Biomedical subjects

G R Hopkins

Publications and source records attributed to G R Hopkins.

7 recordsLinked to original sources

PubMed1999

Thrombolysis with saruplase versus streptokinase in acute myocardial infarction: five-year results of the PRIMI trial.

BACKGROUND: Short-term safety and efficacy of thrombolysis with saruplase in acute myocardial infarction have been shown in several trials. To assess long-term outcome of patients treated with saruplase or streptokinase for myocardial infarction, a 5-year follow-up of patients included in the Pro-Urokinase in Myocardial Infarction Trial was performed. METHODS AND RESULTS: Follow-up data are available from 8 centers on 255 (92.4%) of 276 included patients. The 5-year mortality rate was comparable with 20.8% of patients in the saruplase group and 16.9% in the streptokinase group (odds ratio 1.29, 95% confidence interval 0.69 to 2.42). In both groups, a considerable number of fatal cardiovascular events occurred more than 1 year after study inclusion. Rates of percutaneous transluminal coronary angioplasty and coronary artery bypass grafting were comparable in both groups. Reinfarction within 5 years occurred in 19.0% of patients in the saruplase group and tended to be less frequent at 10.8% after streptokinase treatment (odds ratio 1.94, 95% confidence interval 0.98 to 3.84). In both groups, the majority of reinfarctions took place more than 3 months after study inclusion. The 5-year stroke rate was 3.6% and 7.2% in the saruplase and streptokinase groups, respectively (odds ratio 0.49, 95% confidence interval 0.16 to 1.47). Subjective symptoms of heart failure and angina pectoris were comparable in both groups. CONCLUSIONS: Our data are consistent with a similar long-term outcome for patients treated with saruplase or streptokinase. Despite the low-risk profile of the patient cohort, there were considerable adverse event rates over a 5-year period.

Aged↗

PubMed1998

Randomized, double-blind study comparing saruplase with streptokinase therapy in acute myocardial infarction: the COMPASS Equivalence Trial. Comparison Trial of Saruplase and Streptokinase (COMASS) Investigators.

OBJECTIVES: This study sought to demonstrate the equivalence of saruplase and streptokinase in terms of 30-day mortality. BACKGROUND: The use of thrombolytic agents in the treatment of acute myocardial infarction is well established and has been shown to substantially reduce post-myocardial infarction mortality. METHODS: Three thousand eighty-nine patients with symptoms compatible with those of acute myocardial infarction for < 6 h entered the study at a total of 104 centers and were randomized to receive streptokinase (1.5-MU infusion over 60 min) or saruplase (20-mg bolus and 60-mg infusion over 60 min). In the saruplase group, a bolus of heparin (5,000 IU) was administered before saruplase, and a corresponding blinded double-dummy placebo bolus was administered before streptokinase. All patients received intravenous heparin infusions for > or = 24 h starting 30 min after the end of the thrombolytic infusions; the infusions were titrated to maintain an activated partial thromboplastin time at 1.5 to 2.5 times that of normal. RESULTS: Death of any cause up to 30 days after randomization occurred in 88 (5.7%) of 1,542 patients randomized to receive saruplase and 104 (6.7%) of 1,547 patients randomized to receive streptokinase (odds ratio 0.84, p < 0.01 for equivalence). Hemorrhagic strokes occurred more often in patients receiving saruplase (0.9% vs. 0.3%), whereas thromboembolic strokes were more prevalent in the streptokinase-treated patients (0.5% vs. 1.0%). The rate of bleeding was similar in the two treatment groups (10.4% vs. 10.9%). Hypotension and cardiogenic shock occurred less frequently in the saruplase group. Reinfarction rates were similar. CONCLUSIONS: Saruplase is a clinically safe and effective thrombolytic medication. This profile ranks saruplase favorably among the currently available thrombolytic agents.

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PubMed1997

Effect of changes in liver blood flow on the pharmacokinetics of saruplase in patients with acute myocardial infarction.

BACKGROUND: The recombinant unglycosylated single chain urokinase-type plasminogen activator saruplase is cleared for a large part by the liver. A large interindividual variation in saruplase concentration is found in acute myocardial infarction (AMI) patients. The variable cardiac performance after an infarct may induce differences in liver blood flow that could explain the concentration diversity. This study was performed to investigate the relation between hepatic blood flow and the pharmacokinetic and pharmacodynamic properties of saruplase. METHODS AND RESULTS: Thirteen AMI patients were enrolled in this open label study. Patients received a bolus injection of 20 mg saruplase followed by a one-hour infusion of 60 mg saruplase. Concurrently 36 mg intravenous indocyanine green (ICG) was given over 1 h to measure hepatic blood flow. Blood samples were taken at regular time intervals to measure plasma levels of urokinase-type plasminogen activator (u-PA) antigen and activity, the two-chain form (tcu-PA) activity, indocyanine green, fibrinogen, fibrin and fibrin degradation products, alpha2-antiplasmin and thrombin antithrombin III complex. A correlation was seen between the clearance of ICG and both those of u-PA antigen (r = 0.62; p <0.05) and u-PA activity (r = 0.57; p <0.05). A negative correlation was seen between the area under the curve of tcu-PA activity and the areas under the effect curves of both fibrinogen and alpha2-antiplasmin (r = -0.84; p <0.01 and r = -0.65; p <0.05). CONCLUSIONS: Liver blood flow is an important determinant of the clearance of u-PA antigen and activity and reduction of flow in patients with heart failure will lead to an increase in plasma concentrations. High plasma concentrations of tcu-PA activity lead to increased systemic fibrinogenolysis. These results may be used to optimize saruplase treatment in patients with impaired cardiac function or after co-medication with drugs that affect liver blood flow.

Aged↗

PubMed1996

Hemostatic changes after thrombolytic therapy with saruplase (unglycosylated single-chain urokinase-type plasminogen activator) and urokinase (two-chain urokinase-type plasminogen activator).

Urokinase, or two-chain urokinase-type plasminogen activator (tcu-PA), is an effective thrombolytic agent. Its single-chain precursor (scu-PA), unlike tcu-PA, is able to selectively activate fibrin-bound plasminogen. The induced clot lysis is amplified by plasmin-triggered conversion of scu-PA to tcu-PA. The aim of our study was to compare the hemostatic effects of recombinant unglycosylated scu-PA, INN saruplase, and urokinase, at doses considered optimal (80 mg saruplase and 3 million units urokinase) in patients with acute myocardial infarction, within 6 h of onset of pain. Complete sample sets from more than 230 patients in each treatment group have been analyzed. The median hemostatic changes caused by saruplase and urokinase were virtually identical indicating that saruplase is converted early in vivo to its active tcu-PA derivative with the dose regimen used. Fibrinogen degradation products were higher for saruplase with a maximum at 2h. They rose markedly after saruplase from 0.43 mg/l at 0 h to a maximum of 160 mg/l at 2 h, whereas the increase after urokinase (from 0.45 mg/l to 89.0 mg/l) was significantly smaller (P < 0.001).

Double-Blind Method↗

PubMed1994

Pharmacokinetics and pharmacodynamics of saruplase, an unglycosylated single-chain urokinase-type plasminogen activator, in patients with acute myocardial infarction.

We examined in patients with acute myocardial infarction (AMI) the pharmacokinetics of saruplase, an unglycosylated, single chain, urokinase-type plasminogen activator (rscu-PA) by measuring urokinase-type plasminogen activator (u-PA) antigen and total u-PA activity, its conversion to active two-chain urokinase-type plasminogen activator (tcu-PA) and evaluated its effect on haemostatic parameters. Twelve patients were studied during and after administration of 20 mg bolus plus 60 mg continuous 1 h i.v. infusion of saruplase. For u-PA antigen and total u-PA activity (expressed as protein equivalents), where 234 U corresponds to 1 microgram, respectively, steady state plasma concentrations were 2.75 +/- 8.3 and 2.50 +/- 7.0 micrograms/ml (mean +/- standard deviation) and were reached within 20 min, t1/2 lambda 1 was 9.1 +/- 1.8 and 7.8 +/- 1.3 min, t1/2 lambda 2 1.2 +/- 0.2 and 1.9 +/- 0.5 h, and the total clearance was 393 +/- 110 and 427 +/- 113 ml/min. Inactivation of saruplase in plasma was negligible. After 15 min, tcu-PA was detected in plasma. From the ratio of the areas under the curve of tcu-PA and total u-PA activities it was calculated that 28 +/- 9.3% of the saruplase dose is converted into active tcu-PA. Systemic plasminaemia occurs as shown by a decrease in alpha 2-antiplasmin and fibrinogen and an increase in fibrinogen degradation products. Thrombin-antithrombin complex formation indicated activation of the clotting system. Saruplase is eliminated rapidly from plasma in AMI patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1980

Pneumatic calf compression, fibrinolysis, and the prevention of deep venous thrombosis.

In a previous pilot study that did not reach statistical significance, intermittent single-leg pneumatic compression appeared effective in reducing the incidence of calf vein thrombosis not only in the pumped calf but also in the unpumped leg in 37 patients, using the 125I-fibrinogen (Abbott Laboratories) technique. The present study was undertaken to investigate mechanical induction of local and systemic fibrinolysis. The euglobulin lysis time in the arm venous effluent was determined in five volunteers before and after unilateral arm compression for 1/2 hour. Shortening averaged 19% (not significant). The experiment was repeated using bilateral calf-length boots with femoral vein sampling. Euglobulin lysis decreased 22% (P < 0.001). To uncover possible systemic effects, the protocol was altered using calf boots with sampling from the arm. The euglobulin lysis diminished 6% in 57 volunteers (P < 0.001). In 27 others the effects of thigh-length and calf-length boots were compared. In half, pumping with a short boot was undertaken first, and in the remainder, the long boot was applied initially. One-half hour of pumping was followed by 1/2 hour of rest. Immediately afterward the second period of pumping took place and continued for 1/2 hour. A total of four arm vein samples were obtained, one before and after each pumping period. Although, in retrospect, the 1/2-hour rest period was inadequate to permit the subjects to return to basal conditions, statistically significant decreases in euglobin lysis time (P = 0.05) occurred with the long boots. This study shows intermittent calf compression increases fibrinolytic potential locally and this effect can be demonstrated systemically. The greater the volume of tissue compressed, the greater the response. The efficacy of intermittent venous compression in reducing the incidence of deep venous thrombosis may be due, in part, to localized induction of fibrinolysis.

Adult↗

PubMed1977

Effectiveness of elastic stocking decompression.

The compression effectiveness of the five leading brands of antiembolism stockings was compared and related to criteria previously described (pressure gradient diminishing from 18 mm Hg at the ankle to 8 mm Hg at the thigh). Tests were conducted using a standard leg form in common use within the hosiery industry, fitted with specially developed sensors. All of the stockings achieved pressures higher than recommended-some substantially. Elastic stockings from two manufacturers demonstrated tourniquet effects at the calf. Several brands ceased to preserve a continuously diminishing pressure gradient above the knee. Deviation of leg diameter from standard geometry was accompanied by a substantial increase (decrease) in pressure with increasing (decreasing) girth. Reproducibility of pressure effects produced by identical-sized stockings varied among the brands tested.

Adult↗