A simple solution to deliver a second guidewire without a dual-lumen microcatheter-The sidecar technique.

The sidecar technique represents a simple and inexpensive solution to successfully deliver a second guidewire distally whenever a dual-lumen microcatheter is not available.

[Recanalisation of chronic total coronary occlusions - what is the evidence and which patients will benefit?] / Rekanalisation chronischer Koronarverschlüsse.

Recanalisation of chronic total coronary occlusions - what is the evidence and which patients will benefit? Abstract. Continuous improvement of recanalisation techniques and newer device technologies significantly improved the success of revascularisation in percutaneous coronary intervention (PCI) of chronic total occluded coronary arteries (CTO) in the past few years. The best documented clinical benefit of CTO-PCI is symptom control, based on a reduction of myocardial ischemia. In contrast, there is still an ongoing controversial debate regarding the prognostic benefit of successful CTO-PCI shown in several observational studies. Therefore, the indication for CTO-PCI is primarily based on patients' symptoms and the extent of myocardial ischemia. The risk / benefit ratio for the individual patient has to be estimated from technical complexity of the CTO lesion, the extent of the coronary artery disease and the ventricular function. Recanalisation strategy should be escalating, as most of the CTOs can be successfully recanalised with standard antegrade recanalisation techniques. With the implementation of retrograde CTO techniques, the likelihood for recanalisation success is very high (> 90 %) even in complex anatomies, combined with low complication rates in specialised centers. According to the operator's expertise a complete catheter-based revascularisation can be achieved nowadays even in patients with CTO and coronary multi-vessel disease.

Simple Techniques for Antegrade Guiding Catheter Engagement after Retrograde CTO Crossing.

Interventional treatment of chronic total occlusions (CTOs) is nowadays counting on a wide span of procedural possibilities, and retrograde approaches are becoming more and more frequent as they warrant high success rates at the cost of a slightly higher incidence of donor vessel damage. Retrograde lesion crossing needs to be followed by procedural conversion to an antegrade approach to dilate and stent the lesion, and new techniques are being proposed to address this issue and achieve a safer recanalization of the vessel. In this context, we propose novel and simple techniques to antegrade guiding catheter engagement by the retrograde wire, enhancing the chances for procedural success.

Guiding Principles for Chronic Total Occlusion Percutaneous Coronary Intervention.

Outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have improved because of advancements in equipment and techniques. With global collaboration and knowledge sharing, we have identified 7 common principles that are widely accepted as best practices for CTO-PCI. 1. Ischemic symptom improvement is the primary indication for CTO-PCI. 2. Dual coronary angiography and in-depth and structured review of the angiogram (and, if available, coronary computed tomography angiography) are key for planning and safely performing CTO-PCI. 3. Use of a microcatheter is essential for optimal guidewire manipulation and exchanges. 4. Antegrade wiring, antegrade dissection and reentry, and the retrograde approach are all complementary and necessary crossing strategies. Antegrade wiring is the most common initial technique, whereas retrograde and antegrade dissection and reentry are often required for more complex CTOs. 5. If the initially selected crossing strategy fails, efficient change to an alternative crossing technique increases the likelihood of eventual PCI success, shortens procedure time, and lowers radiation and contrast use. 6. Specific CTO-PCI expertise and volume and the availability of specialized equipment will increase the likelihood of crossing success and facilitate prevention and management of complications, such as perforation. 7. Meticulous attention to lesion preparation and stenting technique, often requiring intracoronary imaging, is required to ensure optimum stent expansion and minimize the risk of short- and long-term adverse events. These principles have been widely adopted by experienced CTO-PCI operators and centers currently achieving high success and acceptable complication rates. Outcomes are less optimal at less experienced centers, highlighting the need for broader adoption of the aforementioned 7 guiding principles along with the development of additional simple and safe CTO crossing and revascularization strategies through ongoing research, education, and training.

A Randomized Trial to Assess Regional Left Ventricular Function After Stent Implantation in Chronic Total Occlusion: The REVASC Trial.

OBJECTIVES: The aim of this study was to investigate whether percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) improves left ventricular function. BACKGROUND: The benefit of PCI in CTOs is still controversial. METHODS: Patients with CTOs who were candidates for PCI were eligible for the study and were randomized to PCI or no PCI of CTO. Relevant coexisting non-CTO lesions were treated as indicated. Patients underwent cardiac magnetic resonance imaging at baseline and at 6 months. The primary endpoint was the change in segmental wall thickening (SWT) in the CTO territory. Secondary endpoints were improvement of regional wall motion and changes in left ventricular volumes and ejection fraction. Furthermore, major adverse coronary events after 12 months were assessed. RESULTS: The CTO PCI group comprised 101 patients and the no CTO PCI group 104 patients. The change in SWT did not differ between the CTO PCI (4.1% [interquartile range: 14.6 to 19.3]) and no CTO PCI (6.0% [interquartile range: 8.6 to 6.0]) groups (p = 0.57). Similar results were obtained for other indexes of regional and global left ventricular function. Subgroup analysis revealed that only in patients without major non-CTO lesions (basal SYNTAX [Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery] score ≤13) CTO PCI was associated with larger improvement in SWT than no CTO PCI (p for interaction = 0.002). Driven by repeat intervention, major adverse coronary event rates at 12 months were significantly lower in the CTO PCI group (16.3% vs. 5.9%; p = 0.02). CONCLUSIONS: No benefit was seen for CTO PCI in terms of the primary endpoint, SWT, or other indexes of left ventricular function. CTO PCI resulted in clinical benefit over no CTO PCI, as evidenced by reduced major adverse coronary event rates at 12 months.

Preprocedural Leucocyte Count Predicts Risk in Patients with Coronary Chronic Total Occlusion.

Background As technologies of percutaneous coronary intervention (PCI) for coronary chronic total occlusions (CTO) have improved, great uncertainty exists regarding patient selection and long-term benefit of CTO-PCI. Given that white blood cell (WBC) count has been associated with cardiovascular risk, we hypothesized that the latter might provide incremental prognostic value in patients undergoing CTO-PCI. Methods and Results Our study population consisted of 1,262 consecutive patients (76.3% males, mean age of 67.7 ± 10.3 years) who underwent elective PCI at our centre between January 2002 and December 2008. Four hundred seventy-five patients had at least one CTO, while 787 patients with non-occlusive coronary lesions served as controls. Baseline WBC count was higher in CTO patients as compared with controls (8,072 ± 3,459/µL vs. 7,469 ± 2,668/µL, p = 0.001) and independently predicted the occurrence of a CTO lesion (odds ratio: 1.8; 95% confidence interval [CI]: 1.3-2.4; p < 0.001). After a median follow-up of 3.1 years (interquartile range: 2.1-4.2 years), CTO patients with WBC counts ranging in the highest tertile had significantly worse outcomes than CTO patients with lower WBC counts (log-rank = 0.009 for all-cause mortality and log-rank = 0.01 for major adverse cardiac events). These associations were not seen in controls. Accordingly, elevated WBC count was identified as a significant predictor for all-cause mortality (adjusted hazard ratio: 3.1; 95% CI: 1.6-6.2; p = 0.001) in CTO patients but not in patients with non-occlusive coronary artery disease (pint = 0.088). Conclusion Assessment of the inflammatory status of CTO patients may be an important element in selecting CTO patients at low risk who may be referred to CTO-PCI.

Rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions: Two-year clinical outcome of the randomized ROTAXUS trial.

BACKGROUND: In the randomized ROTAXUS trial, routine lesion preparation of complex calcified coronary lesions using rotational atherectomy (RA) prior to paclitaxel-eluting stent implantation did not reduce the primary endpoint of angiographic late lumen loss at 9 months compared to stenting without RA. So far, no long-term data of prospective head-to-head comparisons between both treatment strategies have been reported. METHODS AND RESULTS: ROTAXUS randomly assigned patients with complex calcified coronary lesions to RA followed by stenting (n = 120) or stenting without RA (n = 120). The primary endpoint of the current analysis was the occurrence of major adverse cardiac events (MACE) at 2-year follow-up defined as the composite of death, myocardial infarction, and target vessel revascularization (TVR). At 2 years, MACE occurred in 32 patients in the RA group and 37 patients in the standard therapy group (29.4% vs. 34.3%, P = 0.47). The rates of death (8.3% vs. 7.4%, P = 1.00), myocardial infarction (8.3% vs. 6.5%, P = 0.80), target lesion revascularization (TLR, 13.8% vs. 16.7%, P = 0.58), and TVR (19.3% vs. 22.2%, P = 0.62) were similar in both groups. CONCLUSION: Despite high rates of initial angiographic success, nearly one third of patients enrolled in ROTAXUS experienced MACE within 2-year follow-up, with no differences between patients treated with or without RA.

Large platelets but not putative endothelial progenitor cells are associated with low strut coverage after drug-eluting stent implantation.

OBJECTIVES: This study assessed whether different subsets of circulating endothelial and putative endothelial progenitor cells (CEC and EPC) correlate with stent strut coverage (SSC) using second generation optical coherence tomography (OCT). BACKGROUND: Due to the lack of imaging modalities with a resolution down to the magnitude of a few cells, the influence of EPC on endothelialisation of drug-eluting stents has not been assessed in patients. METHODS: In 37 patients, SSC of everolimus-eluting stents was assessed by OCT 5-7months after stent implantation. Different subsets of EPC (CD34(+)KDR(+), CD34(+)KDR(+)CD45(dim), CD133(+), CD3(+)CD31(+)), CEC (CD31(+)CD45(-)CD146(+)), and CD31(+)CD45(-)CD146(-) representing large platelets were analysed by flow cytometry, including viability analyses with 7-AAD. Statistical analysis comprised univariate regression analysis and multivariable models integrating OCT and flow cytometry data as well as clinical variables. RESULTS: SSC and frequency of different cell types were highly comparable with previously published data. EPC defined in part by KDR expression were mostly non-viable. On univariate and in multivariable models, no association between EPC counts and strut coverage was detected. For CD31(+)CD45(-)CD146(-) counts, representing large platelets, an inverse relationship with strut coverage was identified by a multivariable regression model adjusting for age, sex, diabetes mellitus, NYHA and CCS class, CRP, serum triglycerides, glucose and creatinine (beta=-9.42, p=0.006). CONCLUSIONS: There was no significant association between EPC or CEC and healing after drug-eluting stent implantation. Yet, CD31(+)CD45(-)CD146(-) cells were associated with low SSC. These data suggest that large platelets may represent a more important mediator of late stent endothelialisation than EPC.

Comparison of bivalirudin and heparin in patients undergoing rotational atherectomy: a subanalysis of the randomised ROTAXUS trial.

AIMS: Bivalirudin has emerged as a meaningful alternative to heparin in patients undergoing percutaneous coronary intervention (PCI). To date, it is unclear whether bivalirudin has advantages in patients undergoing rotational atherectomy (RA). METHODS AND RESULTS: The current subgroup analysis of the ROTAXUS trial compared patients receiving bivalirudin (n=129) to those receiving unfractionated heparin (UFH) (n=111). Efficacy was assessed by the frequency of periprocedural myocardial infarction (MI) and safety by the frequency of major access-site bleeding (ASB). Baseline characteristics were similar. Periprocedural MI occurred less frequently in the bivalirudin group (22% vs. 37.5%, p=0.02), while ASB did not differ significantly (2.3% vs. 5.5%, p=0.20). This effect was larger in the RA group, where bivalirudin significantly reduced periprocedural MI (15.7% vs. 38.7%, p=0.01) with a trend towards reduced major ASB (2.9% vs. 10.2%, p=0.09). In the control group without RA, bivalirudin was not superior to UFH regarding periprocedural MI (28.6% vs. 36.6%, p=0.42) and major ASB (1.7% vs. 1.7%, p=0.99). CONCLUSIONS: This analysis suggests a differential benefit of bivalirudin in patients treated with RA. Patients receiving bivalirudin during RA showed significantly less periprocedural MI and fewer ASB compared to patients treated with UFH.

Percutaneous mitral valve edge-to-edge repair: in-hospital results and 1-year follow-up of 628 patients of the 2011-2012 Pilot European Sentinel Registry.

BACKGROUND: The use of transcatheter mitral valve repair (TMVR) has gained widespread acceptance in Europe, but data on immediate success, safety, and long-term echocardiographic follow-up in real-world patients are still limited. OBJECTIVES: The aim of this multinational registry is to present a real-world overview of TMVR use in Europe. METHODS: The Transcatheter Valve Treatment Sentinel Pilot Registry is a prospective, independent, consecutive collection of individual patient data. RESULTS: A total of 628 patients (mean age 74.2 ± 9.7 years, 63.1% men) underwent TMVR between January 2011 and December 2012 in 25 centers in 8 European countries. The prevalent pathogenesis was functional mitral regurgitation (FMR) (n = 452 [72.0%]). The majority of patients (85.5%) were highly symptomatic (New York Heart Association functional class III or higher), with a high logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) (20.4 ± 16.7%). Acute procedural success was high (95.4%) and similar in FMR and degenerative mitral regurgitation (p = 0.662). One clip was implanted in 61.4% of patients. In-hospital mortality was low (2.9%), without significant differences between groups. The estimated 1-year mortality was 15.3%, which was similar for FMR and degenerative mitral regurgitation. The estimated 1-year rate of rehospitalization because of heart failure was 22.8%, significantly higher in the FMR group (25.8% vs. 12.0%, p[log-rank] = 0.009). Paired echocardiographic data from the 1-year follow-up, available for 368 consecutive patients in 15 centers, showed a persistent reduction in the degree of mitral regurgitation at 1 year (6.0% of patients with severe mitral regurgitation). CONCLUSIONS: This independent, contemporary registry shows that TMVR is associated with high immediate success, low complication rates, and sustained 1-year reduction of the severity of mitral regurgitation and improvement of clinical symptoms.

High-sensitivity cardiac troponin for risk prediction in patients with and without coronary heart disease.

BACKGROUND: In stable patients with unknown coronary anatomy, higher levels of cardiac troponin are associated with an increased risk of cardiovascular events. It was supposed that this association might be explained by the ability of cardiac troponin to detect minor myocardial necrosis which might be caused by subclinical coronary atherosclerosis. Thus, this analysis tested if the predictive value of high-sensitivity troponin T (hsTnT) in stable patients is dependent of the presence or absence of angiographically documented coronary heart disease. METHODS: Stable patients undergoing elective coronary angiography were enrolled (n=2046). HsTnT was determined before diagnostic procedures. The patients were followed for up to seven years. Primary endpoint was all-cause mortality or non-fatal myocardial infarction. All endpoints were adjudicated by independent physicians. Results were adjusted to a clinical model including independent clinical predictors of the primary endpoint. RESULTS: Out of the 2046 patients enrolled, 1236 (60%) had a diagnosis of obstructive coronary heart disease. HsTnT predicted independently the primary endpoint (adjusted HR 1.33, 95%-CI 1.21-1.46, P<0.001). The use of hsTnT in addition to the clinical model significantly improved discrimination (c-statistic: 0.751 to 0.773, P<0.001) as well as reclassification of the primary endpoint (NRI=0.362, P<0.001). This significant improvement persisted across various subsets and was independent of the presence of clinically detectable coronary heart disease and other variables. CONCLUSION: The use of hsTnT in addition to clinical variables significantly improves discrimination and reclassification of patients with respect to all-cause mortality or non-fatal myocardial infarction irrespective of the presence of clinically detectable coronary heart disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT00457236).

Aortic regurgitation after transcatheter aortic valve implantation with balloon- and self-expandable prostheses: a pooled analysis from a 2-center experience.

OBJECTIVES: This study sought to assess aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) with the self-expandable Medtronic CoreValve (MCV) (Medtronic Inc., Minneapolis, Minnesota) versus balloon-expandable Edwards Sapien XT valve (ESV) (Edwards Lifesciences, Irvine, California). BACKGROUND: AR after TAVI has been associated with poor survival, but limited data exist comparing MCV with ESV. METHODS: We pooled the prospective TAVI databases of 2 German centers. The primary endpoint was more-than-mild post-TAVI AR assessed by echocardiography. We also assessed device success and survival within 1 year. Endpoints were adjudicated according to the Valve Academic Research Consortium criteria and analyzed by unadjusted and propensity-score-adjusted models. RESULTS: A total of 394 patients were included, 276 treated with MCV and 118 with ESV. More-than-mild AR was significantly higher with MCV than with ESV (12.7% vs. 2.6%, p = 0.002). This difference remained significant after propensity adjustment (adjusted odds ratio [OR]: 4.59, 95% confidence interval [CI]: 1.03 to 20.44). The occurrence of any degree of AR was also higher with MCV (71.6% vs. 56.9%, p = 0.004). Device success was mainly influenced by the occurrence of AR and was consequently higher with ESV (95.8% vs. 86.6%, p = 0.007), but this was not significant after propensity adjustment (adjusted OR: 0.34, 95% CI: 0.11 to 1.03, p = 0.06). At 1 year, survival was comparable between both valve types (83.8% MCV vs. 88.2% ESV, p = 0.42), but was significantly worse in patients with more-than-mild AR (69.8% vs. 87.4%, p = 0.004) and in those with device failure (65.6% vs. 87.4%, p < 0.001). CONCLUSIONS: More-than-mild AR after TAVI was more frequent with MCV than with ESV. This finding deserves consideration, as more-than-mild AR was associated with higher mortality at 1 year.

Role of euroSCORE II in predicting long-term outcome after percutaneous catheter intervention for coronary triple vessel disease or left main stenosis.

OBJECTIVES: The SYNTAX score (Ssc) assessing the complexity of coronary anatomy predicts survival after percutaneous coronary intervention (PCI). We tested the hypothesis that the newly developed euroSCORE II (eSC2) can improve the prediction of outcome after complex PCI by the Ssc. METHODS AND RESULTS: Our study comprised 1262 consecutive patients with triple vessel disease or left main stenosis, who were contacted 3 years after elective PCI with drug-eluting stents. We calculated eSC2, Ssc, logistic euroSCORE, and ACEF score. Prediction of 3-year all-cause mortality by these scores was assessed by Cox proportional hazard models. Models were compared by the Hosmer-Lemeshow test for calibration (HL), the C-statistics (AUC) for discrimination and by net reclassification indices (NRI). eSC2 and Ssc were significant predictors of 3-year mortality (unadjusted hazard ratios [95%-confidence limits], 1.050 [1.033-1.067], 1.180 [1.146-1.215], respectively, P<0.001). The predictive value of eSC2 was improved by logarithmic transformation. Adding eSC2 to the model with Ssc improved calibration (HL 7.4 vs. 11.1) and discrimination (increase in AUC [95%-confidence limits] 0.12 [0.07 to 0.17]) and yielded a significant NRI of 0.38 (95%-confidence limits 0.28 to 0.47). The absolute difference in 3-year mortality between strata of Ssc (≤22, >22-32, >32) was smaller with eSC2<1% (1.4%, 3.4%, 9.7%, respectively), than with eSC2>1.6% (11.2%, 20.2%, 30.6%, respectively). The predictive ability of eSC2 was similar to that of the other clinical scores. CONCLUSIONS: eSC2 predicts 3-year mortality after complex PCI and modifies the impact of angiographic complexity on outcome.

Longitudinal compression of the platinum-chromium everolimus-eluting stent during coronary implantation: predisposing mechanical properties, incidence, and predictors in a large patient cohort.

OBJECTIVES: To assess the longitudinal compression behavior of platinum-chromium everolimus-eluting stents, evaluate frequency of inadvertent longitudinal compression during percutaneous intervention, and define patient- and lesion-related predictors of this complication. BACKGROUND: Platinum-chromium stents of Element family have unique design features to improve flexibility that may, however, impair longitudinal stability. Incidence of longitudinal stent compression during implantation and predictors for this complication are not well understood. METHODS: Five contemporary stent platforms were longitudinally compressed in a bench test experiment, and spring constant, yield force, and ultimate strength were calculated from force-strain curves. We also evaluated all coronary cases treated with an Element stent from January 1, 2010, to October 31, 2011, for documented longitudinal compression. We compared baseline characteristics and periprocedural data between patients with and without longitudinal stent compression and assessed predictors for this event by multiple logistic regression models. RESULTS: Yield force and ultimate strength were significantly lower for the Element compared with all other tested stents. In 20 patients (1.4%) and 20 lesions (0.7%) from 1,392 cases with 2,839 atherosclerotic lesions longitudinal stent compression was reported. Ostial segments, number of stents, and the presence of a bifurcation were significant predictors (adjusted odds ratios [95% confidence intervals]: 8.33 [3.30-21.28], 1.57 [1.01-2.45], 3.57 [1.36-9.35], respectively). CONCLUSION: The Element stent exhibits the lowest overall longitudinal strength compared with four contemporary platforms. Longitudinal compression of the Element stent is a rare complication and occurs more frequently in ostial or bifurcation lesions and with multiple stents.

Long-term follow-up after coronary stenting with the sirolimus-eluting stent in clinical practice: results from the prospective multi-center German Cypher Stent Registry.

AIMS: To obtain long-term follow-up data of the sirolimus-eluting coronary stent (SES) and to determine factors associated with clinical events and target vessel revascularization (TVR). METHODS AND RESULTS: Between 2002 and 2005, 5,946 patients were treated with at least one SES. A follow-up after a median of 4.1 years was obtained in 5,247 patients (88.2 %). During the follow-up, death occurred in 9.2 % of patients, nonfatal myocardial infarction in 5.9 %, nonfatal stroke in 2.2 % and MACCE (death/myocardial infarction/stroke) in 16.3 %. Any TVR was performed in 20.3 %. Independent predictors of MACCE were: older age (p < 0.0001), renal insufficiency (p < 0.0001), prior myocardial infarction (p < 0.0001), diabetes mellitus (p < 0.0001), cardiogenic shock (p = 0.0002), three-vessel disease (p = 0.0012), reduced left ventricular function (p = 0.0048), target vessel = bypass graft (p = 0.0122), indication for treatment = ACS (p = 0.0181) and PCI before implantation (p = 0.0308). Independent predictors of TVR were target vessel = coronary bypass (<0.0001), two- or three-vessel disease (p < 0.0001), ostial lesions (p < 0.0001), total length of SES implanted (p = 0.0012) and older age being a protective factor (p = 0.0187). CONCLUSIONS: Long-term follow-up of the SES in clinical practice showed clinical event rates that were comparable to randomized trials with a MACCE rate of 16.3 % and TVR rate of 20.3 %.

Statin effect on thrombin inhibitor effectiveness during percutaneous coronary intervention: a post-hoc analysis from the ISAR-REACT 3 trial.

OBJECTIVE: To determine whether statin therapy influences the efficacy of thrombin inhibitor bivalirudin or unfractionated heparin (UFH) during PCI. SETTING AND PATIENTS: The post-hoc analysis of the ISAR-REACT 3 Trial included 4,570 patients: 3,106 patients were on statin therapy and 1,464 patients were not on statin therapy at the time of PCI procedure. MAIN OUTCOME MEASURES: The primary outcome of this analysis was the 30-day composite of death, myocardial infarction, target vessel revascularization (TVR) or major bleeding. RESULTS: The primary outcome occurred in 7.9% patients (n = 246) in the statin group versus 9.8% (n = 143) in the non-statin group (P = 0.036). There was an interaction in univariate (P = 0.028) and multivariable (P = 0.026) analysis between pre-PCI statin therapy and the type of antithrombotic therapy regarding myocardial infarction. In the statin group, bivalirudin significantly reduced the incidence of major bleeding (2.6 vs. 4.3%, P = 0.013) with no significant difference in the incidence of myocardial infarction (4.9 vs. 5.2%; P = 0.73) compared with UFH. In the non-statin group, bivalirudin was inferior to UFH regarding the incidence of myocardial infarction (7.1 vs. 4.1%, P = 0.013), yet major bleeding remained lower among bivalirudin-treated patients (4.0 vs. 5.2%, P = 0.25). CONCLUSION: This post-hoc analysis suggests the existence of an interaction between statin therapy before PCI and antithrombotic therapy during PCI. Patients receiving bivalirudin therapy at the time of PCI showed less periprocedural myocardial infarction when on pre-PCI statin therapy which has to be investigated in further studies.

Impact of cytochrome P450 2C19 loss-of-function polymorphism and of major demographic characteristics on residual platelet function after loading and maintenance treatment with clopidogrel in patients undergoing elective coronary stent placement.

OBJECTIVES: The aim of this study was to evaluate the relative impact of demographic and clinical variables versus the cytochrome P450 2C19 (CYP2C19) polymorphism on antiplatelet effects of clopidogrel. BACKGROUND: Platelet responses to clopidogrel show a marked interindividual variability with substantial impact on clinical outcome. Several demographic and clinical characteristics as well as a polymorphism of CYP2C19 have been described as predictors for a low response to clopidogrel. METHODS: This analysis enrolled 760 patients undergoing elective coronary stent implantation after loading with 600 mg of clopidogrel. Residual platelet aggregation was determined by optical aggregometry (adenosine diphosphate 5 micromol/l) before discharge. We analyzed the predictive value of the CYP2C19*2 polymorphism and baseline variables for an insufficient antiplatelet response by multivariable regression analysis and classification and regression trees analysis and determined the proportion responsible for the antiplatelet response of these predictors by multivariable linear regression analysis. RESULTS: Major independent predictors for an insufficient antiplatelet response to clopidogrel were CYP2C19*2 carrier status (odds ratio [OR]: 2.74; 95% confidence interval [CI]: 1.93 to 3.90) together with age (OR: 1.03; 95% CI: 1.01 to 1.05), diabetes mellitus (OR: 1.75; 95% CI: 1.19 to 2.56), and body mass index (OR: 1.06; 95% CI: 1.02 to 1.11). The classification and regression trees analysis demonstrated that CYP2C19*2 carrier status followed by diabetes mellitus was the best discriminator between a sufficient and an insufficient antiplatelet response to clopidogrel. The full linear regression model including all these parameters could only explain 11.5% of the antiplatelet response (5.2% by CYP2C19*2 carrier status alone). CONCLUSIONS: Thus, our study does not suggest that, in patients critically dependent on adequate platelet inhibition, genotyping alone or in combination with clinical factors can replace phenotyping of platelet function. (Effect of Clopidogrel Loading and Risk of PCI [EXCELSIOR]; NCT00457236).

Antiplatelet response to the 150-mg maintenance dose of clopidogrel in patients with insufficient platelet inhibition after clopidogrel loading for elective coronary stent placement.

AIMS: Our prospective study sought to investigate whether inadequate platelet responses to clopidogrel can be corrected by increasing the daily maintenance dose from 75 mg to 150 mg. METHODS AND RESULTS: In 117 patients with elective PCI after loading with 600 mg clopidogrel, we determined residual platelet aggregation in response to 5 micromol/l ADP (RPA) by optical aggregometry after the first 75 mg maintenance dose (baseline), and at days 14 and 28. In patients with RPA >14% at baseline, we increased the daily dose to 150 mg. Fifty-seven additional patients without dose adjustment served as historic control. In 39 patients with baseline RPA >14%, the increase in maintenance dose to 150 mg reduced median RPA significantly (P<0.001) from 24% [interquartile range: 18-32%] at baseline to 14% [8-20%1 at 14 days without any further significant change. In patients with RPA < or = 14%, who continued on 75 mg clopidogrel, RPA increased during the first 14 days by 4.5% (0-14%; P<0.001). At 14 days, the study group with selective dose adjustment had a significantly lower RPA than the control group without dose adjustment (10.0% [4-20%1 versus 17.0% [9-32%], P<0.001). CONCLUSIONS: In patients with a low initial response to clopidogrel, platelet inhibition can be improved by increasing the maintenance dose to 150 mg.

Randomized trial on routine vs. provisional T-stenting in the treatment of de novo coronary bifurcation lesions.

AIMS: We investigated whether routine T-stenting reduces restenosis of the side branch as compared with provisional T-stenting in patients with de novo coronary bifurcation lesions. METHODS AND RESULTS: Our randomized study assigned 101 patients with a coronary bifurcation lesion to routine T-stenting with sirolimus-eluting stents (SES) in both branches and 101 patients to provisional T-stenting with SES placement in the main branch followed by kissing-balloon angioplasty and provisional SES placement in the side branch only for inadequate results. Primary endpoint was per cent diameter stenosis of the side branch at 9 month angiographic follow-up. Angiographic follow-up in 192 (95%) patients revealed a per cent stenosis of the side branch of 23.0 +/- 20.2% after provisional T-stenting (19% with side-branch stent) and of 27.7 +/- 24.8% (P = 0.15) after routine T-stenting (98.2% with side-branch stent). The corresponding binary restenosis rates were 9.4 and 12.5% (P = 0.32), prompting re-intervention in 5.0 and 7.9% (P = 0.39), respectively. In the main branch, binary restenosis rates were 7.3% after provisional and 3.1% after routine T-stenting (P = 0.17). The overall 1 year incidence of target lesion re-intervention was 10.9% after provisional and 8.9% after routine T-stenting (P = 0.64). CONCLUSIONS: Routine T-stenting with SES did not improve the angiographic outcome of percutaneous coronary intervention of coronary bifurcation lesions as compared with stenting of the main branch followed by kissing-balloon angioplasty and provisional side-branch stenting.