- Email: [email protected]
Comparison of clinical outcomes using stents versus no stents after percutaneous coronary intervention for proximal left anterior descending versus proximal right and left circumflex coronary arteries
Comparison of Clinical Outcomes Using Stents Versus No Stents After Percutaneous Coronary Intervention for Proximal Left Anterior Descending Versus Proximal Right and Left Circumflex Coronary Arteries Dale T. Ashby, MBBS, PhD, George Dangas, MD, PhD, Roxana Mehran, MD, Alexandra J. Lansky, MD, Raj Narasimaiah, MBBS, Ioannis Iakovou, MD, Sotir Polena, MD, Lowell F. Satler, MD, Augusto D. Pichard, MD, Kenneth M. Kent, MD, PhD, Gregg W. Stone, MD, and Martin B. Leon, MD Previous studies have demonstrated that proximal left anterior descending (LAD) stenoses have higher rates of restenosis after angioplasty than stenoses in other coronary segments. Stenting strategies may reduce this high rate of LAD restenosis. The study population included 1,289 patients with proximal coronary artery stenoses treated with percutaneous coronary interventions (PCI) with or without stents for single-vessel coronary disease between 1994 and 1999. Patients were divided into 4 groups: nonstent PCI in the proximal LAD artery (n ⴝ 168), nonstent PCI in proximal right/circumflex artery (n ⴝ 217), stent in the proximal LAD artery (n ⴝ 364), and stent to proximal right/circumflex artery (n ⴝ 540). Procedural success was higher in the stenting groups, but there were no significant differences in the major in-hospital events between the different lesion locations among the groups. At 1-year follow-up, there was no difference in mortality or myocardial infarction
between the groups. There was no significant difference in the rate of target lesion revascularization (TLR) in the patients with proximal LAD stents compared with the patients with proximal right/circumflex coronary artery stents (10.1% vs 13.8%, p ⴝ 0.11). In the patients who did not receive stents with proximal narrowings, there was a significant increase in TLR in the LAD group compared with the right/circumflex group (21.1% vs 12.5%, p ⴝ 0.04). Thus, patients with proximal stenoses treated with nonstenting strategies have lower procedural success than those treated with stenting strategies; the patients with proximal LAD nonstent PCI have significantly higher rates of clinical restenosis than patients with proximal right and circumflex stenoses. A stenting strategy for proximal LAD stenoses appears to attenuate the differences of clinical restenosis noted after nonstent PCI. 䊚2002 by Excerpta Medica, Inc. (Am J Cardiol 2002;89:1162–1166)
he presence of a proximal left anterior descending (LAD) coronary artery stenosis has often swayed T cardiologists to refer the patient to coronary artery
imal right coronary artery and proximal circumflex coronary artery.
bypass grafting, due to the presumption that narrowings in the proximal LAD artery have significantly higher rates of restenosis after angioplasty than narrowings in the proximal circumflex or proximal right coronary arteries.1,2 Given the reduction in restenosis rates with stenting in large size coronary arteries3,4 we investigated whether the proximal LAD artery treated with stenting continues to have significantly higher rates of restenosis than stented narrowings in the prox-
From the Cardiovascular Research Foundation, New York, New York; and the Washington Hospital Center, Washington, DC. Manuscript received November 21, 2001; revised manuscript received and accepted January 30, 2002. Address for reprints: George Dangas, MD, PhD, Cardiovascular Research Foundation, Lenox Hill Heart and Vascular Institute, 55 East 59th Street, 6th Floor, New York, New York, 10022. E-mail: [email protected].
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©2002 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 89 May 15, 2002
METHODS
Study population: The patient cohort included a consecutive series of 1,289 patients treated with percutaneous coronary intervention (PCI) for de novo narrowings in the proximal segments of native coronary arteries with a reference diameter ⱖ3.0 mm between January 1994 and January 1999 at the Washington Hospital Center. We excluded patients with cardiogenic shock and acute myocardial infarction within 72 hours of PCI and patients with total occlusions. Baseline clinical demographics and in-hospital events were confirmed by independent chart review. Clinical outcomes at 1 year were obtained by serial formal telephone interviews at 1, 3, 6, and 12 months by research nurses. Any late clinical events (death, Q-wave myocardial infarction, target lesion revascularization [TLR], any angioplasty, or bypass) were adjudicated and corroborated by accompanying source documentation by a dedicated data coordinating cen0002-9149/02/$–see front matter PII S0002-9149(02)02297-X
TABLE 1 Baseline Characteristics of the Study Population
Age (yrs) Men Current smoking Systemic hypertension Diabetes mellitus Family history of CAD Hypercholesterolemia Prior myocardial infarction CCS angina class I II III IV Unstable angina Prior coronary bypass Prior coronary angioplasty Left ventricular ejection fraction
LAD No Stent (n ⫽ 168)
Right/LCx No Stent (n ⫽ 217)
p Value
LAD Stent (n ⫽ 364)
Right/LCx Stent (n ⫽ 540)
65.6 ⫾ 12.3 61.3% 17.3% 59.5% 23.8% 59.5% 53.0% 44.0%
65.7 ⫾ 11.0 62.2% 25.0% 61.4% 24.5% 52.1% 63.2% 53.9%
0.93 0.85 0.07 0.71 0.87 0.14 0.08 0.06
61.9 ⫾ 12.0 68.1% 20.7% 55.9% 24.3% 58.8% 63.1% 43.8%
64.5 ⫾ 11.3 66.9% 19.7% 59.4% 26.6% 57.8% 70.0% 50.5%
15.9% 22.9% 26.9% 34.3% 38.1% 11.3% 22.8% 47 ⫾ 14%
20.6% 19.7% 17.5% 42.2% 27.9% 30.0% 29.7% 48 ⫾ 15%
0.21 0.45 0.03 0.12 0.03 ⬍0.001 0.13 0.63
14.7% 25.3% 19.7% 40.3% 34.0% 12.4% 22.1% 48 ⫾ 12%
12.1% 23.0% 22.6% 42.3% 31.1% 24.4% 30.1% 47 ⫾ 14%
0.25 0.44 0.30 0.56 0.37 ⬍0.001 0.01 0.30
p Value
p Value 0.001 0.69 0.71 0.30 0.45 0.75 0.03 0.05
CAD ⫽ coronary artery disease; CCS ⫽ Canadian Cardiovascular Society; LCx ⫽ left circumflex.
TABLE 2 Angiographic Characteristics
Lesion characteristics Eccentricity Thrombus Ulceration Calcium Proximal tortuosity Procedural complications Dissection Abrupt closure No reflow Perforation Quantitative measurements Reference diameter (mm) Preintervention Postintervention (final) Lesion length (mm) Lesion MLD (mm) Preintervention Postintervention (final) Diameter stenosis (%) Preintervention Postintervention (final)
LAD No Stent (n ⫽ 168)
Right/LCx No Stent (n ⫽ 217)
p Value
LAD Stent (n ⫽ 364)
Right/LCx Stent (n ⫽ 540)
50.0% 8.3% 15.2% 50.0% 16.7%
30.8% 15.4% 23.1% 53.8% 23.1%
0.43 0.36 0.22 0.85 0.53
36.7% 11.7% 8.3% 28.3% 3.3%
42.0% 4.9% 14.0% 39.6% 9.8%
0.48 0.12 0.26 0.13 0.16
7.0% 1.2% 1.8% 0%
9.2% 1.7% 3.5% 0%
0.42 0.70 0.37 NA
5.6% 1.8% 1.0% 0%
4.0% 0.5% 1.0% 0.2%
0.25 0.10 0.99 0.99
3.40 ⫾ 0.25 3.42 ⫾ 0.45 7.1 ⫾ 2.8
3.45 ⫾ 0.42 3.34 ⫾ 0.54 8.2 ⫾ 8.7
0.75 0.69 0.71
3.46 ⫾ 0.51 3.33 ⫾ 0.57 14.6 ⫾ 9.7
3.48 ⫾ 0.42 3.50 ⫾ 0.49 9.6 ⫾ 8.1
0.76 0.03 0.0003
0.88 ⫾ 0.53 2.74 ⫾ 0.61
0.86 ⫾ 0.61 2.87 ⫾ 0.64
0.93 0.57
0.93 ⫾ 0.52 2.87 ⫾ 0.64
1.06 ⫾ 0.63 3.19 ⫾ 0.68
0.13 0.002
69 ⫾ 12 20.1 ⫾ 13
69 ⫾ 12 13.3 ⫾ 18
0.95 0.29
71 ⫾ 15 13.6 ⫾ 14
68 ⫾ 17 8.7 ⫾ 16
0.14 0.04
MLD ⫽ minimal luminal diameter; other abbreviation as in Table 1.
ter. These methods have been previously published and described in detail.5–7 Clinical data: Patients were divided into 4 groups according to whether the proximal coronary artery segment treated was the proximal LAD artery or proximal right and circumflex arteries, and then subdivided into whether the narrowing was treated with stenting or a nonstent PCI. There were 168 patients who had proximal LAD narrowings treated without stents, 217 patients who had proximal right/circumflex narrowings treated without stents, 364 patients who had proximal LAD narrowings treated with stents, and 540 patients who had proximal right/circumflex narrowings treated with stents. Anginal symptoms were classified according to the Canadian Cardiovascular Soci-
ety guidelines.8 Q-wave myocardial infarction was defined as the presence of new Q waves on the postprocedure electrocardiogram and a corresponding increase of the serum creatinine kinase-MB fraction to at least fivefold above the upper limits of normal. Non–Q-wave myocardial infarction was defined as an increase of the serum creatinine kinase-MB fraction to at least fivefold above normal limits without the appearance of new Q-waves on the postprocedure electrocardiogram. The choice of PCI, rather than medical or surgical revascularization, was made by the attending cardiologist. Procedural success was defined as angiographic success in the absence of major in-hospital complications (death, Q-wave myocardial infarction, and emer-
CORONARY ARTERY DISEASE/NONSTENTING VERSUS STENTING PROXIMAL CORONARY NARROWINGS
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TABLE 3 Interventional Procedural Characteristics in All Lesions
Procedure type Directional atherectomy Excimer laser Rotational atherectomy No. of stents/narrowing Glycoprotein IIb/IIIa use Intravascular ultrasound guidance
LAD No Stent (n ⫽ 168)
Right/LCx No Stent (n ⫽ 217)
p Value
LAD Stent (n ⫽ 364)
Right/LCx Stent (n ⫽ 540)
p Value
37.2% 9.3% 41.2% — 4.2% 76.7%
21.8% 7.0% 40.6% — 5.5% 66.4%
0.15 0.55 0.16 NA 0.56 0.02
3.8% 4.8% 17.3% 1.23 ⫾ 0.6 6.6% 93.6%
2.2% 2.4% 18.9% 1.21 ⫾ 0.5 5.8% 87.9%
0.08 0.15 0.85 0.84 0.31 0.003
Abbreviation as in Table 1.
TABLE 4 Procedural Results and Clinical Outcome at One Year
In-hospital results Angiographic success Major in-hospital cardiac events* Death Q-wave myocardial infarction Non–Q-wave myocardial infarction Repeat target lesion PCI Emergency bypass surgery Abrupt closure Vascular complications Renal failure 1-yr results Major adverse cardiac events† Death Q-wave myocardial infarction Non–Q-wave myocardial infarction TLR TLR PCI TLR bypass surgery
LAD No Stent (n ⫽ 168)
Right/LCx No Stent (n ⫽ 217)
p Value
LAD Stent (n ⫽ 364)
Right/LCx Stent (n ⫽ 540)
p Value
93.3% 4.2% 0.6% 0% 11.5% 0.6% 3.0% 0% 3.6% 0.6%
88.9% 3.6% 0% 0.5% 12.0% 3.2% 1.8% 0.9% 3.6% 1.8%
0.14 0.77 0.43 1.0 0.88 0.15 0.41 0.51 0.97 0.40
99.4% 2.2% 1.1% 0.3% 14.4% 0.6% 0.6% 0.3% 4.9% 1.9%
99.8% 2.4% 1.3% 0.2% 15.8% 0.9% 0.2% 0.6% 4.2% 2.6%
0.56 0.84 ⬎0.999 ⬎0.999 0.56 0.71 0.16 0.65 0.62 0.51
23.8% 3.4% 0.7% 4.2% 21.1% 12.8% 8.5%
17.5% 5.5% 1.2% 3.5% 12.5% 8.6% 4.0%
0.55 0.37 1.0 0.73 0.04 0.22 0.09
15.8% 6.9% 0.6% 3.4% 10.1% 5.8% 4.9%
19.3% 6.3% 0.8% 3.8% 13.8% 10.2% 4.0%
0.34 0.74 ⬎0.999 0.73 0.11 0.03 0.54
*Major in-hospital cardiac events ⫽ death, Q-wave myocardial infarction, and emergency bypass. †Major adverse cardiac events ⫽ death, myocardial infarction, TLR. Abbreviation as in Table 1.
gency bypass surgery). Patients received 325 mg of aspirin before the procedure, which was continued indefinitely. Coronary stenting was performed by standard methods and the use of on-line intravascular ultrasound imaging. After stent placement, ticlopidine (250 mg twice daily) or clopidogrel (75 mg once daily) was given routinely for 4 weeks. Glycoprotein IIb/IIIa inhibitors were used in ⬍7% of the patients in all treatment groups. Angiographic analysis was performed by independent observers without knowledge of the clinical data using a validated, automated edge-detection algorithm (CMS, MEDIS, Leiden, The Netherlands) as previously described.9 Intravascular ultrasound studies were performed with the Boston Scientific Corporation/Cardiovascular Imaging System (San Diego, California) as previously described.10 Statistical analysis: Statistical analysis was performed using SAS software (SAS Institute Inc., Cary, North Carolina). Categorical data are presented as percent frequencies and compared by chi-square statistics. Continuous variables are presented as mean 1 SD and compared with unpaired t test. Multivariate logistic regression analysis was used to determine the independent predictors of in-hospital mortality; 1-year 1164 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 89
mortality modeling was performed with Cox proportional hazards methods. First univariate logistic regression analysis was performed; then variables with a p value ⬍0.2 were entered into the multivariate model. These variables included age, gender, body mass index, body surface area, diabetes, hypertension, hypercholesterolemia, unstable angina, graft age, left ventricular ejection fraction, directional atherectomy, lesion length, angiographic reference vessel diameter, and preprocedure and final minimum lumen diameter. A p value ⬍0.05 was considered statistically significant.
RESULTS
Baseline demographics: The baseline demographics of the treated patients are listed in Table 1. The groups were well matched, except the group that had a proximal LAD lesion and received a stent was somewhat younger than the other groups, and less of patients with a proximal LAD stenosis had undergone prior bypass surgery. The left ventricular ejection fraction was mildly decreased in all the groups, but did not significantly differ among them. MAY 15, 2002
low in all groups. Intravascular ultrasound was used significantly more often in the stenting groups. Procedural results: The angiographic success was greater in the stenting than the nonstenting groups (Table 4). There were no differences between the groups with regard to combined major in-hospital cardiac events (death, Q-wave myocardial infarction, and emergency bypass) (Figure 1). Likewise, the incidence of non–Q-wave myocardial infarction, abrupt closure, vascular complications, and post-PCI renal failure were similar for all 4 FIGURE 1. Major in-hospital cardiac events (death, Q-wave myocardial infarction, and groups (Table 4). There was a emergency bypass surgery). LC ⴝleft circumflex artery. higher incidence of in-hospital repeat target lesion PCI in the right/ circumflex nonstent group and a higher rate of emergency bypass surgery in the LAD nonstent group. One-year clinical outcomes: Clinical follow-up to 1 year was available in 92.7% of patients; the results are shown in Table 4. There was no significant difference in the overall major adverse cardiac events (death, myocardial infarction, TLR) between the groups. There was no difference in 1-year mortality or myocardial infarction between the groups. The LAD nonstent group had a significantly greater TLR than the right/circumflex nonstent group (21.1% vs 12.5%, p ⫽ 0.04) and the LAD stent group (21.1% vs 10.1%, p ⫽ 0.03) (Figure 2). There was no significant difference in the rate of TLR between the LAD stent group and the right/circumflex stent group. Actuarial event-free survival for any major adverse cardiac event at 1-year follow-up is shown in Figure 3. Event-free survival FIGURE 2. TLR at 1 year. Abbreviation as in Figure 1. was similar in all groups for any cardiac event. Angiographic analysis and procedural characteristics: The angiographic analysis and procedural charac-
teristics are shown in Tables 2 and 3. The lesion characteristics were generally similar with no significant difference in eccentricity, presence of thrombus, or ulceration among the groups. Nonstent PCI in the right/circumflex arteries was performed in more tortuous vessels. The procedural complications were not significantly different in the 4 groups, except for marginally greater no-reflow rate with nonstent PCI in right/circumflex narrowings. There was no significant differences in the pre- and post-PCI angiographic reference diameter among the groups. The preintervention lesion minimal luminal diameter was similar in all groups, but the postinterventional lesion lumen dimensions were significantly larger in the right/circumflex groups than the LAD groups. Adjunctive interventional techniques such as directional and rotational atherectomy and excimer laser atherectomy were used significantly more often in the 2 nonstent groups than the stenting groups. The use of glycoprotein IIb/IIIa antagonists was similarly
DISCUSSION Our study confirms previous findings that in patients with proximal obstructive coronary artery disease who receive treatment with a nonstenting intervention, there is a significantly higher rate of TLR in the proximal LAD artery than for narrowings in the proximal right and circumflex coronary arteries. The novel finding of this study is that when stenting is used for these proximal narrowings, there is no difference in rates of TLR between the proximal LAD group and right/ circumflex groups at 1-year clinical follow-up. The clinical TLR rates with stenting are low and there is a trend toward lower rates of TLR in the LAD artery compared with the right/circumflex arteries with stenting. Management of proximal obstructive coronary artery disease is important due to the large areas of myocardium that are downstream from the stenoses. The proximal LAD artery represents the most important proximal site for an obstructive coronary lesion (after the left main coronary artery) because this artery supplies 40% to 50% of the total left ventricular myocardium, and could result in ischemia to a large area of myocardium.11–13 The results of nonstenting
CORONARY ARTERY DISEASE/NONSTENTING VERSUS STENTING PROXIMAL CORONARY NARROWINGS
1165
FIGURE 3. One-year event-free survival. LCx ⴝ left circumflex; RCA ⴝ right coronary artery.
coronary percutaneous interventions to proximal LAD stenoses is less satisfactory than percutanenous transluminal coronary angioplasty in the proximal right/ circumflex coronary arteries due to the higher rates of restenosis in this area.1,2 In the current stenting era, proximal coronary narrowings are electively treated with stents on most occasions because of the reduced restenosis rates with stenting and improved procedural and angiographic success. Before this study, it was not known if proximal LAD stenoses that were treated with stenting would still have preferentially higher restenosis rates than stented narrowings in similarly sized vessels in the proximal right and circumflex coronary arteries. The Stent Restenosis Study (STRESS) study3 used a stepwise linear regression analysis to show that, irrespective of the procedure used (balloon angioplasty or stenting), the most important predictors of larger luminal diameter at follow-up were the size of the luminal diameter after the procedure, the initial reference vessel diameter, and the location of a lesion in a vessel other than the LAD artery. In our study population, there was no significant difference in TLR in the stented proximal LAD group compared with the stented right and circumflex coronary artery group. There was a trend toward lower TLR in the stented LAD group. In contrast, after nonstent interventions to the proximal stenoses, there was a 21.1% TLR rate with proximal LAD stenoses compared with 12.5% for right/circumflex stenoses (p ⫽ 0.04). After adjusting for baseline differences between the groups, there was still higher rates of TLR in the LAD nonstented group compared with either the LAD stented group (adjusted odds ratio 0.53 for LAD stented group compared with nonstented LAD group, p ⫽ 0.003) and the nonstented right/circumflex group (adjusted odds ratio 1166 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 89
0.60 for the nonstented right/circumflex group compared with the nonstented LAD group, p ⫽ 0.02). In our study, patients with proximal LAD narrowings who received stenting had significantly higher rates of intravascular ultrasound use during their procedures than the other groups. This may have altered the results in favor of the LAD stenting group. The use of intravascular ultrasound after stent implantation to reduce clinical events has been confirmed in a number of trials.14,15 Thus, the high rate of intravascular ultrasound guidance in the LAD stenting group (93.6%) compared with the LAD nonstenting group (76.7%) may have reduced the clinical restenosis rates in the stenting group to a lower level than if intravascular ultrasound was not used. 1. Kurbaan AS, Bowker TJ, Rickards AF. Differential
restenosis rate of individual coronary artery sites after multivessel angioplasty: implications for revascularization strategy. CABRI Investigators. Coronary Angioplasty versus Bypass Revascularisation Investigation. Am Heart J 1998;135:703–708. 2. Weintraub WS, Kosinski AS, Brown CL III, King SB III. Can restenosis after coronary angioplasty be predicted from clinical variables? J Am Coll Cardiol 1993;21:6 –14. 3. Fischman D, Leon M, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M, et al, for The Stent Restenosis Study Investigators. A randomized comparison of coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994;331:496 –501. 4. Serruys P, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P, for The Benestent Study Group. A comparison of balloon expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994;331:489 –495. 5. Dangas G, Mintz GS, Mehran R, Lansky AJ, Kornowski R, Pichard AD, Satler LF, Kent KM, Stone GW, Leon MB. Preintervention arterial remodeling as an independent predictor of target-lesion revascularization after nonstent coronary intervention: an analysis of 777 narrowings with intravascular ultrasound imaging. Circulation 1999;99:3149 –3154. 6. Dangas G, Mehran R, Lansky AJ, Waksman R, Satler LF, Pichard AD, Kent KM, Mintz GS, Stone GW, Leon MB. Acute and long-term results of treatment of diffuse in-stent restenosis in aortocoronary saphenous vein grafts. Am J Cardiol 2000;86:777–779. 7. Mehran R, Dangas G, Mintz GS, Lansky AJ, Pichard AD, Satler LF, Kent KM, Stone GW, Leon MB. Atherosclerotic plaque burden and CK-MB enzyme elevation after coronary interventions: intravascular ultrasound study of 2256 patients. Circulation 2000;10:604 –610. 8. Campeau L. Grading of angina pectoris (letter). Circulation 1976;54:522–523. 9. Lansky AJ, Popma JJ. Qualitative and quantitative angiography. In: Topo E, ed. Textbook of Interventional Cardiology. Philadelphia, PA: WB Saunders, 1999:725–747. 10. Ahmed JM, Hong MK, Mehran R, Mintz GS, Lansky AJ, Pichard AD, Satler LF, Kent KM, Wu H, Stone GW, Leon MB. Comparison of debulking followed by stenting versus stenting alone for saphenous vein graft aortoostial narrowings: immediate and one-year clinical outcomes. J Am Coll Cardiol 2000;35:1560 –1568. 11. Kalbfleisch H, Hort W. Quantitative study on the size of coronary artery supplying areas postmortem. Am Heart J 1977;94:183–188. 12. Mahmarian JJ, Pratt CM, Boyce TM, Verani MS. The variable extent of jeopardized myocardium in patients with single vessel coronary artery disease: quantification by thallium-201 single photon emission computed tomography. J Am Coll Cardiol 1991;17:355–362. 13. Klein LW, Weintraub WS, Agarwal JB, Schneider RM, Seelaus PA, Katz RI, Helfant RH. Prognostic significance of severe narrowing of the proximal portion of the left anterior descending coronary artery. Am J Cardiol 1986;58:42–46. 14. de Jaegere P, Mudra H, Figulla H, Almagor Y, Doucet S, Penn I, Colombo A, Hamm C, Bartorelli A, Rothman M, et al. Intravascular ultrasound-guided optimized stent deployment. Immediate and 6 months clinical and angiographic results from the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study). Eur Heart J 1998;19:1214 –1223. 15. Fitzgerald PJ, Oshima A, Hayase M, Metz JA, Bailey SR, Baim DS, Cleman MW, Deutsch E, Diver DJ, Leon MB, et al. Final results of the Can Routine Ultrasound Influence Stent Expansion (CRUISE) study. Circulation 2000;102: 523–530.
MAY 15, 2002
between the groups. There was no significant difference in the rate of target lesion revascularization (TLR) in the patients with proximal LAD stents compared with the patients with proximal right/circumflex coronary artery stents (10.1% vs 13.8%, p ⴝ 0.11). In the patients who did not receive stents with proximal narrowings, there was a significant increase in TLR in the LAD group compared with the right/circumflex group (21.1% vs 12.5%, p ⴝ 0.04). Thus, patients with proximal stenoses treated with nonstenting strategies have lower procedural success than those treated with stenting strategies; the patients with proximal LAD nonstent PCI have significantly higher rates of clinical restenosis than patients with proximal right and circumflex stenoses. A stenting strategy for proximal LAD stenoses appears to attenuate the differences of clinical restenosis noted after nonstent PCI. 䊚2002 by Excerpta Medica, Inc. (Am J Cardiol 2002;89:1162–1166)
he presence of a proximal left anterior descending (LAD) coronary artery stenosis has often swayed T cardiologists to refer the patient to coronary artery
imal right coronary artery and proximal circumflex coronary artery.
bypass grafting, due to the presumption that narrowings in the proximal LAD artery have significantly higher rates of restenosis after angioplasty than narrowings in the proximal circumflex or proximal right coronary arteries.1,2 Given the reduction in restenosis rates with stenting in large size coronary arteries3,4 we investigated whether the proximal LAD artery treated with stenting continues to have significantly higher rates of restenosis than stented narrowings in the prox-
From the Cardiovascular Research Foundation, New York, New York; and the Washington Hospital Center, Washington, DC. Manuscript received November 21, 2001; revised manuscript received and accepted January 30, 2002. Address for reprints: George Dangas, MD, PhD, Cardiovascular Research Foundation, Lenox Hill Heart and Vascular Institute, 55 East 59th Street, 6th Floor, New York, New York, 10022. E-mail: [email protected].
1162
©2002 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 89 May 15, 2002
METHODS
Study population: The patient cohort included a consecutive series of 1,289 patients treated with percutaneous coronary intervention (PCI) for de novo narrowings in the proximal segments of native coronary arteries with a reference diameter ⱖ3.0 mm between January 1994 and January 1999 at the Washington Hospital Center. We excluded patients with cardiogenic shock and acute myocardial infarction within 72 hours of PCI and patients with total occlusions. Baseline clinical demographics and in-hospital events were confirmed by independent chart review. Clinical outcomes at 1 year were obtained by serial formal telephone interviews at 1, 3, 6, and 12 months by research nurses. Any late clinical events (death, Q-wave myocardial infarction, target lesion revascularization [TLR], any angioplasty, or bypass) were adjudicated and corroborated by accompanying source documentation by a dedicated data coordinating cen0002-9149/02/$–see front matter PII S0002-9149(02)02297-X
TABLE 1 Baseline Characteristics of the Study Population
Age (yrs) Men Current smoking Systemic hypertension Diabetes mellitus Family history of CAD Hypercholesterolemia Prior myocardial infarction CCS angina class I II III IV Unstable angina Prior coronary bypass Prior coronary angioplasty Left ventricular ejection fraction
LAD No Stent (n ⫽ 168)
Right/LCx No Stent (n ⫽ 217)
p Value
LAD Stent (n ⫽ 364)
Right/LCx Stent (n ⫽ 540)
65.6 ⫾ 12.3 61.3% 17.3% 59.5% 23.8% 59.5% 53.0% 44.0%
65.7 ⫾ 11.0 62.2% 25.0% 61.4% 24.5% 52.1% 63.2% 53.9%
0.93 0.85 0.07 0.71 0.87 0.14 0.08 0.06
61.9 ⫾ 12.0 68.1% 20.7% 55.9% 24.3% 58.8% 63.1% 43.8%
64.5 ⫾ 11.3 66.9% 19.7% 59.4% 26.6% 57.8% 70.0% 50.5%
15.9% 22.9% 26.9% 34.3% 38.1% 11.3% 22.8% 47 ⫾ 14%
20.6% 19.7% 17.5% 42.2% 27.9% 30.0% 29.7% 48 ⫾ 15%
0.21 0.45 0.03 0.12 0.03 ⬍0.001 0.13 0.63
14.7% 25.3% 19.7% 40.3% 34.0% 12.4% 22.1% 48 ⫾ 12%
12.1% 23.0% 22.6% 42.3% 31.1% 24.4% 30.1% 47 ⫾ 14%
0.25 0.44 0.30 0.56 0.37 ⬍0.001 0.01 0.30
p Value
p Value 0.001 0.69 0.71 0.30 0.45 0.75 0.03 0.05
CAD ⫽ coronary artery disease; CCS ⫽ Canadian Cardiovascular Society; LCx ⫽ left circumflex.
TABLE 2 Angiographic Characteristics
Lesion characteristics Eccentricity Thrombus Ulceration Calcium Proximal tortuosity Procedural complications Dissection Abrupt closure No reflow Perforation Quantitative measurements Reference diameter (mm) Preintervention Postintervention (final) Lesion length (mm) Lesion MLD (mm) Preintervention Postintervention (final) Diameter stenosis (%) Preintervention Postintervention (final)
LAD No Stent (n ⫽ 168)
Right/LCx No Stent (n ⫽ 217)
p Value
LAD Stent (n ⫽ 364)
Right/LCx Stent (n ⫽ 540)
50.0% 8.3% 15.2% 50.0% 16.7%
30.8% 15.4% 23.1% 53.8% 23.1%
0.43 0.36 0.22 0.85 0.53
36.7% 11.7% 8.3% 28.3% 3.3%
42.0% 4.9% 14.0% 39.6% 9.8%
0.48 0.12 0.26 0.13 0.16
7.0% 1.2% 1.8% 0%
9.2% 1.7% 3.5% 0%
0.42 0.70 0.37 NA
5.6% 1.8% 1.0% 0%
4.0% 0.5% 1.0% 0.2%
0.25 0.10 0.99 0.99
3.40 ⫾ 0.25 3.42 ⫾ 0.45 7.1 ⫾ 2.8
3.45 ⫾ 0.42 3.34 ⫾ 0.54 8.2 ⫾ 8.7
0.75 0.69 0.71
3.46 ⫾ 0.51 3.33 ⫾ 0.57 14.6 ⫾ 9.7
3.48 ⫾ 0.42 3.50 ⫾ 0.49 9.6 ⫾ 8.1
0.76 0.03 0.0003
0.88 ⫾ 0.53 2.74 ⫾ 0.61
0.86 ⫾ 0.61 2.87 ⫾ 0.64
0.93 0.57
0.93 ⫾ 0.52 2.87 ⫾ 0.64
1.06 ⫾ 0.63 3.19 ⫾ 0.68
0.13 0.002
69 ⫾ 12 20.1 ⫾ 13
69 ⫾ 12 13.3 ⫾ 18
0.95 0.29
71 ⫾ 15 13.6 ⫾ 14
68 ⫾ 17 8.7 ⫾ 16
0.14 0.04
MLD ⫽ minimal luminal diameter; other abbreviation as in Table 1.
ter. These methods have been previously published and described in detail.5–7 Clinical data: Patients were divided into 4 groups according to whether the proximal coronary artery segment treated was the proximal LAD artery or proximal right and circumflex arteries, and then subdivided into whether the narrowing was treated with stenting or a nonstent PCI. There were 168 patients who had proximal LAD narrowings treated without stents, 217 patients who had proximal right/circumflex narrowings treated without stents, 364 patients who had proximal LAD narrowings treated with stents, and 540 patients who had proximal right/circumflex narrowings treated with stents. Anginal symptoms were classified according to the Canadian Cardiovascular Soci-
ety guidelines.8 Q-wave myocardial infarction was defined as the presence of new Q waves on the postprocedure electrocardiogram and a corresponding increase of the serum creatinine kinase-MB fraction to at least fivefold above the upper limits of normal. Non–Q-wave myocardial infarction was defined as an increase of the serum creatinine kinase-MB fraction to at least fivefold above normal limits without the appearance of new Q-waves on the postprocedure electrocardiogram. The choice of PCI, rather than medical or surgical revascularization, was made by the attending cardiologist. Procedural success was defined as angiographic success in the absence of major in-hospital complications (death, Q-wave myocardial infarction, and emer-
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TABLE 3 Interventional Procedural Characteristics in All Lesions
Procedure type Directional atherectomy Excimer laser Rotational atherectomy No. of stents/narrowing Glycoprotein IIb/IIIa use Intravascular ultrasound guidance
LAD No Stent (n ⫽ 168)
Right/LCx No Stent (n ⫽ 217)
p Value
LAD Stent (n ⫽ 364)
Right/LCx Stent (n ⫽ 540)
p Value
37.2% 9.3% 41.2% — 4.2% 76.7%
21.8% 7.0% 40.6% — 5.5% 66.4%
0.15 0.55 0.16 NA 0.56 0.02
3.8% 4.8% 17.3% 1.23 ⫾ 0.6 6.6% 93.6%
2.2% 2.4% 18.9% 1.21 ⫾ 0.5 5.8% 87.9%
0.08 0.15 0.85 0.84 0.31 0.003
Abbreviation as in Table 1.
TABLE 4 Procedural Results and Clinical Outcome at One Year
In-hospital results Angiographic success Major in-hospital cardiac events* Death Q-wave myocardial infarction Non–Q-wave myocardial infarction Repeat target lesion PCI Emergency bypass surgery Abrupt closure Vascular complications Renal failure 1-yr results Major adverse cardiac events† Death Q-wave myocardial infarction Non–Q-wave myocardial infarction TLR TLR PCI TLR bypass surgery
LAD No Stent (n ⫽ 168)
Right/LCx No Stent (n ⫽ 217)
p Value
LAD Stent (n ⫽ 364)
Right/LCx Stent (n ⫽ 540)
p Value
93.3% 4.2% 0.6% 0% 11.5% 0.6% 3.0% 0% 3.6% 0.6%
88.9% 3.6% 0% 0.5% 12.0% 3.2% 1.8% 0.9% 3.6% 1.8%
0.14 0.77 0.43 1.0 0.88 0.15 0.41 0.51 0.97 0.40
99.4% 2.2% 1.1% 0.3% 14.4% 0.6% 0.6% 0.3% 4.9% 1.9%
99.8% 2.4% 1.3% 0.2% 15.8% 0.9% 0.2% 0.6% 4.2% 2.6%
0.56 0.84 ⬎0.999 ⬎0.999 0.56 0.71 0.16 0.65 0.62 0.51
23.8% 3.4% 0.7% 4.2% 21.1% 12.8% 8.5%
17.5% 5.5% 1.2% 3.5% 12.5% 8.6% 4.0%
0.55 0.37 1.0 0.73 0.04 0.22 0.09
15.8% 6.9% 0.6% 3.4% 10.1% 5.8% 4.9%
19.3% 6.3% 0.8% 3.8% 13.8% 10.2% 4.0%
0.34 0.74 ⬎0.999 0.73 0.11 0.03 0.54
*Major in-hospital cardiac events ⫽ death, Q-wave myocardial infarction, and emergency bypass. †Major adverse cardiac events ⫽ death, myocardial infarction, TLR. Abbreviation as in Table 1.
gency bypass surgery). Patients received 325 mg of aspirin before the procedure, which was continued indefinitely. Coronary stenting was performed by standard methods and the use of on-line intravascular ultrasound imaging. After stent placement, ticlopidine (250 mg twice daily) or clopidogrel (75 mg once daily) was given routinely for 4 weeks. Glycoprotein IIb/IIIa inhibitors were used in ⬍7% of the patients in all treatment groups. Angiographic analysis was performed by independent observers without knowledge of the clinical data using a validated, automated edge-detection algorithm (CMS, MEDIS, Leiden, The Netherlands) as previously described.9 Intravascular ultrasound studies were performed with the Boston Scientific Corporation/Cardiovascular Imaging System (San Diego, California) as previously described.10 Statistical analysis: Statistical analysis was performed using SAS software (SAS Institute Inc., Cary, North Carolina). Categorical data are presented as percent frequencies and compared by chi-square statistics. Continuous variables are presented as mean 1 SD and compared with unpaired t test. Multivariate logistic regression analysis was used to determine the independent predictors of in-hospital mortality; 1-year 1164 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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mortality modeling was performed with Cox proportional hazards methods. First univariate logistic regression analysis was performed; then variables with a p value ⬍0.2 were entered into the multivariate model. These variables included age, gender, body mass index, body surface area, diabetes, hypertension, hypercholesterolemia, unstable angina, graft age, left ventricular ejection fraction, directional atherectomy, lesion length, angiographic reference vessel diameter, and preprocedure and final minimum lumen diameter. A p value ⬍0.05 was considered statistically significant.
RESULTS
Baseline demographics: The baseline demographics of the treated patients are listed in Table 1. The groups were well matched, except the group that had a proximal LAD lesion and received a stent was somewhat younger than the other groups, and less of patients with a proximal LAD stenosis had undergone prior bypass surgery. The left ventricular ejection fraction was mildly decreased in all the groups, but did not significantly differ among them. MAY 15, 2002
low in all groups. Intravascular ultrasound was used significantly more often in the stenting groups. Procedural results: The angiographic success was greater in the stenting than the nonstenting groups (Table 4). There were no differences between the groups with regard to combined major in-hospital cardiac events (death, Q-wave myocardial infarction, and emergency bypass) (Figure 1). Likewise, the incidence of non–Q-wave myocardial infarction, abrupt closure, vascular complications, and post-PCI renal failure were similar for all 4 FIGURE 1. Major in-hospital cardiac events (death, Q-wave myocardial infarction, and groups (Table 4). There was a emergency bypass surgery). LC ⴝleft circumflex artery. higher incidence of in-hospital repeat target lesion PCI in the right/ circumflex nonstent group and a higher rate of emergency bypass surgery in the LAD nonstent group. One-year clinical outcomes: Clinical follow-up to 1 year was available in 92.7% of patients; the results are shown in Table 4. There was no significant difference in the overall major adverse cardiac events (death, myocardial infarction, TLR) between the groups. There was no difference in 1-year mortality or myocardial infarction between the groups. The LAD nonstent group had a significantly greater TLR than the right/circumflex nonstent group (21.1% vs 12.5%, p ⫽ 0.04) and the LAD stent group (21.1% vs 10.1%, p ⫽ 0.03) (Figure 2). There was no significant difference in the rate of TLR between the LAD stent group and the right/circumflex stent group. Actuarial event-free survival for any major adverse cardiac event at 1-year follow-up is shown in Figure 3. Event-free survival FIGURE 2. TLR at 1 year. Abbreviation as in Figure 1. was similar in all groups for any cardiac event. Angiographic analysis and procedural characteristics: The angiographic analysis and procedural charac-
teristics are shown in Tables 2 and 3. The lesion characteristics were generally similar with no significant difference in eccentricity, presence of thrombus, or ulceration among the groups. Nonstent PCI in the right/circumflex arteries was performed in more tortuous vessels. The procedural complications were not significantly different in the 4 groups, except for marginally greater no-reflow rate with nonstent PCI in right/circumflex narrowings. There was no significant differences in the pre- and post-PCI angiographic reference diameter among the groups. The preintervention lesion minimal luminal diameter was similar in all groups, but the postinterventional lesion lumen dimensions were significantly larger in the right/circumflex groups than the LAD groups. Adjunctive interventional techniques such as directional and rotational atherectomy and excimer laser atherectomy were used significantly more often in the 2 nonstent groups than the stenting groups. The use of glycoprotein IIb/IIIa antagonists was similarly
DISCUSSION Our study confirms previous findings that in patients with proximal obstructive coronary artery disease who receive treatment with a nonstenting intervention, there is a significantly higher rate of TLR in the proximal LAD artery than for narrowings in the proximal right and circumflex coronary arteries. The novel finding of this study is that when stenting is used for these proximal narrowings, there is no difference in rates of TLR between the proximal LAD group and right/ circumflex groups at 1-year clinical follow-up. The clinical TLR rates with stenting are low and there is a trend toward lower rates of TLR in the LAD artery compared with the right/circumflex arteries with stenting. Management of proximal obstructive coronary artery disease is important due to the large areas of myocardium that are downstream from the stenoses. The proximal LAD artery represents the most important proximal site for an obstructive coronary lesion (after the left main coronary artery) because this artery supplies 40% to 50% of the total left ventricular myocardium, and could result in ischemia to a large area of myocardium.11–13 The results of nonstenting
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FIGURE 3. One-year event-free survival. LCx ⴝ left circumflex; RCA ⴝ right coronary artery.
coronary percutaneous interventions to proximal LAD stenoses is less satisfactory than percutanenous transluminal coronary angioplasty in the proximal right/ circumflex coronary arteries due to the higher rates of restenosis in this area.1,2 In the current stenting era, proximal coronary narrowings are electively treated with stents on most occasions because of the reduced restenosis rates with stenting and improved procedural and angiographic success. Before this study, it was not known if proximal LAD stenoses that were treated with stenting would still have preferentially higher restenosis rates than stented narrowings in similarly sized vessels in the proximal right and circumflex coronary arteries. The Stent Restenosis Study (STRESS) study3 used a stepwise linear regression analysis to show that, irrespective of the procedure used (balloon angioplasty or stenting), the most important predictors of larger luminal diameter at follow-up were the size of the luminal diameter after the procedure, the initial reference vessel diameter, and the location of a lesion in a vessel other than the LAD artery. In our study population, there was no significant difference in TLR in the stented proximal LAD group compared with the stented right and circumflex coronary artery group. There was a trend toward lower TLR in the stented LAD group. In contrast, after nonstent interventions to the proximal stenoses, there was a 21.1% TLR rate with proximal LAD stenoses compared with 12.5% for right/circumflex stenoses (p ⫽ 0.04). After adjusting for baseline differences between the groups, there was still higher rates of TLR in the LAD nonstented group compared with either the LAD stented group (adjusted odds ratio 0.53 for LAD stented group compared with nonstented LAD group, p ⫽ 0.003) and the nonstented right/circumflex group (adjusted odds ratio 1166 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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0.60 for the nonstented right/circumflex group compared with the nonstented LAD group, p ⫽ 0.02). In our study, patients with proximal LAD narrowings who received stenting had significantly higher rates of intravascular ultrasound use during their procedures than the other groups. This may have altered the results in favor of the LAD stenting group. The use of intravascular ultrasound after stent implantation to reduce clinical events has been confirmed in a number of trials.14,15 Thus, the high rate of intravascular ultrasound guidance in the LAD stenting group (93.6%) compared with the LAD nonstenting group (76.7%) may have reduced the clinical restenosis rates in the stenting group to a lower level than if intravascular ultrasound was not used. 1. Kurbaan AS, Bowker TJ, Rickards AF. Differential
restenosis rate of individual coronary artery sites after multivessel angioplasty: implications for revascularization strategy. CABRI Investigators. Coronary Angioplasty versus Bypass Revascularisation Investigation. Am Heart J 1998;135:703–708. 2. Weintraub WS, Kosinski AS, Brown CL III, King SB III. Can restenosis after coronary angioplasty be predicted from clinical variables? J Am Coll Cardiol 1993;21:6 –14. 3. Fischman D, Leon M, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M, et al, for The Stent Restenosis Study Investigators. A randomized comparison of coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994;331:496 –501. 4. Serruys P, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P, for The Benestent Study Group. A comparison of balloon expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994;331:489 –495. 5. Dangas G, Mintz GS, Mehran R, Lansky AJ, Kornowski R, Pichard AD, Satler LF, Kent KM, Stone GW, Leon MB. Preintervention arterial remodeling as an independent predictor of target-lesion revascularization after nonstent coronary intervention: an analysis of 777 narrowings with intravascular ultrasound imaging. Circulation 1999;99:3149 –3154. 6. Dangas G, Mehran R, Lansky AJ, Waksman R, Satler LF, Pichard AD, Kent KM, Mintz GS, Stone GW, Leon MB. Acute and long-term results of treatment of diffuse in-stent restenosis in aortocoronary saphenous vein grafts. Am J Cardiol 2000;86:777–779. 7. Mehran R, Dangas G, Mintz GS, Lansky AJ, Pichard AD, Satler LF, Kent KM, Stone GW, Leon MB. Atherosclerotic plaque burden and CK-MB enzyme elevation after coronary interventions: intravascular ultrasound study of 2256 patients. Circulation 2000;10:604 –610. 8. Campeau L. Grading of angina pectoris (letter). Circulation 1976;54:522–523. 9. Lansky AJ, Popma JJ. Qualitative and quantitative angiography. In: Topo E, ed. Textbook of Interventional Cardiology. Philadelphia, PA: WB Saunders, 1999:725–747. 10. Ahmed JM, Hong MK, Mehran R, Mintz GS, Lansky AJ, Pichard AD, Satler LF, Kent KM, Wu H, Stone GW, Leon MB. Comparison of debulking followed by stenting versus stenting alone for saphenous vein graft aortoostial narrowings: immediate and one-year clinical outcomes. J Am Coll Cardiol 2000;35:1560 –1568. 11. Kalbfleisch H, Hort W. Quantitative study on the size of coronary artery supplying areas postmortem. Am Heart J 1977;94:183–188. 12. Mahmarian JJ, Pratt CM, Boyce TM, Verani MS. The variable extent of jeopardized myocardium in patients with single vessel coronary artery disease: quantification by thallium-201 single photon emission computed tomography. J Am Coll Cardiol 1991;17:355–362. 13. Klein LW, Weintraub WS, Agarwal JB, Schneider RM, Seelaus PA, Katz RI, Helfant RH. Prognostic significance of severe narrowing of the proximal portion of the left anterior descending coronary artery. Am J Cardiol 1986;58:42–46. 14. de Jaegere P, Mudra H, Figulla H, Almagor Y, Doucet S, Penn I, Colombo A, Hamm C, Bartorelli A, Rothman M, et al. Intravascular ultrasound-guided optimized stent deployment. Immediate and 6 months clinical and angiographic results from the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study). Eur Heart J 1998;19:1214 –1223. 15. Fitzgerald PJ, Oshima A, Hayase M, Metz JA, Bailey SR, Baim DS, Cleman MW, Deutsch E, Diver DJ, Leon MB, et al. Final results of the Can Routine Ultrasound Influence Stent Expansion (CRUISE) study. Circulation 2000;102: 523–530.
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