Increasing use of anticoagulants in Germany and its impact on hospitalization rates for genitourinary bleeding.

The aim of the study was to compare nationwide time trends of prescribed oral anticoagulants (OAC) with the time trend of genitourinary bleedings (GUB) in Germany from 2005 through 2016. The annual numbers of hospitalized patients with GUB coded as "hematuria", "excessive, frequent and irregular menstruation", "postmenopausal bleeding" or "abnormal uterine and vaginal bleeding" were extracted from the nationwide hospitalization file by the Federal Bureau of Statistics. Hospitalization rates were age-standardized using the German standard population 2011. Defined daily doses (DDD) of prescribed anticoagulants among outpatients for the same calendar period were extracted from reports of the statutory health insurance drug information system. Based on DDD, drug treatment rates per 100,000 person years (py) were calculated. From 2005 to 2016, annual OAC treatment rates per 100,000 py increased by 135.8% (from 901.4 to 2125.9). Until 2011 direct oral anticoagulants (DOAC) represented less than 0.1% of all OAC, but 49.9% in 2016. In the same period age-standardized rates of hospitalizations for hematuria increased continuously (annual change of 1.03 (95% CI 0.94-1.11) per 100,000 py), that of "postmenopausal" (- 1.93; 95% CI - 2.38 to - 1.49) or "excessive, frequent and irregular menstruation" decreased (- 1.25; 95% CI -1.62 to - 0.87) and that of "abnormal uterine and vaginal haemorrhage" remained almost unchanged. From all cases with hematuria 5.3% received at least 1 red blood cell concentrate (RBC) in 2005 and 8.2% in 2016 whereas all cases with the other three types of bleeding counted for 1.9% in 2005 and 3.8% in 2016. The time trends for GUB in all subgroups changed steadily and showed no effect of the disproportional increase of DAOCs until 2011. Our ecologic nationwide comparison of OAC treatment rates in outpatients and hospitalization rates for GUBs revealed that despite increasing OAC treatment rates from 2011 to 2016 the hospitalization rates for GUB showed steady annual changes unaffected by the increasing prescription rates of DOACs since 2011.

Correlation between obesity and manual lymphatic drainage in Germany - a retrospective analysis from 2008 to 2016.

Backgrounds: Costs for manual lymphatic drainage (MLD) paid by the Statutory Health Insurances (SHI) have increased disproportionately in Germany in the last decade. There is no obvious reason that this increase is due to an increasing number of patients with lymph edema. We therefore assume that there are large numbers of patients with obesity and obesity-associated dependency syndrome who drive the cost of MLD and did a retrospective analysis of the correlation between hospitalization rates for lymph edema and obesity and MLD prescription rates in outpatients. PATIENTS AND METHODS: Roughly 90 % of the German population is insured by the Statutory Health Insurance. From its reports we extracted data regarding costs and numbers of MLD session prescribed annually. Hospitalization rates for lymph edema (codes I89.*, I97.2 and Q82.0) and for obesity (ICD E66.*) were provided by the Federal Statistical Office after a specific remote analyses. RESULTS: In the years 2008 to 2016, the MLD prescriptions in the individual federal states increased by + 43.5 % in Berlin to + 109.3 % in Mecklenburg-Western Pomerania. Number of hospitalizations with the principal diagnosis (condition, which caused the admission) hereditary and postmastectomy lymph edema are low and decreased in most federal states. Number of hospitalizations with the additional diagnosis (conditions that coexist at the time of admission or develop subsequently) obesity increased with a range from + 4.8 % in Baden-Württemberg to + 86.4 % in Mecklenburg-Western Pomerania. The correlation between the increase in prescribed MLD in the individual federal state and the increase in hospitalization rates per 1000 inhabitants of cases with obesity is greater (R2 0.4696) than with lymph edema (R2 0.0987). CONCLUSIONS: Our analysis is in line with the hypothesis that there is a correlation between the increasing prescription rate of MLD and the increasing burden of obesity in Germany.

Use of maggot debridement therapy in hospitalised patients in Germany.

Exact data regarding the clinical role of maggot debridement therapy (MDT) for wound care in a specific country are not available. Thus, we analysed the use of MDT in hospitalised patients in Germany. Detailed lists of all hospitalised cases treated with MDT in Germany for the years 2011 to 2016 were provided by the Federal Statistical Office as well as the lists of the 15 most frequent principal and additional diagnoses, respectively, and the 10 most frequent procedures documented with MDT in 2016. Within the 6-year time period of the study, the number of cases treated with MDT increased by 11% from 4513 in 2011 to 5.017 in 2016. Lower leg and foot were the most frequent anatomic sides of treatment counting up to 83.9% of all cases. In addition, MDT procedures for temporary soft tissue coverage including negative pressure wound therapy were often performed: for treatment of large areas in 36.7% and small areas in 6.2%. 41.3% of all cases treated with MDT had infection with Escherichia coli and 35.9% of all cases with Bacillus fragilis. Our analysis shows a limited use of MDT with a small increase only in the last 6 years in German hospitals. MDT is predominately used to treat foot or leg ulcers.

Thromboembolic disease in females and males aged 10 to 39 years in Germany.

BACKGROUND: We analysed differences in hospitalization rates for venous diseases such as pulmonary embolism (PE), deep vein thrombosis (DVT), sinus vein thrombosis (SVT), portal vein thrombosis (PVT), and Budd-Chiari syndrome (BCS) as well as for arterial diseases such as myocardial infarction (MI) and embolic stroke (ES) in females and males aged 10 to 39 years. PATIENTS AND METHODS: Detailed lists of hospitalizations with the principal and additional diagnoses for PE (ICD-code I26.0 + I26.9), DVT (I80.0-I80.9), SVT (I67.6), PVT (I81), BCS (I82.0), MI (I21.0-I21.9), and ES (I63.1 + I63.4) in males and females aged 10 to 39 years in the years 2006 to 2015 were provided by the Federal Statistical Office in Germany. RESULTS: Considering the 10-year period there were more female than male cases hospitalized with the principal diagnoses for PE, DVT, SVT, and BCS. Looking at the principal diagnosis of the year 2015, one can see a steep increase in numbers of hospitalization for PE, DVT, and SVT in females ranging from the ages 12 to 13 and 14 to 15 years compared to males. The curves of PE and DVT meet again in the age group between 32 and 33 years, but not for SVT. The greatest differences are seen at the end of the second and at the beginning of the third decade of life. In contrast, MI was more frequent in young males beginning at the age of 18 to 19 years. The number of female and male cases with ES and PVT were almost similar in the different age groups. CONCLUSIONS: The presented data show higher hospitalization rates for females in the age group 10 to 39 years for different venous thrombosis but not for MI and ES.

Mortality in endovascular and open abdominal aneurysm repair - trends in Germany.

BACKGROUND: We analysed trends in mortality of endovascular (EVAR) and open aortic repair (OAR) in patients hospitalized for abdominal aortic aneurysms (AAA) in Germany from 2005 to 2015. PATIENTS AND METHODS: We used national statistics published by the Federal Statistical Office in Germany to calculate mortality rate of patients hospitalized with ruptured (rAAA, n = 2,448 in 2005, n = 2,180 in 2015) and non-ruptured (iAAA, n = 11,626 in 2005, n = 14,205 in 2015) AAA. RESULTS: Considering only those who were treated with EVAR or OAR, treatment rates of iAAA with EVAR increased to 78.2 % in males and 72.6 % in females in 2015 and treatment rates of rAAA to 36.9 % and 40.7 %, respectively. In cases with iAAA, death rates associated with EVAR decreased in males from 2.1 to 1.1 % (p = 0.0005) in the period from 2005 to 2015 but not in females (1.8 % in 2005 and 2.3 % in 2015, p = 0.8511). Similar trends are seen in cases with rAAA (males 30.1 % and 24 %, p = 0.1034, females 36.4 to 37.3 %, p = 0.8511). Death rates associated with OAR increased in males from 4.7 % in 2005 to 5.7 % in 2015 (p = 0.0103) and tended to increase in females from 6.8 to 8.2 % (p = 0.1476). In cases of rAAA, there were no changes. EVAR treatment rates increased in cases with iAAA in both genders with age, as well as in males with rAAA, but not in females. OAR associated death rates increased with age in rAAA (from around 30 % in the sixth/seventh decade of life to almost 80 % in cases with patients over the age of 90) and in iAAA (from 1.1 to 20 %). CONCLUSIONS: The general increase in EVAR procedures in males and females hospitalized for rAAA and iAAA went along with a decrease in in-hospital mortality in males treated with EVAR for iAAA only and an increasing mortality in males treated with OAR for iAAA.

Ten-year analyses of the German DRG data about negative pressure wound therapy.

Exact data regarding the clinical role of negative pressure wound therapy (NPWT) for wound care in a specific country are not available. Thus, we analysed the use of NPWT in hospitalised patients in Germany. Detailed lists of all hospitalised cases treated with NPWT in Germany for each of the years from 2005 to 2014 were obtained from the Federal Statistical Office, as well as lists of the 15 most frequent principal and additional diagnoses documented with NPWT in 2014. Within the 10-year time period of the study, the number of cases treated with NPWT increased by 349%, from 37 053 in 2005 to 129 269 in 2014. The rate of all hospitalised cases treated with NPWT increased form 0·22% to 0·66% in Germany. In 2014, wounds affecting skin and subcutaneous tissue (5-916.a0) are the most frequent documented indication for NPWT followed by deep wounds involving bones and joints at the limbs (5-916.a1). Open abdomens (5-916.a3) count for higher numbers than deep wounds of the thorax, mediastinum and sternum (5-916.a2). Fifty percent of all cases hospitalised for stage IV pressure ulcers at sacrum or ischium and around one third (32.2%) of cases with pyothorax received NPWT. Every fourth to fifth case hospitalised for disruption of surgical wounds or infections following a procedure (24·1%), as well as for infections and inflammations because of internal joint prosthesis or because of an internal fixation device was treated with NPWT (22·9%). In cases with diabetic foot syndrome, it is still every tenth case (10·1%). This analysis shows a substantial increase in the use of NPWT in the last decade for hospitalised patients. NPWT has a fixed role in the treatment of stage IV pressure ulcers at sacrum or ischium, pyothorax, infection and inflammation because of internal joint prosthesis or an internal fixation device and diabetic foot syndrome.

Determinants of decreasing major amputation rates in Germany.

BACKGROUND: We analysed a potential association between the decrease in major amputations in Germany and the number of doctors, prescribed podologic foot care (PFC) and antidiabetic drugs, and performed percutaneous endoluminal angioplasties (PTA). PATIENTS AND METHODS: Data of all lower limb major amputations between 2007 and 2011, the cases hospitalised with an additional diagnosis of diabetes mellitus, and the numbers of PTAs, and the number of doctors in private practices and in hospitals were obtained from the Federal Statistical Office. Furthermore, the number of PFC treatments and prescribed antidiabetics for each of the five years were derived from the federal report of the statutory health insurance. RESULTS: Within the 5 year time period, major amputations decreased by 19.0%, from 17,846 in 2007 to 14,463 in 2011. There is an inverse relation between the number of major amputations and the increasing number of prescribed PFC, of doctors working in hospital and of below-the-knee PTA in the multiple Poisson regression analysis. The number of prescribed antidiabetics and that of all PTA showed a positive relation. In the multiple linear regression analysis with the dependent variable ratio of amputations and the cases hospitalised with an additional diagnosis of diabetes mellitus, only numbers of prescribed PFC and below-the-knee PTA still showed an inverse relation that reached a level of significance. CONCLUSIONS: While substantial improvements in patients care by doctors, endovascular interventions, prescriptions of PFC and antidiabetic drugs are under discussion to reduce major amputation rates, in this approach including comprehensive data from Germany, only prescriptions of PFC and the number of below-the-knee PTA had an independent and significant impact on the reduction of major amputations. It has to be pointed out that such a statistical association does not prove any causality.

Prophylaxis of venous thromboembolism in physically restrained psychiatric patients.

OBJECTIVE: We analysed the rate of physical restraint in acute and chronic psychiatric patients and looked at the safety of waiving venous thromboembolic disease (VTE) prophylaxis in the case of restraining of less than 24 h. METHODS: We did a retrospective analysis of all episodes of restraining in 2012 and 2013, diagnosis of restrained patients, time of restraining and use of low molecular weight heparin (LMWH) for prophylaxis of VTE associated with restraining. RESULTS: Overall, 12 734 patients were hospitalised. The number of episodes of restraining was 1035 and involved 469 (7.4%) patients. Only 79 episodes of restraining lasted more than 24 h and affected only 36 (0.3%) individual patients. The most frequent psychiatric diagnoses were unstable borderline personality in 41 (52%) and schizophrenic or schizoaffective psychosis in 26 (33%) episodes. None of these prolonged restraints and none of the 956 episodes of restraining for less than 24 h were associated with clinical symptoms or signs of VTE that would have required additional diagnostic consequences. CONCLUSION: The concept of waiving VTE prophylaxis within the first 24 h of restraining seems to be safe. On the other hand, LMWH sufficiently protected the small sample being restrained for more than 24 h.

Prescription of enoxaparin is associated with decreasing pulmonary embolism mortality rate in Germany.

We analysed time trends in the pulmonary embolism (PE) mortality rates in Germany from 2004 and assessed for an association between the use of anticoagulants and PE caused mortality. We extracted age-specific number of deaths due to PE (ICD-10 I26) from 2004 to 2011 as available from the WHO mortality databases. In addition we derived defined daily dosage (DDD) of prescribed anticoagulants and the low molecular heparin Enoxaparin for the years 2004-2011 from the statutory health insurance-drug-information system reports. Age-standardized PE mortality per 100,000 decreased from 5.9283 in year 2004 to 4.4876 in 2011 (-24.3 %). Amounts of prescribed anticoagulants increased in this period from 271,810.7 × 1000 DDD to 416,611.8 × 1000 DDD (+53.3 %), that of Enoxaparin increased from 27,071.1 × 1000 DDD in 2004 97,276.5 × 1000 DDD in 2011. The PE mortality is negatively correlated with anticoagulants (-0.9463, p = 0.0004) as well as with enoxaparin (-0.9740, p < 0.0001) and of DDD of Enoxaparin per 1000 insured (-0.9682, p < 0.0001). In univariate linear regression model, anticoagulants, Enoxaparin and Enoxaparin per 1000 insured all reach significance (p = 0.0004, p = 4.31 × 10(-5) and p = 0.0001 respectively). Multiple regression models show that Enoxaparin has the most robust effect. Including the time trend in the model does not alter the results. Our study shows that increasing number of prescribed Enoxaparin in an outpatient setting might be one determinant of decreasing PE mortality rate in Germany since 2004.

Sonography of subcutaneous tissue cannot determine causes of lower limb edema.

BACKGROUND: To clarify the clinical use of sonography for differentiation of edema we tried to answer the question whether a group of doctors can differentiate lymphedema from cardiac, hepatic or venous edema just by analysing sonographic images of the edema. PATIENTS AND METHODS: 38 (70 ± 12 years, 22 (58 %) females) patients with lower limb edema were recruited according the clinical diagnosis: 10 (26 %) lymphedema, 16 (42 %) heart insufficiency, 6 (16 %) venous disorders, 6 (16 %) chronic hepatic disease. Edema was depicted sonographically at the most affected leg in a standardised way at distal and proximal calf. 38 sets of images were anonymised and send to 5 experienced doctors. They were asked whether they can see criteria for lymphedema: 1. anechoic gaps, 2. horizontal gaps and 3. echoic rims. RESULTS: Accepting an edema as lymphedema if only one doctor sees at least one of the three criteria for lymphatic edema on each single image all edema would be classified as lymphatic. Accepting lymphedema only if all doctors see at least one of the three criteria on the distal image of the same patient 80 % of the patients supposed to have lymphedema are classified as such, but also the majority of cardiac, venous and hepatic edema. Accepting lymphedema only if all doctors see all three criteria on the distal image of the same patients no edema would be classified as lymphatic. In addition we separated patients by Stemmers’ sign in those with positive and negative sign. The interpretation of the images was not different between both groups. CONCLUSIONS: Our analysis shows that it is not possible to differentiate lymphedema from other lower limb edema sonographically.

Increasing Use of Anticoagulants in Germany and Its Impact on Hospitalization for Tooth Extraction.

OBJECTIVES: This article aimed to compare nationwide time trends of oral anticoagulant prescriptions with the time trend of hospitalization for tooth extraction (TE) in Germany from 2006 through 2017. PATIENTS AND METHODS: We derived the annual number of hospital admissions for TE from the Nationwide Hospital Referral File of the Federal Bureau of Statistics and defined daily doses (DDD) of prescribed anticoagulants in outpatients from reports of the drug information system of the statutory health insurance. RESULTS: From 2005 to 2017, annual oral anticoagulation (OAC) treatment rates increased by 143.7%. In 2017, direct oral anticoagulants (DOACs) represented 57.1% of all OAC treatments. The number of cases hospitalized for TE increased by 28.0 only. From all the cases hospitalized for TE in Germany in 2006, 14.2% had a documented history of long-term use of OACs. This proportion increased to 19.6% in 2017. Age-standardized hospitalization rates for all TE cases with long-term use of OACs increased from 6.6 in 2006 to 10.5 cases per 100,000 person-years in 2014 and remained almost unchanged thereafter. CONCLUSION: Our comparison showed that the large increase in OAC treatment rates in general from 2006 to 2017 had only a small impact on hospitalized TE cases with long-term use of OAC which flattens since 2014.

Platelet dysfunction and inhibition of multiple electrode platelet aggregometry caused by penicillin.

Beta-lactam antibiotics, e.g. penicillin, may inhibit platelet function and lead to reduced response in light transmission aggregometry and adhesion. However, influence on platelet function tests more commonly used in clinical practice, such as multiple electrode platelet aggregometry (MEA), have not been described so far. We report a case of a patient with local streptococcus infection. Treatment with penicillin resulted in mild bleeding tendency after 3 days. While coagulation parameters were normal, assessment of platelet function by MEA revealed strong platelet inhibition of both ADP and arachidonic acid induced platelet aggregation comparable to normal responders to antiplatelet therapy. Change of antibiotic regime resulted in recovery of platelet function. Thus, penicillin therapy may impact on platelet function and consecutively commonly used platelet function assays, e.g. MEA.

Comparison of Endovascular and Open Carotid Artery Treatment in Germany: A Retrospective Analysis from 2010 to 2015.

INTRODUCTION: We analyzed trends in carotid artery stenting (CAS) and carotid endarterectomy (CEA) in hospitalized cases in Germany in the years 2010-2015. METHODS: Data from national statistics (DRG statistics) published by the Federal Statistical Office in Germany describing the number of hospitalized patients treated with CEA and CAS were used. In addition, numbers of patients hospitalized with the principal diagnosis stroke associated with precerebral lesions (ICD code I63), transitory cerebral ischemic attacks (G45) and precerebral carotid artery stenosis (I65) treated by CEA and CAS were analyzed for the year 2015. RESULTS: Total number of CEA decreased by 4.0% from 24.067 (2010) to 23.104 (2015) and CAS increased by 5.1% from 5.703 to 5.992. In 2015, 79.4% of all procedures coded concerning the internal carotid artery were CEA and 21.6% CAS. From 27.798 cases hospitalized with the principal diagnosis stroke associated with precerebral lesions, CEA was performed in 3.921 (14.1%) and in 2.132 (7.7%) CAS was documented, with CAS making up one-third of all treatments within the stroke group. In 28.273 cases hospitalized with a TIA, CEA was specified in 853 (3.0%) and CAS in 255 (0.9%) cases. In 27.553 cases with an occlusion and stenosis of precerebral arteries, not resulting in cerebral infarction, 17.036 (61.8%) had a CEA and 3.156 (11.5%) a CAS procedure. CONCLUSION: CEA is still the primary treatment of extracranial artery stenosis. The impact of CAS becomes mainly apparent in cases presenting with acute strokes.

Impact of body mass index on platelet aggregation after administration of a high loading dose of 600 mg of clopidogrel before percutaneous coronary intervention.

This study assessed the effect of body mass index (BMI) on platelet aggregation after administration of a high loading dose of clopidogrel 600 mg. Blood samples of 402 patients before percutaneous coronary intervention were collected >or=2 hours after administration of clopidogrel 600 mg. Platelet aggregation was measured in response to adenosine diphosphate (ADP; 5 and 20 microM). Patients were categorized as normal weight (BMI <25 kg/m(2)) or overweight (BMI >or=25 kg/m(2)). ADP-induced platelet aggregation was significantly higher in overweight patients than in normal-weight patients (46.0 +/- 21.8% vs 38.2 +/- 19.3% for ADP 5 microM, p = 0.0007; 55.1 +/- 22.7% vs 45.2 +/- 21.7% for ADP 20 microM, p <0.0001). Multivariate analyses demonstrated high BMI as the only independent predictor for increased ADP-induced platelet aggregation (p

Platelet function in clopidogrel-treated patients with acute coronary syndrome.

Percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS) is associated with increased risk of thrombotic complications. ACS enhances platelet activation; whether pretreatment with clopidogrel is sufficient to suppress platelet function in patients with ACS is not known. This study assessed platelet function in patients with and without ACS prior to PCI and after pretreatment with a single dose of 600 mg clopidogrel. Blood samples of 402 patients prior to PCI with (n = 119) or without (n = 283) ACS were collected at least 2 h after 600 mg clopidogrel administration. Maximal platelet aggregation in response to ADP (5 and 20 micromol/l), collagen (4 microg/ml) and TRAP (25 micromol/l) was measured with optical aggregometry. Surface expression of glycoprotein IIb/IIIa and P-selectin was assessed with flow cytometry at baseline and after stimulation with 5 and 20 micromol/l ADP. Agonist-induced platelet aggregation did not differ significantly between patients with and without ACS (P > or = 0.15). Parameters of platelet activation (glycoprotein IIb/IIIa and P-selectin surface expression) were significantly higher in ACS patients at baseline and after 5 and 20 micromol/l ADP stimulation (P < 0.0001). Patients with ACS continue to exhibit increased platelet activation after pretreatment with 600 mg clopidogrel. This finding supports the need for additional platelet function inhibition during PCI in patients with ACS.

Prognostic value of N-terminal pro-brain natriuretic peptide in patients with chronic stable angina.

BACKGROUND: Patients with chronic stable angina are poorly characterized in terms of biomarkers that help in the assessment of prognosis. We investigated whether plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) may be used as a prognostic marker in patients with chronic stable angina treated with coronary stenting. METHODS AND RESULTS: Plasma levels of NT-proBNP were measured in 1059 patients with chronic stable angina and coronary angiographic confirmation of significant coronary artery disease. The primary end point of the study was mortality. After a median of 3.6 years (interquartile range, 3.3 to 4.5 years), there were 106 deaths. Kaplan-Meier estimates of 5-year mortality were 4.7% in the first quartile, 7.8% in the second quartile, 11.4% in the third quartile, and 32.7% in the fourth quartile of NT-proBNP (P<0.001). A Cox proportional hazards model showed that NT-proBNP was the strongest correlate of mortality (adjusted hazards ratio [HR], 5.83 [95% confidence interval: 2.07 to 16.44] for the fourth versus the first quartile). A similar prognostic value of NT-proBNP was demonstrated for cardiovascular mortality (HR, 5.98 [1.55 to 23.13] for the fourth versus the first quartile) and for patients with New York Heart Association class I and II (HR, 6.03 [2.07 to 17.52] for the fourth versus the first quartile). CONCLUSIONS: Circulating levels of NT-proBNP are a strong prognostic biomarker for patients with chronic stable angina.

P2Y12 gene H2 haplotype is not associated with increased adenosine diphosphate-induced platelet aggregation after initiation of clopidogrel therapy with a high loading dose.

A large variability in the antiplatelet response to clopidogrel has been consistently reported. Recently, a P2Y12 haplotype was shown to be associated with enhanced adenosine diphosphate (ADP)-induced platelet aggregation in healthy volunteers. The aim of this study was to test in patients (n = 416) scheduled for coronary artery stenting whether P2Y12 haplotype H2 carriage is associated with increased ADP-induced platelet aggregation after administration of a 600 mg loading dose of clopidogrel. Blood was drawn from the arterial sheath at least 2 h after administration of 100 mg aspirin and 600 mg clopidogrel. ADP-induced platelet aggregation was assessed in platelet-rich plasma with light-transmission aggregometry. P2Y12 haplotypes (H1/H2) and P2Y12 C32T genotypes were determined with TaqMan assays. Haplotype combinations and genotypes were not associated with parameters of ADP-induced platelet aggregation after administration of a 600 mg loading dose of clopidogrel. Maximal ADP (5 mumol/l)-induced platelet aggregation was similar in patients carrying haplotype H2 and homozygous carriers of haplotype H1 (43.9 +/- 21.4 versus 43.2 +/- 21.1%, respectively; P = 0.77). Carriage of P2Y12 H2 haplotype does not seem to affect the platelet response to a 600 mg loading dose of clopidogrel in coronary artery disease patients prior to stenting.

Plasminogen activator inhibitor-1 4G/5G polymorphism and efficacy of reperfusion therapy in acute myocardial infarction.

Plasminogen activator inhibitor-1 (PAI-1) plays a central role in the modulation of intravascular thrombosis and thrombolysis. The level of transcription and the plasma level of PAI-1 are in part determined by the 4G/5G polymorphism in the promoter region of the gene. In this study we investigate the effect of 4G/5G polymorphism on the efficacy of reperfusion therapy in acute myocardial infarction (AMI). Two hundred and ninety-three patients were enrolled in two randomized trials comparing stenting plus abciximab with thrombolysis (alteplase alone or alteplase plus abciximab) in AMI. Patients were genotyped for the PAI-1 4G/5G polymorphism with a TaqMan assay. Technetium-99m sestamibi was injected before and 1-2 weeks after reperfusion treatment. Scintigrams were used to calculate the initial perfusion defect, the final infarct size and the salvage index representing the proportion of the initial defect salvaged by reperfusion. An 18-month clinical follow-up was carried out after reperfusion treatment. The distribution of genotypes was as follows: 4G4G in 28.0%, 4G5G in 49.5% and 5G5G in 22.5% of the patients. No significant differences between the three genotypes were detected for the final infarct size (%) of the left ventricle [median (interquartile range); 13.5 (5.0--27.0) for 4G4G patients, 12.0 (5.2--24.6) for 4G5G patients and 16 (7.1--31.2) for 5G5G patients; P=0.36], the salvage index [0.49 (0.25--0.75) in 4G4G patients, 0.47 (0.18--0.73) in 4G5G patients and 0.46 (0.22--0.62) in 5G5G patients; P=0.58] and the mortality 18 months after treatment (8.5% for 4G4G patients, 7.6% for 4G5G patients and 6.1% for 5G5G patients; P=0.85). There was no association in any of the two treatment groups (stenting and thrombolysis) between the 4G/5G genotype and myocardial salvage. The PAI-1 4G/5G polymorphism has no impact on the amount of myocardial salvage achieved by reperfusion with stenting or thrombolysis in patients with AMI.

N-terminal probrain natriuretic peptide and C-reactive protein in stable coronary heart disease.

PURPOSE: C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) provide prognostic information in patients with stable coronary heart disease. The aim of the study was to investigate whether combined use of NT-proBNP and CRP improves risk stratification in these patients. METHODS: This cohort study included 989 patients with stable coronary heart disease who underwent coronary stenting. CRP and NT-proBNP were measured before angiography. The primary end point of the study was all-cause mortality. Using median values of NT-proBNP (279.9 ng/L) and CRP (1.2 mg/L), patients were divided into 4 groups: low NT-proBNP-low CRP group (305 patients with NT-proBNP or =median; high NT-proBNP-low CRP group (237 patients with NT-proBNP> or =median and CRP or =median and CRP> or =median). RESULTS: During a median follow-up of 3.6 years (interquartile range 3.3 to 4.5 years), there were 85 deaths: 6 deaths in the low NT-proBNP-low CRP group, 11 deaths in the low NT-proBNP-high CRP group, 20 deaths in the high NT-proBNP-low CRP group, and 48 deaths in the high NT-proBNP-high CRP group with Kaplan-Meier mortality estimates of 2.7%, 8.9%, 12.1% and 35.6%, respectively (P <.001). Cox proportional hazards model showed that combination NT-proBNP-CRP was the strongest independent correlate of mortality (hazard ratio [HR] 4.3, 95% confidence interval [CI], 2.0-9.3; P <.001 for high NT-proBNP-high CRP vs low NT-proBNP-low CRP). CONCLUSION: Combined use of NT-proBNP and CRP improves long-term risk prediction of mortality in patients with stable coronary heart disease.