results of our randomized, controlled trial on this subject.3 In that trial, we found that the use of 20 mg of atorvastatin reduced cardiac events in all patients referred for vascular surgery. Despite the fact that we did not have prespecified risk index as an exclusion criterion, we conclude that the available evidence does not provide support for the use of statins to reduce the risk of cardiac events among all patients.

Danielle Menosi Gualandro, M.D.
Daniela Calderaro, M.D., Ph.D.
Bruno Caramelli, M.D., Ph.D.
Heart Institute, São Paulo, Brazil
danielle.gualandro@incor.usp.br

3 References

1. 1

   Schouten O, Boersma E, Hoeks SE, et al. Fluvastatin and perioperative events in patients undergoing vascular surgery. N Engl J Med 2009;361:980-989
   Full Text | Web of Science | Medline

2. 2

   Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. Circulation 2007;116:e418-e499
   CrossRef | Web of Science | Medline

3. 3

   Durazzo AE, Machado FS, Ikeoka DT, et al. Reduction in cardiovascular events after vascular surgery with atorva statin: a randomized trial. J Vasc Surg 2004;39:967-975
   CrossRef | Web of Science | Medline

To the Editor:

Schouten et al. report that fluvastatin reduced postoperative cardiac complications in the DECREASE III trial. However, ischemia was monitored by means of continuous 12-lead electrocardiographic (ECG) recording for only 48 hours after surgery and followed later by three samples of 12-lead ECG recordings and troponin T measurements only on postoperative days 3, 7, and 30. The widely separated timing of the subsequent ECG and troponin T data cannot account for the daily changes in the rates of ischemia, myocardial infarction, and death from cardiovascular causes shown in Figure 1 of the article. Moreover, since the rates of death and myocardial infarction did not diverge until postoperative day 3, the initial 48 hours of continuous monitoring for ischemia contributed minimally to the reported differences.

Myocardial infarction was diagnosed if two of three criteria (chest pain, ECG changes, or an elevation in troponin T level) were present. This definition is inconsistent with the referenced universal definition of myocardial infarction published in 2007.1

Multiple studies have shown that typical ischemic chest pain is rare postoperatively, ST-segment elevation ischemia occurs in only 0 to 2% of events, and short-duration ST-segment deviation has minimal, if any, effect on postoperative cardiac complications and survival.2-4

Giora Landesberg, M.D., D.Sc.
Hadassah Medical Center, Jerusalem, Israel
gio@cc.huji.ac.il

Scott W. Beattie, M.D., Ph.D.
University of Toronto, Toronto, ON, Canada

Joseph S. Alpert, M.D.
University of Arizona College of Medicine, Tucson, AZ

4 References

1. 1

   Thygesen K, Alpert JS, White HD, et al. Universal definition of myocardial infarction. Circulation 2007;116:2634-2653
   CrossRef | Web of Science | Medline

2. 2

   Landesberg G, Shatz V, Akopnik I, et al. Association of cardiac troponin, CK-MB, and postoperative myocardial ischemia with long-term survival after major vascular surgery. J Am Coll Cardiol 2003;42:1547-1554
   CrossRef | Web of Science | Medline

3. 3

   Priebe HJ. Perioperative myocardial infarction -- aetiology and prevention. Br J Anaesth 2005;95:3-19
   CrossRef | Web of Science | Medline

4. 4

   Landesberg G, Beattie WS, Mosseri M, Jaffe AS, Alpert JS. Perioperative myocardial infarction. Circulation 2009;119:2936-2944
   CrossRef | Web of Science | Medline

Author/Editor Response

Statins are recommended for patients with peripheral arterial disease. The focus of the DECREASE III trial was whether these drugs should be initiated before surgery in patients who have not received statins, since safety concerns had been raised in previous guidelines.1 The study by Durazzo et al. evaluated the effect of atorvastatin in patients who had undergone vascular surgery. Though the trial was not powered to assess 30-day postoperative outcomes, there was a trend suggesting a beneficial effect of atorvastatin (odds ratio, 0.23; 95% confidence interval, 0.09 to 1.30).2 The present study was sufficiently powered and confirmed these initial results. We disagree with Gualandro et al. that the population in the current study did not reflect daily clinical practice. In fact, the study population was comparable to that in the study by Durazzo et al., since 91% of the patients in that trial had a risk index of more than 51 points (Durazzo AE: personal communication) and 20% of the patients in the current study were at low risk for postoperative cardiac events.3 The recent guidelines on perioperative care from the European Society of Cardiology also recommend perioperative statins for all patients who undergo vascular surgery.4

With regard to the comments by Landesberg et al.: symptoms of perioperative cardiac complications are difficult to recognize in the early postoperative phase. Therefore, objective tests such as ECG monitoring and troponin T measurements are of critical importance. These tests were repeated with a low threshold for suspecting complications, adding information beyond the prespecified times of monitoring. However, approximately 75% of episodes of myocardial ischemia occurred within the first 3 days after surgery. Continuous ECG monitoring improved the understanding of the pathophysiology of perioperative cardiac events. Indeed, the vast majority of patients had ST-segment depression, but fatal cardiac events were preceded by ST-segment elevations in nearly all patients. Since the study protocol was designed in 2003, the definitions of myocardial infarction from 2000 were used and should have been referenced.5 However, all patients who were classified as having a myocardial infarction had troponin T levels above the 99th percentile in addition to either symptoms of ischemia or ECG changes that were indicative of new ischemia, or the development of pathologic Q waves in the ECG; this definition of myocardial infarction was recommended in the universal definition proposed in 2007.

Olaf Schouten, M.D., Ph.D.
Sanne E. Hoeks, M.Sc.
Don Poldermans, M.D., Ph.D.
Erasmus Medical Center, Rotterdam, the Netherlands
d.poldermans@erasmusmc.nl

5 References

1. 1

   Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al. ACC/AHA/NHLBI Clinical Advisory on the use and safety of statins. Circulation 2002;106:1024-1028
   CrossRef | Web of Science | Medline

2. 2

   Durazzo AE, Machado FS, Ikeoka DT, et al. Reduction in cardiovascular events after vascular surgery with atorva statin: a randomized trial. J Vasc Surg 2004;39:967-975
   CrossRef | Web of Science | Medline

3. 3

   Boersma E, Poldermans D, Bax JJ, et al. Predictors of cardiac events after major vascular surgery: role of clinical characteristics, dobutamine echocardiography, and beta-blocker therapy. JAMA 2001;285:1865-1873
   CrossRef | Web of Science | Medline

4. 4

   Poldermans D, Bax JJ, Boersma E, et al. Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery: The Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in Non-cardiac Surgery of the European Society of Cardiology (ESC) and endorsed by the European Society of Anaesthesiology (ESA). Eur Heart J 2009 August 27 (Epub ahead of print).
   

5. 5

   Myocardial infarction redefined -- a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513
   CrossRef | Web of Science | Medline