This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schühlen, H. Articles by Schömig, A. Search for Related Content PubMed PubMed Citation Articles by Schühlen, H. Articles by Schömig, A.

(Circulation. 1998;98:104-111.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

Intracoronary Stenting and Risk for Major Adverse Cardiac Events During the First Month

Helmut Schühlen, MD; Adnan Kastrati, MD; Josef Dirschinger, MD; Jörg Hausleiter, MD; Shpend Elezi, MD; Anne Wehinger, MD; Jürgen Pache, MD; Martin Hadamitzky, MD; ; Albert Schömig, MD

From the Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Germany.

Correspondence to Dr Helmut Schühlen, 1. Medizinische Klinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger Str 22, D-81675 München, Germany. E-mail h.schuehlen{at}med1.med.tu-muenchen.de

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background—Our rationale for this study was to analyze the risk for procedural failure of attempted stenting and the risk for major adverse cardiac events (MACE) after success and to develop a risk stratification protocol for successful procedures.

Methods and Results—Stenting was attempted in 2894 procedures during the 5-year study period (success in 98.3% of 3815 lesions). After failure, the MACE rate was 42.6%. The risk for failure was higher for lesions in the left circumflex coronary artery or in venous bypass grafts and after an acute occlusion before stenting; it increased with stenosis length or grade and decreased with vessel size and growing institutional experience in stenting. After success, death occurred in 0.8%, death or myocardial infarction in 2.0%, and any MACE in 3.6%. Independent risk factors for MACE were older age, diabetes, acute myocardial infarction, unstable angina, impaired left ventricular function, residual dissections, stent overlap, longer stented segments, and a postprocedural regimen without ticlopidine. Procedural factors were substantially stronger predictors than operator-independent variables available before procedures. Overall, the risk declined after the first 3 days. Two major factors exhibited time-dependent variations of their influence: while residual dissections were the dominant risk factor within the first 3 days with a reduction after that, no protective effect of ticlopidine could be identified before day 3. From these results, we derived a risk stratification protocol for individual procedures.

Conclusions—These results underscore the importance of optimal angiographic results and the need for antiplatelet regimens with immediate onset. Our risk stratification protocol may guide individual postprocedural care and allow us to compare risk profiles of different study populations and to devise quality control programs for stenting.

Key Words: stents • coronary disease • risk factors • platelet aggregation inhibitors

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Coronary stenting has become an established treatment for suboptimal results after conventional angioplasty (PTCA),^{1 2 3 4} and it reduces restenosis rates in comparison with PTCA.^{5 6} The use of stents has been growing continuously beyond these indications, and today stents are a ubiquitous routine in interventional cardiology.

Although stenting is technically more difficult than standard PTCA, it can be achieved with a high primary success rate (94% to 97%).^{5 6 7 8} However, most studies reporting procedural success rates have included only selected patients, for example, those with less complex stenoses. These data might not be applicable to many patients in the increasing routine use of stents. A comprehensive analysis of the risk of procedural failure and the associated risk of MACE is warranted.

Technical refinements and improvements of postprocedural antithrombotic therapy have reduced the rate of MACE during early follow-up.^{9 10 11 12} However, the MACE rates may vary substantially, depending on clinical, angiographic, and procedural characteristics,¹³ and a comprehensive analysis of the risk for MACE is not available. A protocol for individual risk stratification may not only guide the necessary follow-up care and treatment but also allow us to devise quality control programs for interventional procedures with stent placement.

The rationale of the present study was therefore to analyze the risk for procedural failure of attempted stent placement and the risk for MACE after successful stenting and to develop a risk stratification protocol for successful procedures.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patient Population
During the 5-year study period between May 1992 and May 1997, stent placement was attempted during 2894 consecutive procedures (2444 patients, 3815 lesions); 73 additional procedures in patients with cardiogenic shock or mechanical ventilation before PTCA were excluded from this analysis.

Stent Placement
Before stenting, no additional alternative technique (ie, rotational ablation, laser, or other debulking devices) was used. Implantation of various slotted-tube–type stents was performed as previously described.² The majority were hand-crimped on the angioplasty balloon catheters (95.4%). Intravascular ultrasound studies were performed in only a minority of procedures (8.3%).

Clinical Management After Success
Three different antithrombotic regimens were used: full anticoagulation (18.7% of procedures), combined antiplatelet therapy (79.7%), and aspirin alone (1.6%). All patients were given aspirin (100 mg BID) and intravenous heparin for 12 hours (target partial thromboplastin time, 80 to 100 seconds). Patients with full anticoagulation received the coumarin derivative phenprocoumon (Marcumar; Hoffmann-La Roche), and intravenous heparin was continued until a target international normalized ratio of 3.5 to 4.5 was achieved. Patients assigned to combined antiplatelet therapy received ticlopidine (250 mg BID; Tiklyd, Sanofi-Winthrop). Ticlopidine or phenprocoumon was given for 4 weeks. Because of the pivotal role of ticlopidine,^{9 11 12} postprocedural regimens are categorized as either with or without ticlopidine.

A complete 30-day follow-up is available for all procedures; all patients were seen as outpatients 1 month after discharge or were contacted by telephone.

Definitions
Procedural success was defined as successful stent placement at the desired position with <30% residual stenosis. MACE were death of cardiac or procedure-related origin, MI, and repeat target lesion revascularization by PTCA or coronary artery bypass graft surgery during a 30-day follow-up. Institutional experience was the time between the day of the procedure and the beginning of the study (May 1, 1992). The following assessments were performed by the operator at the end of the procedure: LV function was categorized as normal in the absence of wall motion abnormalities, slightly impaired if 1 or 2 of 7 ventricular segments were hypokinetic, impaired if several segments were hypokinetic or 1 or 2 akinetic, and severely impaired if several segments were akinetic with only 1 or 2 normal segments. A residual dissection was noted in the presence of a small (<5-mm) dissection in the stented or adjacent segment; dissections >5 mm for which a necessary coverage with additional stents could not be achieved for procedural or technical reasons were defined as substantial residual dissections. Quantitative angiographic analysis was performed off-line on a commercially available system with edge-detection algorithms (CMS, Medis Medical Imaging Systems) by trained technicians not involved in the procedures and unaware of the operator's qualitative assessments. Measurements of minimal luminal diameter and reference diameter (before and at the conclusion of the procedure), of stenosis length, of the minimal diameter of the largest balloon at maximum inflation pressure, and of the length of the stented segment were obtained.

Data Analysis and Statistics
Data were continuously assessed and entered into a relational database. Clinical data were recorded to define procedures, and angiographic data were assessed for individual lesions treated during a procedure. Analyses were performed with S-Plus software (MathSoft), expanded by a function library by Harrell.¹⁴ Statistical significance was assumed at P<0.05.

The risk of procedural failure was calculated per lesion with a logistic regression model based on factors available before procedures. Odds ratios were computed for significant correlates. For continuous variables, these refer to the ratio between the odds for the 1st and 3rd quartiles. No significant changes in regression coefficients were observed in 1000 bootstrap replications,¹⁵ even after a potential clustering effect for interventions in >1 lesion was accounted for. We did not limit the number of variables entered into the analysis. However, an unrestricted model yielded the best Akaike's information criterion (model ² minus twice the number of parameters aside from the intercept).¹⁴ The reliability of the model was assessed by cross-validation. The model was fitted to 200 bootstrap replications (training sample) and to the original data (test sample) with a good agreement (bootstrap estimate for slope shrinkage, -0.70).¹⁴

The risk for MACE was analyzed per procedure with Cox proportional hazard models. Hazard ratios were computed for significant correlates. For interventions in >1 lesion, angiographic variables of 1 randomly assigned lesion were entered into the analysis; for lesion length and length of stented segments, we analyzed the sum of measurements of all lesions to avoid missing an additive role. For the Cox model, the proportional hazard assumption over time was initially tested for each variable. A time-dependent covariable was added to variables that did not satisfy this assumption (product of variable with log-transformed time-to-event). The Cox model was validated in 2 ways: first, the model was fitted to 200 bootstrap samples (training sample) and to the original data (test sample); the resulting correlation was very close (bootstrap estimate for slope shrinkage, 0.79). Second, the survival predicted from 200 bootstrap replications correlated well with the actual Kaplan-Meier survival in all time intervals analyzed. To define subgroups of patients with different risks for MACE, linear risk predictors for each procedure were derived from Cox model analysis. Quartile values were used to differentiate risk groups. On the basis of this model, we developed software to predict the risk for MACE. The program assigns a patient to 1 predicted risk group after actual parameters are entered. Detailed subgroup analysis was made by use of the CART.¹⁶ The knots of the first 4 divisions are presented unless a subgroup had <50 cases and <10 events.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Stent placement was attempted in 3815 lesions during 2894 procedures in 2444 patients. Procedural success was achieved in 98.3% of lesions and 97.9% of procedures. The reasons for procedural failure were inability to reach or cross the primary target lesion with the stent (n=19), inability to cross an already placed stent with another stent to reach an additional distal target lesion (as defined by a residual stenosis >30% or a substantial dissection extending distally; n=29), inability to achieve adequate flow or a distal thrombus with TIMI flow <2 (n=12), and a perforation of a venous bypass graft (n=1). In 53 procedures, a stent was lost before implantation (0.8% of total number of stents implanted); in 6 of these, no final success could be achieved (resulting in 1 MACE). In 47 procedures, the stent could be withdrawn from the coronary circulation and was lost in the aorta or the peripheral circulation without any associated clinical complication. In 6 of the 53 procedures, a stent was lost within the coronary circulation. Five of these were recovered; 1 was pressed against the vessel wall with an additional stent. All 6 cases were finished successfully without any subsequent MACE.

Failure was associated with a 42.6% MACE rate compared with 3.6% after successful procedures (OR=19.9; 95% CI, 11.0 to 35.3), with 8.2% deaths compared with 0.9% (OR=10.5; CI, 3.0 to 29.3) and 14.8% death or MI compared with 2.0% (OR=8.4; CI, 3.5 to 18.3). Unsuccessful procedures with MACE (n=26) differed from uneventful procedures with regard to vessel size (2.80±0.62 versus 3.11±0.61 mm; P=0.05), and they showed a trend toward more unstable angina (42% versus 17%; P=0.06).

Risk for Procedural Failure of Stent Placement
In view of the poor outcome after failure, we analyzed all variables available before procedures to identify risk factors for failure. All procedures with attempted stent placement are described in Table 1, distinguishing successful from unsuccessful procedures. All factors were entered into a multivariate logistic regression analysis; the resulting P values are listed in the Table. The 6 significant risk factors for procedural failure are illustrated in Figure 1: the risk increased with stenosis length and grade but decreased with vessel size; it was higher in the case of an acute occlusion before stenting (after the initial PTCA) and for lesions in venous bypass grafts or the LCx. The most significant factor was the institutional experience in stent placement technique: with increasing practice during the 5 years, procedural failure was less likely (Figure 2).

View this table: [in this window] [in a new window]   Table 1. Factors Analyzed for Risk of Procedural Failure

View larger version (14K): [in this window] [in a new window]   Figure 1. Odds ratios for independent risk factors for procedural failure as identified by multivariate analysis (for target vessel, LCx [CX] or venous bypass graft vs all other lesion locations; for continuous variables calculated for 1st vs 3rd quartile, ie, for vessel size, reference diameter 3.38 vs 2.66 mm; stenosis grade, 86.0% vs 63.4% grade stenosis before intervention; stenosis length, 13.6 vs 6.8 mm; institutional experience in stent placement technique, 4th vs 1st year); odds ratios are displayed on logarithmic scale.

View larger version (12K): [in this window] [in a new window]   Figure 2. Risk for procedural failure (odds) as a function of institutional experience in stent placement technique, adjusted for all other covariates.

Risk for MACE After Successful Stent Placement
The overall incidence of MACE was 3.6% (n=102). In 65 events, the cause was stent occlusion verified by angiography or autopsy; 20 were repeat PTCAs with patent stents but nonocclusive dissections in neighboring segments or side branches; 3 were MIs due to side branch occlusions after stenting; 12 were deaths of cardiac origin without evidence of stent occlusion; and 2 were procedure-related noncardiac deaths. No other deaths occurred during the study period. The association of all factors with MACE is summarized in Table 2, with P values from the Cox model. Independent risk factors were older age, diabetes, acute MI, unstable angina, impaired LV function, residual dissections, stent overlap, and longer stented segments; a postprocedural regimen with ticlopidine was a significant protective factor (Figure 3).

View this table: [in this window] [in a new window]   Table 2. Factors Analyzed for Risk of MACE After Successful Stent Placement

View larger version (16K): [in this window] [in a new window]   Figure 3. Hazard ratios for independent risk factors for MACE after successful stenting identified by Cox analysis (for age calculated for 1st vs 3rd quartile; ie, 71.1 vs 55.8 years; for impaired LV function, impaired vs normal; for length of stented segment, 30 vs 15 mm; for residual dissection, substantial vs no residual dissection); hazard ratios are displayed on a logarithmic scale.

This analysis is based on 4 categories of factors: (1) clinical data; (2) lesion characteristics, both available before procedures and operator-independent; (3) procedural factors describing the intervention and the final results; and (4) the postprocedural antithrombotic regimen (categorized as with or without ticlopidine). These 4 categories are separated by thin lines in Table 2. To assess the contribution of each category to the strength of the final Cox model, we analyzed partial models with variables from the respective categories. These results are illustrated in Figure 4 in a comparison of the ² of the partial models. The models with variables available before the procedure that are operator-independent yield a relatively low ², indicating only a minor contribution to the strength of the full model. The model with procedural variables yields a high ², which is further increased if the adjunct postprocedural regimen is included. These analyses indicate a dominant contribution of these operator-dependent factors to the risk for MACE.

View larger version (38K): [in this window] [in a new window]   Figure 4. Comparison of strength of partial models of Cox regression analysis (ie, 2) for risk for MACE: result for full model with all variables is displayed by top bar. 2 for 3 partial models with only 1 category of variables are shown in middle (these categories of variables are separated by thin lines in Table 2). Bottom, 2 for a model including all variables available before procedure, ie, clinical and lesion variables, is compared with 2 of a model combining procedural variables with postprocedural ticlopidine regimen. Graph illustrates dominant influence of operator-dependent variables.

Time Dependency of Risk Factors
Figure 5A shows the cumulative incidence of MACE. There is an apparent decline in the risk for MACE, with >50% of events occurring in week 1. This decreasing hazard as a function of time is illustrated in Figure 5B. All significant factors were tested for temporal variations of their influence. The 2 factors identified are illustrated in Figure 5C. Residual dissections constituted a major risk factor during the first 3 days, with a decreasing weight afterward. An opposing effect was seen for a regimen without ticlopidine: during the first 2 days, this did not constitute a significant risk; however, the hazard ratio later increased significantly, peaking after 1 week. This signifies that a protective effect of ticlopidine could not be identified before day 3.

View larger version (13K): [in this window] [in a new window]   Figure 5. A, Cumulative incidence of all MACE during first 30 days after successful stent placement (TLR indicates target lesion revascularization, ie, repeat PTCA or bypass grafting of target lesion). B, Instantaneous hazard rate for MACE during time course of 30 days. Graph illustrates that risk for MACE decreases rapidly within first 5 days. C, Time-dependent contribution of 2 factors to risk for MACE, residual dissection, and a postprocedural regimen without ticlopidine: for both factors, hazard ratio is illustrated as a function of time for study period of 30 days.

Risk Stratification
We used a CART model to define subgroups with distinct MACE rates (Figure 6). The primary risk factor was the grade of residual dissection: in its presence, the MACE rate increased from 2.1% to 8.4%. It increases further for subgroups with length of stented segment >15 mm and substantial residual dissections to a maximum of 27.8%. Conversely, the lowest event rate of 0.5% could be found in a large group of 30% of all procedures (n=844) in patients with normal LV function, a postprocedural regimen with ticlopidine, and no acute MI.

View larger version (32K): [in this window] [in a new window]   Figure 6. CART model constructed with independent risk factors for MACE. Knots identify subgroups of procedures with different MACE rates. Area of a circle indicates size of a subgroup relative to whole group (n=2833). Discriminating factors of knots are indicated; group with higher event rate is always positioned on right branch.

To calculate individual risks of procedures based on actual parameters, linear risk predictors were derived from the Cox model with all variables. This risk stratification protocol defines 3 risk groups on the basis of the quartiles of the study population. The 2 quartiles with the lowest risk were condensed to 1 low-risk group because the quartile values were not significantly different (0.4% and 1.0%). This model therefore identified a large group with a low risk and 2 smaller groups with intermediate and high risk. Figure 7 shows the cumulative MACE rates for these groups. This graph illustrates that in the high and intermediate risk groups, events occurred throughout the observation period. In the low-risk group, however, no event occurred after day 15.

View larger version (14K): [in this window] [in a new window]   Figure 7. Observed cumulative event rate for 3 risk groups as stratified by Cox model. Risk stratification into 3 groups is based on quartiles of study population (2 low-risk quartiles are condensed to 1 group because risk of these 2 quartiles was not significantly different).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
In the present study, we provide a comprehensive analysis of the risk for procedural failure of coronary stenting as well as the risk for MACE after procedural success, and we describe a protocol for individual risk stratification. This analysis included all patients treated at our institutions during a 5-year period; only patients with cardiogenic shock or mechanical ventilation before the procedure were excluded. Therefore, the study population represents the full spectrum of symptomatic coronary artery disease, including many patients with acute coronary syndromes and technically complex lesions who had been excluded from several previous trials.

Procedural success was achieved in 97.9% of procedures. This success rate is higher than reported for several studies that had included only selected patients.^{5 6 7 8} However, most of these studies used stents premounted on delivery systems with unfavorable balloon catheter profiles and limited trackability. The majority of our procedures were performed with hand-mounted stents on low-profile, rapid-exchange catheters. In our analysis, procedural failure was more likely in venous bypass grafts or lesions in the LCx, after an acute occlusion before stenting (after the initial PTCA), and in smaller vessels with tighter or longer lesions. The main factor for success, however, was the institutional experience in stent placement technique. This time-dependent protective factor reflects our institutional learning curve together with continuing improvements in technique. In view of the high MACE rate observed after unsuccessful procedures, these data underscore the need for optimization of technical equipment as well as operational skills.

Our data indicate that MACE rates after successful stenting may vary substantially. CART analysis (Figure 6) shows that there are well-defined subgroups with particular high or low event rates ranging from 0.5% to 27.8%. Because these depend on applicable risk factors identified by the Cox model, any comparison with other studies would have to account for differences in risk profiles.

We had included a very large number of factors: clinical data and lesion characteristics available before an intervention, procedural factors referring to the intervention and the final results, and the postprocedural antithrombotic regimen. Nine characteristics were identified as significant and independent risk factors for MACE. Several of these factors had already been suggested by logistic regression analyses focusing on thrombotic stent occlusion in smaller patient cohorts.^{3 19 20 21 22 23} Five of the significant factors are operator-independent, because they refer to a patient's status before the intervention (age, diabetes, acute MI, unstable angina, impaired LV function); 4 are operator-dependent, because they refer to either the procedure itself with final results (length of stented segment, residual dissection, stent overlap) or the postprocedural regimen (ticlopidine). The 3 most significant factors were all procedural variables (residual dissection, postprocedural regimen, and length of stented segment). Furthermore, in our analysis of partial models (Figure 4), the models with procedural variables and ticlopidine were the strongest, whereas models with data available before the intervention contributed only a minor part to the strength of the final model. These data suggest that factors describing the procedure and the final result are the major determinants of early outcome, with a smaller contribution by factors describing the patient's status before the procedure.

Our data indicate that the risk for MACE is highest during the first 3 days and decreases rapidly after that. However, only after procedures with a low-risk profile, no event occurred after week 2 (Figure 7B). Therefore, this study provides only limited support for concepts of a shorter ticlopidine regimen of only 2 weeks. We had identified 2 factors with significant temporal variations of their influence: the risk associated with residual dissections peaks during the first 3 days, with a decrease after that, and a protective effect of ticlopidine cannot be identified before day 3. Residual dissections represent a suboptimal final result. They have been identified as the major risk factor for thrombotic stent occlusions,¹² which have been the predominant cause of MACE in virtually all studies on stenting.²³ The delayed protective effect of ticlopidine reflects the well-known slow onset of action of this drug.²⁴ The contrasting effects of these 2 factors might be interrelated, suggesting that the early "gap" of ticlopidine action should be compensated for either by pretreatment with ticlopidine for several days or by more potent antiplatelet drugs with immediate onset of action (ie, glycoprotein IIb/IIIa receptor inhibitors) given during the procedure and the first few days. Further studies on optimal strategies for this early period after stenting are warranted.

Some factors included in our analyses for MACE have been subject to major debate, for example, maximum balloon pressure and balloon-to-vessel ratio. Neither variable was identified as a significant factor. Both were initially deemed important for the transition from full anticoagulation to combined antiplatelet therapy.²⁵ However, although high-pressure stent dilatations are widely performed, controlled data are not available.¹⁷ Retrospective analyses looking at the influence of high pressure and subsequent events did not identify an independent role of balloon pressure,^{12 22} and preliminary results from 2 randomized trials did not indicate a significant benefit for patients treated with high-pressure balloon inflations.^{26 27} Final results of these and possibly other randomized trials are necessary to define the role of balloon pressure.

Limitations
The rate of procedural failure was low. This might have affected the ability of the study to detect specific aspects or predictive factors for failure and might have increased the risk of a type II error.

All significant risk factors for procedural failure or MACE that are available before procedures were only weak predictors in our analysis (except for institutional experience); therefore, no inferences can be made that these might constitute contraindications for stenting.

Postprocedural increases in creatine kinase have been associated with adverse outcome, particularly with an increase in late mortality.²⁸ In our study, routine measurements of creatine kinase were used only to confirm a diagnosis of the adverse event of acute MI (in all our studies defined as twice the upper limit of normal²); small increases in enzyme levels were not recorded in the database. Therefore, we cannot evaluate the possible role of such a rise below the index limit.

Intravascular ultrasound studies were performed in only a minority of procedures. Therefore, this study does not allow for a meaningful analysis of the role of intravascular ultrasound or intravascular ultrasound measurements. We used predominantly hand-mounted slotted-tube stents; an unrestricted applicability of our results to other types (ie, with delivery systems or coil stents) would have to be verified in specific studies.

Bootstrapping procedures were performed to validate the results of our models; additional prospective or randomized trials may be necessary to further validate the findings of our study.

Summary
The main findings of the present study can be summarized as follows. Procedural success can be achieved in a very high number of procedures. Failure is associated with a >10-fold increase in MACE. The risk for procedural failure is higher after an acute occlusion before stenting (after initial PTCA) and for target lesions in the LCx or in venous bypass grafts; it increases with stenosis length and grade and decreases with vessel size and growing institutional experience in stenting. These data underscore the need for optimization of technical equipment as well as operational skills and training. After success, the risk for MACE depends predominantly on procedural characteristics: it is higher in the presence of residual dissections or stent overlap and increases with the length of the stented segment. Furthermore, the risk is significantly lower with postprocedural ticlopidine therapy. The risk for MACE depends to a lesser extent on operator-independent patient characteristics available before a procedure (age, diabetes, acute MI, unstable angina, impaired LV function). The risk for MACE declines after the first 3 days. Residual dissections are the most important risk factor for this early period, with a decline later. Ticlopidine has no effect on the risk for this early period but is a dominant protective factor later. These results underscore the importance of an optimal angiographic result and the need for an additional or alternative antiplatelet regimen with immediate onset. The risk stratification protocol based on our model calculations may allow us to study more precisely the necessary individual follow-up care, ie, the low-risk group may be the subject of future studies on the necessary duration of antithrombotic therapy, and the high-risk group may be the subject of studies on additional or more effective antithrombotic regimens. Furthermore, this protocol may permit an accurate comparison of different study populations. Finally, because this protocol identified procedural factors in particular, it may help to establish quality control programs for coronary stenting, which are undoubtedly needed in the future.

	Selected Abbreviations and Acronyms

 

CART = classification-and-regression tree LCx = left circumflex coronary artery LV = left ventricular MACE = major adverse cardiac event(s) MI = myocardial infarction PTCA = percutaneous transluminal coronary angioplasty

Received December 2, 1997; revision received February 18, 1998; accepted March 17, 1998.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Sigwart U, Puel J, Mirkovitch V, Joffre F, Kappenberger L. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N Engl J Med. 1987;316:701–706.[Abstract]

2. Schömig A, Kastrati A, Mudra H, Blasini R, Schühlen H, Klauss V, Richardt G, Neumann FJ. Four-year experience with Palmaz-Schatz stenting in coronary angioplasty complicated by dissection with threatened or present vessel closure. Circulation. 1994;90:2716–2724.[Abstract/Free Full Text]

3. George BS, Voorhees WD, Roubin GS, Fearnot NE, Pinkerton CA, Raizner AE, King SB, Holmes DR, Topol ER, Kereiakes DJ, Hartzler GO. Multicenter investigation of coronary stenting to treat acute or threatened closure after percutaneous transluminal coronary angioplasty: clinical and angiographic outcomes. J Am Coll Cardiol. 1993;22:135–143.[Abstract]

4. Pepine CJ, Holmes DR, Block PC, Brikner JA, Mark DB, Mullins CE, Nissen SE, Topol EJ, Williams DO, Goldberg S, Hirshfeld HW, Serruys PW. ACC Expert Consensus Document: coronary artery stents. J Am Coll Cardiol. 1996;28:782–794.[Medline] [Order article via Infotrieve]

5. Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M, Cleman M, Heuser R, Almond D, Teirstein PS, Fish RD, Colombo A, Brinker J, Moses J, Shaknovich A, Hirshfeld J, Bailey S, Ellis S, Rake R, Goldberg S. 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.[Abstract/Free Full Text]

6. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelson H, Marco J, Legrand V, Materne P, Belardi J, Sigwart U, Colombo A, Goy JJ, van den Heuvel P, Delcan J, Morel MA. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med. 1994;331:489–495.[Abstract/Free Full Text]

7. Schatz RA, Baim DS, Leon M, Ellis SG, Goldberg S, Hirshfeld JW, Cleman MW, Cabin HS, Walker C, Stagg J, Buchbinder M, Teirstein PS, Topol EJ, Savage M, Perez JA, Curry RC, Whitworth H, Soussa JE, Tio F, Almagor Y, Ponder R, Penn IM, Leonard B, Levine SL, Fish RD, Palmaz JC. Clinical experience with the Palmaz-Schatz coronary stent: initial results of a multicenter study. Circulation. 1991;83:148–161.[Abstract/Free Full Text]

8. Albiero R, Hall P, Itoh A, Blengino S, Nakamura S, Martini G, Ferraro M, Colombo A. Results of a consecutive series of patients receiving only antiplatelet therapy after optimized stent implantation: comparison of aspirin alone versus combined ticlopidine and aspirin therapy. Circulation. 1997;95:1145–1156.[Abstract/Free Full Text]

9. Schömig A, Neumann FJ, Kastrati A, Schühlen H, Blasini R, Hadamitzky M, Walter H, Zitzmann-Roth EM, Richardt G, Alt E, Schmitt C, Ulm K. A randomized comparison of antiplatelet and anticoagulation therapy after coronary stent placement. N Engl J Med. 1996;334:1084–1089.[Abstract/Free Full Text]

10. Colombo A, Hall P, Nakamura S, Almagor Y, Maiello L, Martini G, Gaglione A, Goldberg SL, Tobis JM. Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance. Circulation. 1995;91:1676–1688.[Abstract/Free Full Text]

11. Leon MB, Baim DS, Gordon P, Giambartolomei A, Williams DO, Diver DJ, Senerchia C, Fitzpatrick M, Popma JJ, Kuntz RE. Clinical and angiographic results from the Stent Anticoagulation Regimen Study (STARS). Circulation. 1996;94(suppl I):I-685. Abstract.

12. Karillon GJ, Morice MC, Benveniste E, Bunouf P, Aubry P, Cattan S, Chevalier B, Commeau P, Cribier A, Eiferman C, Grollier G, Guerin Y, Henry M, Lefevre T, Livarek B, Louvard Y, Marco J, Makowski S, Monassier JP, Pernes JM, Rioux P, Spaulding C, Zemour G. Intracoronary stent implantation without ultrasound guidance and with replacement of conventional anticoagulation by antiplatelet therapy: 30-day clinical outcome of the French Registry Study. Circulation. 1996;94:1519–1527.[Abstract/Free Full Text]

13. Schühlen H, Hadamitzky M, Walter H, Ulm K, Schömig A. Major benefit from antiplatelet therapy for patients at high risk for adverse cardiac events after coronary Palmaz-Schatz stent placement: analysis of a prospective risk stratification protocol in the Intracoronary Stenting and Antithrombotic Regimen (ISAR) Trial. Circulation. 1997;95:2015–2021.[Abstract/Free Full Text]

14. Harrell FE. Predicting Outcomes: Applied Survival Analysis and Logistic Regression. Charlottesville, Va: University of Virginia Press; 1997.

15. Efron B, Tibshirani R. An Introduction to the Bootstrap. New York, NY: Chapman & Hall; 1993.

16. Breiman L, Friedman JH, Olshen RA, Stone CJ. Classification and Regression Trees. Pacific Grove, Calif: Wadsworth & Brooks/Cole; 1984.

17. Ellis SG, Vandormael MG, Cowley MJ, DiSciascio G, Deligonul U, Topol EJ, Bulle TM, and the Multivessel Angioplasty Prognosis Study Group. Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease: implications for patient selection. Circulation. 1990;82:1193–1202.[Abstract/Free Full Text]

18. The Thrombolysis in Myocardial Infarction (TIMI) Trial. N Engl J Med. 1985;312:932–936.[Medline] [Order article via Infotrieve]

19. Agrawal SK, Ho DSW, Liu MW, Iyer SS, Hearn JA, Cannon RA, Macander PJ, Dean LS, Baxley WA, Roubin GS. Predictors of thrombotic complications following placement of the flexible coil stent. Am J Cardiol. 1995;73:1216–1219.

20. Liu MW, Voorhees WD III, Agrawal S, Dean LS, Roubin GS. Stratification of the risk of thrombosis after intracoronary stenting for threatened or acute closure complicating coronary balloon angioplasty: a Cook registry study. Am Heart J. 1995;130:8–13.[Medline] [Order article via Infotrieve]

21. Foley JB, Brown RIG, Penn IM. Thrombosis and restenosis after stenting in failed angioplasty: comparison with elective stenting. Am Heart J. 1994;128:12–20.[Medline] [Order article via Infotrieve]

22. Moussa I, Di Mario C, Reimers B, Akiyama T, Tobis J, Colombo A. Subacute stent thrombosis in the era of intravascular ultrasound-guided coronary stenting without anticoagulation: frequency, predictors and clinical outcome. J Am Coll Cardiol. 1997;29:6–12.[Abstract]

23. Mak KH, Belli G, Ellis SG, Moliterno DJ. Subacute stent thrombosis: evolving issues and current concepts. J Am Coll Cardiol. 1996;27:494–503.[Abstract]

24. Harker LA, Bruno JB. Ticlopidine's mechanism of action on human platelets. In: Hass WK, Easton JD, eds. Ticlopidine, Platelets and Vascular Disease. New York, NY: Springer; 1993:41–59.

25. Nakamura S, Colombo A, Gaglione A, Almagor Y, Goldberg SL, Maiello L, Finci L, Tobis JM. Intracoronary ultrasound observations during stent implantation. Circulation. 1994;89:2026–2034.[Free Full Text]

26. Glogar D, Yang P, Hassan A, Heyer G, Klein W, Luha O, Mühlberger V, Maurer E, Pachinger O, Sochor H, Sykora J, Weber H, Weidinger F. Does high-pressure balloon post-dilation improve long-term results of Wiktor coil stent? (Austrian Wiktor Stent Trial). J Am Coll Cardiol. 1997;29(suppl A):313A. Abstract.

27. Dirschinger J, Schühlen H, Hausleiter J, Elezi S, Boekstegers P, Giehrl W, Pache J, Walter H, Alt E, Neumann FJ, Steinbeck G, Schömig A. A randomized trial of low versus high balloon pressure for coronary stent placement: analysis of early outcome. Circulation. 1997;96(suppl I):I-653. Abstract.

28. Abdelmeguid AE, Topol EJ. The myth of the myocardial "infarctlet" during percutaneous coronary revascularization procedures. Circulation. 1996;94:3369–3375.[Free Full Text]

This article has been cited by other articles:

				B. Lagerqvist, J. Carlsson, O. Frobert, J. Lindback, F. Schersten, U. Stenestrand, S. K. James, and for the Swedish Coronary Angiography and Angioplas Stent Thrombosis in Sweden: A Report From the Swedish Coronary Angiography and Angioplasty Registry Circ Cardiovasc Interv, October 1, 2009; 2(5): 401 - 408. [Abstract] [Full Text] [PDF]

				J. Mehilli, A. Kastrati, S. Schulz, S. Frungel, S. G. Nekolla, W. Moshage, F. Dotzer, K. Huber, J. Pache, J. Dirschinger, et al. Abciximab in Patients With Acute ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention After Clopidogrel Loading: A Randomized Double-Blind Trial Circulation, April 14, 2009; 119(14): 1933 - 1940. [Abstract] [Full Text] [PDF]

				J. Aoki, A. J. Lansky, R. Mehran, J. Moses, M. E. Bertrand, B. T. McLaurin, D. A. Cox, A. M. Lincoff, E. M. Ohman, H. D. White, et al. Early Stent Thrombosis in Patients With Acute Coronary Syndromes Treated With Drug-Eluting and Bare Metal Stents: The Acute Catheterization and Urgent Intervention Triage Strategy Trial Circulation, February 10, 2009; 119(5): 687 - 698. [Abstract] [Full Text] [PDF]

				J. D. Douketis, P. B. Berger, A. S. Dunn, A. K. Jaffer, A. C. Spyropoulos, R. C. Becker, and J. Ansell The Perioperative Management of Antithrombotic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 299S - 339S. [Abstract] [Full Text] [PDF]

				S. Windecker and B. Meier Late Coronary Stent Thrombosis Circulation, October 23, 2007; 116(17): 1952 - 1965. [Full Text] [PDF]

				J. Daemen and P. W. Serruys Drug-Eluting Stent Update 2007: Part II: Unsettled Issues Circulation, August 21, 2007; 116(8): 961 - 968. [Full Text] [PDF]

				J. L. Anderson, C. D. Adams, E. M. Antman, C. R. Bridges, R. M. Califf, D. E. Casey Jr, W. E. Chavey II, F. M. Fesmire, J. S. Hochman, T. N. Levin, et al. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine J. Am. Coll. Cardiol., August 14, 2007; 50(7): e1 - e157. [Full Text] [PDF]

				J. L. Anderson, C. D. Adams, E. M. Antman, C. R. Bridges, R. M. Califf, D. E. Casey Jr, W. E. Chavey II, F. M. Fesmire, J. S. Hochman, T. N. Levin, et al. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine J. Am. Coll. Cardiol., August 14, 2007; 50(7): 652 - 726. [Full Text] [PDF]

				T. F. Luscher, J. Steffel, F. R. Eberli, M. Joner, G. Nakazawa, F. C. Tanner, and R. Virmani Drug-Eluting Stent and Coronary Thrombosis: Biological Mechanisms and Clinical Implications Circulation, February 27, 2007; 115(8): 1051 - 1058. [Abstract] [Full Text] [PDF]

				P. K. Kuchulakanti, W. W. Chu, R. Torguson, P. Ohlmann, S.-W. Rha, L. C. Clavijo, S.-W. Kim, A. Bui, N. Gevorkian, Z. Xue, et al. Correlates and Long-Term Outcomes of Angiographically Proven Stent Thrombosis With Sirolimus- and Paclitaxel-Eluting Stents Circulation, February 28, 2006; 113(8): 1108 - 1113. [Abstract] [Full Text] [PDF]

				L. Ge, F. Airoldi, I. Iakovou, J. Cosgrave, I. Michev, G. M. Sangiorgi, M. Montorfano, A. Chieffo, M. Carlino, N. Corvaja, et al. Clinical and Angiographic Outcome After Implantation of Drug-Eluting Stents in Bifurcation Lesions With the Crush Stent Technique: Importance of Final Kissing Balloon Post-Dilation J. Am. Coll. Cardiol., August 16, 2005; 46(4): 613 - 620. [Abstract] [Full Text] [PDF]

				L. Ge, I. Iakovou, J. Cosgrave, A. Chieffo, M. Montorfano, I. Michev, F. Airoldi, M. Carlino, G. Melzi, G. M. Sangiorgi, et al. Immediate and mid-term outcomes of sirolimus-eluting stent implantation for chronic total occlusions Eur. Heart J., June 1, 2005; 26(11): 1056 - 1062. [Abstract] [Full Text] [PDF]

				I. Iakovou, T. Schmidt, E. Bonizzoni, L. Ge, G. M. Sangiorgi, G. Stankovic, F. Airoldi, A. Chieffo, M. Montorfano, M. Carlino, et al. Incidence, Predictors, and Outcome of Thrombosis After Successful Implantation of Drug-Eluting Stents JAMA, May 4, 2005; 293(17): 2126 - 2130. [Abstract] [Full Text] [PDF]

				A. Chieffo, E. Bonizzoni, D. Orlic, G. Stankovic, R. Rogacka, F. Airoldi, G. W. Mikhail, M. Montorfano, I. Michev, M. Carlino, et al. Intraprocedural Stent Thrombosis During Implantation of Sirolimus-Eluting Stents Circulation, June 8, 2004; 109(22): 2732 - 2736. [Abstract] [Full Text] [PDF]

				A. Kastrati, J. Mehilli, H. Schuhlen, J. Dirschinger, F. Dotzer, J. M. ten Berg, F.-J. Neumann, H. Bollwein, C. Volmer, M. Gawaz, et al. A Clinical Trial of Abciximab in Elective Percutaneous Coronary Intervention after Pretreatment with Clopidogrel N. Engl. J. Med., January 15, 2004; 350(3): 232 - 238. [Abstract] [Full Text] [PDF]

				F.-J. Neumann, A. Kastrati, G. Pogatsa-Murray, J. Mehilli, H. Bollwein, H.-P. Bestehorn, C. Schmitt, M. Seyfarth, J. Dirschinger, and A. Schomig Evaluation of Prolonged Antithrombotic Pretreatment ("Cooling-Off" Strategy) Before Intervention in Patients With Unstable Coronary Syndromes: A Randomized Controlled Trial JAMA, September 24, 2003; 290(12): 1593 - 1599. [Abstract] [Full Text] [PDF]

				M. J. Ross, H. C. Herrmann, D. J. Moliterno, J. C. Blankenship, L. Demopoulos, P. M. DiBattiste, S. G. Ellis, Z. Ghazzal, J. L. Martin, J. White, et al. Angiographic variables predict increased riskfor adverse ischemic events after coronarystenting with glycoprotein IIb/IIIa inhibition: Results from the TARGET trial J. Am. Coll. Cardiol., September 17, 2003; 42(6): 981 - 988. [Abstract] [Full Text] [PDF]

				Y. Honda and P. J. Fitzgerald Stent Thrombosis: An Issue Revisited in a Changing World Circulation, July 8, 2003; 108(1): 2 - 5. [Full Text] [PDF]

				P. A. Gurbel, K. P. Bliden, B. L. Hiatt, and C. M. O'Connor Clopidogrel for Coronary Stenting: Response Variability, Drug Resistance, and the Effect of Pretreatment Platelet Reactivity Circulation, June 17, 2003; 107(23): 2908 - 2913. [Abstract] [Full Text] [PDF]

				P. A. Lemos, C.-h. Lee, M. Degertekin, F. Saia, K. Tanabe, C. A. Arampatzis, A. Hoye, M. van Duuren, G. Sianos, P. C. Smits, et al. Early outcome after sirolimus-eluting stent implantation in patients with acute coronary syndromes: Insights from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry J. Am. Coll. Cardiol., June 4, 2003; 41(11): 2093 - 2099. [Abstract] [Full Text] [PDF]

				S. R. Steinhubl, P. B. Berger, J. T. Mann III, E. T. A. Fry, A. DeLago, C. Wilmer, E. J. Topol, and for the CREDO Investigators Early and Sustained Dual Oral Antiplatelet Therapy Following Percutaneous Coronary Intervention: A Randomized Controlled Trial JAMA, November 20, 2002; 288(19): 2411 - 2420. [Abstract] [Full Text] [PDF]

				J.o. Hausleiter, A. Kastrati, J. Mehilli, H. Schuhlen, J.u. Pache, F. Dotzer, J. Dirschinger, and A. Schomig Predictive factors for early cardiac events and angiographic restenosis after coronary stent placement in small coronary arteries J. Am. Coll. Cardiol., September 4, 2002; 40(5): 882 - 889. [Abstract] [Full Text] [PDF]

				H. Sasao, A. Endo, T. Hasegawa, Y. Ichikawa, R. Noda, H. Oimatsu, and T. Takada Long-Term Follow-up After Coronary Stent Implantation in Patients with Coronary Artery Disease Angiology, March 1, 2002; 53(2): 149 - 156. [Abstract] [PDF]

				S. B. King Stent thrombosis: '(ultra)sound the warning' Eur. Heart J., January 2, 2002; 23(2): 97 - 98. [Full Text] [PDF]

				D. L. Bhatt, M. E. Bertrand, P. B. Berger, P. L. L'Allier, I. Moussa, J. W. Moses, G. Dangas, M. Taniuchi, J. M. Lasala, D. R. Holmes, et al. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting J. Am. Coll. Cardiol., January 2, 2002; 39(1): 9 - 14. [Abstract] [Full Text] [PDF]

				N.G. Uren, S.P. Schwarzacher, J.A. Metz, D.P. Lee, Y. Honda, A.C. Yeung, P.J. Fitzgerald, and P.G. Yock Predictors and outcomes of stent thrombosis. An intravascular ultrasound registry Eur. Heart J., January 2, 2002; 23(2): 124 - 132. [Abstract] [Full Text] [PDF]

				H. Schuhlen, A. Kastrati, J.u. Pache, J. Dirschinger, and A. Schomig Incidence of thrombotic occlusion and major adverse cardiac events between two and four weeks after coronary stent placement: analysis of 5,678 patients with a four-week ticlopidine regimen J. Am. Coll. Cardiol., June 15, 2001; 37(8): 2066 - 2073. [Abstract] [Full Text] [PDF]

				D. H. Walter, S. Fichtlscherer, M. Sellwig, W. Auch-Schwelk, V. Schachinger, and A. M. Zeiher Preprocedural C-reactive protein levels and cardiovascular events after coronary stent implantation J. Am. Coll. Cardiol., March 1, 2001; 37(3): 839 - 846. [Abstract] [Full Text] [PDF]

				A. Kastrati, A. Schomig, J. Dirschinger, J. Mehilli, F. Dotzer, N. von Welser, and F.-J. Neumann A Randomized Trial Comparing Stenting With Balloon Angioplasty in Small Vessels in Patients With Symptomatic Coronary Artery Disease Circulation, November 21, 2000; 102(21): 2593 - 2598. [Abstract] [Full Text] [PDF]

				J. Mehilli, A. Kastrati, J. Dirschinger, H. Bollwein, F.-J. Neumann, and A. Schomig Differences in Prognostic Factors and Outcomes Between Women and Men Undergoing Coronary Artery Stenting JAMA, October 11, 2000; 284(14): 1799 - 1805. [Abstract] [Full Text] [PDF]

				E. Braunwald, E. M. Antman, J. W. Beasley, R. M. Califf, M. D. Cheitlin, J. S. Hochman, R. H. Jones, D. Kereiakes, J. Kupersmith, T. N. Levin, et al. ACC/AHA guidelines for the management of patients with unstable angina and non-st-segment elevation myocardial infarction: A report of the american college of cardiology/ american heart association task force on practice guidelines (committee on the management of patients with unstable angina) J. Am. Coll. Cardiol., September 1, 2000; 36(3): 970 - 1062. [Full Text] [PDF]

				A. Kastrati, W. Koch, M. Gawaz, J. Mehilli, C. Bottiger, K. Schomig, N. von Beckerath, and A. Schomig PlA polymorphism of glycoprotein IIIa and risk of adverse events after coronary stent placement J. Am. Coll. Cardiol., July 1, 2000; 36(1): 84 - 89. [Abstract] [Full Text] [PDF]

				R. Zahn, R. Schiele, K. Seidl, T. Kapp, H. G. Glunz, E. Jagodzinski, T. Voigtlander, M. Gottwik, G. Berg, H. Thomas, et al. Acute myocardial infarction occurring in versus out of the hospital: patient characteristics and clinical outcome J. Am. Coll. Cardiol., June 1, 2000; 35(7): 1820 - 1826. [Abstract] [Full Text] [PDF]

				N. von Beckerath, W. Koch, J. Mehilli, C. Bottiger, A. Schomig, and A. Kastrati Glycoprotein Ia gene C807T polymorphism and risk for major adverse cardiac events within the first 30 days after coronary artery stenting Blood, June 1, 2000; 95(11): 3297 - 3301. [Abstract] [Full Text] [PDF]

				M. Gyongyosi, P. Yang, A. Khorsand, D. Glogar, on behalf of the Austrian Wiktor Stent Study Group, and European Paragon Stent Investigators Longitudinal straightening effect of stents is an additional predictor for major adverse cardiac events J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1580 - 1589. [Abstract] [Full Text] [PDF]

				S. H. Wilson, P. B. Berger, V. Mathew, M. R. Bell, K. N. Garratt, C. S. Rihal, J. F. Bresnahan, D. E. Grill, S. Melby, and D. R. Holmes Jr. Immediate and late outcomes after direct stent implantation without balloon predilation J. Am. Coll. Cardiol., March 15, 2000; 35(4): 937 - 943. [Abstract] [Full Text] [PDF]

				F.-J. Neumann, A. Kastrati, T. Miethke, G. Pogatsa-Murray, M. Seyfarth, and A. Schomig Previous Cytomegalovirus Infection and Risk of Coronary Thrombotic Events After Stent Placement Circulation, January 4, 2000; 101(1): 11 - 13. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schühlen, H. Articles by Schömig, A. Search for Related Content PubMed PubMed Citation Articles by Schühlen, H. Articles by Schömig, A.