Heinz Joachim Büttner

Universitäts-Herzzentrum Freiburg - Bad Krozingen, باد کروزینگن, Baden-Württemberg, Germany

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Publications (55)386.31 Total impact

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    ABSTRACT: 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).
    08/2014; 10(4):458-65.
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    ABSTRACT: 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.
    International journal of cardiology. 08/2014;
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    ABSTRACT: 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.
    JACC Cardiovascular Interventions 01/2014; 7(3):284–292. · 7.42 Impact Factor
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    ABSTRACT: 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 3years 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.
    International journal of cardiology 05/2013; · 6.18 Impact Factor
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    ABSTRACT: OBJECTIVES: This study sought to determine the effect of rotational atherectomy (RA) on drug-eluting stent (DES) effectiveness. BACKGROUND: DES are frequently used in complex lesions, including calcified stenoses, which may challenge DES delivery, expansion, and effectiveness. RA can adequately modify calcified plaques and facilitate stent delivery and expansion. Its impact on DES effectiveness is widely unknown. METHODS: The ROTAXUS (Rotational Atherectomy Prior to TAXUS Stent Treatment for Complex Native Coronary Artery Disease) study randomly assigned 240 patients with complex calcified native coronary lesions to RA followed by stenting (n = 120) or stenting without RA (n = 120, standard therapy group). Stenting was performed using a polymer-based slow-release paclitaxel-eluting stent. The primary endpoint was in-stent late lumen loss at 9 months. Secondary endpoints included angiographic and strategy success, binary restenosis, definite stent thrombosis, and major adverse cardiac events at 9 months. RESULTS: Despite similar baseline characteristics, significantly more patients in the standard therapy group were crossed over (12.5% vs. 4.2%, p = 0.02), resulting in higher strategy success in the rotablation group (92.5% vs. 83.3%, p = 0.03). At 9 months, in-stent late lumen loss was higher in the rotablation group (0.44 ± 0.58 vs. 0.31 ± 0.52, p = 0.04), despite an initially higher acute lumen gain (1.56 ± 0.43 vs. 1.44 ± 0.49 mm, p = 0.01). In-stent binary restenosis (11.4% vs. 10.6%, p = 0.71), target lesion revascularization (11.7% vs. 12.5%, p = 0.84), definite stent thrombosis (0.8% vs. 0%, p = 1.0), and major adverse cardiac events (24.2% vs. 28.3%, p = 0.46) were similar in both groups. CONCLUSIONS: Routine lesion preparation using RA did not reduce late lumen loss of DES at 9 months. Balloon dilation with only provisional rotablation remains the default strategy for complex calcified lesions before DES implantation. (Rotational Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary Artery Disease. A Multicenter, Prospective, Randomized Controlled Trial [ROTAXUS]; NCT00380809).
    JACC. Cardiovascular Interventions 12/2012; · 1.07 Impact Factor
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    ABSTRACT: OBJECTIVE: 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. BACKGROUN: 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. METHOD: 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. RESULT: Yield force and ultimate strength were significantly lower for the Element compared with all other tested stents. In twenty 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 to 21.28], 1.57 [1.01 to 2.45], 3.57 [1.36 to 9.35], respectively). CONCLUSIO: The Element stent exhibits the lowest overall longitudinal strength compared with 4 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. © 2012 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 05/2012; · 2.51 Impact Factor
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    ABSTRACT: To determine whether statin therapy influences the efficacy of thrombin inhibitor bivalirudin or unfractionated heparin (UFH) during PCI. 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. The primary outcome of this analysis was the 30-day composite of death, myocardial infarction, target vessel revascularization (TVR) or major bleeding. 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). 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.
    Clinical Research in Cardiology 02/2011; 100(7):579-85. · 3.67 Impact Factor
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    ABSTRACT: 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. 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. 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. 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). 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).
    Journal of the American College of Cardiology 06/2010; 55(22):2427-34. · 14.09 Impact Factor
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    ABSTRACT: The purpose of this study was to assess the long-term risks and benefits of drug-eluting stents (DESs) compared with bare-metal stents (BMSs) for treatment of coronary bifurcation lesions. Our registry comprised 1,038 patients treated for coronary bifurcation lesion according to the provisional T-stenting strategy who were followed up for 3 years. Target lesion revascularization rates were 24.3% for BMSs (n = 337), 15.6% for sirolimus-eluting stents (SESs, n = 422), and 17.3% for paclitaxel-eluting stents (PESs, n = 279) (P = .003 BMSs vs DESs, P = .54 SESs vs PESs). The respective incidences were 11.4%, 9.5%, and 14.8% (P = .65, P = .13) for death and myocardial infarction and 9.9%, 6.5%, and 10.6% (P = .72, P = .19) for death. Propensity score adjusted hazard ratios (95% CI) for DESs versus BMSs were 0.49 (0.35-0.68, P < .001) for target lesion revascularization, 0.94 (0.64-1.40, P = .078) for death and myocardial infarction, and 0.85 (0.55-1.32, P = .47) for death. We did not find any significant differences between SESs and PESs, except for an increased risk of death after PESs compared with SESs (but not BMSs) in the subgroup receiving a side-branch stent (adjusted hazard ratio 2.45, 95% CI 1.05-5.73, P = .035). Compared with BMSs, both PESs and SESs substantially reduced the long-term need for repeated revascularization but did not increase the risk of death and myocardial infarction.
    American heart journal 03/2010; 159(3):454-61. · 4.65 Impact Factor
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    ABSTRACT: Bleeding complications in the groin are one of the major disadvantages of femoral catheter procedures. The immobilisation of the patient and the compression bandages can jeopardize the patients' comfort. Aim of the study was a randomized comparison of safety and patient comfort of mechanical pressure followed by pressure bandage overnight using two different haemostatic pads after femoral artery sheath removal. Nine hundred and eight consecutive patients undergoing diagnostic or therapeutic procedures via a 5 or 6 F femoral sheath were randomly selected either for mechanical compression therapy followed by a compression bandage (302 patients, group 1), or manual compression with application of a calcium ion releasing device (compression bandage only after application of > 5000 IU of heparin; 303 patients; group 2), or manual compression with a thrombin covered PAD without compression bandage (303 patients, group 3). No major hemorrhage or death occurred. A false aneurysm was found in 10 (3.3%), 13 (4.3%), and 10 patients (3.3%) of group 1, 2, and 3, respectively (p = 0.38). Three patients (0.3%) needed surgical treatment. 69 (22.7%) patients in thrombin covered PAD-group required a compression bandage overnight due to seeping hemorrhage after 15 minutes. In the calcium ion releasing PAD-group 124 (40.9%) patients had continued bandaging, 46 (15.2%) due to seeping hemorrhage after 15 min, and 78 (25.7%) due to application of heparin > 5000 IU. The use of mechanical compression combined with a pressure bandage, and the use of haemostatic wound dressing assisted sheath removal technique offer a comparable level of safety. Patient comfort is improved with the usage of PAD devices, however the technical failure rate of the PAD should be taken into account.
    VASA.: Zeitschrift für Gefässkrankheiten. Journal for vascular diseases 03/2009; 38(1):53-9. · 1.01 Impact Factor
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    ABSTRACT: 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. 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). 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.
    European Heart Journal 11/2008; 29(23):2859-67. · 14.72 Impact Factor
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    ABSTRACT: Whether bivalirudin is superior to unfractionated heparin in patients with stable or unstable angina who undergo percutaneous coronary intervention (PCI) after pretreatment with clopidogrel is unknown. We enrolled 4570 patients with stable or unstable angina (with normal levels of troponin T and creatine kinase MB) who were undergoing PCI after pretreatment with a 600-mg dose of clopidogrel at least 2 hours before the procedure; 2289 patients were randomly assigned in a double-blind manner to receive bivalirudin, and 2281 to receive unfractionated heparin. The primary end point was the composite of death, myocardial infarction, urgent target-vessel revascularization due to myocardial ischemia within 30 days after randomization, or major bleeding during the index hospitalization (with a net clinical benefit defined as a reduction in the incidence of the end point). The secondary end point was the composite of death, myocardial infarction, or urgent target-vessel revascularization. The incidence of the primary end point was 8.3% (190 patients) in the bivalirudin group as compared with 8.7% (199 patients) in the unfractionated-heparin group (relative risk, 0.94; 95% confidence interval [CI], 0.77 to 1.15; P=0.57). The secondary end point occurred in 134 patients (5.9%) in the bivalirudin group and 115 patients (5.0%) in the unfractionated-heparin group (relative risk, 1.16; 95% CI, 0.91 to 1.49; P=0.23). The incidence of major bleeding was 3.1% (70 patients) in the bivalirudin group and 4.6% (104 patients) in the unfractionated-heparin group (relative risk, 0.66; 95% CI, 0.49 to 0.90; P=0.008). In patients with stable and unstable angina who underwent PCI after pretreatment with clopidogrel, bivalirudin did not provide a net clinical benefit (i.e., it did not reduce the incidence of the composite end point of death, myocardial infarction, urgent target-vessel revascularization, or major bleeding) as compared with unfractionated heparin, but it did significantly reduce the incidence of major bleeding. (ClinicalTrials.gov number, NCT00262054.)
    New England Journal of Medicine 09/2008; 359(7):688-96. · 54.42 Impact Factor
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    ABSTRACT: 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. 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). In patients with a low initial response to clopidogrel, platelet inhibition can be improved by increasing the maintenance dose to 150 mg.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 08/2008; 4(2):214-21. · 3.17 Impact Factor
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    ABSTRACT: New European Society of Cardiology/American College of Cardiology guidelines classify patients with acute coronary syndrome and increased cardiac troponins as non-ST-segment elevation myocardial infarction (NSTEMI) who would have been classified as unstable angina pectoris (UAP) using the older World Health Organization (WHO) definition. The optimal revascularization strategy in these patients is poorly defined. This prospective cohort study included 1,024 consecutive patients with acute coronary syndrome classified as UAP, NSTEMI according to the WHO definition (WHO NSTEMI), and NSTEMI additionally identified by the novel European Society of Cardiology/American College of Cardiology definition (additional NSTEMI). All patients underwent coronary angiography within 24 hours and were treated with immediate percutaneous coronary intervention (PCI) or early coronary artery bypass grafting (CABG). The primary end point was all-cause mortality during follow-up of 36 months. Patients with additional NSTEMI showed excessive cumulative 3-year mortality if undergoing CABG (hazard ratio 5.9, 95% confidence interval 2.7 to 13.1, p <0.001). In patients with UAP or WHO NSTEMI, mortality was similar in the CABG and PCI groups. In conclusion, in the absence of randomized trials specifically including patients with additional NSTEMI, the excessive mortality observed with CABG in this cohort study suggested that PCI may be the preferable revascularization strategy in this subgroup.
    The American Journal of Cardiology 07/2008; 102(2):173-9. · 3.21 Impact Factor
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    ABSTRACT: The use of cardiac troponin allows the identification of additional patients developing myocardial necrosis during an acute coronary syndrome. Novel guidelines of European and American cardiac societies recommend labeling these events as myocardial infarction. Our study evaluated the long-term mortality in the group of patients with non-ST segment elevation myocardial infarction not meeting the older World Health Organization (WHO) criteria (creatine phosphokinase) but additionally identified by the novel definition of myocardial infarction. This cohort study included 1024 consecutive patients with non-ST segment elevation acute coronary syndrome classified into "unstable angina," myocardial infarction according to the WHO definition ("WHO criteria"), and myocardial infarction additionally identified by the novel definition ("additional criteria"). All patients were treated with an early invasive strategy. The primary end point was all-cause mortality during follow-up of up to 36 months. During long-term follow-up (median 16 months, interquartile range 6-29 months), 67 deaths occurred. Kaplan-Meier analysis showed cumulative 3-year mortality rates of 5.6% in patients with "unstable angina," 9.1% in patients identified by "WHO criteria," and 17.5% in patients identified by "additional criteria" (P <.001). Cox regression analysis confirmed the "additional criteria" as a significant predictor of mortality (hazard ratio 3.1; 95% confidence interval, 1.9-5.0; P <.001). The new definition of myocardial infarction based on cardiac troponin testing identifies a high-risk group of additional patients with acute coronary syndrome that is, therefore, appropriately classified as myocardial infarction. In fact, long-term mortality in "additional criteria" patients is higher than in "WHO criteria" patients.
    The American journal of medicine 05/2008; 121(5):399-405. · 5.30 Impact Factor
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    ABSTRACT: The present study was performed to determine the effect of combined intravenous and oral volume supplementation on the incidence of contrast-induced nephropathy (CIN) in patients undergoing percutaneous coronary intervention (PCI). Consecutive patients (n = 958) receiving iomeprol 350 during PCI were evaluated prospectively for the development of CIN. All patients received protocol-defined intravenous and oral volume supplementation. CIN was defined as an increase in serum creatinine of at least 44 micromol/l within 48 h. Of the 958 patients enrolled in the study, 147 (15%) were diabetic and 107 (11%) had stage III renal disease. The average baseline glomerular filtration rate was 88 +/- 25 ml/min/1.73 m(2). During the intervention an average of 238 +/- 86 ml of contrast medium was administered. CIN developed in 13 of 958 (1.4%; 95% confidence interval 0.6-2.1%) patients. The incidence of CIN was low even in predefined risk subgroups (women: 2.4%, diabetics: 2.7%, patients with stage III kidney disease: 6.5%). The incidence of CIN is low when preprocedural fluid volume supplementation is used.
    Medical Principles and Practice 02/2008; 17(5):409-14. · 0.96 Impact Factor
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    ABSTRACT: Early studies suggested interactions between statins and clopidogrel. Based on the outcome and platelet data, there is now huge evidence of no interactions between statins and 75 to 300 mg clopidogrel; however, data with 600-mg loading are lacking. In a pre-specified analysis of the EXCELSIOR cohort, we investigated the interaction between statins, especially cytochrome P4503A4-metabolized atorvastatin and simvastatin, and the antiplatelet effects of a 600-mg loading dose of clopidogrel. We analyzed 1,395 patients scheduled for coronary angiography (CA). Patients received clopidogrel 600 mg at least two hours before CA and 75 mg daily thereafter in case of percutaneous coronary intervention (PCI). Statin medication on admission was continued unaltered until discharge. Platelet function was assessed by optical aggregometry and flow cytometry of adenosine diphosphate (ADP)-stimulated surface expression of CD62P, CD63 and PAC-1 before clopidogrel and immediately before CA. Residual platelet aggregation (RPA) after addition of ADP 5 muM was similar irrespective of statin treatment at baseline (p = 0.968). RPA at CA was 46.2 +/- 16.8% in patients without statin (n = 682), 45.5 +/- 17.0% in patients with atorvastatin (n = 255), 45.8 +/- 16.3% with simvastatin (n = 335), 47.3 +/- 14.9% with fluvastatin (n = 42) and 45.9 +/- 16.2% with pravastatin (n = 81; p = 0.962). Consistent results were obtained by flow cytometry. In patients with PCI (n = 553), the one-year incidence of death, myocardial infarction and target lesion reintervention did not differ between cohorts stratified according to statin co-medication (p = 0.645). Thus, peri-interventional atorvastatin and simvastatin had no effect on the antiplatelet activity of a loading dose of clopidogrel 600 mg and did not affect clinical outcome after PCI.
    Thrombosis and Haemostasis 02/2008; 99(1):174-81. · 5.76 Impact Factor
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    ABSTRACT: We investigated whether the loss of function CYP2C19 681G>A *2 polymorphism is associated with high (>14%) residual platelet aggregation (RPA) on clopidogrel and whether high on-clopidogrel RPA impacts clinical outcome after elective coronary stent placement. The cytochrome P450 (CYP)-dependent conversion of clopidogrel to its active metabolite may contribute to the variability in antiplatelet effect of clopidogrel. The study included 797 consecutive patients undergoing percutaneous coronary intervention, who were followed-up for 1 year. Adenosine-diphosphate-induced (5 mumol/l) RPA was assessed after a 600-mg loading dose and after the first 75-mg maintenance dose of clopidogrel before discharge. CYP2C19 genotype was analyzed by real-time polymerase chain reaction. Of the patients included, 552 (69.3%) were CYP2C19 wild-type homozygotes (*1/*1) and 245 (30.7%) carried at least one *2 allele. Residual platelet aggregation at baseline did not differ significantly between genotypes. On clopidogrel, RPA was significantly (p < 0.001) higher in *2 carriers than in wild-type homozygotes (23.0% [interquartile range (IQR) 8.0% to 38.0%] vs. 11.0% [IQR 3.0% to 28.0%] after loading; 11.0% [IQR 5.0% to 22.0%] vs. 7.0% [IQR 3.0% to 14.0%] at pre-discharge). Between *2 carriers and wild-type homozygotes, we found significant (p < 0.001) differences in the proportion of patients with RPA >14%, both after loading (62.4% vs. 43.4%) and at pre-discharge (41.3% vs. 22.5%). Residual platelet aggregation >14% at pre-discharge incurred a 3.0-fold increase (95% confidence interval 1.4 to 6.8; p = 0.004) in the 1-year incidence of death and myocardial infarction. Patients carrying at least one CYP2C19*2 allele are more prone to high-on clopidogrel platelet reactivity, which is associated with poor clinical outcome after coronary stent placement (Effect of Clopidogrel Loading and Risk of PCI [EXCELSIOR]; NCT00457236).
    Journal of the American College of Cardiology 01/2008; 51(20):1925-1934. · 14.09 Impact Factor
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    Heinz Joachim Büttner, Franz-Josef Neumann
    Journal of the American College of Cardiology 12/2007; 50(21):2037-8. · 14.09 Impact Factor
  • Heinz Joachim Buettner, Christian Mueller
    European Heart Journal 10/2007; · 14.72 Impact Factor