PubMed Health⌕ Search

Biomedical subjects

D R Lowry

Publications and source records attributed to D R Lowry.

11 recordsLinked to original sources
PubMed2006

Rebound platelet activation after termination of prasugrel and aspirin therapy due to confirmed non-compliance in patient enrolled in the JUMBO Trial.

Therapy with aspirin and/or adenosine diphosphate (ADP) receptor blockers is associated with better outcomes via inhibition of platelet activity, and subsequent reduction of ischemic vascular events. Non-compliance (NC) is a well-recognised hazard limiting the clinical utility of antiplatelet agents, and, probably worsening outcomes. However, comprehensive platelet characteristics of a confirmed NC patient after acute vascular event have never been reported within a major randomised trial with ADP-receptor antagonists. A 48-year-old male patient, well-educated, was among patients enrolled in the platelet sub-study for the JUMBO trial. He received 325 mg of aspirin daily for 9 months, presented with unstable angina for urgent coronary intervention, and was successfully reperfused with two intracoronary stents. The patient was randomised to a 60 mg prasugrel loading dose, and 10 mg of prasugrel daily for 30 days. Platelets were assessed at baseline, 4 and 24 h, and at 30 days after acute coronary event utilising ADP-, and collagen-induced conventional aggregometry, rapid cartridge-based analyser and flow cytometry. Loading with prasugrel resulted in significant inhibition of platelet activity during and after stenting. However, after assessing platelet biomarkers at 30 days, voluntary withdrawal from the antiplatelet agents was suspected. Based on the platelet activity characteristics, NC was later confirmed, and the patient admitted that he stopped taking both prasugrel and aspirin shortly after discharge due to minor bleeding episodes after shaving. Major platelet activity biomarkers of the index NC patient were compared with those from compliant prasugrel-, clopidogrel-treated patients, and healthy controls. The platelet tests uniformly revealed rebound activation by all platelet measures (at least twofold increase) while being especially high for ADP-, and collagen-induced aggregation, platelet/endothelial cell adhesion molecule-1 (PECAM-1), glycoprotein (GP)Ib, GPIIb/IIIa activity, P-selectin, protease activated receptor (PAR)-1 thrombin receptor (activated and intact epitopes), and thrombospondin expression. The clinical benefits of antiplatelet agents are not only denied in NC outpatients, but may put them at additional risk for worsened vascular outcomes due to the rebound platelet activation. Proclaimed 'resistance' to antiplatelet agents may at least in part be a result of NC, especially in the chronic uncontrolled setting. Enforcing compliance will improve outcomes in the clinical trials, and save lives of patients really receiving antiplatelet therapy.

Angina Pectoris↗
PubMed2006

Platelet inhibition with prasugrel (CS-747) compared with clopidogrel in patients undergoing coronary stenting: the subset from the JUMBO study.

BACKGROUND: Based on the preclinical and phase 1 studies, prasugrel, a novel platelet ADP P2Y12 receptor blocker, may be a more potent platelet inhibitor than clopidogrel. This study compared the antiplatelet properties of prasugrel in a small subset of patients enrolled in the JUMBO trial, and compared with historic clopidogrel treated controls. METHODS AND RESULTS: Nine patients undergoing coronary stenting were randomised to one of three arms of prasugrel (40 mg loading, and 7.5 mg maintenance, n = 1; 60/10 mg, n = 4; or 60/15 mg, n = 2), or clopidogrel (300/75 mg, n = 2). Aspirin and GP IIb/IIIa inhibitors were permitted. Platelet activity was assessed at baseline, at 4, and 24 hours, and at 30 days after stent implantation in substudy participants, and compared with 124 historic controls who received clopidogrel. Independent of the loading, or maintenance dose, patients treated with prasugrel exhibited significantly more potent platelet inhibition as determined by ADP, and collagen induced aggregation, Ultegra Analyser, and surface expression of PECAM-1, GPIIb/IIIa antigen, and activity with PAC-1 antibody, GPIb, P-selectin, CD40-ligand, GP37, and thrombospondin receptor expression when compared with those treated with clopidogrel. There were no differences between antiplatelet agents with regard to vitronectin, LAMP-1, PAR-1 (intact and cleaved epitopes) thrombin receptor expression, or formation of platelet-monocyte microparticles. Expression of GPIIb antigen, vitronectin, and LAMP-3 receptor were not affected by both agents. Two patients treated with prasugrel 10 mg/daily exhibited complete inhibition of collagen induced aggregation at 30 days. CONCLUSION: At the dosing regimens chosen in the JUMBO trial, it seems that prasugrel is a more potent antiplatelet agent than clopidogrel. Two episodes of profound platelet inhibition, which are not seen with clopidogrel, raise the possibility of higher bleeding risks especially during long term prasugrel use. Whether stronger platelet inhibition will yield better clinical outcomes and/or increased bleeding remains to be determined in an ongoing comparative phase 3 superiority trial (TRITON).

Clopidogrel↗
PubMed2000

Moderate alcohol consumption is associated with decreased platelet activity in patients presenting with acute myocardial infarction.

Moderate alcohol consumption (MAC) and platelet inhibition have been independently associated with a reduced risk for the development of acute myocardial infarction (AMI). The effects of MAC on the initial platelet status in patients presenting with AMI are not elucidated. Here we sought to define the effects of MAC on platelet characteristics in AMI patients before applying any reperfusion strategies. The study was designed as an analysis within the cohort study in 23 patients with AMI enrolled in the GUSTO-III. Platelets were investigated by different techniques, including aggregometry, flow cytometry, and ELISA. MAC patients exhibited mild, but consistent, inhibition of platelet aggregability, surface receptor expression, and released substances as compared to non-alcohol consuming patients. These differences were significant for 5 microM ADP (p = 0.04), 10 microM ADP-induced aggregation (p = 0.02); P-selectin (p = 0.01), and PECAM-1 (p = 0.02) platelet-bound expression. Our study confirms that moderate alcohol consumption is associated with diminished platelet activation in patients presenting with AMI. The ability of MAC to favorably modulate the pre-reperfusion platelet status in such patients is of clinical importance, and further investigation in large-scale clinical trials seem warranted.

Aged↗
PubMed1999

Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: the Amiodarone Reduction in Coronary Heart (ARCH) trial.

OBJECTIVES: This study was designed to test whether intravenous (i.v.) amiodarone would prevent atrial fibrillation and decrease hospital stay after open heart surgery. BACKGROUND: Atrial fibrillation commonly occurs after open heart procedures and is thought to be a significant determinant for prolongation of hospitalization. Oral amiodarone given preoperatively appears to reduce the incidence of atrial fibrillation. This study was designed to test whether the more rapid-acting i.v. formulation of amiodarone given postoperatively would reduce the incidence of atrial fibrillation. METHODS: Three hundred patients undergoing standard open heart surgery were randomized in a double-blind fashion to i.v. amiodarone (1 g/day for 2 days) versus placebo immediately after open heart surgery. The primary end points of the trial were incidence of atrial fibrillation and length of hospital stay. Baseline clinical variables and mortality and morbidity data were collected. RESULTS: Atrial fibrillation occurred in 67/142 (47%) patients on placebo versus 56/158 (35%) on amiodarone (p = 0.01). Length of hospital stay for the placebo group was 8.2 +/- 6.2 days, and 7.6 +/- 5.9 days for the amiodarone group (p = 0.34). No differences were noted in baseline variables, morbidity or mortality. CONCLUSIONS: Low-dose i.v. amiodarone was safe and effective in reducing the incidence of atrial fibrillation after heart surgery, but did not significantly alter length of hospital stay.

Aged↗
PubMed1999

Increased soluble platelet/endothelial cellular adhesion molecule-1 and osteonectin levels in patients with severe congestive heart failure. Independence of disease etiology, and antecedent aspirin therapy.

BACKGROUND: Platelet-endothelial interactions modulated by adhesion molecules, may play an important role in the pathogenesis of congestive heart failure (CHF). Soluble levels of these molecules and platelet-derived substances are reportedly elevated in patients with CHF. However, no data are available on the plasma levels of Platelet/Endothelial Cell Adhesion Molecule-1 (PECAM-1), and platelet-derived osteonectin in this growing population. METHODS AND RESULTS: Soluble levels by ELISA were prospectively determined in patients with severe CHF (n = 37) and correlated to etiology and antecedent aspirin use, and compared with 14 healthy control subjects. Left ventricular dysfunction was attributed to idiopathic dilated cardiomyopathy in 18 and coronary artery disease in 19 patients. Twenty-one patients were aspirin-free and 16 patients were using aspirin (81-500 mg daily). Elevated soluble PECAM-1 (51.31+/-2.44 ng/ml, P = 0.0001), and osteonectin (826.27+/-22.37 ng/ml, P = 0.0001) were observed in patients with CHF, as compared to healthy controls (32.56+/-1.21 ng/ml, and 478.02+/-31.32 ng/ml, respectively). Neither etiology of CHF, nor antecedent aspirin therapy significantly affects the levels of PECAM-1 or osteonectin. CONCLUSIONS: Despite long-term aspirin therapy and independently of the etiology of the disease, soluble PECAM-1 and osteonectin were elevated in the majority of patients with severe CHF, suggesting platelet-endothelial activation. The present data provide additional evidence that more potent anti-platelet and endothelial preservation regimens deserve further study in the heart failure population.

Aged↗
PubMed1999

Plasma thromboxane and prostacyclin are linear related and increased in patients presenting with acute myocardial infarction.

The role of prostanoids in patients with ischemic heart disease including acute myocardial infarction (AMI) has been recognized. However, there is very limited knowledge of the baseline TXB2 and 6-keto-PGF1a plasma levels in patients with AMI before therapy has been administered. We compared plasma levels of TXB2 and 6-keto-PGF1a by enzyme immunoassay in 18 AMI patients before thrombolysis, with those of 13 healthy controls. Plasma levels of TXB2 (319.78+/-16.50 pg/ml) and 6-keto-PGF1a (536.72+/-56.71 pg/ml) were heterogeneous, but significantly higher in the AMI patients than in controls (175.92+/-17.29 pg/ml and 192.08+/-26.11 pg/ml, respectively). In some patients, long-term aspirin therapy mildly inhibits baseline prostanoid levels, however, limited data prevents us from further speculations on this issue. Although, the contributions by prostanoids to the pathogenesis of AMI have been well proposed, their plasma concentrations are not uniformly elevated, and it is still unclear whether the resultant changes are indicative of clinically meaningful effects.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Antecedent aspirin therapy inhibits baseline platelet activity in patients presenting with acute myocardial infarction. The GUSTO-III Platelet Substudy.

Aspirin therapy and platelet inhibition reduce the risk for the development of acute myocardial infarction (AMI). However, the effects of aspirin on baseline platelet activity in patients presenting with AMI are not known. We determined the effect of long-term aspirin use on baseline platelet activity in patients presenting with AMI, enrolled in the GUSTO-III Platelet Study. Platelet characteristics were investigated by aggregometry, flow cytometry and enzyme-linked immunosorbent assay in 23 patients before thrombolysis. Sixteen AMI patients were aspirin free, and 7 patients were using aspirin (81-500 mg/daily). The aspirin-treated patients exhibited a mild but consistent reduction of platelet activity which reached significance for 5 microM (p = 0.02), and 10 microM (p = 0.01) adenosine diphosphate induced aggregation. The surface expression of P-selectin (p = 0.02) and PECAM-1 (p = 0.03) and the plasma level of soluble P-selectin (p = 0.02) were also reduced. As previously observed in normal humans and patients with stable coronary artery disease, long-term aspirin therapy is also associated with diminished platelet activation in patients presenting with AMI. Long-term aspirin therapy mildly reduces baseline platelet activity; however, this degree of relative platelet inhibition does not appear to be cardioprotective.

Adenosine Diphosphate↗
PubMed1998

Depressed plasma platelet-activating factor acetylhydrolase in patients presenting with acute myocardial infarction.

Cell membrane phospholipids, including platelet-activating factor (PAF), participate in the pathogenesis of acute myocardial infarction (AMI). The plasma level of PAF acetylhydrolase (AH) was determined in 18 patients at presentation with AMI before thrombolysis, and the administration of adjunctive therapy, and compared with 13 healthy controls. Plasma levels of PAF-AH were significantly lower in the AMI patients (23.15 +/- 1.75 nmol/min/ml) than in the controls (30.43 +/- 2.13 nmol/min/ml; p = 0.027). Considering normal plasma levels of PAF and lyso-PAF, and lack of evidence that anti-PAF antibodies are really beneficial in myocardial ischemia-reperfusion, it is reasonable to speculate that an inability of systemic PAF to 'turn on' PAF-AH enzymatic activity could contribute substantially to the observed events. Decreased PAF-AH activity in AMI patients may represent not a consequence, but rather, a risk factor for the development of acute coronary syndromes.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1991

Lipoprotein-cholesterol analysis during screening: accuracy and reliability.

OBJECTIVE: To evaluate the accuracy and reliability of lipoprotein-cholesterol measurements obtained during screening. DESIGN: Cross-sectional study. PARTICIPANTS: From November 1989 to January 1990, 154 adults were screened. MEASUREMENTS: Split venous samples from fasting participants were analyzed for total cholesterol, triglyceride, and high-density-lipoprotein (HDL) cholesterol with screening and standardized laboratory methods. Low-density-lipoprotein (LDL)-cholesterol levels were calculated using the Friedewald equation. Split venous samples from nonfasting participants were analyzed for total cholesterol. Capillary blood samples were analyzed for total cholesterol with the screening method. MAIN RESULTS: Total cholesterol measurements in screening venous blood samples were 5.4% and 3.8% lower than the laboratory values in samples from fasting and nonfasting participants, respectively. Triglyceride and HDL-cholesterol values in venous samples obtained from fasting participants were, on average, 9.8% and 11.2% lower than the respective laboratory measurements. Screening HDL-cholesterol values varied, differing from the laboratory values by as much as 40% in 95% of participants. In fasting participants, total cholesterol in capillary samples averaged 5.5% higher than in venous samples; in nonfasting participants the capillary samples were 3.1% higher. Screening for either total cholesterol or LDL cholesterol identified 93% of the persons with LDL-cholesterol values of 3.36 mmol/L (130 mg/dL) or higher. CONCLUSIONS: Total cholesterol can be reliably measured in samples from fasting or nonfasting persons. The values in capillary blood samples were slightly higher than those in venous samples. Screening HDL-cholesterol values were too variable to establish the HDL-cholesterol level reliably. Participants with high LDL-cholesterol levels were identified as accurately by measuring total cholesterol only when compared with calculating the LDL-cholesterol level from total cholesterol, triglyceride, and HDL-cholesterol concentrations.

Adult↗