12 research outputs found
Angiographic findings in patients with refractory unstable angina according to troponin T status
BACKGROUND: The CAPTURE (C7E3 fab AntiPlatelet Therapy in Unstable
REfactory angina) trial enrolled patients with refractory unstable angina
and documented a therapeutic benefit for abciximab, a platelet
glycoprotein IIb/IIIa receptor antagonist, that was particularly evident
in patients with elevated troponin T (TnT) levels. In the current study,
we related the angiographic data to the TnT status of the CAPTURE
patients. METHODS AND RESULTS: In 853 patients, angiographic data at
baseline and 18 to 24 hours after treatment were available and assessed by
an Angiographic Committee with respect to TIMI flow, lesion severity, and
visibility of thrombus. TnT levels >0.1 microg/L were found in 30.9% of
the patients. Before randomization, thrombus was visible in 14.6% of
TnT-positive patients (TnT levels >0.1 microg/L) and 4.2% of TnT-negative
patients (P=0.004). Complex lesion characteristics B2+/C (72.0% versus
53.9%; P<0.001) and TIMI flow <2 (15.6% versus 5. 1%; P<0.001) were more
frequent in TnT-positive patients. Abciximab was effective with respect to
reduction of visible thrombus, increase of TIMI flow, and reduction of
cardiac events in TnT-positive patients only. Multivariate analysis
identified TnT status, but not angiographic findings, as an independent
predictor for both outcome and efficacy of treatment with abciximab.
CONCLUSIONS: Complex lesion characteristics and visible thrombus formation
at baseline were significantly linked to TnT elevation. However, TnT
st
Prognostic Significance of Angiogenic Growth Factor Serum Levels in Patients With Acute Coronary Syndromes
BACKGROUND: In patients with acute coronary syndromes, compensatory processes are initiated, including angiogenesis and endothelial regeneration of ruptured or eroded plaques. Angiogenic growth factors like vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and basic fibroblast growth factor (bFGF) are upregulated during ischemia.
However, it is unknown whether their serum levels are related to clinical outcome. METHODS AND RESULTS: We measured VEGF, HGF, and bFGF levels in 1090 patients with acute coronary syndromes. Angiographic evaluation was performed at baseline as well as death, and nonfatal myocardial infarctions were recorded during 6-month follow-up. HGF and VEGF, but not bFGF, were significantly and independently associated with the patients' outcome. Patients with elevated VEGF serum levels suffered from adverse outcome (adjusted hazard ratio, 2.50 [1.52 to 4.82]; P=0.002). VEGF elevation was associated with evidence of ischemia and was a significant predictor of the effect of glycoprotein IIb/IIIa inhibition. In contrast, patients with high HGF levels had a significantly lower event rate compared with patients with low HGF levels (adjusted hazard ratio, 0.33 [0.21 to 0.51]; P<0.001). HGF levels did not correlate with evidence of ischemia and did not predict the effect of abciximab. Intriguingly, however, HGF levels significantly correlated with angiographically visible collateralization of the target vessel (22.4% versus 10.5%; P<0.001).
CONCLUSIONS: The angiogenic growth factors VEGF and HGF are independent predictors of the patients' prognosis in acute coronary syndromes. Whereas
VEGF elevation correlated with the evidence of myocardial ischemia and indicated an adverse outcome, HGF elevation was independent of ischemia and associated with improved collateralization as well as a favorable prognosis
Myeloperoxidase Serum Levels Predict Risk in Patients With Acute Coronary Syndromes
BACKGROUND: Polymorphonuclear neutrophils (PMNs) have gained attention as critical mediators of acute coronary syndromes (ACS). Myeloperoxidase (MPO), a hemoprotein abundantly expressed by PMNs and secreted during activation, possesses potent proinflammatory properties and may contribute directly to tissue injury. However, whether MPO also provides prognostic information in patients with ACS remains unknown. METHODS AND RESULTS: MPO serum levels were assessed in 1090 patients with ACS. We recorded death and myocardial infarctions during 6 months of follow-up. MPO levels did not correlate with troponin T, soluble CD40 ligand, or C-reactive protein levels or with ST-segment changes. However, patients with elevated MPO levels (>350 microg/L; 31.3%) experienced a markedly increased cardiac risk (adjusted hazard ratio [HR] 2.25 [1.32 to 3.82]; P=0.003). In particular, MPO serum levels identified patients at risk who had troponin T levels below 0.01 microg/L (adjusted HR 7.48 [95% CI 1.98 to 28.29]; P=0.001). In a multivariate model that included other biochemical markers, troponin T (HR 1.99; P=0.023), C-reactive protein (1.25; P=0.044), vascular endothelial growth factor (HR 1.87; P=0.041), soluble CD40 ligand (HR 2.78; P<0.001), and MPO (HR 2.11; P=0.008) were all independent predictors of the patient's 6-month outcome. CONCLUSIONS: In patients with ACS, MPO serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers. Given its proinflammatory properties, MPO may serve as both a marker and mediator of vascular inflammation and further points toward the significance of PMN activation in the pathophysiology of ACS
Soluble CD40 ligand in acute coronary syndromes
BACKGROUND: CD40 ligand is expressed on platelets and released from them on activation. We investigated the predictive value of soluble CD40 ligand as a marker for clinical outcome and the therapeutic effect of glycoprotein IIb/IIIa receptor inhibition in patients with acute coronary syndromes. METHODS: Serum levels of soluble CD40 ligand were measured in 1088 patients with acute coronary syndromes who had previously been enrolled in a randomized trial comparing abciximab with placebo before coronary angioplasty and in 626 patients with acute chest pain. RESULTS: The levels of soluble CD40 ligand were elevated (above 5.0 microg per liter) in 221 patients with acute coronary syndromes (40.6 percent). Among patients receiving placebo, elevated soluble CD40 ligand levels indicated a significantly increased risk of death or nonfatal myocardial infarction during six months of follow-up (adjusted hazard ratio as compared with patients with low levels of the ligand [< or =5.0 microg per liter], 2.71; 95 percent confidence interval, 1.51 to 5.35; P=0.001). The prognostic value of this marker was validated in the patients with chest pain, among whom elevated soluble CD40 ligand levels identified those with acute coronary syndromes who were at high risk for death or nonfatal myocardial infarction (adjusted hazard ratio as compared with those with low levels of the ligand, 6.65; 95 percent confidence interval, 3.18 to 13.89; P<0.001). The increased risk in patients with elevated soluble CD40 ligand levels was significantly reduced by treatment with abciximab (adjusted hazard ratio as compared with those receiving placebo, 0.37; 95 percent confidence interval, 0.20 to 0.68; P=0.001), whereas there was no significant treatment effect of abciximab in patients with low levels of soluble CD40 ligand. CONCLUSIONS: In patients with unstable coronary artery disease, elevation of soluble CD40 ligand levels indicated an increased risk of cardiovascular events. El
Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels.
BACKGROUND: In patients with refractory unstable angina, the platelet
glycoprotein IIb/IIIa-receptor antibody abciximab reduces the incidence of
cardiac events before and during coronary angioplasty. We investigated
whether serum troponin T levels identify patients most likely to benefit
from therapy with this drug. METHODS: Among 1265 patients with unstable
angina who were enrolled in the c7E3 Fab Antiplatelet Therapy in Unstable
Refractory Angina (CAPTURE) trial, serum samples drawn at the time of
randomization to abciximab or placebo were available from 890 patients; we
used these samples for the determination of troponin T and creatine kinase
MB levels. Patients with postinfarction angina were not included. RESULTS:
Serum troponin T levels at the time of study entry were elevated (above
0.1 ng per milliliter) in 275 patients (30.9 percent). Among patients
receiving placebo, the risk of death or nonfatal myocardial infarction was
related to troponin T levels. The six-month cumulative event rate was 23.9
percent among patients with elevated troponin T levels, as compared with
7.5 percent among patients without elevated troponin T levels (P<0.001).
Among patients treated with abciximab, the respective six-month event
rates were 9.5 percent for patients with elevated troponin T levels and
9.4 percent for those without elevated levels. As compared with placebo,
the relative risk of death or nonfatal myocardial infarction associated
with treatment with abciximab in patients with elevated troponin T levels
was 0.32 (95 percent confidence interval, 0.14 to 0.62; P=0.002). The
lower event rates in patients receiving abciximab were attributable to a
reduction in the rate of myocardial infarction (odds ratio, 0.23; 95
percent confidence interval, 0.12 to 0.49; P<0.001). In patients without
elevated troponin T levels, there was no benefit of treatment with respect
to the relative risk of death or myocardial infarction at six months (odds
ratio, 1.26; 95 percent confidence interval, 0.74 to 2.31; P=0.47).
CONCLUSIONS: The serum troponin T level, which is considered to be a
surrogate marker for thrombus formation, identifies a high-risk subgroup
of patients with refractory unstable angina suitable for coronary
angioplasty who will particul
Recanalization of total coronary occlusions using a laser guidewire (The European TOTAL Surveillance Study)
Rationale and design of a prospective substudy of clinical endpoint adjudication processes within an investigator-reported randomised controlled trial in patients with coronary artery disease: the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY)
pragmatic and superiority randomised controlled trial
designed to challenge the current treatment paradigm of dual
antiplatelet therapy (DAPT) for 12 months followed by aspirin
monotherapy among patients undergoing percutaneous
coronary intervention. By design, all study endpoints are
investigator reported (IR) and not subject to formal adjudication
by an independent Clinical Event Committee (CEC), which may
introduce detection, reporting or ascertainment bias.
Methods and analysis We designed the GLOBAL LEADERS
Adjudication Sub-StudY (GLASSY) to prospectively implement,
in a large sample of patients enrolled within the GLOBAL
LEADERS trial (7585 of 15 991, 47.5%), an independent
adjudication process of reported and unreported potential
endpoints, using standardised CEC procedures, in order
to assess whether 23-month ticagrelor monotherapy
(90mg twice daily) after 1-month DAPT is non-inferior to a
standard regimen of DAPT for 12 months followed by aspirin
monotherapy for the primary efficacy endpoint of death, nonfatal myocardial infarction, non-fatal stroke or urgent target
vessel revascularisation and superior for the primary safety
endpoint of type 3 or 5 bleeding according to the Bleeding
Academic Research Consortium criteria. This study will
comprehensively assess the comparative safety and efficacy
of the two tested antithrombotic strategies on CEC-adjudicated
ischaemic and bleeding endpoints and will provide insights
into the role of a standardised CEC adjudication process on
the interpretation of study findings by quantifying the level
of concordance between IR-reported and CEC-adjudicated
events.
Ethics and dissemination GLASSY has been approved
by local ethics committee of all study sites and/or by the
central ethics committee for the country depending on
country-specific regulations. In all cases, they deemed that
it was not neces
Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation
Efficacy of high dose intravenous heparin for treatment of left ventricular thrombi with high embolic risk
Short- and long-term health related quality-of-life and anginal status of the Arterial Revascularisation Therapies Study part II, ARTS-II; sirolimus-eluting stents for the treatment of patients with multivessel coronary artery disease
Aims: Assessment of health related quality-of-life (HRQL) has become increasingly important as not only the clinician's view of the technical success, but also the patient's perception is being measured. We evaluated the HRQL following sirolimus-eluting coronary stent (SES) (CYPHER®; Cordis, Johnson & Johnson, Warren, NJ, USA) implantation in patients with multivessel disease, comparing the outcomes with the historical surgical and bare metal stent (BMS) arms of the ARTS-I study. Methods and results: The HRQL outcomes were compared to the outcome of the historical cohorts of the randomised ARTS-I trial using the same inclusion and exclusion criteria. HRQL was evaluated at baseline, at one month and at 6, 12 and 36 months after revascularisation using the SF-36 in patients treated with SES (n=585), BMS (n=483) or coronary artery bypass graft (CABG) (n=492). The HRQL compliance rates varied from 100% at baseline to 92% at 36 months. Both stenting and CABG resulted in significant improvement of HRQL and anginal status. There was a trend towards better HRQL after CABG than BMS beyond six months. Already from the first month up to three years, SES patients had, on average, 10% significantly better HRQL than BMS patients on the HRQL subscales physical functioning, role physical functioning, role emotional functioning and mental health (p<0.01) and a trend towards better HRQL in the other subscales. Up to 12 months, the HRQL was better after SES than CABG and was identical thereafter. At all time points, angina was more prevalent in the BMS group than in both the SES and CABG groups, in which the incidence of angina was similar. At three years, 10% of the SES patients suffered from angina, 13% of the CABG patients and 20% of the BMS patients. Conclusions: Both stenting and CABG resulted in a significant improvement in HRQL and angina. Along with a substantial reduction of restenosis, HRQL after SES was significantly improved as compared with BMS, and was similar to CABG