Quality of Life after PCI with Drug-Eluting Stents or Coronary-Artery Bypass Surgery

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1 T h e n e w e ngl a nd j o u r na l o f m e dic i n e original article Quality of Life after with Drug-Eluting Stents or Coronary-Artery Bypass Surgery David J. Cohen, M.D., Ben Van Hout, Ph.D., Patrick W. Serruys, M.D., Ph.D., Friedrich W. Mohr, M.D., Ph.D., Carlos Macaya, M.D., Peter den Heijer, M.D., Ph.D., M.M. Vrakking, M.D., Kaijun Wang, Ph.D., Elizabeth M. Mahoney, Sc.D., Salma Audi, M.Sc., Katrin Leadley, M.D., Keith D. Dawkins, M.D., and A. Pieter Kappetein, M.D., Ph.D., for the Synergy between with Taxus and Cardiac Surgery (SYNTAX) Investigators A BS TR AC T From Saint Luke s Mid America Heart Institute, University of Missouri Kansas City, Kansas City (D.J.C., K.W., E.M.M.); University of Sheffield, Sheffield, United Kingdom (B.V.H.); Erasmus University Medical Center Rotterdam, Rotterdam (P.W.S., A.P.K.); and Amphia Ziekenhuis, Breda (P.H., M.M.V.) both in the Netherlands; Herzzentrum Universität Leipzig, Leipzig, Germany (F.W.M.); Hospital Clinico Universitario San Carlos, Madrid (C.M.); and Boston Scientific, Natick, MA (S.A., K.L., K.D.D.). Address reprint requests to Dr. Cohen at Saint Luke s Mid America Heart Institute, 441 Wornall Rd., Kansas City, MO 64111, or at dcohen@ saint-lukes.org. N Engl J Med 211;364: Copyright 211 Massachusetts Medical Society. Background Previous studies have shown that among patients undergoing multivessel revascularization, coronary-artery bypass grafting (), as compared with percutaneous coronary intervention () either by means of balloon angioplasty or with the use of bare-metal stents, results in greater relief from angina and improved quality of life. The effect of with the use of drug-eluting stents on these outcomes is unknown. Methods In a large, randomized trial, we assigned 18 patients with three-vessel or left main coronary artery disease to undergo either (897 patients) or with paclitaxeleluting stents (93 patients). Health-related quality of life was assessed at baseline and at 1, 6, and 12 months with the use of the Seattle Angina Questionnaire (SAQ) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The primary end point was the score on the angina-frequency subscale of the SAQ (on which scores range from to 1, with higher scores indicating better health status). Results The scores on each of the SAQ and SF-36 subscales were significantly higher at 6 and 12 months than at baseline in both groups. The score on the angina-frequency subscale of the SAQ increased to a greater extent with than with at both 6 and 12 months (P =.4 and P =.3, respectively), but the between-group differences were small (mean treatment effect of 1.7 points at both time points). The proportion of patients who were free from angina was similar in the two groups at 1 month and 6 months and was higher in the group than in the group at 12 months (76.3% vs. 71.6%, P =.5). s on all the other SAQ and SF-36 subscales were either higher in the group (mainly at 1 month) or were similar in the two groups throughout the follow-up period. Conclusions Among patients with three-vessel or left main coronary artery disease, there was greater relief from angina after than after at 6 and 12 months, although the extent of the benefit was small. (Funded by Boston Scientific; ClinicalTrials.gov number, NCT ) 116 n engl j med 364;11 nejm.org march 17, 211 Downloaded from nejm.org on December 24, 217. For personal use only. No other uses without permission. Copyright 211 Massachusetts Medical Society. All rights reserved.

2 Quality of Life after or Percutaneous coronary intervention () and coronary-artery bypass grafting () are alternative revascularization procedures for patients with multivessel coronary artery disease. The Synergy between with Taxus and Cardiac Surgery (SYNTAX) study was a large, randomized trial in which the outcomes of with the use of paclitaxel-eluting stents were compared with those of among patients with three-vessel or left main coronary artery disease. In the SYNTAX trial, the rate of the composite primary end point (death, myocardial infarction, stroke, or repeat revascularization) was lower with than with at 1 year. 1 This result was driven largely by a significant reduction in the need for repeat revascularization. However, there were no significant differences between the two strategies in the composite end point of irreversible outcomes (death, myocardial infarction, or stroke). Therefore, from a patient s perspective, other considerations, including relief from angina and quality of life, may play a critical role in selecting a revascularization strategy. To evaluate these outcomes, we performed a prospective quality-of-life substudy as part of the SYNTAX trial. Me thods Study Design and Oversight The design of the SYNTAX trial and the enrollment criteria have been described previously. 1,2 We randomly assigned patients with previously untreated three-vessel or left main coronary artery disease who were suitable candidates for revascularization by means of either or to undergo revascularization with the use of one of these two techniques. In both groups, patients were treated with the goal of revascularizing all vessels that were at least 1.5 mm in diameter. Patients who were assigned to underwent surgical treatment with the use of standard techniques. Paclitaxel-eluting stents (Taxus Express, Boston Scientific) were used for all procedures. The institutional review board at each participating center approved the protocol, and all patients provided written informed consent. The study was sponsored by Boston Scientific and was designed collaboratively by the steering committee and the sponsor. The data were collected by the investigators at each site, managed by Mapi Values (a contract research organization), and analyzed by the Health Economics and Technology Assessment Group at Saint Luke s Mid America Heart Institute. The first author wrote the first draft of the manuscript; all the authors participated in the writing of subsequent drafts, made the decision to submit the manuscript for publication, and vouch for the veracity and completeness of its content, as well as the fidelity of the study to the protocol. The protocol, including the statistical analysis plan, is available with the full text of this article at NEJM.org. Measurement of Health Status Health status (which includes symptoms, functional limitations, and quality of life) was assessed directly from patients with the use of standardized, written questionnaires at baseline and at 1, 6, and 12 months after randomization (details are provided in the Supplementary Appendix, available at NEJM.org). The baseline questionnaires were completed before the patients underwent randomization. Subsequent questionnaires were completed in person at the time of scheduled follow-up visits or were sent by mail. Disease-specific health status was assessed with the use of the Seattle Angina Questionnaire (SAQ), which is a 19-item questionnaire that measures five domains of health status related to coronary artery disease: angina frequency, physical limitations, quality of life, angina stability, and treatment satisfaction. 3,4 s range from to 1, with higher scores indicating fewer symptoms and better health status. General health status was assessed with the use of the Medical Outcomes Study 36-Item Short- Form Health Survey (SF-36) 5 and the European Quality of Life 5 Dimensions (EQ-5D) instrument. 6 The SF-36 evaluates eight dimensions of health: physical functioning, role limitations due to physical problems, bodily pain, vitality, general health perception, social function, role limitations due to emotional problems, and mental health. s for each domain range from to 1, with higher scores indicating better health status. In addition, the SF-36 provides summary scales for overall physical and mental health with the use of norm-based methods that standardize the scores to a mean of 5 and a standard deviation of 1 (higher scores indicate better health status). 7 The EQ-5D is a five-item instrument that assesses mobility, self-care, usual activity, pain or n engl j med 364;11 nejm.org march 17, Downloaded from nejm.org on December 24, 217. For personal use only. No other uses without permission. Copyright 211 Massachusetts Medical Society. All rights reserved.

3 T h e n e w e ngl a nd j o u r na l o f m e dic i n e discomfort, and anxiety or depression. For this study, individual domain scores were converted to a summary index representing utility weights for the U.S. population, as described previously. 8 Utility weights are measures of a person s strength of preference for his or her state of health on the basis of a scale from to 1, with representing the worst possible health state (usually death) and 1 representing ideal health. 9,1 Questionnaires were administered in each patient s native language. Validated translations were available for the SAQ in 15 of 18 countries that participated in the trial, for the SF-36 in all 18 countries, and for the EQ-5D in 17 countries (see Table 1 in the Supplementary Appendix for details). Missing items for each subscale were accounted for according to the published guidelines provided by the developer of each instrument. 3,4,8,11 Statistical Analysis The prespecified primary end point of the qualityof-life analysis was the score on the SAQ anginafrequency subscale. All scores on other scales were considered to be secondary end points. Baseline characteristics were compared between treatment groups with the use of the chi-square test for categorical variables and Student s t-test for continuous variables. For the primary analysis, mean quality-of-life scores were compared between groups at each time point by means of analysis of covariance in order to adjust for baseline scores. Categorical analyses of the primary end point were also performed in which patients were classified as having no angina (SAQ anginafrequency score of 1) versus any angina and in which patients were classified as having an increase from baseline in the SAQ angina-frequency score of 2 points or more (which was considered Table 1. Baseline Characteristics of the Patients.* Characteristic (N = 93) (N = 897) P Value Demographic Age (yr) 65.2± ± Male sex (%) White race (%) Clinical Diabetes (%) Receiving treatment Insulin-dependent Current smoker (%) Previous myocardial infarction (%) Angina, as reported by investigator (%) Stable Unstable Extent of coronary artery disease (%) Any left main disease Left main and -, 1-, or 2-vessel disease Left main and 3-vessel disease Three-vessel disease without left main disease SYNTAX score 28.4± ± Quality of life s on SAQ subscales Angina frequency 69.6± ± Physical limitations 65.5± ± Quality of life 45.6± ± Treatment satisfaction 85.8± ± Angina stability 43.3± ± n engl j med 364;11 nejm.org march 17, 211 Downloaded from nejm.org on December 24, 217. For personal use only. No other uses without permission. Copyright 211 Massachusetts Medical Society. All rights reserved.

4 Quality of Life after or Table 1. (Continued.) Characteristic (N = 93) (N = 897) P Value Angina frequency (%).87 Daily Weekly Monthly None s on SF-36 Physical-component summary 4.4±1. 4.4± Mental-component summary 45.2± ± EQ-5D utilities**.75±.19.74± * Plus minus values are means ±SD. denotes coronary-artery bypass grafting, and percutaneous coronary intervention. Race was determined by the investigator. The SYNTAX (Synergy between with Taxus and Cardiac Surgery) score is an anatomical assessment of the severity of coronary disease on the basis of the diagnostic angiogram. The SYNTAX score ranges from to 115, with higher scores indicating more complex disease. 1 The Seattle Angina Questionnaire (SAQ) is a 19-item questionnaire that measures five domains of health status related to coronary artery disease: angina frequency, physical limitations, quality of life, angina stability, and treatment satisfaction. 3,4 s range from to 1, with higher scores indicating fewer symptoms and better health status. Angina frequency was assessed with the use of the SAQ angina-frequency subscale. A score of to 3 indicates daily angina, 4 to 6 weekly angina, 7 to 9 monthly angina, and 1 no angina. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) evaluates eight dimensions of health: physical functioning, role limitations due to physical problems, bodily pain, vitality, general health perception, social function, role limitations due to emotional problems, and mental health. s for each domain range from to 1, with higher scores indicating better health status. The SF-36 also provides summary scales for overall physical and mental health with the use of norm-based methods that standardize the scores to a mean of 5 and a standard deviation of 1 (higher scores indicate better health status). 7 ** The European Quality of Life 5 Dimensions (EQ-5D) is a five-item instrument that assesses mobility, self-care, usual activity, pain or discomfort, and anxiety or depression. For this study, individual domain scores were converted to a summary index representing utility weights for the U.S. population, as described previously. 8 Utility weights are measures of a person s strength of preference for his or her state of health on the basis of a scale from to 1, where represents the worst possible health state (usually death) and 1 represents ideal health. to be substantial improvement) versus an increase of less than 2 points. 12,13 To account for missing data, secondary analyses were performed with the use of longitudinal random-effect growth-curve models to determine the effect of as compared with over time on each quality-of-life outcome. 14 These prespecified analyses incorporated all available quality-of-life scores, including those for patients who subsequently died, withdrew from the study, or were lost to follow-up. The variables included in the models were treatment assignment, presence or absence of left main coronary artery disease, follow-up time, and interactions between treatment and time. The intercept and linear time effects were estimated with the use of both fixed and random effects, whereas quadratic and cubic effects of time were modeled as fixed effects to avoid over-parameterization. Stratified analyses were performed to compare the effect of treatment assignment on the SAQ angina-frequency score within the following prespecified subgroups: age of less than 75 years versus 75 years of age or older, any left main coronary artery disease versus no left main coronary artery disease, presence or absence of diabetes, and baseline angina frequency, classified as daily or weekly (SAQ angina-frequency score of to 6), monthly (SAQ angina-frequency score of 7 to 9), or none (SAQ angina-frequency score of 1). A prespecified subgroup analysis was also performed with subjects grouped in thirds according to the SYNTAX score, which is an anatomical assessment of the severity of coronary disease on the basis of the findings on the diagnostic angiogram. The SYNTAX score ranges from to 115, with higher scores indicating more complex disease. 1 In the study population, the SYNTAX scores in the three groupings were to 22, 23 to 32, and 33 to 83. n engl j med 364;11 nejm.org march 17, Downloaded from nejm.org on December 24, 217. For personal use only. No other uses without permission. Copyright 211 Massachusetts Medical Society. All rights reserved.

5 T h e n e w e ngl a nd j o u r na l o f m e dic i n e All tests of statistical significance were twotailed. P values of less than.5 were considered to indicate statistical significance for the primary end point. For all other end points, P values of less than.1 were considered to indicate statistical significance; there has been no formal adjustment for multiple comparisons. All analyses were performed with the use of SAS for Windows software, version 9.1 (SAS Institute). R esult s Patient Population Between March 25 and April 27, a total of 18 patients with three-vessel or left main coronary artery disease were randomly assigned to with paclitaxel-eluting stents (93 patients) or (897 patients). There were no significant differences between the two groups in baseline characteristics or quality-of-life scores (Table 1). At baseline, approximately 12% of the patients reported experiencing daily angina during the month before randomization, whereas approximately 2% reported no angina. Outcomes with Respect to Disease-Specific Health Status The overall rate of response for quality-of-life assessments among surviving patients was more than 9% at all time points (96.2% at baseline, 9.5% at 1 month, 9.3% at 6 months, and 9.5% at 12 months). The rates of response for individual subscales were similar (Table 2 in the Supplementary Appendix). The unadjusted mean scores on the SAQ angina-frequency scale at baseline and at 1, 6, and 12 months are summarized in Table 2. As compared with baseline, both groups showed improvement in the SAQ angina-frequency scores at 1 month, with no significant between-group difference (9.2 vs. 88.7, P =.17). At 6 months, however, the scores were slightly higher in the Table 2. Relief from Angina over Time, as Assessed by the Seattle Angina Questionnaire (SAQ) Angina-Frequency Subscale.* Variable SAQ angina-frequency score Difference between and (95% CI) P Value Baseline 69.6± ± ( 2.7 to 2.4).91 1 mo 9.2± ± ( 3.1 to.5).17 6 mo 91.1± ± (.1 to 3.3).4 12 mo 92.4± ± (.2 to 3.2).3 Substantial improvement (%) 1 mo ( 7.5 to 2.8).37 6 mo ( 4.2 to 6.2) mo ( 4.6 to 5.9).81 Freedom from angina (%) Baseline ( 4.2 to 3.9).94 1 mo ( 7.7 to 2.1).27 6 mo ( 1.2 to 8.2) mo (.1 to 9.2).5 * Plus minus values are means ±SD. The angina-frequency subscale is one of five subscales of the SAQ, which is a 19- item questionnaire that measures five domains of health status related to coronary artery disease. 3,4 s range from to 1, with higher scores indicating fewer symptoms and better health status. The minimum clinically important difference for the SAQ angina-frequency subscale is 8 to 1 points. denotes coronary-artery bypass grafting, and percutaneous coronary intervention. The difference between the and groups was adjusted for baseline values; negative values indicate better outcomes with. Substantial improvement was defined as an increase of 2 points or more over baseline in the scores on the SAQ angina-frequency subscale. Freedom from angina was defined as a score of 1 on the SAQ angina-frequency subscale. 12 n engl j med 364;11 nejm.org march 17, 211 Downloaded from nejm.org on December 24, 217. For personal use only. No other uses without permission. Copyright 211 Massachusetts Medical Society. All rights reserved.

6 Quality of Life after or group than in the group (92.8 vs. 91.1, P =.4), and this difference was sustained at 12 months (93.8 vs. 92.4, P =.3). The proportion of patients with a substantial reduction in angina frequency (i.e., an increase from baseline in the SAQ angina-frequency score of 2 points or more) ranged from 52.4% to 58.3% at each time point and did not differ significantly between groups. The proportion of patients who were free from angina also did not differ significantly between the two groups at 1 and 6 months but was higher in the group than in the group at 12 months (76.3% vs. 71.6%, P =.5). The results for each of the other components of the SAQ are shown in Figure 1 and in Table 3 in the Supplementary Appendix. Although both A SAQ Angina Frequency P=.17 P=.4 P=.3 B SAQ Physical Limitation P<.1 P=.13 P= C SAQ Treatment Satisfaction P<.1 P=.4 P=.87 D SAQ Quality of Life P<.1 P=.13 P= E SAQ Angina Stability P=.67 P=.11 P= Figure 1. Unadjusted s for Disease-Specific Health Status, According to Treatment Group. Disease-specific health status was assessed with the use of the Seattle Angina Questionnaire (SAQ). The SAQ is a 19-item questionnaire that measures five domains of health status related to coronary artery disease: angina frequency, physical limitations, treatment satisfaction, quality of life, and angina stability. 3,4 s range from to 1, with higher scores indicating fewer symptoms and better health status. denotes coronary-artery bypass grafting, and percutaneous coronary intervention. n engl j med 364;11 nejm.org march 17, Downloaded from nejm.org on December 24, 217. For personal use only. No other uses without permission. Copyright 211 Massachusetts Medical Society. All rights reserved.

7 T h e n e w e ngl a nd j o u r na l o f m e dic i n e groups had significant and sustained benefits across each of the SAQ subscales, the pattern and extent of improvement tended to differ over time. At 1 month, the scores on the subscales for physical limitations, quality of life, and treatment satisfaction were higher with than with (P<.1 for all comparisons). These differences were no longer apparent at 6 months, however, and the scores on the SAQ quality-of-life subscale were higher in the group than in the group at 12 months (difference between groups, 2.4 points; P =.3). Antianginal medications (with the exception of beta-blockers) tended to be used more often by patients in the group than by those in the group (Table 4 in the Supplementary Appendix). Outcomes with Respect to General Health Status The unadjusted mean scores for each SF-36 domain and the EQ-5D utility weights are shown in Figure 2 and in Table 5 in the Supplementary Appendix. At 1 month, there were marked benefits of over in seven of the eight SF-36 domains, with particularly large differences in the subscales related to physical health, including physical functioning, role limitations due to physical problems, bodily pain, and vitality (P<.1 for all comparisons). With the exception of role limitations due to physical problems, however, none of these differences persisted at 6 months. By 12 months, the scores on the general health subscale were higher in the group than in the group, but there were no significant differences in the other SF-36 domains. The results for the EQ-5D utility scale followed a similar pattern. Although utilities improved in both groups, they were significantly better with than with at 1 month (.85 vs..77, P<.1). Utilities were virtually identical for and at 6 and 12 months. Longitudinal and Sensitivity Analyses As compared with the unadjusted results, the predicted mean scores from the fully adjusted longitudinal random-effect growth-curve models, showed a similar pattern of differences between treatment groups at all time points for both disease-specific and general health status domains (Table 3). The adjusted difference in the scores on the SAQ angina-frequency scale was 1.8 points at 6 months (P =.3) and 1.6 points at 12 months Figure 2 (facing page). Unadjusted s for General Health Status, According to Treatment Group. General health status was assessed with the use of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the European Quality of Life 5 Dimensions (EQ-5D) instrument. The SF-36 evaluates eight dimensions of health: physical functioning, role limitations due to physical problems, bodily pain, vitality, general health perception, social function, role limitations due to emotional problems, and mental health. s for each domain range from to 1, with higher scores indicating better health status. The EQ-5D is a five-item instrument that assesses mobility, self-care, usual activity, pain or discomfort, and anxiety or depression. For this study, individual domain scores were converted to a summary index representing utility weights for the U.S. population, as described previously. 8 Utility weights are measures of a person s strength of preference for his or her state of health on the basis of a scale from to 1, where represents the worst possible health state (usually death) and 1 represents ideal health. denotes coronary-artery bypass grafting, and percutaneous coronary intervention. (P =.4), with scores in the group higher than those in the group at both time points. Results of post hoc sensitivity analyses in which worst case values were imputed for patients with missing data who had had a stroke or myocardial infarction during the follow-up period were consistent with our main findings (Tables 6 and 7 in the Supplementary Appendix), although some differences were no longer significant. Subgroup Analyses The results of analyses of the effect of treatment on the SAQ angina-frequency score in prespecified subgroups are summarized in Figures 1 and 2 in the Supplementary Appendix. In the case of most of the subgroups, there was no evidence of a significant difference between the effect of and that of at either 6 or 12 months. However, there was a significant interaction between baseline angina frequency and the benefits of as compared with. At 6 months, among patients who had had daily or weekly angina at baseline, those in the group had greater relief from angina than did those in the group (mean adjusted difference, 4.4 points); in contrast, among patients who had had only monthly angina or no angina at baseline, the mean adjusted difference in SAQ angina-frequency scores between the group and the group was.4 and.6 points, respectively, with 122 n engl j med 364;11 nejm.org march 17, 211 Downloaded from nejm.org on December 24, 217. For personal use only. No other uses without permission. Copyright 211 Massachusetts Medical Society. All rights reserved.

8 Quality of Life after or A SF-36 Physical Functioning B SF-36 Role Limitations Due to Physical Problems C SF-36 Bodily Pain D SF-36 Vitality E SF-36 General Health Perception F SF-36 Social Function G SF-36 Role Limitations Due to Emotional Problems I EQ-5D Utility Weights H SF-36 Mental Health P<.1 P=.7 P= P<.1 P=.74 P=.14 P<.1 P=.48 P=.73 P<.1 P=.33 P= P<.1 P=.5 P=.89 P=.12 P=.79 P=.8 P<.1 P=.39 P= P<.1 P=.6 P=.76 P<.1 P=.9 P= n engl j med 364;11 nejm.org march 17, Downloaded from nejm.org on December 24, 217. For personal use only. No other uses without permission. Copyright 211 Massachusetts Medical Society. All rights reserved.

9 T h e n e w e ngl a nd j o u r na l o f m e dic i n e Table 3. Adjusted Effect of versus on Disease-Specific and General Measures of Health Status, According to Longitudinal Analysis.* Measure Difference between and 1 mo P Value 6 mo P Value 12 mo P Value SAQ subscales Angina frequency 1.2 ( 3.1 to.6) NS 1.8 (.2 to 3.4) (.1 to 3.1).4 Physical limitations 12.1 ( 14.6 to 9.7) < ( 3.6 to.8) NS.8 ( 1.3 to 3.) NS Quality of life 5. ( 7.3 to 2.7) < (.8 to 3.6) NS 2.3 (.1 to 4.5).4 Treatment satisfaction 3.3 ( 4.7 to 1.9) <.1 2. ( 3.4 to.5).8.4 ( 1.9 to 1.1) NS Angina stability.5 ( 1.9 to 2.8) NS 1.6 (.5 to 3.7) NS.6 ( 1.4 to 2.5) NS SF-36 subscales Physical function 14.3 ( 16.7 to 11.9) <.1. ( 2.4 to 2.3) NS 1.1 ( 1.4 to 3.5) NS Role physical 24.1 ( 26.9 to 21.4) <.1 4. ( 6.7 to 1.4).3.3 ( 3. to 2.3) NS Bodily pain 22.4 ( 24.8 to 2.) < ( 4.3 to.5) NS.8 ( 1.7 to 3.2) NS Vitality 1.8 ( 12.9 to 8.7) <.1 1. ( 3. to 1.) NS.1 ( 1.9 to 2.1) NS General health 1.4 ( 3.2 to.4) NS.2 ( 1.8 to 2.1) NS 2.2 (.1 to 4.1).4 Social function 15. ( 17.6 to 12.5) < ( 4.5 to.) NS.5 ( 2.6 to 1.7) NS Role emotional 11.5 ( 14.4 to 8.7) < ( 3.9 to 1.2) NS.8 ( 3.3 to 1.7) NS Mental health 5.4 ( 7.3 to 3.5) <.1.9 ( 2.7 to 1.) NS.2 ( 2. to 1.7) NS Summary measures SF-36 Physical 7.7 ( 8.6 to 6.8) <.1.4 ( 1.3 to.5) NS.8 (.2 to 1.7) NS SF-36 Mental 3.2 ( 4.3 to 2.1) <.1.6 ( 1.7 to.5) NS.5 ( 1.5 to.6) NS EQ-5D utilities.8 (.1 to.7) <.1.1 (.3 to.) NS. (.2 to.1) NS * The treatment effect was analyzed with the use of longitudinal random-effect growth-curve models and is expressed as the adjusted difference, with 95% confidence intervals in parentheses, in scores on measures of health status between patients who underwent coronary-artery bypass grafting () and those who underwent percutaneous coronary intervention (). Negative values indicate better health status with, and positive values indicate better health status with. NS denotes not significant. The Seattle Angina Questionnaire (SAQ) is a 19-item questionnaire that measures five domains of health status related to coronary artery disease. 3,4 s range from to 1, with higher scores indicating fewer symptoms and better health status. The minimum clinically important difference is 8 to 1 points for the SAQ angina-frequency, physical-limitations, and quality-of-life subscales and 5 points for the treatment-satisfaction subscale. 3 These values are based on population means and differ from levels of substantial improvement derived from a review of individual items in the instrument. 12 The minimum clinically important difference for the SAQ angina-stability scale is undefined. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) assesses eight dimensions of health. s for each domain range from to 1, with higher scores indicating better health status. A change of.2 to.5 SD may be considered clinically important, 15 corresponding to differences of 5 to 1 points on the individual subscales. The SF-36 provides summary scales for overall physical and mental health with the use of norm-based methods that standardize the scores to a mean of 5 and a standard deviation of 1 (higher scores indicate better health status). 7 A change of.2 to.5 SD may be considered clinically important, 15 corresponding to differences of 2.5 to 5. points on the physical and mental summary scales. The European Quality of Life 5 Dimensions (EQ-5D) is a five-item instrument that assesses mobility, self-care, usual activity, pain or discomfort, and anxiety or depression. For this study, individual domain scores were converted to a summary index representing utility weights for the U.S. population, as described previously. 8 Utility weights are measures of a person s strength of preference for his or her state of health on the basis of a scale from to 1, where represents the worst possible health state (usually death) and 1 represents ideal health. The minimum clinically important difference for the EQ-5D is not known. the positive value indicating better health status with and the negative value indicating better health status with (P =.3 for the interaction). Similar findings were noted at 12 months (P =.2 for the interaction). Among patients with daily or weekly angina at baseline, the proportion of patients who were free from angina was also greater with than with at both 6 months (65.4% vs. 56.9%, P =.2) and 12 months (7.3% vs. 6.%, P =.2). Discussion In this trial, we compared the outcomes of with those of with the use of paclitaxel-eluting stents among patients with three-vessel or left 124 n engl j med 364;11 nejm.org march 17, 211 Downloaded from nejm.org on December 24, 217. For personal use only. No other uses without permission. Copyright 211 Massachusetts Medical Society. All rights reserved.

10 Quality of Life after or main coronary artery disease. Both and led to significant improvements in disease-specific and general health status over the course of 12 months. With respect to the primary quality-oflife end point the score on the SAQ anginafrequency subscale the extent of improvement was slightly greater with than with at 6 and 12 months, with a mean between-group difference of 1.7 points at both time points. There were no consistent differences in the scores on any other components of the SAQ at these later time points. In contrast, there were marked benefits with as compared with in general health-related quality of life as assessed by the SF-36 as well as EQ-5D utility weights at 1 month, but these differences had largely disappeared by 6 months. Subgroup analyses showed that the benefits of with respect to relief from angina were consistent over a broad range of patient characteristics. There was, however, evidence of heterogeneity according to the frequency of angina at baseline. Among patients with daily or weekly angina, was associated with greater relief from angina than was at both 6 months and 12 months, whereas there was no significant between-group difference in relief from angina among the two thirds of the study population with less frequent angina at baseline. Numerous previous studies have examined health-related quality of life after or. These studies, in which was performed with the use of either balloon angioplasty or baremetal stents, have generally shown that results in superior relief from angina over the course of the first 1 to 3 years after the initial revascularization Our study shows that despite our inclusion of patients with more complex coronary artery disease than those in previous trials, the continued evolution of techniques, including the use of drug-eluting stents, has narrowed the gap in health-related quality of life between patients who undergo and those who undergo. For example, in the Stent or Surgery (SOS) trial (in which 57% of participants had two-vessel disease and 43% had three-vessel disease), the difference in the SAQ angina-frequency scores between patients who underwent (with baremetal stents) and those who underwent was approximately 6 points at 6 months and approximately 3 points at 12 months, with the group having higher scores, indicating better health. 2 In the SYNTAX trial, despite the fact that patients with more extensive coronary disease were included (66% with three-vessel disease and 34% with left main coronary artery disease), the difference in the SAQ angina-frequency scores between patients who underwent (with paclitaxel-eluting stents) and those who underwent was only 1.7 points, with the group having higher scores, at both 6 months and 12 months. This difference is less than the difference of 3 to 6 points for the comparison of plus optimal medical therapy with optimal medical therapy alone in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial (COURAGE; ClinicalTrials.gov number, NCT7657), in which the group had higher scores. 13 It is also much less than the minimum clinically important difference of 8 to 1 points for the SAQ that has been reported previously. 3 In contrast to the small differences in diseasespecific quality of life at 6 and 12 months, the early benefits of on general health status in our study were large. For example, the difference of 7.8 points between and in the SF-36 physical-component summary score at 1 month exceeds the effect on physical health of a variety of chronic conditions, including sciatica (3.8 points), chronic lung disease (3.1 points), and heart failure (7.2 points). 21 Our study has several limitations. As with any clinical trial, our findings may not be generalizable to all patients with three-vessel or left main coronary artery disease, many of whom were excluded from the study on the basis of unfavorable anatomy for or excessive surgical risk. In addition, these results reflect only the first year of follow-up after revascularization; whether similar effects are observed over the long term is currently unknown. Previous studies comparing with that were conducted before the availability of drug-eluting stents have tended to show a gradual convergence of health status over time. 16,19,22-24 A third limitation is the fact that some data were missing, which may have biased our results. Our response rates were quite high, however, and our results were generally unchanged both in longitudinal analyses that accounted for missing data and in analyses that assigned the worst possible outcomes for patients with missing data. n engl j med 364;11 nejm.org march 17, Downloaded from nejm.org on December 24, 217. For personal use only. No other uses without permission. Copyright 211 Massachusetts Medical Society. All rights reserved.

11 Quality of Life after or Recently, several clinical trials have shown that the rates of target-lesion revascularization and myocardial infarction were higher with the paclitaxel-eluting stent that was used in the SYNTAX trial than with the second-generation everolimuseluting stent. 25,26 Whether use of everolimuseluting stents would have reduced or even eliminated the advantage of over with respect to the extent of relief from angina during the first year after the procedure is unknown. Finally, there were differences in the use of both calcium-channel blockers and long-acting nitrates during the follow-up period, which may have mitigated the benefits of with respect to angina and other health status measures. In conclusion, among patients with threevessel or left main coronary artery disease who were suitable candidates for either or, both strategies resulted in significant relief from angina and improvements in overall health status over the first year of follow-up. At both 6 and 12 months, there was a small but significant reduction in angina frequency with as compared with in the overall population. These symptomatic benefits of were counterbalanced by the more rapid recovery and improved short-term health status achieved with. Supported by Boston Scientific. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank Anita A. Joshi, Ph.D. (Boston Scientific), for editorial assistance in the preparation of this manuscript and the personnel at Mapi Values for assistance with protocol development, data management, and statistical analysis. References 1. Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 29;36: Ong AT, Serruys PW, Mohr FW, et al. The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) study: design, rationale, and run-in phase. 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Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial. Lancet 21;375: Stone GW, Rizvi A, Newman W, et al. Everolimus-eluting versus paclitaxeleluting stents in coronary artery disease. N Engl J Med 21;362: Copyright 211 Massachusetts Medical Society. 126 n engl j med 364;11 nejm.org march 17, 211 Downloaded from nejm.org on December 24, 217. For personal use only. No other uses without permission. Copyright 211 Massachusetts Medical Society. All rights reserved.