Author + information
- Received September 18, 1996
- Revision received March 14, 1997
- Accepted March 31, 1997
- Published online July 1, 1997.
- Roger J. Laham, MDA,
- Kalon K.L. Ho, MD, MSc, FACCA,
- Donald S. Baim, MD, FACCA,
- Richard E. Kuntz, MD, MSc, FACCA,
- David J. Cohen, MD, MScA and
- Joseph P. Carrozza Jr., MD, FACCA,*
- ↵*Dr. Joseph P. Carrozza, Cardiovascular Division, Harvard Medical School, Beth Israel Hospital, 330 Brookline Avenue, Boston, Massachusetts 02215.
Objectives. To determine whether the benefits outlined in Backgroundmight extend to patients with multivessel disease, we examined the short- and long-term outcome of multivessel Palmaz-Schatz stenting.
Background. Percutaneous transluminal coronary angioplasty (PTCA) has become the dominant treatment for most patients with single-vessel coronary artery disease and has emerged as an alternative treatment for selected patients with multivessel coronary artery disease. Although multivessel angioplasty has excellent early results and low procedural complication rates, long-term outcome is tempered by the frequent need for repeat revascularization. In patients with single-vessel coronary artery disease, Palmaz-Schatz stenting has been shown to have a higher success rate and a lower restenosis rate than conventional PTCA.
Methods. A total of 103 patients (mean age 64 ± 11 years, 78 men and 25 women) underwent stenting of 212 vessels (saphenous vein graft [53%], left anterior descending coronary artery [20%], left circumflex artery [12%] and right coronary artery [15%]). In 88 patients (85%), multivessel stenting was performed during the same procedure, whereas the remaining 15 patients (15%) had staged multivessel stenting within 1 week of the index stent. Stenting involved only native coronary arteries in 33 patients and only vein grafts in 51 patients.
Results. Angiographic success was achieved in 102 patients (99%). Major complications developed in three patients: one patient died, and two patients had Q wave myocardial infarction, with no emergency coronary artery bypass graft surgery or stent thrombosis. Eleven additional patients (11%) developed non–Q wave myocardial infarction, and nine patients (9%) had local vascular complications requiring surgical repair. Clinical follow-up was available in all patients at a mean of 13 ± 8 months. At 1 year, survival was 98%, with an event-free survival rate of 80%, reflecting predominantly repeat revascularization (17% overall, with 9% target site revascularization). Multivessel native coronary stenting resulted in a higher event-free survival rate and a lower probability of repeat revascularization than did multivessel saphenous vein graft stenting.
Conclusions. In selected patients, multivessel Palmaz-Schatz stenting is technically feasible and carries both excellent early results and favorable 1-year clinical outcome.
(J Am Coll Cardiol 1997;30:180–5)
Percutaneous transluminal coronary angioplasty (PTCA) began as a treatment for proximal, noncalcified stenoses in a single coronary artery (). With advances in catheter design and angioplasty techniques, availability of new devices and increasing operator experience, PTCA has become the dominant treatment for most patients with symptomatic single-vessel coronary artery disease and has been extended to selected patients with multivessel coronary artery disease ([2–6]). Initial evaluation of multivessel angioplasty consisted of descriptive studies ([2–6]) and retrospective matched studies comparing it to coronary artery bypass graft surgery (CABG) ([7–9]). Although these studies showed excellent early success and low procedural complication rates, longer term outcome was tempered by the need for repeat revascularization in 38% to 47% of patients ([2–9]). Within the past 6 years, several long-term, randomized trials comparing multivessel conventional balloon angioplasty to CABG have been completed ([10–14]), showing similar short- and intermediate-term (3 to 5 years) mortality, but a significantly higher (two- to threefold) rate of repeat revascularization in the PTCA group ([10–14]). The majority of percutaneous revascularizations performed in these studies consisted of conventional balloon angioplasty, because these studies predated U.S. Food and Drug Administration approval of the Gianturco-Roubin stent (July 1993) and the Palmaz-Schatz stent (August 1994).
The Stent Restenosis Study (STRESS) () and Belgian Netherlands Stent study (BENESTENT) () trials have recently demonstrated that Palmaz-Schatz stenting of single, de novo lesions in native coronary arteries is associated with greater early procedural success and lower incidences of in-hospital events, angiographic restenosis and 1-year target vessel revascularization (TVR) compared with conventional balloon angioplasty. In addition, Palmaz-Schatz stenting of aortocoronary saphenous vein grafts (SVG) appears to have a higher success rate and a lower restenosis rate than historic balloon angioplasty controls (). This raises the question of whether the benefits of single-vessel stenting would extend to multivessel intervention. Encouraged by favorable results of multivessel Palmaz-Schatz stenting in a small group of patients (), we have continued to apply this approach to selected patients. In this study, we report the early and 1-year outcome of a 103-patient cohort who underwent multivessel stenting.
1.1 Study Patients.
Between July 1988 and December 1995, more than 1,000 patients underwent Palmaz-Schatz stent placement at Beth Israel Hospital in Boston. This includes the 103 patients described in this report, who underwent elective placement of 273 Palmaz-Schatz stents in 212 vessels. Patients were selected for multivessel stenting if they had significant focal or tubular stenoses in more than one native coronary artery or vein graft suitable for stent placement, as well as evidence of myocardial ischemia. Exclusion criteria included contraindication to antiplatelet or anticoagulation therapy; poor distal runoff; small (<2.75 mm), diffusely diseased vessels; involvement of a major (>2 mm) side branch; or significant valvular disease.
1.2 Pharmacologic Protocol.
All patients received soluble, nonenteric-coated aspirin (325 mg, continued indefinitely in an enteric-coated form) and a calcium antagonist before the procedure. In addition, 38 patients treated before August 1994 received dipyridamole (225 mg/d), and 65 patients treated thereafter received ticlopidine (500 mg/d) for 1 month after the procedure. Before August 1994, 1 liter of low molecular weight dextran (Dextran 40) was infused starting 3 h before the procedure and continued for 12 h after the procedure. During the procedure, 10,000 U of heparin was administered intravenously, with additional heparin given to maintain an activated clotting time >300 s. After sheath removal, an infusion of heparin was continued until warfarin therapy brought the international normalized ratio to 2.0 to 3.0, where it was maintained for 1 to 2 months.
1.3 Stent Implantation and Angiographic Analysis.
All patients received Palmaz-Schatz stents (175 coronary stents and 98 biliary stents [] [Johnson & Johnson Interventional Systems]). Lesions were predilated using an undersized balloon. After deployment of the stent, full stent expansion was performed using adjunctive high pressure (14 to 18 atm) balloon (1.0 to 1.1 balloon/artery ratio) dilation as required, to achieve <10% residual stenosis. Angiography was performed in two orthogonal views. Each stented lesion was measured from an optically magnified cine frame showing the lesion in its tightest view, using the guiding catheter as a reference object. Measurements were performed by using digital calipers (Fowler Ultra-Cal II) and included guiding catheter diameter, proximal and distal reference segment diameter and minimal lumen diameter before and after stenting.
All patients were contacted by the investigators at 6 weeks, 4 and 6 months, 1 year and then yearly thereafter to assess for clinical events (death, myocardial infarction or any revascularization). Repeat revascularization referred to any revascularization (percutaneous or surgical) performed during the study period. Revascularization was further categorized as TVR and target site revascularization (TSR, defined as any revascularization involving the stent itself or adjacent unstented vessel within 5 mm proximal or distal to the index stent). Clinical follow-up was available for all 103 patients and averaged 13 ± 8 months (range 2.4 to 35.1). Follow-up for at least 6 months was available in 93 patients (90%). Survival and event-free survival were calculated from the date of the procedure to the date of death or last follow-up.
1.5 Statistical Analysis.
Data are expressed as mean value ± SD. Continuous variables were compared using the unpaired Student ttest, and categoric variables were compared by chi-square analysis (). Survival and event-free survival (freedom from death, myocardial infarction or repeat revascularization) were estimated by Kaplan-Meier curves and compared using the log-rank statistic ([20, 21]). All p values were two-tailed, and p ≤ 0.05 was considered statistically significant.
2.1 Patient Characteristics.
The study cohort consisted of 103 patients (78 men and 25 women) who underwent placement of 273 stents in 212 vessels (left anterior descending coronary artery [LAD, 20%], left circumflex coronary artery [LCx, 12%], right coronary artery [RCA, 15%] and SVG [53%]). The baseline characteristics are summarized in Table 1. The patients’ mean age was 64 ± 11 years. Seventy-two patients (70%) had previous CABG, 17 patients (17%) had a recent myocardial infarction and 60 patients (58%) had unstable angina. In 88 patients (85%), multivessel stenting was performed during a single procedure. Staged interventions (within 1 week) were performed in the remaining 15 patients (15%). Multivessel stenting involved purely native coronary arteries in 33 patients (32%) and purely saphenous vein bypass grafts in 51 patients (49%). Treated lesions represented recurrence after a previous intervention in 10% of vessels.
2.2 Early Procedural Outcome.
Angiographic success (defined as <50% diameter stenosis with Thrombolysis in Myocardial Infarction trial [TIMI] flow grade 3) was achieved in 210 stented vessels (99%). Overall, stenting resulted in a reduction in diameter stenosis from 79 ± 14% to 2 ± 8% (Fig. 1). One patient (1%) died 2 days after successful stenting of two vessels in the setting of cardiogenic shock, and two patients (2%) sustained a Q wave myocardial infarction. Non–Q wave myocardial infarction (peak creatine kinase, MB fraction 39 ± 25 IU/liter [normal <13 IU/liter]) occurred in 11 patients (11%). No patient required emergency CABG, and neither acute nor subacute stent thrombosis was observed. Nine patients (9%) sustained local vascular complications requiring surgical repair and 12 patients (12%) required blood transfusion.
2.3 Long-Term Outcome.
Clinical follow-up was available in all patients and averaged 13 ± 8 months (range 2.4 to 35.1). Follow-up of at least 6 months was available in 93 patients (90%). At most recent follow-up, 21 patients (21%) had sustained major events: 4 patients (4%) died, 4 patients (4%) had a myocardial infarction and 17 patients (17%) required repeat revascularization. No patient required CABG. Of the 17 patients who underwent repeat revascularization of the target vessel, nine (9%) had revascularization of the stented site (TSR). At last follow-up, 81 patients (79%) were free from angina.
The cumulative probability of overall survival (98% at 1 year) and event-free survival (80% at 1 year) is shown in Fig. 2(Kaplan-Meier curves). The cumulative probabilities of undergoing repeat revascularization or TVR (18% at 1 year) and TSR (9% at 1 year) are shown in Fig. 3.
2.4 Multinative versus Multi-SVG Stenting.
Multivessel stenting was confined to saphenous vein bypass grafts in 51 patients and to native coronary arteries in 33 patients (27 patients underwent stenting of two vessels, and six patients underwent stenting of all three native vessels). Their clinical characteristics are detailed and compared in Table 2. These two groups had similar baseline clinical characteristics, except that only four patients (12%) in the native group had undergone previous CABG. The procedural success rate was 97% for the native vessel group and 98% for the SVG group. Non–Q wave myocardial infarction tended to be less common in the native vessel group (three patients [9%] in the native vessel group vs. seven patients [14%] in the SVG group, p = 0.08). During follow-up, fewer major events occurred in the native vessel group compared with the SVG group (6% vs. 25%, p = 0.01). This difference reflected predominantly more repeat revascularizations in the SVG group than in the native vessel group (22% vs. 3%, p = 0.04). This difference may be explained, in part, by the slightly longer mean follow-up duration in patients with multi-SVG stenting compared with multinative stenting (14 ± 9 months [range 2.4 to 35.1] vs. 10 ± 8 months [range 2.6 to 30.9], p = 0.06). At last follow-up, three (9.4%) of 33 patients with native coronary stenting and 13 (25.5%) of 51 patients with vein graft stenting reported angina (p = 0.2). Fig. 4shows that event-free survival was better for native vessel treatment compared with SVG treatment (92% vs. 74%, p = 0.01). Although the cumulative probability of any subsequent revascularization was higher in the SVG group than in the native vessel group (1-year repeat revascularization 23% vs. 5%, p = 0.01), the need for revascularization of the target sitewas similar in the two groups (1-year TSR of 10% for SVG and 5% for native vessels, p = 0.5) (Fig. 5).
Five randomized trials comparing multivessel conventional PTCA to CABG have been published ([10–14]), all showing similar rates of late (3 to 5 years) death or myocardial infarction but higher incidences of angina and repeat revascularization in patients treated with PTCA (). The main limitation of multivessel PTCA thus remains its substantial need for repeat revascularization, generally driven by clinically significant restenosis occurring within the first 6 to 12 months of initial treatment. In patients with single-vessel de novo native coronary lesions, Palmaz-Schatz stenting is associated with a reduction in restenosis and TVR compared with conventional PTCA ([15–17]). Extension of this approach to selected patients with multivessel disease might thus reduce the need for early repeat revascularizations and prolong the symptom-free interval.
Over the last 5 years, we have applied multivessel stenting to selected patients, many of whom (70%) had previous CABG, which made percutaneous revascularization a more attractive strategy than repeat CABG. Although the majority of patients treated with stenting in our early experience underwent stenting of a single vessel, the 103 patients in this series represent 10% of our cumulative experience with stenting to date. The 99% angiographic success rate and 3% major complications rate (1% death, 2% Q wave myocardial infarction) underscore the high level of reliability that stenting offers in the treatment of both native coronary and vein graft disease ([16–18, 22–24]). These early outcomes compare favorably with previous reports of balloon angioplasty in which multivessel disease and multivessel intervention were identified as predictors of adverse events ([2–4]).
Randomized trials of conventional PTCA in multivessel disease, however, have identified restenosis (requiring repeat revascularization) and recurrent angina as the main limitations of PTCA versus CABG. In the present analysis, the 1-year repeat revascularization rate was 18% (5% for multinative vessel and 23% for multi-SVG stenting). According to Kaplan-Meier estimates, the 1-year overall survival rate was 98% and the 1-year event-free survival rate was 80%. Of the repeat revascularization procedures, all were percutaneous and only 9% were related to the stented site (TSR, 5% for native vessel and 10% for SVG), reflecting the fact that repeat revascularization was being performed mainly to treat progression of disease at other sites, particularly after SVG stenting. These TVR and TSR rates are similar to other reported series of Palmaz-Schatz stenting ([16–18, 22–24]). Most important, all measures of 1-year clinical outcome (including survival, event-free survival, freedom from myocardial infarction, TVR and TSR) compared favorably with reported series of multivessel angioplasty ([2–13]).
When the analysis is restricted to just the 33 patients who underwent multivessel stenting limited to native coronary arteries, the 5% one-year repeat revascularization rate is lower than that reported for conventional PTCA in multivessel disease. Even for those patients who underwent multivessel stenting of saphenous vein grafts, the 23% one-year repeat revascularization rate and 10% one-year TSR rate are excellent for a subset of patients that characteristically has a high (40% to 60%) restenosis rate (), and below those rates seen for both balloon angioplasty and directional atherectomy in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT II) ().
3.1 Study Limitations.
This study has several important limitations. First, because it represents an observational study, no directcomparison with CABG or multivessel PTCA can be made. Second, this study represents a highly selected subset of patients with multivessel disease. A large proportion of patients with multivessel coronary artery disease are not eligible for complete revascularization by stenting, because <20% of patients with multivessel disease were found eligible for conventional PTCA in the randomized trials of PTCA versus CABG ([10–14]) owing to disease in small, diffusely diseased or totally occluded vessels. Thus, this cohort represents a select minority of patients chosen for clinical and angiographic characteristics favorable for stenting, which limits the extrapolation of its findings to the majority of patients with multivessel disease.
The present study demonstrates that in a highly selected group of patients with multivessel coronary artery disease suitable for stenting, this approach is technically feasible, with excellent early results and a favorable long-term clinical outcome. Larger, randomized trials comparing multivessel stenting to CABG are warranted to allow direct comparison between these revascularization strategies.
☆ Dr. Laham was supported in part by a Hewlett-Packard fellowship award.
- coronary artery bypass graft surgery
- left anterior descending coronary artery
- left circumflex coronary artery
- percutaneous transluminal coronary angioplasty
- right coronary artery
- saphenous vein graft
- target vessel revascularization
- target site revascularization
- Received September 18, 1996.
- Revision received March 14, 1997.
- Accepted March 31, 1997.
- The American College of Cardiology
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