Long-Term Outcomes of Percutaneous Coronary Interventions or Coronary Artery Bypass Grafting for Left Main Coronary Artery Disease in Octogenarians (from a Drug-Eluting stent for LefT main Artery Registry Substudy) Federico Conrotto, MDa,*, Paolo Scacciatella, MDa, Fabrizio D’Ascenzo, MDb, Alaide Chieffo, MD, PhDc, Azeem Latib, MD, PhDc, Seung Jung Park, MDd, Young Hak Kim, MDd, Yoshinobu Onuma, MD, PhDe, Piera Capranzano, MDf, Sanda Jegere, MDg,h, Raj Makkar, MDi, Igor Palacios, MDj, Pawel Buszman, MDk, Tarun Chakravarty, MDi, Roxana Mehran, MDl, Christoph Naber, MDm, Ronan Margey, MDj, Martin Leon, MDl, Jeffrey Moses, MDl, Jean Fajadet, MDn, Thierry Lefèvre, MDo, Marie Claude Morice, MDo, Andrejs Erglis, MDg,h, Corrado Tamburino, MDf, Ottavio Alfieri, MDc, Maurizio D’Amico, MDa, Sebastiano Marra, MDa, Patrick W. Serruys, MD, PhDe, Antonio Colombo, MDc, and Emanuele Meliga, MD, PhDp Percutaneous coronary intervention (PCI) with drug-eluting stents is an accepted alternative to surgery for the treatment of unprotected left main coronary artery (ULMCA) disease, but the long-term outcome in elderly patients is unclear. Aim of our study was to compare the clinical outcomes of octogenarians with ULMCA disease treated either with PCI with drug-eluting stents or coronary artery bypass grafting (CABG). The primary study end point was the composite of death, cerebrovascular accident, and myocardial infarction at follow-up. A total of 304 consecutive patients with ULMCA stenosis treated with PCI or CABG and aged ‡80 years were selected and analyzed in a large multinational registry. Two hundred eighteen were treated with PCI and 86 with CABG. During the hospitalization, a trend toward a higher mortality rate was reported in PCI-treated patients (3.5% vs 7.3%, p [ 0.32). At a median follow-up of 1,088 days, the incidence of the primary end point was similar in the 2 groups (32.6% vs 30.2%, p [ 0.69). Incidence of target vessel revascularization at follow-up was higher in PCI-treated patients (10% vs 4.2%, p [ 0.05). At multivariate analysis, left ventricular ejection fraction was the only independent predictor of the primary end point (hazard ratio 0.95, 95% confidence interval 0.91 to 0.98, p [ 0.001). After adjustment with propensity score, the revascularization strategy was not significantly correlated to the incidence of the primary end point (hazard ratio 0.98, 95% confidence interval 0.57 to 1.71, p [ 0.95). In octogenarians, no difference was observed in the occurrence of the primary end point after PCI or CABG for the treatment of ULMCA disease. However, the rate of target vessel revascularization was higher in the PCI group. Ó 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;-:-e-) The incidence of left main disease increases with age,1 but elderly patients are commonly underrepresented in studies comparing outcomes after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).2 To date, only few registries3e7 have specifically

evaluated risks and benefits of PCI and CABG in patients >70 years with unprotected left main coronary artery (ULMCA) disease, and only 1 study was conducted in octogenarians.8 This high-risk population could obtain a large benefit from less invasive procedures as very elderly

a Department of Cardiology, Città della Salute e della Scienza Hospital, Turin, Italy; bDivision of Cardiology, Department of Internal Medicine, University of Turin, Turin, Italy; cDepartment of Cardio-Thoracic and Vascular Diseases, San Raffaele Scientific Institute, Milan, Italy; dDepartment of Cardiology, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; e Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands; f Ferrarotto Hospital, University of Catania, Catania, Italy; gLatvian Centre of Cardiology, Pauls Stradins Clinical University Hospital, Riga, Latvia; h Institute of Cardiology, University of Latvia, Riga, Latvia; iCedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California; j Cardiac Catheterization Laboratory, Massachusetts General Hospital and

Harvard Medical School, Boston, Massachusetts; kAmerican Heart of Poland, Medical University of Silesia, Katowice, Poland; lColumbia University Medical Center and Cardiovascular Research Foundation, New York, New York; mDepartment of Cardiology, University Hospital, Essen, Germany; nClinique Pasteur, Toulouse, France; oInstitut Hospitalier Jacques Cartier, Massy, France; and pInterventional Cardiology Unit, A.O. Ordine Mauriziano Umberto I, Turin, Italy. Manuscript received January 17, 2014; revised manuscript received and accepted March 8, 2014. See page 5 for disclosure information. *Corresponding author: Tel: (þ39) 0116335564; fax: (þ39) 0116335565. E-mail address: [email protected] (F. Conrotto).

0002-9149/14/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2014.03.044

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patients often have several co-morbidities and an increased surgical risk. Not surprisingly, although mortality rate of CABG surgery in elderly patients has decreased in the last 2 decades,9 the Society of Thoracic Surgeons (STS) score and the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II still include age as an incremental risk factor.10,11 Given the limited evidence of PCI and CABG outcomes in older patients, we investigated the short- and long-term outcomes of PCI versus CABG for ULMCA disease in patients aged >80 years who participated in the Drug-Eluting stent for LefT main Artery (DELTA) registry.12 Methods The study population consisted of 304 “all-comer” patients aged >80 years with ULMCA stenosis treated with PCI and first-generation drug-eluting stent (DES; sirolimus- and paclitaxel-eluting stents) implantation or CABG from April 2002 to April 2006 in 14 international centers, within the 2,775 patients of the DELTA registry. In all institutions, the revascularization strategy was determined by both interventional cardiologists and cardiac surgeons, on the basis of (1) hemodynamic conditions, (2) lesion characteristics, (3) vessel size, (4) presence of co-morbidities, (5) quality of arterial and/ or venous conduits for grafting, and (6) patient and/or referring physician preferences. In all cases, the selected revascularization approach seemed suitable to guarantee complete revascularization. All data related to hospital admissions, procedures, and outcomes were collected in each center with the hospital recording network. Information with regard to the clinical status at the latest clinical follow-up available was collected by clinical visits, telephone interviews, and referring physicians. Dual antiplatelet therapy (i.e., aspirin 100 mg/day and clopidogrel 75 mg/day or ticlopidine 250 mg twice daily) was administered for at least 12 months in patients treated with PCI. In the Korean center, cilostazol was also prescribed. Detailed information on adherence as well as reasons and date for discontinuation of dual antiplatelet therapy were obtained in all patients. Angiographic follow-up was scheduled according to hospital practice or if a noninvasive evaluation or clinical presentation suggested ischemia. Data analysis was performed with the approval of the institutional ethics committees of the hospitals and/or universities involved. In this report, the following events were analyzed cumulatively at latest clinical follow-up available: cardiac and overall death, myocardial infarction (MI), cerebrovascular accident (CVA), and target vessel revascularization (TVR). The occurrence of stent thrombosis (ST) was defined on the basis of the Academic Research Consortium definitions13 in the PCI group. ST was defined as acute, subacute, late, and very late if the event occurred within 24 hours, 30 days, 1 year, respectively, after the procedure. Deaths were classified as either cardiac or noncardiac. Cardiac death was defined as any death due to a cardiac cause (e.g., MI, lowoutput failure, fatal arrhythmia), procedure-related deaths, and death of unknown cause; TVR was defined as any repeat intervention of any segment of the target vessel, defined as the entire major coronary vessel proximal and distal to the target lesion, including upstream and downstream branches and the target lesion itself. CVA were defined as stroke, transient ischemic attacks, and reversible ischemic

Table 1 Baseline clinical and angiographic characteristics Variable Men Age (years) Hypertension* Hypercholesterolemia† Smoker (Current/Former) Diabetes mellitus Stable angina pectoris/inducible ischemia Unstable angina pectoris NSTEMI STEMI Urgent procedure Left ventricular ejection fraction Renal failure Previous coronary by pass Previous PCI Multivessel coronary disease RCA disease LM distal narrowing Coronary vessels treated EuroSCORE Syntax (synergy between percutaneous coronary intervention with taxus and cardiac surgery) score

PCI (n ¼ 218)

CABG (n ¼ 86)

P

141 (64.7%) 83.6  3.2 167 (76.6%) 131 (60%) 64 (29.4%) 57 (26.1%) 100 (45.9%)

47 (54.7%) 83  2.9 64 (74.1%) 55 (63.9%) 25 (29.1%) 20 (23.2%) 32 (37.2%)

0.11 0.13 0.69 0.53 0.96 0.6 0.17

76 (34.9%) 35 (16.1%) 7 (3.2%) 60 (27.5%) 49.8  14.3 24 (11%) 24 (11%) 38 (17.4%) 179 (82.1%) 79 (36.2%) 144 (66.1%) 1.7  0.9 9.1  4.3 32  12.5

37 (43%) 17 (19.8%) 0 25 (29.1%) 53.3  11.4 6 (7%) 3 (3.5%) 7 (8.1%) 76 (88.4%) 52 (72.2%) 47 (54.6%) 2.2  0.9 8.3  2.7 35  9.5

0.19 0.44 0.19 0.79 0.008 0.29 0.04 0.04 0.18 0.0001 0.03 0.006 0.06 0.22

LM ¼ left main; NSTEMI ¼ noneST-segment elevation myocardial infarction; RCA ¼ right coronary artery; STEMI ¼ ST-segment elevation myocardial infarction. * Blood pressure >140/90 mm Hg or previous pharmacologic treatment. † Total cholesterol >190 mg/dl or previous pharmacologic treatment.

neurologic deficits adjudicated by a neurologist and confirmed by computed tomography scanning. In-hospital noneQ-wave MI was defined as the elevation of the serum creatine kinase (CK) isoenzyme myocardial band that was 3 times the upper limit of normal in the PCI group and 5 times the upper limit of normal in the CABG group, in the absence of new pathologic Q waves.14 In this analysis, cumulative MI included (1) all Q-wave MI that occurred during hospital stay and follow-up and (2) all spontaneous MI occurring after hospital discharge. Q-wave MI was defined as the development of new pathologic Q waves in 2 contiguous leads with or without CK or CK-myocardial band levels elevated above normal. Spontaneous MI was defined as the occurrence after hospital discharge of any value of troponin and/or CK-myocardial band greater than the upper limit of normal if associated with clinical and/or electrocardiographic change. Major adverse cardiac and cerebrovascular event (MACCE) was defined as the composite end point of death, CVA, MI, and TVR. The EuroSCORE,15 which is based on patient-, cardiac-, and operation-related factors, was used to stratify the risk of death at 30 days. Diagnostic angiograms were scored according to the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score algorithm at the site laboratory.16 The primary study end point was the composite of death (overall and cardiac), CVA, and MI at longest available followup. The secondary study end points were the occurrence of death (overall and cardiac), TVR, and MACCE.

Coronary Artery Disease/Left Main Treatment in Octogenarians

3

Table 2 In hospital major adverse cardiac and cerebrovascular events PCI (n ¼ 218) Hospital death Hospital cardiac death Hospital MI Hospital rePCI/reCABG Hospital CABG Hospital cerebrovascular event Infections Hospital major adverse cardiac and cerebrovascular events

16 12 13 2

(7.3%) (5.5%) (6%) (0.9%) 0 0 0 28 (12.8%)

CABG (n ¼ 86)

p

3 (3.5%) 1 (1.2%) 6 (7%) 0 0 0 12 (14%) 9 (10.5%)

0.32 0.15 0.74 0.54 0.0001 0.57

Data are presented as absolute number and percentages. CABG ¼ coronary artery bypass grafting. MI ¼ myocardial infarction; PCI ¼ percutaneous coronary intervention;

Table 3 Cumulative incidence of major adverse cardiac and cerebrovascular events at follow-up Variable Death Cardiac death Non cardiac death Myocardial infarction CABG RePCI Target vessel revascularization Cerebrovascular event Definite/probable stent thrombosis Primary composite endpoint (death, MI, CVA) MACCE

PCI (n ¼ 218) 63 30 33 10 3 23 22 7 4

(29%) (13.8%) (15.2%) (4.6%) (1.4%) (10.5%) (10%) (3.2%) (1.8%)

CABG (n ¼ 86) 19 12 7 3 1 4 3 4

Figure 1. Freedom from death, MI, and CVA after PCI (blue line) versus CABG (green line; 27.6% vs 31.1%, log-rank p ¼ 0.98).

p

(22.1%) (14.0%) (6.1%) (3.5%) (1.2%) (4.7%) (4.2%) (4.7%) 0

0.23 0.96 0.1 0.67 0.88 0.1 0.05 0.36 0.57

71 (32.6%)

26 (30.2%)

0.69

85 (39%)

28 (32.6%)

0.3

Data are presented as absolute number and percentages. CABG ¼ coronary artery bypass grafting; CVA ¼ cerebrovascular accident; MACCE ¼ major adverse cardiac and cerebrovascular events; MI ¼ myocardial infarction; PCI ¼ percutaneous coronary intervention.

Data are presented as percentage and mean  SD. In general, differences in proportions were tested with chisquare test or Fisher’s exact test, and differences in continuous variables were tested with a Student t test. Cumulative event curves were generated with the KaplanMeier method and compared by the log-rank test. Independent predictors of events at follow-up were analyzed using the Cox proportional hazards regression model including all variables listed in Tables 1 and 2 with a p