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Gerald Yong,
Jamie Rankin,
Louise Ferguson,
Jim Thom,
John French,
David Brieger,
Derek P Chew,
Ron Dick,
David Eccleston,
Bernard Hockings,
Darren Walters,
Alan Whelan,
John W Eikelboom
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ABSTRACT: There is uncertainty about the benefit of a higher loading dose (LD) of clopidogrel in patients with non-ST elevation acute coronary syndrome (NSTEACS) undergoing early percutaneous coronary intervention (PCI).
We compared the effects of a 600- versus a 300-mg LD of clopidogrel on inhibition of platelet aggregation, myonecrosis, and clinical outcomes in patients with NSTEACS undergoing an early invasive management strategy. Patients with NSTEACS (n = 256, mean age 63 years, 81.6% elevated troponin) without thienopyridine for at least 7 days were randomized to receive 600- or 300-mg LD of clopidogrel. Percutaneous coronary intervention was performed in 140 patients, with glycoprotein IIb/IIIa inhibitor use in 68.6%. Adenosine diphosphate (ADP)-induced platelet aggregation was measured by optical platelet aggregometry immediately before coronary angiography.
Post-PCI myonecrosis was defined as a next-day troponin I greater than 5 times the upper limit of reference range and greater than baseline levels. Clopidogrel 600-mg LD compared with 300-mg LD was associated with significantly reduced ADP-induced platelet aggregation (49.7% vs 55.7% with ADP 20 micromol/L) but did not reduce post-PCI myonecrosis or adverse clinical outcomes to 6 months. There was no association between preprocedural platelet aggregation and outcome.
These data confirm a modest incremental antiplatelet effect of a 600-mg clopidogrel LD compared with 300-mg LD but provide no support for a clinical benefit in patients with NSTEACS managed with an early invasive strategy including a high rate (69%) of glycoprotein IIb/IIIa inhibitor use during PCI.
American heart journal 02/2009; 157(1):60.e1-9. · 4.65 Impact Factor
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ABSTRACT: Platelet activation occurs in a variety of clinical situations in which it directly contributes to the pathology. This study reports a simple flow cytometric assay for platelet activation which measures platelet-derived microparticles, activated platelets and platelet-monocyte complexes. Pre- and post analytical conditions were investigated and optimized and a normal range established on 20 healthy controls. Twenty patients pre- and post percutaneous coronary intervention (PCI) were tested with the technique. Soluble activation markers sCD40 ligand and sP-selectin and plasma phospholipid levels were measured in both groups. There was a significant increase in activated platelets and platelet-monocyte complexes between normal and pre-PCI (P = 0.005 and 0.0275, respectively) suggesting an activated state. There was a significant fall in activated platelets post-PCI (P = 0.0027) which was mirrored by a fall in soluble CD40 ligand, soluble P-selectin and plasma phospholipid levels (P = 0.0066, <0.0001 and 0.0032, respectively) consistent with antiplatelet therapy administered during the process. This is a reliable and rapid method for the assessment of ex vivo platelet activation which may be an aid in diagnosis and help guide therapy for patients with thrombotic disease.
International journal of laboratory hematology 05/2008; 31(4):430-9. · 1.30 Impact Factor
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ABSTRACT: Hemorrhagic complications of acute coronary syndromes and percutaneous coronary intervention (PCI) are associated with increased mortality. Upper gastrointestinal (UGI) bleeding after PCI is a potential target for preventative strategies.
To evaluate the risk factors for UGI bleeding in a large cohort of contemporary PCI patients and assess the outcomes of medical and endoscopic management.
A case-control study evaluating UGI bleeding in the 30 days following PCI for stable angina and acute coronary syndromes, at one institution between 1998 and 2005. Cases were identified and outcomes assessed using linkage analysis of data from institutional PCI and endoscopy databases, statewide vital statistics and hospital discharge registries, and a detailed review of medical notes for each case and three matched controls. Analysis of the case and control groups for risk and protective factors was performed using the chi2 test with Fisher's exact P value and logistic regression.
The incidence of UGI bleeding following PCI was 1.2% (70 of 5,673 patients). The etiologies of these bleeds were diverse. Risk factors for UGI bleeding were primary PCI (OR 27.80, 95% CI 6.28-123.05, P < 0.001), cardiac arrest (OR 6.17, 95% CI 1.82-20.84, P= 0.003), inotropic requirement (OR 5.85, 95% CI 1.98-17.27, P= 0.001), thienopyridine use before PCI (OR 2.40, 95% CI 1.04-5.53, P= 0.02), and advanced age (OR 1.08, 95% CI 1.04-1.12, P < 0.001). Proton pump inhibitor use after PCI (OR 0.08, 95% CI 0.02-0.40, P= 0.002) was accompanied by a reduced risk of UGI bleeding. Endoscopy provided therapeutic intervention in 33% of patients. There were no serious complications of endoscopy. The 30-day mortality for cases was 11.9% and 0.5% for controls (P= 0.001).
UGI bleeding after PCI is relatively common and associated with increased mortality. Those undergoing PCI for acute myocardial infarction or in the presence hemodynamic instability are at highest risk. Proton pump inhibition following PCI may reduce the bleeding risk, though when UGI bleeding occurs, therapeutic endoscopy is safe.
The American Journal of Gastroenterology 11/2007; 102(11):2411-6. · 7.28 Impact Factor
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ABSTRACT: Despite the importance of both lipid metabolism and physical activity to cardiovascular health, few studies have examined the effect of exercise training on vascular function in hypercholesterolaemic humans.
A randomized, cross-over design investigated the effect of 8 weeks of combined aerobic and resistance exercise training on conduit and resistance vessel function in 11 untreated subjects with hypercholesterolaemia and 11 subjects taking lipid-lowering medication. High-resolution vascular ultrasonography following forearm ischaemia and glyceryl trinitrate administration determined conduit vessel endothelium-dependent and independent function. Strain-gauge plethysmography, with intra-aerial infusions of acetylcholine, sodium nitroprusside and N(G)-monomethyl-L-arginine, determined resistance vessel function. Flow-mediated dilation and the forearm blood flow response to acetylcholine improved significantly following training in the treated subgroup (both P<0.05) but not the untreated, although the blood flow response to N(G)-monomethyl-L-arginine was augmented following training in the untreated subjects (P<0.05), indicating greater basal nitric oxide bioactivity. Training did not alter responsiveness to glyceryl trinitrate or sodium nitroprusside.
Combined aerobic and resistance training improves endothelium-dependent conduit and resistance vessel function in hypercholesterolaemic subjects taking lipid-lowering medications and basal nitric oxide bioactivity in untreated hypercholesterolaemic subjects. Exercise training may provide additional cardiovascular benefits for hypercholesterolaemic patients including those taking lipid-lowering medication.
European Heart Journal 09/2003; 24(18):1681-9. · 10.48 Impact Factor
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ABSTRACT: Aims Despite the importance of both lipid metabolism and physical activity to cardiovascular health, few studies have examined the effect of exercise training on vascular function in hypercholesterolaemic humans. Methods and results A randomized, cross-over design investigated the effect of 8 weeks of combined aerobic and resistance exercise training on conduit and resistance vessel function in 11 untreated subjects with hypercholesterolaemia and 11 subjects taking lipid-lowering medication. High-resolution vascular ultrasonography following forearm ischaemia and glyceryl trinitrate administration determined conduit vessel endothelium-dependent and independent function. Strain-gauge plethysmography, with intra-aerial infusions of acetylcholine, sodium nitroprusside and NG-monomethyl-L-arginine, determined resistance vessel function. Flow-mediated dilation and the forearm blood flow response to acetylcholine improved significantly following training in the treated subgroup (both P <0.05) but not the untreated, although the blood flow response to NG-monomethyl-L-arginine was augmented following training in the untreated subjects ( P <0.05), indicating greater basal nitric oxide bioactivity. Training did not alter responsiveness to glyceryl trinitrate or sodium nitroprusside. Conclusions Combined aerobic and resistance training improves endothelium-dependent conduit and resistance vessel function in hypercholesterolaemic subjects taking lipid-lowering medications and basal nitric oxide bioactivity in untreated hypercholesterolaemic subjects. Exercise training may provide additional cardiovascular benefits for hypercholesterolaemic patients including those taking lipid-lowering medication.
