Combination Pharmacotherapy

2006 ◽  
Author(s):  
Richard C. Becker ◽  
Frederick A. Spencer
Keyword(s):  
Myocardial Infarction ◽  
Low Dose ◽  
Standard Dose ◽  
Major Hemorrhage ◽  
Flow Rates ◽  
St Segment Elevation ◽  
Treatment Groups ◽  
Speed Group ◽  
Two Phases ◽  
To Receive

The goal of improving coronary arterial patency, microcirculatory blood flow, and myocardial perfusion represents the essence of fibrinolytic–adjunctive therapy combinations. Because fibrinolytic resistance, patency without perfusion, and reocclusion are platelet-mediated phenomena, considerable emphasis has been placed on the development of platelet antagonists. Coronary arterial thrombi consist of platelets and fibrin bound in a tightly packed meshwork. Platelets modify the intrinsic properties of the fibrin network, causing changes in permeability and vasoelasticity, which decrease fibrinolysis rates. The addition of aspirin and the glycoprotein (GP) IIb/IIIa receptor antagonist abciximab modulates the interaction of platelets and fibrin, improving both accessibility to fibrinolytics and the overall rates of fibrinolysis (Collet et al., 2001). The Thrombolysis in Myocardial Infarction (TIMI) 14 trial (Antman et al., 1999) randomized 888 patients with ST-segment elevation myocardial infarction (MI) to receive (1) accelerated tissue plasminogen activator (tPA; ≤100 mg) plus standard dose of unfractionated heparin (UFH); (2) tPA (920 mg bolus) plus abciximab (0.25 mg/kg bolus, 7 μg/min); (3) streptokinase (800,000 to 1.5 million units) and low-dose UFH; or (4) abciximab plus low-dose UFH. TIMI 3 flow rates 90 minutes from treatment initiation were 52%, 53%, 42%, and 32%, respectively. In subsequent dose/strategy studies, a combination of tPA (35 mg) plus abciximab and tPA (15 mg bolus, 31 mg over 60 minutes) plus abciximab revealed 63% and 73% TIMI 3 flow rates, respectively. Rates of major hemorrhage were similar in all tPA treatment groups. The Strategies for Patency Enhancement in the Emergency Department (SPEED) trial (SPEED Group, 2000) included two phases. Phase A (n = 241) randomized patients to receive either abciximab (bolus plus infusion) alone or combined with 5 U, 7.5 U, 10 U, 5 U + 2.5 U, or 5U + 5 U of reteplase. Phase B tested the best strategy from phase A (abciximab plus 5 U + 5 U of reteplase) against 10 U + 10 U of reteplase. In phase A, 62% of the abciximab–reteplase 5 U + 5 U patient group had TIMI 3 flow rates at 60 to 90 minutes vs. 27% of those given abciximab alone (p = .001).

scholarly journals Lack of Efficacy of Propofol in the Treatment of Early Postoperative Nausea and Vomiting

1998 ◽  
Vol 26 (4) ◽  
pp. 366-370 ◽  
Author(s):  
I. Harper ◽  
E. Della-Marta ◽  
H. Owen ◽  
J. Plummer ◽  
A. Ilsley
Keyword(s):  
Low Dose ◽  
Dose Range ◽  
Postoperative Nausea And Vomiting ◽  
Nausea And Vomiting ◽  
Test Drug ◽  
Gynaecological Surgery ◽  
Treatment Groups ◽  
Sedation Scores ◽  
To Receive ◽  
Rescue Antiemetic

The anti-nauseant efficacy of low-dose propofol was investigated in a blinded, randomized trial. Patients who complained of nausea and/or vomiting following laparoscopic gynaecological surgery and who requested antiemetic were randomly assigned to receive placebo, propofol 3 mg, propofol 9 mg or propofol 27 mg by intravenous injection. Nausea, vomiting and sedation were recorded by a blinded observer for 90 minutes following administration of the test drug, prior to discharge, and 24 hours following surgery. Rescue antiemetic (droperidol 1.0 mg IV) was available from 10 minutes after administration of test drug. Propofol failed to reduce nausea scores and did not reduce the incidence of vomiting. Numbers of patients receiving rescue antiemetic were similar in the four treatment groups. In the first 10 minutes following test drug administration, sedation scores were increased by propofol in a dose-related manner. We conclude that, in the dose range studied, propofol is ineffective for the treatment of nausea and vomiting occurring soon after laparoscopic gynaecological surgery.

One-year, low-dose neuroleptic study of in-patients with chronic schizophrenia characterised by persistent negative symptoms

1997 ◽  
Vol 171 (6) ◽  
pp. 564-568 ◽  
Author(s):  
Jeremy C. Speller ◽  
Thomas R. E. Barnes ◽  
David A. Curson ◽  
Christos Pantelis ◽  
J. L. Alberts
Keyword(s):  
Negative Symptoms ◽  
Low Dose ◽  
Chronic Schizophrenia ◽  
Anticholinergic Medication ◽  
Treatment Groups ◽  
Substituted Benzamide ◽  
One Year ◽  
To Receive ◽  
Persistent Negative Symptoms

BackgroundAmisulpride is a potent substituted benzamide antipsychotic drug claimed to improve the negative symptoms of schizophrenia, particularly at low dosage.MethodSixty long-term in-patients with schizophrenia and selected for predominant negative symptoms were randomised to receive either haloperidol or amisulpride. Over a year there was systematic dose reduction, as symptoms allowed.ResultsThere were no significant differences between the treatment groups in the proportion receiving low-dose treatment, the control of positive symptoms, or ratings of social behaviour, side-effects or tardive dyskinesia. For negative symptoms, there were consistent but non-significant trends in favour of amisulpride. The amisulpride patients required significantly less anticholinergic medication.ConclusionsIn chronically-hospitalised in-patients with schizophrenia characterised by persistent negative symptoms, amisulpride was a well-tolerated maintenance antipsychotic medication. The drug had only a limited effect in reducing negative symptoms, which were relatively stable, enduring phenomena in this sample, despite dosage reduction.

Combined Carbimazole-131I Treatment for Thyrotoxicosis

1972 ◽  
Vol 17 (2) ◽  
pp. 57-61 ◽  
Author(s):  
J. R. McDougall ◽  
W. R. Greig
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Radioactive Iodine ◽  
Standard Dose ◽  
Antithyroid Drugs ◽  
131I Treatment ◽  
Therapeutic Regime ◽  
The Individual ◽  
To Receive

A sequential therapeutic regime was prescribed for 74 thyrotoxic patients. Every patient received carbimazole in conventional doses for 20 weeks; the average time to obtain control was 10.2 weeks. The patients although older than those usually treated with antithyroid drugs (range 38–68 years) showed no difference in the expected rate of control or in the recognised incidence of side effects. Following the carbimazole therapy the patients were alternatively allotted to receive standard or low (50% of standard) doses of 131I, the individual doses being calculated from simple formulae. After the radio-iodine all of the patients were treated with carbimazole for a further 20 weeks. Review of the patients after completion of the trial and subsequent follow up without therapy shows that 42.1 per cent of the standard dose group remain euthyroid after one therapy dose of 131I, 36.8 per cent have relapsed and 21.1 per cent have become hypothyroid. In the low dose group 44.4 per cent are euthyroid, 47.2 per cent have had a recurrence and 8.4 per cent have become hypothyroid. The results are discussed in the light of current views about the treatment of thyrotoxicosis with drugs and with radioactive iodine.

scholarly journals Thrombolysis with Low-Dose Versus Standard-Dose Alteplase in 4.5 Hours After Acute Ischemic Stroke; A Four-Months Prospective Study.

2020 ◽  
pp. 1-13
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Ischemic Stroke ◽  
Systolic Blood Pressure ◽  
Cerebral Hemorrhage ◽  
Low Dose ◽  
Standard Dose ◽  
Favorable Outcome ◽  
Safety And Efficacy ◽  
To Receive

Abstract Background: In Japan, Pakistan and Vietnam, 0.6 mg of Alteplase per kilogram body weight within 3 hours was approved for standard guideline, although the safety and efficacy in acute ischemic stroke within 4.5 hours has not been established. We conducted four-month prospective study to compare the safety and efficacy of 0.6 mg, 0.75 mg and 0.9 mg of Alteplase per kilogram body weight. Methods: In cohort A, the patients were randomly assigned to receive intravenous 0.6 mg or 0.75 mg or 0.9 mg of Alteplase per kilogram body weight in a 1:1:1. Interim analysis was performed after complete cohort A. In cohort B, patients were assigned to receive 0.9 mg of Alteplase per kilogram body weight (standard-dose). The primary end points were death, favorable outcome at discharge and 90-day and intra-cerebral hemorrhage. The secondary end points were good outcomes, Improved mRS at discharged and 90-day, number of patients with length of hospital stay <7 days and overall complications. Results: In Cohort A, 78 were randomly assigned to receive 0.6 mg or 0.75 mg (low-dose) or 0.9 mg of intravenous Alteplase per kilogram body weight. Less patients had favorable outcomes in 0.6 mg and 7.5 mg than 0.9 mg of Alteplase per kilogram body weight at discharge (P=0.0004) and at 90-day (P=0.05). In Cohort B, 330 were assigned to receive standard-dose Alteplase. Finally, 408 patients were enrolled with median time of Alteplase administration by 2 hours 49 min. There was no different onset to needle and death between low-dose and standard-dose Alteplase (P=0.82 and P=0.85). Less patients had favorable outcome and intra-cerebral hemorrhage with low-dose than standard-dose Alteplase (favorable outcomes: Relative risk (RR), 1.18; 95% confidence interval (CI), 1.09 to 1.27; P <0.001 at discharge and RR, 1.25; 95%CI, 1.07 to 1.46; P=0.003 at 90 day, intra-cerebral hemorrhage: RR, 0.05; 95%CI, 0.00 to 0.95; P=0.04. Less patients had improved modified Rankin Scale [mRS] at 90-day with low-dose than standard-dose Alteplase (RR, 1.66; 95%CI, 1.22 to 2.25; P=0.001; especially in the patients with initial systolic blood pressure <180 mmHg ; RR, 1.86; 95%CI, 1.35 to 2.56; P=0.0001). In patients with initial systolic blood pressure >180 mmHg, low-dose Alteplase group had more patients with mRS of 0-3 at 90-day and less patients with of mRS 4-6 at 90-day than standard-dose Alteplase (P=0.002). There was no significant different in length of stay and overall complications with low-dose than standard-dose Alteplase (P=0.15). Conclusion: As compared with standard-dose, intravenous low-dose Alteplase administered within 4.5 hours after the onset of stroke significant less favorable outcome, intra-cerebral hemorrhage, but not different in death, especially in the patients with initial systolic blood pressure <180 mmHg. However, patients with initial systolic blood pressure >180 mmHg, intravenous low-dose Alteplase had less patients with disability and death and more patient’s recovery with mRS of 0-3 at 90-day. (ClinicalTrial.gov Number, NCT03847883).

2387Recurrent cardiovascular events and mortality in relation to antiplatelet therapy in patients with myocardial infarction without obstructive coronary artery disease (MINOCA)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Bossard ◽  
S Yusuf ◽  
J F Tanguay ◽  
D P Faxon ◽  
W E Boden ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Antiplatelet Therapy ◽  
Standard Dose ◽  
Obstructive Coronary Artery Disease ◽  
Double Dose ◽  
St Segment Elevation ◽  
Artery Disease

Abstract Background Approximately 10% of patients presenting with myocardial infarction (MI) do not have obstructive coronary artery disease (MINOCA). The role of antiplatelet therapy and outcomes in this group remain unclear. We assessed prognosis and the effect of an intensified clopidogrel regimen in MINOCA patients. Methods We analyzed data from the CURRENT-OASIS 7 trial, which randomized 25,086 patients with acute coronary syndromes (ACS) referred for early intervention to receive either double-dose (600mg day 1; 150mg days 2–7; then 75mg daily) or standard-dose (300mg day 1; then 75mg daily) clopidogrel. We evaluated clinical outcomes at 30-days in patients with versus without obstructive CAD and in relation to standard versus double-dose clopidogrel. Results Overall, 23,783 MI patients were included, of which 1,599 (6.7%) had MINOCA. MINOCA patients were younger, more frequently presented with non-ST-segment elevation MI and had fewer comorbidities. Rates of all-cause mortality (0.7% versus 2.4%, p=0.0046), cardiovascular mortality (0.6 versus 2.2%, p=0.0056), repeat MI (0.5% versus 2.3%, p=0.0009) and major bleedings (0.7% versus 2.5%, p=0.0001) were significantly lower among patients with MINOCA versus those with obstructive CAD. Compared with the standard-dose clopidogrel regimen, the double-dose regimen appeared to increase the risk of cardiovascular death, MI or stroke in MINOCA patients (0.8% versus 2.1%, hazard ratio (HR) 2.74, P=0.033). There was no difference in those with obstructive CAD (4.7% versus 4.4%, HR 0.93, P=0.226; P-for-interaction=0.023) (see Figure 1A). Major bleeding did not occur more frequently in MINOCA patients with double- versus standard-dose clopidogrel regimen (0.7% versus 0.6%, (HR 1.16 (95% CI 0.35–3.80), p=0.805), but their rate was higher In MI patients with obstructive CAD (2.7% versus 2.2% (HR 1.26 (95% CI 1.06–1.49), p=0.008) (Figure 1B). Figure 1A & B Conclusions Compared to MI patients with obstructive CAD, patients presenting with MINOCA represent a distinct cohort, which is generally younger, has a higher NSTEMI prevalence and fewer comorbidities. Their risk for adverse events, especially repeat MI, stroke, death, and bleeding, is low (<1%) at 30 days. Applying an intensified clopidogrel regimen in MINOCA patients appears to be related to a higher risk for CV death, MI and stroke. Accordingly, more potent antiplatelet regimens might be harmful among MINOCA patients and should not be administered routinely. Nevertheless, there is a need for more prospective studies evaluating the role of dual antiplatelet therapies in MINOCA patients. Acknowledgement/Funding The CURRENT-OASIS 7 trial was sponsored by Sanofi-Aventis and Bristol-Myers Squibb.

scholarly journals Effects of low dose of aliskiren on isoproterenol-induced acute myocardial infarction in rats

2018 ◽  
Vol 105 (2) ◽  
pp. 127-144 ◽  
Author(s):  
I Bin-Jaliah ◽  
AM Hussein ◽  
HF Sakr ◽  
EA Eid
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Low Dose ◽  
Myocardial Damage ◽  
Significant Rise ◽  
Albino Rats ◽  
Cardiac Enzymes ◽  
St Segment Elevation ◽  
Direct Renin Inhibitor ◽  
Myocardial Oxidative Stress

This study examined the effects of aliskiren (Ali) (direct renin inhibitor) on serum cardiac enzymes (LDH and CK-MB), electrocardiography (ECG) changes, myocardial oxidative stress markers (MDA, CAT, and GSH) and the expression of Bcl2, HO-1, and Nrf2 genes in isoproterenol (ISO)-induced myocardial infarction (MI). A total of 40 male albino rats were allocated into four groups, (1) normal control (NC) group, (2) Ali group (rats received Ali at 10 mg/kg/day p.o. for 5 days), (3) ISO group (rats received ISO 150 mg/kg i.p. for two consecutive days at 24 h intervals), and (4) Ali + ISO group (rats received ISO + Ali at 10 mg/kg/day p.o. for 5 days from the 2nd dose of ISO). ISO group showed significant rise in serum cardiac enzymes (CK-MB and LDH), myocardial damage scores, myocardial MDA, HO-1, myocardial Nrf2 expression with significant reduction in myocardial antioxidants (CAT and GSH), and Bcl2 expression compared to the normal group (p < 0.05). ECG showed ST segment elevation, prolonged QT interval and QRS complex, and increased heart rate in ISO group. Co-administration of Ali and ISO caused significant increase in cardiac enzymes and morphology with increase in MDA, serum K, and creatinine with significant decrease in Bcl2, HO-1, and Nrf2 without significant changes in ECG parameters compared to ISO group. We concluded that low dose of Ali seems to exacerbate the myocardial injury in ISO-MI, which might be due to the enhanced oxidative stress and apoptosis.

scholarly journals Low-dose intracoronary alteplase during primary percutaneous coronary intervention in patients with acute myocardial infarction: the T-TIME three-arm RCT

2020 ◽  
Vol 7 (5) ◽  
pp. 1-86
Author(s):  
Peter J McCartney ◽  
Hany Eteiba ◽  
Annette M Maznyczka ◽  
Margaret McEntegart ◽  
John P Greenwood ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Placebo Group ◽  
Coronary Artery ◽  
Primary Outcome ◽  
Low Dose ◽  
Microvascular Obstruction ◽  
Secondary Analysis ◽  
Left Ventricular ◽  
Primary Analysis ◽  
St Segment Elevation

Background Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction and is independently associated with adverse outcomes. Objective To determine whether or not a strategy involving low-dose intracoronary fibrinolytic therapy infused early after coronary reperfusion will reduce microvascular obstruction. Design This was a multicentre, randomised, double-blind, parallel-group, placebo-controlled, dose-ranging trial. Setting The trial took place at 11 hospitals in the UK between 17 March 2016 and 21 December 2017. Participants Patients with acute ST-segment elevation myocardial infarction and a symptom onset to reperfusion time of ≤ 6 hours were eligible for randomisation. Radial artery access was a requirement, and further angiographic criteria included a proximal-to-middle coronary artery occlusion or impaired coronary flow in the presence of a definite thrombus in the culprit coronary artery. Exclusion criteria included a functional coronary collateral supply to the infarct-related artery, any contraindication to fibrinolysis and lack of informed consent. Additional exclusion criteria for safety were (1) requirement for immunosuppressive drug therapy for ≤ 3 months and (2) treatment with an antimicrobial agent. Intervention A total of 440 participants were randomly assigned 1 : 1 : 1 to treatment with placebo (n = 151), 10 mg of alteplase (n = 144) or 20 mg of alteplase (n = 145) administered by manual infusion directly into the infarct-related coronary artery over 5–10 minutes. The intervention was scheduled to happen after reperfusion and before stent implantation. Outcomes The primary outcome was the amount of microvascular obstruction (percentage of left ventricular mass) demonstrated by contrast-enhanced cardiac magnetic resonance imaging at 2–7 days after enrolment. The primary analysis was the comparison between the 20 mg of alteplase group and the placebo group; if this comparison was not significant, the comparison of the 10 mg of alteplase group with the placebo group was considered as a secondary analysis. Sample size A total of 618 patients (minimum of 558 patients). Recruitment was halted on 21 December 2017 given that conditional power for the primary outcome based on a prespecified analysis of the first 267 randomised participants was < 30% in both treatment groups (futility criterion). Methods The primary outcome was compared between groups using a stratified Wilcoxon rank-sum test (van Elteren test), stratified by the location of the myocardial infarction. Results Among the 440 patients (mean age of 60.5 years; 15% women), the primary end point was measured in 396 (90%) patients, 17 (3.9%) withdrew, seven died and all other patients were followed up to 3 months. The amount (mean percentage of left ventricular mass) of microvascular obstruction was 2.3% versus 2.6% versus 3.5% in the placebo, 10 mg of alteplase and 20 mg of alteplase groups, respectively. In the primary analysis, microvascular obstruction did not differ between the 20 mg of alteplase group and the placebo group: 3.5% versus 2.3%, estimated difference 1.16% (95% confidence interval –0.08% to 2.41%; p = 0.32). In the secondary analysis, microvascular obstruction did not differ between the 10 mg of alteplase group and the placebo group: 2.6% versus 2.3%, estimated difference 0.29% (95% confidence interval –0.76% to 1.35%; p = 0.74). By 3 months, major adverse cardiac events (cardiac death, non-fatal myocardial infarction and unplanned hospitalisation for heart failure) had occurred in 15 (10.1%) patients in the placebo group, 18 (12.9%) in the 10 mg of alteplase group and 12 (8.2%) in the 20 mg of alteplase group. Conclusions Adjunctive low-dose intracoronary alteplase given during the primary percutaneous intervention did not reduce microvascular obstruction compared with placebo. Limitations Premature discontinuation of enrolment limited the power of the secondary and safety analyses. Future work Low-dose intracoronary alteplase or tenecteplase could be compared with placebo at the end of primary percutaneous coronary intervention in patients with an ischaemic time of < 4 hours. Trial registration This trial is registered as ClinicalTrials.gov NCT02257294. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 5. See the NIHR Journals Library website for further project information.

Bivalirudin Versus Heparin Monotherapy in ST-Segment–Elevation Myocardial Infarction

2021 ◽  
Author(s):  
Stefan James ◽  
Sasha Koul ◽  
Jonas Andersson ◽  
Oskar Angerås ◽  
Pallonji Bhiladvala ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Percutaneous Coronary Intervention ◽  
Major Bleeding ◽  
Primary Percutaneous Coronary Intervention ◽  
Coronary Intervention ◽  
St Segment Elevation ◽  
Radial Access ◽  
St Segment ◽  
Percutaneous Coronary ◽  
To Receive

Background: Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y 12 -inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy–Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry). Methods: In this prespecified separately powered subgroup analysis, we included patients with ST-segment–elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days. Results: Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment–elevation MI were randomized to receive bivalirudin or heparin. The mean age was 66.8 years. According to protocol recommendations, 87% were treated with potent oral P2Y 12 -inhibitors before start of angiography and radial access was used in 90%. GPI was used in 51 (3.4%) and 74 (4.9%) of patients randomized to receive bivalirudin and heparin, respectively. The primary end point occurred in 12.5% (187 of 1501) and 13.0% (196 of 1504; hazard ratio [HR], 0.95 [95% CI, 0.78–1.17], P =0.64) with consistent results in all major subgroups. All-cause death occurred in 3.9% versus 3.9% (HR, 1.00 [0.70–1.45], P =0.98), MI in 1.7% versus 2.2% (HR, 0.76 [0.45–1.28], P =0.30), major bleeding in 8.3% versus 8.0% (HR, 1.04 [0.81–1.33], P =0.78), and definite stent thrombosis in 0.5% versus 1.3% (HR, 0.42 [0.18–0.96], P =0.04). Conclusions: In patients with ST-segment–elevation MI undergoing primary percutaneous coronary intervention with radial access and receiving current recommended treatments with potent P2Y 12 -inhibitors rate of the composite of all-cause death, MI, or major bleeding was not lower in those randomized to receive bivalirudin as compared with heparin. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02311231.

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