[Show abstract][Hide abstract] ABSTRACT: To evaluate the clinical utility of individualising dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in an all-comers population, including ST-elevation myocardial infarction (STEMI) patients.
BMJ Open 10/2014; 4(10):e005781. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This was a prospective study comparing two groups: personalized and non-personalized treatment with P2Y12 receptor blockers during a 12-month follow-up. We aimed to investigate whether personalized antiplatelet treatment in patients with high on treatment platelet reactivity (HTPR) improves clinical outcome. Platelet reactivity was assessed by adenosine diphosphate induced aggregation using a multiple electrode aggregometry (MEA) in 798 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). Patients with HTPR received up to four repeated loading doses of clopidogrel or prasugrel in the personalized treatment group (n=403), while no change in the treatment strategy was undertaken in patients with HTPR in the non-personalized treatment group (n=395). There were fewer major adverse cardiac events (MACE) in the personalized treatment group than in the non- personalized treatment group (7.4% vs. 15.3%; respectively; p<0.001). The multivariate Cox regression analysis showed that the relative risk to develop MACE was 51% lower in the personalized treatment group as compared to the non-personalized treatment group (HR=0.49; 95%CI: 0.31-0.77; p<0.001). Similarly, there was a clear net benefit of the personalized antiplatelet treatment over the non-personalized treatment (ischemic and bleedings events: 8.2% vs. 18.7%; respectively; HR=0.46; 95%CI: 0.29-0.70; p<0.001). Further analysis indicated that patients with aggregation values within the therapeutic window (21-49U) experienced the lowest event rates (stent thrombosis and major bleeding: 2.5%) as compared to poor responders (>50U: 5.4%) or ultra-responders (0-20U: 5.2%). In conclusion, personalized antiplatelet treatment improved patients outcome without increasing bleeding complications compared to the non-personalized treatment during a 12-month follow-up.
Clinical science (London, England : 1979). 08/2014;
[Show abstract][Hide abstract] ABSTRACT: Aims: Drug-eluting stents (DES) reduce late lumen loss compared to bare metal stents but were not able to eradicate in-stent restenosis (ISR) fully. Vascular endothelial growth factor (VEGF) may inhibit late lumen loss through accelerated reendothelialisation, but may also promote neointima formation by proinflammatory effects. The aim of this study was to evaluate whether endogenous plasma levels of VEGF are associated with development of ISR after implantation of DES. Methods and results: We studied 85 patients who were treated with 159 DES. VEGF plasma levels were determined before and 24 hours after PCI. During the eight-month follow-up period, two patients (2.4%) died of cardiovascular causes and 12 patients (14.5% of patients, 7.6% of stents) developed angiographic ISR. Basal VEGF plasma levels were not different in patients with and without ISR at follow-up. In contrast to patients without ISR, VEGF increased significantly upon PCI in patients with ISR (p<0.005). Patients with a decrease of VEGF after PCI had a restenosis rate of 2.4% compared to a restenosis rate of 26.2% in patients with an increase of VEGF after the procedure (p<0.05). This was independent from clinical and angiographic risk factors. Conclusions: Basal plasma levels of VEGF are not associated with the development of ISR. However, an increase of VEGF after PCI is associated with a dramatically increased ISR rate after implantation of DES.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 10/2013; · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Current guidelines still recommend the bolus and infusion administration of glycoprotein IIbIIIa inhibitors in patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention. We sought to evaluate the extent of platelet inhibition by a blocking and bridging strategy with intracoronary abciximab bolus-only administration and oral loading of adenosine diphosphate receptor antagonists.
Fifty-six consecutive high-risk acute coronary syndrome patients with bolus-only abciximab administration (0.25mg/kg i.c.) and loading with 600mg clopidogrel (55%) or 60mg prasugrel (45%) were included in this study. Platelet aggregation induced by thrombin receptor-activating peptide and adenosine diphosphate was measured by multiple electrode aggregometry up to 7days.
Thrombin receptor-activating peptide induced platelet aggregation was significantly suppressed for a minimum of 48h (45±17U) and returned to a normal range (>84U) after 6days (90±26U; p<0.001). Co-medication with prasugrel significantly reduced adenosine diphosphate-induced (p=0.002) and thrombin receptor-activating peptide-induced (p=0.02) platelet aggregation compared with clopidogrel throughout the observation period. No stent thrombosis or repeat myocardial infarction occurred at 30-day follow-up.
Immediate blocking of platelet aggregation in high-risk acute coronary syndrome patients by intracoronary abciximab bolus-only administration and bridging to prolonged inhibition via oral blockade of ADP receptors effectively inhibited overall platelet reactivity for at least 48h, questioning the value of continuous abciximab infusion. Co-medication with prasugrel vs. clopidogrel synergistically augmented platelet inhibition.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND OBJECTIVES: Clopidogrel non-responsiveness is associated with adverse clinical outcome. We aimed to investigate whether individualized antiplatelet treatment in clopidogrel non-responders is an effective and safe strategy. METHODS: This was a prospective non-randomized non-blinded study comparing two cohorts (guided and non-guided treatment) with a follow-up of 1-month. Responsiveness to clopidogrel was assessed by multiple electrode aggregometry (MEA) in 798 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). In the guided group (n=403) clopidogrel non-responders received repeated loading doses of clopidogrel or prasugrel, in the non-guided group (n=395) clopidogrel non-responders did not undergo any change in treatment. RESULTS: Stent thrombosis occurred significantly less often in the guided group than in the non-guided group (0.2% vs. 1.9%; p=0.027). The multivariate Cox regression analysis showed that patients in the non-guided group were at a 7.9-fold higher risk to develop stent thrombosis compared to the guided group (OR: 7.9; 95% CI: 1.08-69.2; p=0.048). In line with this, acute coronary syndrome occurred significantly less often in the guided group than in the non-guided group (0% vs. 2.5%; p=0.001) whereas there was no difference in the event rates of cardiac death (2% vs. 1.3%; p=0.422) or major bleedings (1% vs. 0.3%; p=0.186). CONCLUSION: Personalized antiplatelet treatment according to the platelet function testing with MEA resulted in an improved efficacy with an equal safety compared to the standard treatment.
International journal of cardiology 05/2012; · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: High platelet reactivity (HPR) under treatment with clopidogrel or aspirin is associated with adverse outcome. We aimed to investigate whether high platelet reactivity (HPR) to both aspirin and clopidogrel is a stronger predictor of adverse events compared to isolated HPR to clopidogrel or aspirin. METHODS: In this prospective cohort study platelet reactivity to adenosine diphosphate (ADP) and arachidonic acid (AA) was assessed by Multiple Electrode Aggregometry (MEA) in 403 patients undergoing percutaneous coronary intervention. The rates of the composite of cardiac adverse events (acute coronary syndrome, stent thrombosis, stroke, death and revascularization) were recorded during 12-month follow-up. RESULTS: The composite endpoint of cardiovascular adverse events occurred more often in patients with high platelet reactivity (HPR) to both agonists ADP and AA (37.5%) than in those with isolated HPR to ADP (33.3%), AA (25.6%) or without any HPR (18.6%; p=0.003). Classification tree analysis indicated that any HPR emerged as an independent predictor influencing outcome, which was associated with a 1.75 higher risk of cardiac adverse events (OR=1.75: 95%CI=1.1-2.9). Interestingly, the predictive value of HPR tended to be greater among patients with diabetes mellitus (OR=2.18; 95%CI=1.20-3.95). C-reactive protein and diabetes mellitus were independent predictors of high platelet reactivity to both agonists. CONCLUSIONS: Dual low responsiveness to clopidogrel and aspirin is a strong predictor of cardiac adverse events, especially in patients with diabetes mellitus, which underlines the need for personalized antiplatelet treatment.
International journal of cardiology 02/2012; · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We present the case of a 51-year-old male patient who received adjuvant chemotherapy consisting of oxaliplatin, bolus and continuous 5-fluorouracil (5-FU) and leucovorin after anterior resection because of locally advanced rectal cancer. Preoperative chemotherapy with capecitabine (an oral 5-FU prodrug) had been well tolerated. Two days after initiation of the first course of chemotherapy, the patient reported typical chest pain. The ECG showed ST elevations and prominent T waves in almost all leads. Due to suspicion of a high-risk acute coronary syndrome, an urgent cardiac catheterization was performed. It showed a generally reduced coronary flow with multiple significant stenoses (including the ostia of the left and right coronary artery), as well as a highly reduced left ventricular function with diffuse hypokinesia. Due to the meanwhile completely stable situation of the patient after medical acute coronary syndrome treatment, no ad hoc intervention was performed to allow further discussion of the optimal management. Thereafter, the patient remained clinically asymptomatic, without any rise in cardiac necrosis parameters; only NT-pro-BNP was significantly elevated. A control cardiac catheterization 2 days later revealed a restored normal coronary artery flow with only coronary calcifications without significant stenoses, as well as a normal left ventricular ejection fraction. Cardiovascular symptoms occurred on the second day of continuous 5-FU treatment. As cardiotoxic effects seem to appear more frequently under continuous application of 5-FU, compared to the earlier established 5-FU bolus regimens, treating medical oncologists should pay special attention to occurring cardiac symptoms and immediately interrupt 5-FU chemotherapy and start a cardiologic work-up.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to evaluate improvement opportunities in the emergency department for timely ST-segment elevation myocardial infarction management and evaluated the new process flow.
In a prospective study, we compared time from door to cath laboratory before and after implementation of a new ST-segment elevation myocardial infarction (STEMI) protocol. The new protocol included a blend of strategies to reduce door to cath laboratory time.
We included 55 patients. After implementing a new STEMI protocol, we included 54 patients. Time to cath laboratory was 21 (interquartile range, 9-40) minutes before and 10 (interquartile range 5-25) minutes after initiation of the new protocol (P = .02). A door to cath laboratory time less than 15 minutes was reached in 36% of our patients in phase 1 and in 61% in phase 2 (odds ratio; 0.36, 95% confidence interval, 0.16-0.81; P = .01).
Simple changes in organizational strategies resulted in a significantly faster care for patients with acute uncomplicated STEMI.
The American journal of emergency medicine 07/2011; 29(6):650-5. · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ST-elevation myocardial infarction (STEMI) results from acute thrombotic obstruction of a coronary artery. Percutaneous coronary intervention (PCI) is the treatment of choice to restore blood flow. The incidence of guidewire-induced reopening of the infarct-related coronary artery (IRA) and its association with post-procedural TIMI flow and long-term mortality were assessed. Angiograms of consecutive STEMI patients admitted to the catheter laboratory of the Medical University of Vienna between January 2003 and December 2005 were analysed. TIMI flow was graded prior to and after guidewire insertion into the distality of the IRA, and at the end of the procedure. Initial TIMI 0 flow was present in 476 (47.0%) of 1,012 cases. Target vessel reopening after guidewire insertion defined as any flow >TIMI 0 flow occurred in 150 patients (37.2%), and was associated with improved survival after a median of 914 (609-1,238) days (p=0.017). Reflow after guidewire insertion was an independent predictor of post-procedural TIMI flow (odds ratio=3.10, 95% confidence interval [CI]=1.64 - 5.86], p<0.001) and mortality (hazard ratio=0.51, CI=0.28 - 0.94], p=0.029). Target vessel reopening by guidewire insertion is a new predictor of prognosis. Target vessel flow after guidewire insertion should be assessed in a standardised fashion during PCI.
Thrombosis and Haemostasis 01/2011; 105(1):52-8. · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Enhanced platelet inhibition by clopidogrel decreases the risk of ischemic events but carries a risk for a concomitant increase in bleeding.
To compare the efficacy and safety of two clopidogrel loading regimens (300mg vs. 600mg) in patients undergoing percutaneous coronary intervention (PCI) at one month after start of therapy.
A systematic literature search of MEDLINE, EMBASE, CENTRAL, and Web of Science databases using predefined search terms for relevant articles in any language.
Randomised controlled trials and non-randomised studies reporting adjusted effect estimates were included. Summary estimates of the risks ratios (RRs) with therapy were calculated using a random-effect model. Outcomes evaluated were combined major adverse cardiovascular events (MACE) and major bleedings. Results Seven studies met the inclusion criteria and included 25,383 patients. A 600mg clopidogrel loading was associated with a 34% relative risk reduction of MACE (RR=0.66; 95% confidence intervals CI=0.52-0.84; p<0.001). Sub-analysis revealed a 47% risk reduction of MACE in randomised trials (RR=0.53; 95%CI=0.32-0.88; p=0.01) and a 31% relative risk reduction in non-randomised trials (RR=0.69; 95%CI=0.54-0.90; p=0.005) in patients receiving 600mg loading with clopidogrel. In patients suffering from acute coronary syndrome, 600mg clopidogrel loading was associated with a 24% relative risk reduction in MACE (RR=0.76; 95%CI=0.60-0.95; p=0.02). Importantly, the 600mg clopidogrel loading dose was not associated with an increased risk of major bleedings (RR=0.91; 95%CI=0.73-1.15; p=0.44).
This meta-analysis demonstrates that intensified clopidogrel loading with 600mg reduces the rate of major cardiovascular events without increase in major bleeding compared to 300mg in patients undergoing PCI during one month follow-up.
[Show abstract][Hide abstract] ABSTRACT: To investigate whether proton pump inhibitors (PPIs) negatively affect clinical outcome in patients treated with clopidogrel. Systematic review and meta-analysis. Outcomes evaluated were combined major adverse cardiac events (MACE), myocardial infarction (MI), stent thrombosis, death and gastrointestinal bleeding. Studies included were randomized trials or post-hoc analyzes of randomized trials and observational studies reporting adjusted effect estimates. Twenty five studies met the selection criteria and included 159 138 patients. Administration of PPIs together with clopidogrel corresponded to a 29% increased risk of combined major cardiovascular events [risk ratio (RR) = 1.29, 95% confidence intervals (CI) = 1.15-1.45] and a 31% increased risk of MI (RR = 1.31, 95%CI = 1.12-1.53). In contrast, PPI use did not negatively influence the mortality (RR = 1.04, 95%CI = 0.93-1.16), whereas the risk of developing a gastrointestinal bleed under PPI treatment decreased by 50% (RR = 0.50, 95% CI = 0.37-0.69). The presence of significant heterogeneity might indicate that the evidence is biased, confounded or inconsistent. The sensitivity analysis, however, yielded that the direction of the effect remained unchanged irrespective of the publication type, study quality, study size or risk of developing an event. Two studies indicate that PPIs have a negative effect irrespective of clopidogrel exposure. In conclusion, concomitant PPI use might be associated with an increased risk of cardiovascular events but does not influence the risk of death. Prospective randomized trials are required to investigate whether a cause-and-effect relationship truly exists and to explore whether different PPIs worsen clinical outcome in clopidogrel treated patients as the PPI-clopidogrel drug-drug interaction does not seem to be a class effect.
Journal of Thrombosis and Haemostasis 12/2010; 8(12):2624-41. · 6.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our aim was to test whether serum levels of matrix metalloproteinase (MMP)-2 and -9 are associated with the development of in-stent restenosis (ISR) after implantation of drug-eluting stents (DES).
With the introduction of DES coronary ISR could be reduced dramatically. However, it still plays a significant role, particularly after treatment of multiple, complex lesions.
We studied 85 patients who were treated with 159 DES. Blood samples for measurement of MMP-2 and -9 antigen and activity were taken directly before and 24 h after percutaneous coronary intervention (PCI). Restenosis was evaluated at 6 to 8 months by coronary angiography.
During the follow-up period, 2 patients (2.4%) died of cardiovascular causes, and 12 patients developed angiographic ISR. Patients with ISR showed significantly higher serum activity of MMP-9 at baseline (p = 0.017) and of MMP-2 (p < 0.0001) and MMP-9 (p < 0.0001) after the procedure. The PCI increased serum activity of MMP-2 (p = 0.005) and MMP-9 (p = 0.008) only in patients with ISR. The restenosis rates of patients in the highest quartile of MMP-2 after and MMP-9 before and after PCI were 40.0%, 38.9%, and 42.9% compared with 6.3%, 7.7%, and 4.0% in the lower quartiles, respectively. This was independent of clinical and procedural characteristics.
Elevated serum activities of MMP-2 and -9 are associated with dramatically increased restenosis rates after PCI with implantation of DES. Determination of MMP levels might be useful for identification of patients who are at high risk for ISR despite implantation of DES.
[Show abstract][Hide abstract] ABSTRACT: The prognostic value of the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay and multiple electrode aggregometry (MEA) for thrombotic adverse events has been shown in independent studies. As no direct comparison between the two methods has been made so far, we investigated which laboratory approach has a better predictive value for stent thrombosis.
The VASP phosphorylation assay and MEA were performed in 416 patients with coronary artery disease undergoing percutaneous coronary intervention. The rate of stent thrombosis was recorded during a 6-month follow-up.
Definite stent thrombosis occurred in three patients (0.7%) and probable stent thrombosis in four (1%). Receiver operating characteristic (ROC) analysis demonstrated that MEA distinguishes between patients with or without subsequent stent thrombosis better than the VASP phosphorylation assay: the area under the ROC curve was higher for MEA (0.92; P=0.012) than for the VASP phosphorylation assay (0.60; P=0.55). At equal levels of sensitivity (100%), the specificity was greater for MEA than for the VASP phosphorylation assay (86% vs. 37%). Stent thrombosis occurred in 9% of patients with platelet hyperreactivity in MEA, who were simultaneously clopidogrel non-responders in the VASP phosphorylation assay. Interestingly, clopidogrel non-responders in the VASP phosphorylation assay without platelet hyperreactivity in MEA did not suffer from stent thrombosis.
Platelet hyperreactivity in MEA might be a better risk predictor for stent thrombosis than the assessment of the specific clopidogrel effect with the VASP phosphorylation assay.
Journal of Thrombosis and Haemostasis 11/2009; 8(2):351-9. · 6.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The multicenter AUTAX (Austrian Multivessel TAXUS-Stent) registry investigated the 2-year clinical/angiographic outcomes of patients with multivessel coronary artery disease after implantation of TAXUS Express stents (Boston Scientific, Natick, Massachusetts), in a "real-world" setting.
The AUTAX registry included patients with 2- or 3-vessel disease, with/without previous percutaneous coronary intervention (PCI) and concomitant surgery.
Patients (n = 441, 64 +/- 12 years, 78% men) (n = 1,080 lesions) with possible complete revascularization by PCI were prospectively included. Median clinical follow-up was 753 (quartiles 728 to 775) days after PCI in 95.7%, with control angiography of 78% at 6 months. The primary end point was the composite of major adverse cardiac (nonfatal acute myocardial infarction [AMI], all-cause mortality, target lesion revascularization [TLR]) and cerebrovascular events (MACCE). Potential risk factor effects on 2-year MACCE were evaluated using Cox regression.
Complete revascularization was successful in 90.5%, with left main PCI of 6.8%. Rates of acute, subacute, and late stent thrombosis were 0.7%, 0.5%, and 0.5%. Two-year follow-up identified AMI (1.4%), death (3.6%), stroke (0.2%), and TLR (13.1%), for a composite MACCE of 18.3%. The binary restenosis rate was 10.8%. The median of cumulative SYNTAX score was 23.0 (range 12.0 to 56.5). The SYNTAX score did not predict TLR or MACCE, due to lack of scoring of restenotic or bypass stenoses (29.8%). Age (hazard ratio [HR]: 1.03, p = 0.019) and acute coronary syndrome (HR: 2.1, p = 0.001) were significant predictors of 2-year MACCE. Incomplete revascularization predicted death or AMI (HR: 3.84, p = 0.002).
With the aim of complete revascularization, TAXUS stent implantations can be safe for patients with multivessel disease. The AUTAX registry including patients with post-PCI lesions provides additional information to the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) study. (Austrian Multivessel TAXUS-Stent Registry; NCT00738686).
[Show abstract][Hide abstract] ABSTRACT: Drug eluting stents (DES) reduce recurrent luminal narrowing through anti-migratory and anti-proliferative effects. However, recent concerns arose that DES may also induce significant chronic inflammatory responses that may impair vascular healing and lead to in-stent restenosis (ISR). As the complement components C3a and C5a exert particularly strong chemotactic and proinflammatory effects, we examined the association of serum levels of C3a and C5a and ISR after implantation of DES.
We included 82 patients that were treated with 151 DES. Blood samples were taken directly before and 24h after PCI. Serum levels of C3a and C5a were measured by specific ELISA and restenosis was evaluated at 6-8 months by coronary angiography.
C5a but not C3a increased after implantation of DES (p<0.05). During the follow-up period, two patients (2.4%) died of cardiovascular causes and 12 patients (7.9% of stents, 15% of patients) developed ISR. Serum levels of C3a before and 24h after PCI as well as C5a levels at baseline were significantly higher in patients that developed ISR at follow-up. C3a and C5a at baseline were significantly associated to angiographic late lumen loss independent from clinical and procedural risk factors.
Increased complement activation as measured by higher levels of C3a and C5a before PCI is significantly associated with late lumen loss. Inhibition of the complement cascade to prevent ISR warrants further investigation.
[Show abstract][Hide abstract] ABSTRACT: Clopidogrel is activated by CYP2C19, which also metabolizes proton pump inhibitors (PPI). As proton pump inhibitors are metabolized to varying degrees by CYP2C19, we hypothesized that the reported negative omeprazole-clopidogrel drug interaction may not be a class effect.
Responsiveness to clopidogrel was assessed by the vasodilator-stimulated phosphoprotein phosphorylation (VASP) assay and aggregometry (Multiplate Analyzer) in 300 patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).
The mean platelet reactivity index (PRI, assessed by the VASP assay) was nearly the same in patients with (n = 226; PRI = 51%) or without PPI treatment (n = 74; PRI = 49%; P = .724). Likewise, the adenosine diphosphate-induced platelet aggregation did not differ significantly between patients with or without PPI treatment (45 vs. 41 U; P = .619). Similarly, there was no difference in the PRI or the adenosine diphosphate-induced platelet aggregation between patients with pantoprazole (n = 152; PRI = 50%; aggregation = 47 U), esomeprazole (n = 74; PRI = 54%; aggregation = 42 U), or without PPI (n = 74; PRI = 49%; aggregation = 41 U; P = .382).
In contrast to the reported negative omeprazole-clopidogrel drug interaction, the intake of pantoprazole or esomeprazole is not associated with impaired response to clopidogrel.
American heart journal 02/2009; 157(1):148.e1-5. · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Because of the known CYP3A4 inhibition by calcium-channel blockers (CCBs), we hypothesized that there might be a drug-drug interaction between clopidogrel and dihydropyridines in patients with coronary artery disease.
Clopidogrel is activated by CYP3A4, which also metabolizes CCBs of the dihydropyridine class.
Responsiveness to clopidogrel was assessed by the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay and aggregometry in 200 patients with coronary artery disease undergoing percutaneous coronary intervention.
The platelet reactivity index (PRI) (in the VASP assay, normal range 69% to 100%) was higher in patients receiving both clopidogrel and CCBs (61%) as compared with patients receiving clopidogrel without CCBs (48%). The absolute difference was 13% (95% confidence interval: 6% to 20%; p = 0.001), and the relative difference approached 21%. A decreased platelet inhibition by clopidogrel (PRI >69%) was seen in 40% of patients with concomitant CCB treatment and in 20% of patients without concomitant treatment (chi-square test, p = 0.008). Intake of CCB remained an independent predictor of reduced platelet inhibition by clopidogrel after adjustment for cardiovascular risk factors. Adenosine diphosphate-induced platelet aggregation was 30% higher in patients on concomitant CCB treatment compared with patients without CCBs (p = 0.046). Moreover, intake of CCBs was associated with adverse clinical outcome. In vitro incubation with CCBs (nimodipine, verapamil, amlodipine, and diltiazem) did not alter the PRI or the adenosine diphosphate-induced platelet aggregation of patients taking clopidogrel. This finding indicates that the negative effect occurs in vivo, conceivably at the level of the CYP3A4 cytochrome.
Coadministration of CCBs is associated with decreased platelet inhibition by clopidogrel.
Journal of the American College of Cardiology 12/2008; 52(19):1557-63. · 15.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Combined intracoronary and intramyocardial administration might improve outcomes for bone-marrow-derived stem cell therapy for acute myocardial infarction (AMI). We compared the safety and feasibility of early and late delivery of stem cells with combined therapy approaches.
Patients with left ventricular ejection fraction less than 45% after AMI were randomly assigned stem cell delivery via intramyocardial injection and intracoronary infusion 3-6 weeks or 3-4 months after AMI. Primary end points were changes in infarct size and left ventricular ejection fraction 3 months after therapy.
A total of 60 patients were treated. The mean changes in infarct size at 3 months were -3.5 +/- 5.1% (95% CI -5.5% to -1.5%, P = 0.001) in the early group and -3.9 +/- 5.6% (95% CI -6.1% to -1.6%, P = 0.002) in the late group, and changes in ejection fraction were 3.5 +/- 5.6% (95% CI 1.3-5.6%, P = 0.003) and 3.4 +/- 7.0% (95% CI 0.7-6.1%, P = 0.017), respectively. At 9-12 months after AMI, ejection fraction remained significantly higher than at baseline in both groups. In the early and late groups, a mean of 200.3 +/- 68.7 x 10(6) and 194.8 +/- 60.4 x 10(6) stem cells, respectively, were delivered to the myocardium, and 1.30 +/- 0.68 x 10(9) and 1.29 +/- 0.41 x 10(9) cells, respectively, were delivered into the artery. A high number of cells was required for significant improvements in the primary end points.
Combined cardiac stem cell delivery induces a moderate but significant improvement in myocardial infarct size and left ventricular function.
Nature Clinical Practice Cardiovascular Medicine 12/2008; 6(1):70-81. · 7.04 Impact Factor