Comparison of Long-term Efficacy of Medical Treatment versus Percutaneous Transluminal Coronary Angioplasty (PTCA) in Single-vessel Disease

Transcription

1 Comparison of Long-term Efficacy of Medical Treatment versus Percutaneous Transluminal Coronary Angioplasty (PTCA) in Single-vessel Disease Shinichiro NISHIYAMA, M.D., Takashi IWASE, M.D., Sugao ISHIWATA, M.D., Nobuyuki KOMIYAMA, M.D., Yoshiki YANAGISHITA, M.D., Shigemoto NAKANISHI, M.D., and Akira SEKI, M.D. SUMMARY The long-term outcome of PTCA and medical therapy were compared in patients with SVD. All patients were confirmed to have _??_75% stenosis of a major coronary artery by coronary arteriogram. The 5-year survival rates were 96.0% for medical therapy and 98.9% for successful angioplasty. Both therapies achieved an equally good long-term outcome for SVD. The incidence of nonfatal cardiac events during follow up was higher in patients treated by PTCA than in those on medical therapy, but there was no difference between the two groups in the incidence of nonfatal MI at 5 years (2.5% vs 1.8%). The most common cardiac event in patients undergoing successful PTCA was repeat intervention associated with restenosis. In view of the long-term efficacy of PTCA, the high restenosis rate remains an important problem and it is necessary to elucidate the causes of restenosis and develop countermeasures as soon as possible. (Jpn Heart J 36: ,1995) Key words: Single-vessel disease Medical treatment PTCA Long-term prognosis Survival rate Nonfatal MI I NTERVENTIONAL therapy, including percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG), is the mainstay of the treatment of coronary artery disease. PTCA is a treatment modality that is well established in terms of technique. Its short-term efficacy in relieving angina and improving exercise capacity has also been proven to be satisfactory.1) Large-scale prospective randomized trials are now in progress in Europe and the United States to clarify whether PTCA reduces the incidence of cardiac events, including myocardial infarction (MI), during long-term follow-up From the Cardiovascular Center, Division of Cardiology, Toranomon Hospital, Tokyo, Japan. Address for correspondence: Shinichiro Nishiyama, M.D., Cardiovascular Center, Division of Cardiology, Toranomon Hosptal, Toranomon, Minato-ku, Tokyo 105, Japan. Received for publication May 15, Accepted July 12,

2 566 NISHIYAMA ET AL Jpn Heart J September 1995 and whether it improves the long-term outcome for coronary artery disease, but no conclusions have yet been reached.2,3) On the other hand, medical therapy plays a significant part in the control of risk factors in patients with coronary artery disease due to atherosclerosis. We have previously reported that the long-term outcome of coronary artery disease is good in Japanese patients treated by medical therapy.4,5) In the present study, the results of PTCA and medical therapy were retrospectively compared in patients with single-vessel disease to investigate the long-term outcome and clinical course achieved with these two therapeutic modalities. SUBJECTS AND METHODS The subjects comprised 373 patients (group P) with single-vessel disease (SVD) and significant stenosis (_??_75%) of a major coronary artery on coronary angiography who underwent initial PTCA (excluding those with previous CABG) and 490 patients (group M) treated medically, excluding patients treated surgically within one year of the initial coronary arteriogram. Patients were enrolled between September 1973 and February 1984 (when PTCA was introduced at our institution) for group M and between February 1984 and December 1989 for group P. Follow-up information was obtained by telephone or letter using a questionnaire. The subjects or their family members were asked about survival status. Surviving subjects were questioned about treatment (PTCA or CABG) as well as the presence/absence and timing of complications, including acute myocardial infarction (AMI) and heart failure. When subjects died, the date and cause of death were determined. The date of coronary angiography was defined as the entry of follow-up, and final follow-up was performed on August 31, 1990 for group M and August 31, 1991 for group P. This study was performed retrospectively, so there was a difference in background between the two groups. All the patients in group M were initially seen before the introduction of PTCA at our hospital in 1984, and most of them were enrolled even before the establishment of a department of cardiovascular surgery at our hospital in Therefore, even when anginal symptoms worsened, there was no alternative but to continue medical therapy or perform CABG. On the other hand, the patients in group P were enrolled in the era of coronary intervention, so they could be treated interventionally when indicated. Statistical analysis: Cumulative survival curves were prepared by the Kaplan- Meier method using cardiac death and noncardiac death as well as PTCA/ CABG while on medical therapy as the endpoints. Clinical profile (Table I): The average age of the patients was 53.5 years in

3 Vol 36 LONG-TERM PROGNOSIS OF SVD 567 No 5 Table I. Patient Characteristics MI=myocardial infarction. group M and 57.8 years in group P. The mean follow-up period was months and 42.6 months in groups M and P, respectively, with the difference being significant. There was a history of myocardial infarction in 60.9% of group M and 27.6% of group P. The follow-up rates were 92.1% and 96.2% for groups M and P, respectively. RESULTS Initial results of PTCA: Initial success was achieved in 89.4% of the patients. There were no deaths, but acute coronary artery occlusion occurred in 14 patients (3.8%), AMI occurred in 8 patients (2.1%), and urgent CABG was needed in 3 patients (0.8%). The restenosis rate was 33.8%. Clinical course after successful PTCA: Of the 321 patients with successful angioplasty, 44 did not undergo confirmatory angiography, 93 suffered restenosis, and 184 had no restenosis. Figure 1 shows the clinical course of the 184 patients without restenosis. AMI, PTCA, and CABG during the follow-up period were defined as nonfatal cardiac events, and such events occurred in 21 patients (11.4%). Four patients developed AMI and 17 patients underwent PTCA for new lesions (not repeat angioplasty at the previous site). CABG was performed in 4 patients, cardiac death occurred in 4, and noncardiac death occurred in 3. Figure 2 shows the clinical course of the 93 patients with restenosis. AMI occurred in 4 patients, PTCA was done in 52 patients, and CABG was done in 16 patients. All PTCA procedures performed in the restenosis group were for repeat angioplasty. There was only one cardiac death. Clinical course after unsuccessful PTCA: Of the 38 patients with unsuccessful angioplasty, 3 underwent urgent CABG and 7 had elective CABG. During the follow-up period, there were no episodes of AMI and only one cardiac death. Cardiac events in the PTCA and medical therapy groups during the initial 5 years (Table II): The incidence of cardiac events in group M during the initial

4 568 NISHIYAMA ET AL J pn Heart J September 1995 Figure 1. Clinical course of patients with successful PTCA without restenosis Figure 2. Clinical course of patients with successful PTCA with subsequent restenosis 5 years of follow-up was compared with that in group P. The incidence of cardiac death in group P was 1.9% (6 patients), which was lower than the rate of 3.8% (17 patients) in group M, although the difference was not significant. Nonfatal cardiac events occurred in 27 patients (6.0%) from group M, including AMI in 8 patients (1.8%), PTCA in 7 (1.5%), and CABG in 13 (2.9%). In group P, these events occurred in 114 patients (36.2%). The incidence of AMI was 2.5% (8 patients) and lower than the rate of 3.4% in patients without MI on medical therapy, showing no difference from group M. However, interventional treat-

5 Vol 36 LONG-TERM PROGNOSIS OF SVD 569 No 5 Table II. Incidence of Cardiac Events in Patients with SVD during the 5 Year Follow-up Period *Total number of nonfatal cardiac events indicates number of patients. AMI=acute myocardial infarction; PTCA=percutaneous transluminal coronary angioplasty; CABG=coronary artery bypass graft surgery. Figure 3. Cumulative survival curves comparing patients undergoing successful PTCA and those treated medically ment including PTCA (69 patients, 21.9%) and CABG (30 patients, 9.5%) was far more common in group P. The frequency of angioplasty was 9.2% even in the patients without restenosis, while repeat angioplasty was done in 55.9% of the patients with restenosis and CABG was done in 17.2%. CABG was performed in 26.3% of the patients with unsuccessful PTCA. Cumulative survival of the successful PTCA and medical therapy groups (Figure 3): The 5-year and 10-year survival rates were, respectively, 96.0% and 91.9% for group M. The 5-year survival rate was 98.9% after successful angioplasty and no significant difference was noted between the two groups. Thus, both types of therapy achieved good survival in patients with SVD. Event-free survival rates for the successful PTCA and medical therapy groups (Cardiac death, AMI, PTCA, and CABG) (Figure 4): The 5-year and 10-year cumulative event-free survival rates were, respectively, 95.3% and 83.7% for group M, indicating that most cardiac events occurred from 5 years onwards.

6 570 NISHIYAMA ET AL Jpn Heart J September 1995 Figure 4. Cumulative event-free survival curves in patients undergoing successful PTCA, with and without restenosis and those treated medically After successful PTCA excluding repeat angioplasty, the 5-year cumulative event-free survival rate was 85.2%. However, the 5-year cumulative event-free survival rate after PTCA including those with repeat angioplasty was markedly lower at 65.5%. DISCUSSION SVD has been reported to have a good prognosis irrespective of whether it is treated medically or surgically.6-9) Recently, it has been reported that surgical therapy is only of value for patients with triple-vessel disease and poor left ventricular function, and also that surgery does not reduce the incidence of AMI or improve survival in patients with SVD during follow-up.10) On the other hand, PTCA is a well established treatment that has been reported to achieve better short-term results than medical therapy, including relief of angina and improvement of exercise capacity.1) Its long-term benefit, however, has not been fully determined. The objective of the present study was, therefore, to compare retrospectively the results of PTCA and medical therapy for SVD at our hospital with emphasis on the long-term outcome. Five-year survival: Gruentzig followed 169 patients for 5-8 years and reported a 6-year post-ptca survival rate of 96%.11) Kramer performed a retrospective investigation of the results of PTCA for SVD of the left anterior descending coronary artery (LAD) and found that the 5-year survival rate was 95%.12) In addition, Tarrey found that the 5-year survival rate of SVD patients was 98.4%.13) In the present study, the 5-year survival rate was 98.9% after PTCA, which was similar to the rates reported earlier for PTCA.14) The 5-year survival rate was 96.0% for patients receiving medical therapy, which was better than

7 Vol 36 No 5 LONG-TERM PROGNOSIS OF SVD 571 those reported in Europe and the United States,8-10)and was equal to the result achieved with PTCA in this study. Thus, both therapies were associated with a favorable outcome of SVD. Nonfatal cardiac events: In this study, the incidence of nonfatal cardiac events was 36.2% during the initial 5 years after PTCA and there was no difference between the two groups in the incidence of nonfatal MI (2.5% in group P versus 1.8% in group M). The most common cardiac event associated with PTCA was interventional treatment, including PTCA (21.9%) and CABG (9.5%), during the follow-up period. In group P, the frequency of angioplasty for new lesions was increased during the follow-up period even among the patients without restenosis. This was probably due to the retrospective nature of the study and the different times of enrollment as mentioned in the methods. Hence, the high frequency of PTCA does not necessarily mean that nonfatal cardiac events were increased by PTCA, and the different backgrounds of the patients in each group are thought to be the cause of this difference in the frequency of events. If the worsening of angina or the development of unstable angina had also been defined as nonfatal cardiac events, there would presumably have been no significant difference between the two groups. Gruentzig reported that the 6-year post-ptca cumulative event-free rate (death, MI, and CABG) was 79%,11) and Tarrey reported that the 5-year eventfree rate (cardiac death, MI, and CABG) was 80.3%.13) In our group P, the 5-year event-free rate excluding repeat PTCA (cardiac death, MI, PTCA for new lesions, and CABG) was 85.2%, but that including repeat PTCA was 65.5%, which was markedly lower than in group M. Kramer reported that the 5-year cumulative event-free rate (death, MI, PTCA, and CABG) was 62% for patients with SVD of the LAD, and mentioned that acute complications as well as restenosis were indicators of a poor prognosis.12) The results of our study agreed with these findings, suggesting that restenosis after PTCA is an important factor affecting both the short-term and long-term outcome. Thus, it is necessary to elucidate the causes of restenosis and develop countermeasures as soon as possible. Subjects for future investigation: In the present study, PTCA failed to achieve a better 5-year survival rate than medical therapy, although the incidence of cardiac death and nonfatal MI was lower. PTCA has been proven to be effective in relieving angina and improving exercise capacity. From our results, PTCA for SVD might be indicated for those patients who have severe angina or impaired quality of life in spite of medical therapy. Problems to be considered include whether repeat PTCA can achieve a decrease in the incidence of cardiac events in patients with SVD from 5 years onwards, which is when the frequency of such events increases with medical

8 572 NISHIYAMA ET AL Jpn Heart J September 1995 therapy, and whether PTCA can achieve an improvement in survival. However, we have previously pointed out that AMI and unstable angina occurring during the follow-up of SVD develop primarily at sites unrelated to the lesions identified by previous coronary arteriography, and are instead associated with new lesions in the same or another vessel.15) Hence, it may be difficult for PTCA to significantly reduce the incidence of new cardiac events when compared with medical therapy in SVD. REFERENCES 1. Parisi AF, Folland ED, Hartigan P: A comparison of angioplasty with medical therapy in the treatment of single-vessel coronary artery disease; on behalf of the Veterans Affairs ACME Investigators. N Engl Med J 326: 10, Hamm CW, Reimers J, Ischinger T, Rupperecht HJ, Berger J, Bleifeld W.: A randomized study of coronary angioplasty compared with bypass surgery in patients with symptomatic multivessel coronary disease. N Engl Med J 331: 1037, King SB III, Lembo NJ, Weintraub WS, Kosinski AS, Barnhart HX, Kutner MH, Alazraki NP, Guyton RA, Zhao XQ: A randomized trial comparing coronary angioplasty with coronary bypass surgery. N Engl Med J 331: 1044, Nishiyama S, Kato K, Nakanishi S, Seki A, Yamaguchi H: Long-term prognosis in 990 medically treated Japanese patients with coronary artery disease. Jpn Heart J 34: 539, Nishiyama S: Long-term prognosis of 554 medically treated Japanese patients with myocardial infarction. (in Japanese) J Jpn Coll Angiol 34: 31, Califf RM, Tomabechi Y, Lee KL, Phillips H, Pryor DB, Harrel FE Jr, Harris PJ, Peter RH, Behar VS, Kong Y, Rosati RA: Outcome in one-vessel coronary artery disease. Circulation 67: 283, Klein LW, Weintraub WS, Agarwal JB, Schneider RM, Seelaus PD, Katz RI, Helfant RH: Prognostic significance of severe narrowing of the proximal portion of the left anterior descending coronary artery. Am J Cardiol 58: 42, Varnauskas E, and European Coronary Surgery Study Group: Twelve-year follow-up of survival in the randomized European Coronary Surgery Study. N Engl Med J 319: 332, The VA Coronary Artery Bypass Surgery Cooperative Study Group: Eighteen-year follow-up in the Veterans Affairs Cooperative Study of coronary artery bypass surgery for stable angina. Circulation 86: 121, Alderman EL, Bourassa MG, Cohen LS, Davis KB, Kaiser GG, Killip T, Mock MB, Pettinger M, and Robertson TL, for the CASS investigators; ten-year follow-up survival and infarction in the randomized coronary artery study. Circulation 82: 1629, Gruentzig AR, King SB III, Schlumpf M, Siegenthaler W: Long-term follow-up after percutaneous transluminal coronary angioplasty; the early Zurich experience. N Engl Med J 316: 1127, Kramer JR, Proudfit WL, Loop FD, Goormastic M, Zimmerman K, Simpfendorfer C, Horner G: Late follow-up of 781 patients undergoing percutaneous transluminal coronary angioplasty or coronary artery bypass grafting for an isolated obstruction in the left anterior descending coronary artery. Am Heart J 118: 1144, Tarry JD, Hurst JW, King SB III, Douglas JS Jr, Roubin GS, Gruentzing AR, Anderson HV, Weintraub WS: Clinical outcome 5 years after attempted percutaneous transluminal coronary angioplasty in 427 patients. Circulation 77: 820, Ellis SG, Fisher L, Dushman-Ellis S, Pettinger M, King SB III, Roubin GS, Alderman E: Comparison of angioplasty with medical treatment for single- and double-vessel coronary disease with left anterior descending coronary involvement; long-term outcome based on an Emory-CASS registry study. Am Heart J 118: 208, Nishimura S, Nakanishi S, Nishiyama S, Seki A, Yamaguchi H: Progression of obstructive lesion in left anterior descending artery and clinical symptoms in patients with coronary artery disease. (in Japanese) J Jpn Soc Int Med 76: 375, 1987