To the Editor: With regard to the results of the SYNTAX (Synergybetween PCI [percutaneous coronary intervention] with Taxusand Cardiac Surgery) study (ClinicalTrials.gov number, NCT00114972
[ClinicalTrials.gov]
)reported by Serruys et al. (March 5 issue),1 we wish to highlighta few factors that require clarification and may influence thedifferences observed between the study groups. The timing ofstrokes and rates of atrial fibrillation are not reported. Thesedata, in combination with the differences in pharmacologic therapiesbetween cohorts, may account for the excess number of strokesseen in the coronary-artery bypass grafting (CABG) cohort. Clarificationof the timing of strokes may help to explain whether they werethromboembolic or due to surgical handling of the aorta. Furthermore,the range and influence of PCI strategies, including the useof adjuvant intravascular ultrasonography adopted by the investigatorsfor complex lesions, are not reported; these factors could haveaffected restenosis rates.
Ravinay Bhindi, M.D., Ph.D. Gemma A. Figtree, M.D., D.Phil. Royal North Shore Hospital Sydney, NSW 2065, Australia
References
Serruys PW, Morice M-C, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009;360:961-972. [Free Full Text]
To the Editor: In the SYNTAX trial, the rate of stroke was significantlyhigher in the CABG group than in the PCI group (2.2% vs. 0.6%).The authors speculate that a lower rate of thienopyridine usein the CABG group contributed to this finding. However, althoughthe benefit of dual-antiplatelet therapy after PCI1 or acutecoronary syndrome2 is well established, the number of patientsin the CABG group with evidence-based indications for dual-antiplatelettherapy is not reported. Furthermore, the major trials comparingprolonged dual-antiplatelet therapy with aspirin alone haveshown only modest reductions in stroke, with relative risk reductionsranging from 10% to 21%.1,2,3 Thus, differential rates of thienopyridineuse played at most a minor role in the SYNTAX findings. Dataon the timing of strokes with respect to the intervention mayshed light on the extent to which stroke is an unavoidable riskof CABG versus a consequence of differential postinterventionmedical treatment.
Jonathan L. Edwards, M.D. Summa Barberton Hospital Barberton, OH 44203 jedwards{at}barbhosp.com
References
Steinhubl SR, Berger PB, Mann JT III, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;288:2411-2420. [Erratum, JAMA 2003;289:987.] [Free Full Text]
The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502. [Erratum, N Engl J Med 2001;345:1506, 1716.] [Free Full Text]
Bhatt DL, Fox KAA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006;354:1706-1717. [Free Full Text]
To the Editor: It is regrettable that the organizers of theSYNTAX trial chose to compare a percutaneous stenting procedurewith a standard CABG operation known to confer a risk of strokeof 1 to 2%.
Evidence is accumulating1,2,3 that the prevalence of procedure-relatedstroke is significantly diminished when "anaortic" techniques(i.e., surgery conducted without cardiopulmonary bypass andwithout aortic manipulation) are used. Three reports each describemore than 1000 such CABG operations, and with all these operationsthe rate of stroke was less than 0.3%.
To our knowledge, no randomized trial has compared standardwith anaortic coronary surgery; however, in our experience,it is a safe procedure in almost all patients with triple-vesseldisease or stenosis of the left main coronary artery.
The statement that the incidence of stroke is higher with surgerythan with stenting4 may be true for some operations, but itis not true for others. The incidence of stroke at Royal NorthShore Hospital, Sydney, from 2002 through 2006 and the incidenceof stroke at two other institutions are shown in Table 1.
Table 1. Rate of Stroke Associated with Anaortic CABG as Compared with Conventional On-Pump and Off-Pump CABG.
Russell J.L. Brereton, F.R.A.C.S. Royal North Shore Hospital Sydney, NSW 2065, Australia saltwaterotter{at}mac.com
Martin Misfeld, M.D., Ph.D. University of Lübeck 23538 Lübeck, Germany
Donald E. Ross, F.R.A.C.S. Royal North Shore Hospital Sydney, NSW 2065, Australia
References
Vallely MP, Potger K, McMillan D, et al. Anaortic techniques reduce neurological morbidity after off-pump coronary artery bypass surgery. Heart Lung Circ 2008;17:299-304. [CrossRef][Web of Science][Medline]
Calafiore AM, Di Mauro M, Teodori G, et al. Impact of aortic manipulation on incidence of cerebrovascular accidents after surgical myocardial revascularization. Ann Thorac Surg 2002;73:1387-1393. [Free Full Text]
Prapas SN, Panagiotopoulos IA, Hamed Abdelsalam A, et al. Predictors of prolonged mechanical ventilation following aorta no-touch off-pump coronary artery bypass surgery. Eur J Cardiothorac Surg 2007;32:488-492. [Free Full Text]
Lee TH, Hillis LD, Nabel EG. CABG vs. stenting — clinical implications of the SYNTAX trial. N Engl J Med 2009;360:e10 (Web only). (Available at http://NEJM.org.)
To the Editor: The study results reported by the SYNTAX investigatorsshow that at 12 months, the rate of stroke was significantlyhigher in the CABG group than in the PCI group (2.2% vs. 0.6%,P=0.003). At baseline, the proportion of patients with a historyof stroke was 3.9% in the PCI group and was slightly higher(4.8%) in the CABG group (P=0.33). Abundant data provide supportfor the use of statins in patients undergoing CABG unless statintherapy is contraindicated.1 Multiple meta-analyses have shownthe usefulness of statin therapy for primary and secondary preventionof stroke because of its lipid-lowering and pleiotropic effects.2,3Therefore, it is surprising to see that in the SYNTAX trial,only 74.5% of patients in the CABG group received statin therapy,whereas in the PCI group, 86.7% of patients received statintherapy (P<0.001). We believe it is important to know theincidence of stroke and also the contraindications to statintherapy, if any, in the subgroup in which subjects did not receivestatin therapy after CABG as compared with other subgroups.
Asit B. Shil, M.D. Thinzar Aung, M.D. Maureen P. Strohm,M.D. University of Southern California Los Angeles, CA 90015 shil{at}usc.edu
References
Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation 2004;110:1168-1176. [Erratum, Circulation 2005;111:2014.] [Free Full Text]
Rodríguez-Yáñez M, Agulla J, Rodríguez-González R, Sobrino T, Castillo J. Statins and stroke. Ther Adv Cardiovasc Dis 2008;2:157-66.
To the Editor: Serruys et al. compared the 1-year outcomes ofPCI with those of CABG in patients with multivessel disease.The reported superiority of CABG was based solely on a lowerrate of repeat revascularization in the CABG group. However,no information is provided on the criteria leading to repeatcoronary angiography. Was documentation of ischemia required?This information is critical, since it is known that the thresholdfor coronary angiography and for coronary revascularizationin clinical practice is lower after PCI than after CABG.1 Indeed,repeat surgery or PCI of a native vessel in patients who previouslyunderwent CABG is associated with an increased procedural riskand worse outcomes.2,3,4 Therefore, we would like to know whetherthe proportion of patients with any signs or symptoms of ischemiaat follow-up who underwent angiographic assessment and the proportionof such patients who subsequently underwent revascularizationwere similar in the two groups. In our view, the lower thresholdbias for coronary angiography and for repeat revascularizationin the PCI group may have significantly influenced the overallstudy results.
Robert F. Bonvini, M.D. Fabrice Rapp, M.D. Marco Roffi, M.D. Geneva University Hospital CH-1211 Geneva, Switzerland robert.bonvini{at}hcuge.ch
References
Loponen P, Korpilahti K, Luther M, Huhtala H, Tarkka MR. Repeat intervention after invasive treatment of coronary arteries. Eur J Cardiothorac Surg 2009;35:43-47. [Free Full Text]
Mathew V, Clavell AL, Lennon RJ, Grill DE, Holmes DR Jr. Percutaneous coronary interventions in patients with prior coronary artery bypass surgery: changes in patient characteristics and outcome during two decades. Am J Med 2000;108:127-135. [CrossRef][Web of Science][Medline]
Borowski A, Vchivkov I, Ghodsizad A, Gams E. Coronary artery disease progression in patients who need repeat surgical revascularisation: the surgeon's point of view. J Cardiovasc Med (Hagerstown) 2008;9:85-88. [Medline]
Brener SJ, Lytle BW, Casserly IP, Ellis SG, Topol EJ, Lauer MS. Predictors of revascularization method and long-term outcome of percutaneous coronary intervention or repeat coronary bypass surgery in patients with multivessel coronary disease and previous coronary bypass surgery. Eur Heart J 2006;27:413-418. [Free Full Text]
The authors reply: Bhindi and Figtree ask whether the timingof strokes or rates of atrial fibrillation might explain theexcess strokes in the CABG group. Similarly, Edwards commentsthat data on the timing of strokes relative to the interventionmay shed light on this difference. Of the 19 strokes that occurredin the CABG group, more than 40% were periprocedural or occurredwithin 5 days after the procedure. Three of the strokes occurredbefore the index procedure and were not related to the surgerybut were included in the count, reflecting the intention-to-treatanalysis. Rates of atrial fibrillation were low among the patientsin the CABG group who had a stroke. Given these numbers, neitherpreprocedural stroke nor atrial fibrillation contributed tothe increased rate of stroke in the CABG group. Bhindi and Figtreealso discuss the potential influence of the use of adjuvantintravascular ultrasonography on restenosis rates. In the PCIgroup, 113 patients (12.5%) underwent intravascular ultrasonography.
Brereton et al. are correct in stating that not all surgicaltechniques are associated with the same risk of stroke; however,we tested the current, standard techniques used in Europe andthe United States. Off-pump CABG was performed in 15% of patientsin the CABG group; this rate is similar to the rates observedin the United Kingdom and the United States (approximately 20%).1,2Data on whether a surgical procedure was a "no-touch" CABG,avoiding manipulations of the aorta, were not captured in theSYNTAX trial.
Shil et al. express concern regarding statin use in patientstreated with CABG. Of the patients who had a stroke, 58% ofpatients in the CABG group and 50% of patients in the PCI groupreceived statins; these rates were lower than those in the overallpatient groups (at 12 months, 82% of patients in the CABG groupand 86% of patients in the PCI group received statins). Dataon the contraindications for statin use were not collected.
In response to the comments of Bonvini et al.: angiographicassessment was not required by the protocol within the first12 months. Therefore, any angiographic assessment was performedat the physicians' discretion. Some study sites followed theirinstitutional guidelines, which at the time of the study calledfor routine follow-up angiograms, particularly in patients withlesions in the left main coronary artery. In total, 207 angiogramswere obtained within 12 months (in 56 patients in the CABG groupand in 151 patients in the PCI group). The primary indicationsleading to angiography were angina in 29 patients in the CABGgroup (14.0%) and 95 patients in the PCI group (45.9%), myocardialinfarction in 10 patients in the CABG group (4.8%) and 19 patientsin the PCI group (9.2%), an abnormal stress test in 5 patientsin the CABG group (2.4%) and 2 patients in the PCI group (1.0%),and myocardial ischemia in 1 patient in the CABG group (0.5%)and 12 patients in the PCI group (5.8%).
Patrick W. Serruys, M.D., Ph.D. Erasmus University Medical Center Rotterdam 3015 GD Rotterdam, the Netherlands p.w.j.c.serruys{at}erasmusmc.nl
Friedrich W. Mohr, M.D., Ph.D. Herzzentrum Universität Leipzig 4289 Leipzig, Germany
for the SYNTAX Investigators
References
Keogh B, Kinsman B, Society of Cardiothoracic Surgeons of Great Britain and Ireland. Fifth national adult cardiac surgical database report, 2003: improving outcomes for patients. Oxfordshire, United Kingdom: Dendrite Clinical Systems, 2003. (Accessed May 19, 2009, at http://www.scts.org/documents/PDF/5thBlueBook2003.pdf.)
Society of Thoracic Surgeons National Adult Cardiac Database: spring report 2007. Durham, NC: Duke Clinical Research Institute, June 2007.
Previous
