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PubMed2000

Placebo effect of carbohydrate feedings during a 40-km cycling time trial.

PURPOSE: The placebo effect, a favorable outcome from belief that one has received a beneficial treatment, may be an important phenomenon in athletic performance. We have therefore investigated the placebo effect of a carbohydrate supplement on endurance performance. METHODS: Forty-three competitive endurance cyclists (2 female, 41 male) performed two simulated 40-km time trials on an air-braked ergometer. In the first trial they ingested water to establish baseline performance (mean power 265 +/- 46 W for 58 +/- 4 min, mean +/- SD). For the second trial 6-8 d later they were randomized to two groups: one group ingested 16 mL x kg(-1) of a drink containing 7.6 g x 100 mL(-1) carbohydrate; the other ingested an indistinguishable noncaloric placebo drink. Cyclists in each group were further randomized to three subgroups according to whether they were told the drink contained carbohydrate, placebo, or either (not told). RESULTS: Changes in mean power in the second trial were: told carbohydrate, 4.3 +/- 4.8%; told placebo, 0.5 +/- 5.8%; and not told, -1.1 +/- 8.5%. The difference between the told-carbohydrate and told-placebo groups was 3.8% (95% likely range 7.9 to -0.2%). The change in performance in the not-told group was more variable than that of the told groups by a factor of 1.6 (2.6 to 1.0). The real effect of carbohydrate was a slight reduction in power of 0.3% (4.4 to -3.8%). CONCLUSIONS: (a) The placebo effect of a potentially ergogenic treatment during unblinded laboratory time trials lasting approximately 1 h is probably a small but worthwhile increase in endurance power. (b) Blinding subjects to the treatment increases individual differences in endurance effort, which may reduce precision of performance outcomes in controlled trials.

Adult↗

PubMed1998

Mexiletine for HIV-infected patients with painful peripheral neuropathy: a double-blind, placebo-controlled, crossover treatment trial.

Although mexiletine, an antiarrhythmic with local anesthetic properties, has been reported to relieve discomfort in diabetic neuropathy, its usefulness in the treatment of HIV-related painful peripheral neuropathy (PPN) has not been determined. The tolerance and effectiveness of mexiletine in HIV-related PPN were assessed in 22 patients who were randomized to receive mexiletine (maximum dose, 600 mg/day) or placebo for 6 weeks, followed by the alternative intervention for 6 weeks after a 1-week washout period. The daily pain response was assessed using a visual analogue scale card in 19 patients who received at least 2 weeks of the drug, 16 of whom were crossed-over to receive the alternate agent. No statistically significant difference was found between the mean daily pain scores for patients receiving mexiletine versus placebo, irrespective of the order in which the agents were received. Comparing the mean individual daily pain scores for each phase of study, 5 patients (31%) had significantly less pain while receiving mexiletine compared with their response to placebo, 5 patients (31%) had significantly less pain while receiving placebo, and no difference was noted in 6 patients (38%). Crossover and multivariate analyses for repeated measures showed no apparent difference in the response to mexiletine versus placebo. Dose-limiting adverse events occurred in 39% of those receiving mexiletine, but only 1 patient (5%) discontinued placebo. Mexiletine was only modestly well tolerated despite its relatively brief period of administration, and no evidence was found to support its benefit in HIV-related PPN. Although a first-drug effect was not demonstrated, a powerful placebo effect was seen in some patients.

Adult↗

PubMed2006

Paroxetine treatment in children and adolescents with major depressive disorder: a randomized, multicenter, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the efficacy and tolerability of paroxetine in pediatric major depressive disorder. METHOD: Subjects 7 to 17 years old with major depressive disorder received paroxetine (10-50 mg/day) or placebo for 8 weeks from 2000 to 2001. The primary efficacy measure was change from baseline in the Children's Depression Rating Scale-Revised total score at week 8 last observation carried forward). Safety was primarily assessed by spontaneous reporting of adverse events. RESULTS: A total of 206 patients (intent to treat) were randomized to paroxetine (n = 104) or placebo (n = 102). Week 8 Children's Depression Rating Scale-Revised total score adjusted mean changes from baseline for patients receiving paroxetine and placebo were -22.58 (SE 1.47) and -23.38 points (SE 1.60), respectively (0.80, 95% confidence interval -3.09 to 4.69, p = 0.684). Increased cough (5.9% versus 2.9%), dyspepsia (5.9% versus 2.9%), vomiting (5.9% versus 2.0%), and dizziness (5.0% versus 1.0%) occurred in >or=5% of the paroxetine group and at least twice that of the placebo group. Six of 104 (5.8%) paroxetine patients reported serious adverse events compared to 1 placebo patient (1.0%). The incidence of adverse events of suicidal behavior and/or ideation while taking study medication (excluding taper) was 1.92% (2/104) for paroxetine versus 0.98% (1/102) for placebo. CONCLUSIONS: Paroxetine was not shown to be more efficacious than placebo for treating pediatric major depressive disorder.

Adolescent↗

PubMed2005

Placebo control groups in trials of major depressive disorder among older patients.

BACKGROUND: Ethical concerns have been raised regarding the continued use of placebo control groups in randomized controlled trials of antidepressant medications for major depressive disorder. These concerns may be especially relevant for geriatric patients who may experience significant morbidity related to major depressive disorder. METHODS: Sixty-eight randomized placebo-controlled trials of antidepressant medication for major depressive disorder were examined, 6 of which measured response to medication and placebo in elderly patients. RESULTS: Although this review is limited by the small number of studies focusing on older individuals, there are a number of similarities and some differences in geriatric studies in comparison to other studies of adults with major depressive disorder. In comparison to studies of younger adults, the proportion of patients responding to placebo in studies of older individuals was slightly higher, and the proportion of patients responding to active medication was lower, leading to a significantly reduced effect size. CONCLUSIONS: The scientific importance of using control groups in studies of major depression poses ethical challenges. However, the substantial and variable response to placebo and the inability to predict accurately the response to placebo or medication raise serious doubts about the scientific value of trials of new medications in which there is no placebo group.

Adult↗

PubMed2006

A meta-analysis of early sustained response rates between antidepressants and placebo for the treatment of major depressive disorder.

CONTEXT: Pattern analysis suggests that "true" drug response is characterized by clinical improvement that is not subsequently followed by a worsening of symptoms (sustained clinical response). To date, several reports demonstrate that early response rates are equivalent between antidepressant-treated and placebo-treated groups of patients with major depressive disorder, suggesting that patients who demonstrate significant and sustained symptom improvement during the first 2 weeks of treatment are not responding to the antidepressant itself, but to nonspecific, placebo-like factors. OBJECTIVE: To compare early sustained response rates between antidepressant- and placebo-treated adults with major depressive disorder. DATA SOURCES: Medline/Pubmed were searched. No year of publication limits were used. STUDY SELECTION: Randomized, double-blind, placebo-controlled antidepressant trials or pooled reports/meta-analyses of such trials reporting early sustained response rates for major depressive disorder. The decision to include studies in the meta-analysis was performed by 2 reviewers. DATA EXTRACTION: Data were extracted with the use of a precoded form. DATA SYNTHESIS: Analyses were performed on the proportion of patients who achieved a sustained response the first 2 weeks of treatment, as well as the first week of treatment. A random-effects model with fixed drug effects was used to combine the studies and make comparisons of sustained early response rates between antidepressant- and placebo-treated groups. Data from 8 reports involving a total of 7121 major depressive disorder patients (4076 randomized to treatment with an antidepressant and 3045 randomized to placebo) were analyzed. Antidepressant-treated patients were more likely to demonstrate sustained clinical response by 2 weeks (odds ratio 2.06, 95% CI: 1.52-2.8) or 1 week of treatment (odds ratio 1.50, 95% CI: 1.08-2.08) than placebo-treated patients. CONCLUSIONS: The results of the present analysis suggest that "true" drug response can occur the first 2 week as well as the first week of treatment of major depressive disorder with conventional antidepressants.

Antidepressive Agents↗

PubMedDate not supplied

The effects of manipulating expectations through placebo and nocebo administration on gastric tachyarrhythmia and motion-induced nausea.

BACKGROUND: Interest in the role of expectation in the development of nausea and other adverse conditions has existed for decades. The purpose of this study was to examine the effects of manipulating expectations through the administration of placebos and nocebos on nausea and gastric tachyarrhythmia provoked by a rotating optokinetic drum. METHOD: Seventy-five participants were assigned to one of three groups. Positive-expectancy group participants were given placebo pills that would allegedly protect them against the development of nausea and motion sickness. Negative-expectancy group participants were given the same pills as nocebos; they were led to believe there was a tendency for them to make nausea somewhat worse. Placebo-control group participants were told the pills were indeed placebos that would have no effect whatsoever. RESULTS: Subjective symptoms of motion sickness were significantly lower among negative-expectancy group participants than positive-expectancy and placebo-control group participants (p<0.05). Gastric tachyarrhythmia, the abnormal stomach activity that frequently accompanies nausea, was also significantly lower among negative-expectancy group participants than positive-expectancy and Placebo-Control Group participants during drum rotation (p<.05) [corrected] CONCLUSIONS: Inducing negative expectations through nocebo administration reduced nausea and gastric dysrhythmia during exposure to provocative motion, whereas positive placebos were ineffective for preventing symptom development. That manipulation of expectation affected gastric physiological responses as well as reports of symptoms, suggests an unspecified psychophysiological mechanism was responsible for the observed group differences. These results also suggest that patients preparing for difficult medical procedures may benefit most from being provided with detailed information about how unpleasant their condition may become.

Adolescent↗

PubMed2006

Zolmitriptan oral tablet in migraine treatment: high placebo responses in adolescents.

OBJECTIVE: The objective of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy and tolerability of the zolmitriptan conventional tablet at three different doses for the treatment of a single migraine attack in adolescents. BACKGROUND: Preliminary data from an open-label study suggested that the zolmitriptan conventional tablet could be effective in the treatment of acute migraine in adolescent patients. METHODS: Migraine patients aged 12 to 17 years (n = 850) were randomized to receive zolmitriptan 2.5, 5, or 10 mg, or placebo for treatment of a single migraine attack. Patients recorded migraine headache intensity before and after treatment using a 4-point scale. RESULTS: There was no statistically significant improvement between zolmitriptan 10 mg (2 x 5 mg tablet) and placebo for the primary efficacy variable, headache response at 2 hours, nor any of the secondary variables tested. Two-hour headache response rates were 54%, 53%, and 57% for zolmitriptan 10, 5, and 2.5 mg, respectively, and 58% for placebo. Two-hour pain-free rates were 25%, 19%, and 23% for zolmitriptan 10, 5, and 2.5 mg, respectively, and 20% for placebo. Zolmitriptan was well tolerated, with a tolerability profile similar to the pattern seen in adults. CONCLUSION: The similar efficacy between zolmitriptan and placebo appears to be the result of the high placebo response rate. This is a recognized issue in pediatric migraine studies and there is an ongoing debate on ways to address this problem. Since this study was initiated, there has been some debate on the appropriateness of the 2-hour endpoint for response rates in adolescent studies, given the shorter duration of headache pain in adolescents compared with adults. Furthermore, accurate information regarding the timeliness of treatment and reporting of headache-related information by adolescents is difficult.

Adolescent↗

PubMed1989

Placebo responding in the same direction as alcohol in women.

Pavlovian conditioning studies with alcohol in humans have been performed exclusively with men subjects. Men demonstrate a placebo response opposite in direction to alcohol, which Newlin (Alcohol Clin Exp Res 9:411-416, 1985) termed an antagonistic placebo response. The current study used normal women subjects given alcohol, placebo, or a soft drink control. Placebo significantly (p less than 0.05) increased heart rate compared to the control condition, and this placebo response was in the same direction as the effect of alcohol. The correlation of heart rate change with reported intoxication was +0.44 in women, when it was negative in men (Newlin DB: Alcohol Clin Exp Res 9:411-416, 1985). These results, when considered in relation to other data concerning individual differences in antagonistic placebo responding, suggest a pattern in which risk for alcoholism is negatively related to placebo responding.

Adult↗

PubMed2000

A double-blind, placebo-controlled, multicenter study of Cerebrolysin for Alzheimer's disease.

OBJECTIVE: To assess the efficacy and safety of Cerebrolysin over 4 weeks in patients with probable Alzheimer's disease (AD). DESIGN: A 4-week randomized, double-blind, placebo-controlled, multicenter clinical trial. An unequal (Cerebrolysin:placebo = 2:1) randomization was used to assign more patients to the treatment group. SETTINGS: University medical centers and community geriatric hospitals in Korea. PARTICIPANTS: Fifty-three men and women at least 50 years of age admitted to hospitals with mild to moderate AD and otherwise in good health. INTERVENTION: The treatment group (n = 34) received Cerebrolysin (30 mL Cerebrolysin in 100 mL physiologic saline IV) once a day from Monday to Friday for 4 weeks. The control group (n = 19) received placebo. MEASUREMENTS: Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Clinical Global Impression of Severity/ Change (CGIS/C). Secondary outcome measures included Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Katz Index of Activities of Daily Living (ADL), and Lawton Instrumental Activities of Daily Living (IADL) Scale. RESULTS: After 4 weeks of treatment, Cerebrolysin-treated patients demonstrated significant improvements in the ADAS-Cog (P = .02), CGIS/C (P = .01), and MMSE (P = .04) compared with placebo-treated patients. Among Cerebrolysin-treated patients, 82%, 62%, and 44% were rated improved on ADAS-Cog, CGIS/C, and MMSE, respectively, compared with 31.6%, 22%, and 17% of placebo-treated patients, respectively. However, there were no significant improvements in the Cerebrolysin group compared with the placebo group on the GDS, ADL, and IADL. There were no dropouts in either groups, with 100% compliance to Cerebrolysin and placebo. Only one patient reported a febrile sensation, which was transient and mild in severity. CONCLUSIONS: This study indicates that Cerebrolysin is a safe drug that improves the cognitive deficits and global function in patients with mild to moderate AD. Long-term efficacy and safety of Cerebrolysin in Alzheimer's patients should be evaluated in the future.

Activities of Daily Living↗

PubMed2002

A double blind, randomized, placebo-controlled trial of proton pump inhibitor therapy in patients with uninvestigated dyspepsia.

OBJECTIVES: In patients with uninvestigated dyspepsia, a common initial management strategy in primary care is to prescribe a course of empiric antisecretory therapy and to refer those patients who do not respond for endoscopy. The objective of this research was to evaluate the effects of an empiric course of antisecretory therapy on dyspepsia-related health in patients with uninvestigated dyspepsia. METHODS: We conducted a double blind, randomized, placebo-controlled trial in which patients with uninvestigated dyspepsia were randomized to a 6-wk course of omeprazole 20 mg p.o. b.id. versus placebo capsules p.o. bi.d. and followed over 1 yr. The patients were at least 18 yr old with at least a 1-wk history of dyspepsia without alarm features. Dyspepsia-related health was measured using the Severity of Dyspepsia Assessment (SODA), a valid, reliable, disease-specific outcome measure. The primary outcome was treatment failure, defined by a SODA Pain Intensity score > or = 29 (scores, 2-47) during follow-up. Patients who were treatment failures underwent endoscopy. RESULTS: We enrolled 140 patients. The mean age was 51 yr, and seven (5%) were women. At 2 wk there were fewer treatment failures in the omeprazole group: 12 of 71 patients (17%) in the omeprazole group failed compared with 24 of 69 (35%) in the placebo group (p = 0.037, log rank test). Also, at 6 wk there were fewer failures in the omeprazole group: 21 of 71 patients (30%) in the omeprazole group failed compared with 31 of 69 (45%) in the placebo group in 0.067, log rank test). However, at the 1-yr follow-up, there was no significant difference in treatment failure rates in the two groups: 37 of 71 patients (52%) in the omeprazole group failed compared with 41 of 69 (59%) in the placebo group (p = 0.28, log rank test). CONCLUSIONS: In patients with uninvestigated dyspepsia, as compared with a strategy that would entail prompt endoscopy for all patients, an initial 6-wk course of either placebo or omeprazole reduces the need for endoscopy over a 1-yr follow-up. Compared with placebo, an initial 6-wk course of omeprazole delays, but does not reduce, the need for endoscopy. For proton pump inhibitor therapy to reduce the need for endoscopy, it may need to be given continuously.

Administration, Oral↗

PubMed1986

Does short term placebo treatment of chronic schizophrenia produce long term harm?

A randomised double blind placebo controlled trial is the most reliable method of assessing putative new developments in medical treatment. In schizophrenia, however, some clinicians believe that relapse contributes to long term deterioration and therefore that patients exposed to either placebo or an inactive new treatment may be put at a disadvantage in the long run if the trial leads to an additional relapse. A seven year follow up of patients included in a randomised placebo controlled trial of fluphenazine decanoate, in which 66% of the group given placebo relapsed compared with 8% of those who received the active drug, permitted examination of any long term adverse consequences in those patients who had received placebo. Seventy six (94%) of the 81 patients in the original trial were followed up. At the end of the follow up period there were no consistent or important differences in any measure of clinical or social outcome between the patients who had received placebo and those who had received the active drug. This negative finding has implications for the debate on the risk of placebo controlled trials of maintenance treatment in chronic schizophrenia.

Chronic Disease↗

PubMed1995

Denial of effective treatment and poor quality of clinical information in placebo controlled trials of ondansetron for postoperative nausea and vomiting: a review of published trials.

OBJECTIVE: To determine how many patients were deprived of treatment by being given placebo as comparator in trials of ondansetron for postoperative nausea and vomiting. DESIGN: Review of published trials of ondansetron during 1991 to July 1994. SETTING: Medline search in a university department of anaesthesia. SUBJECTS: 8806 patients who had been included in 18 indexed placebo controlled trials of ondansetron as prophylaxis against or treatment of postoperative nausea and vomiting. RESULTS: Five studies (1236 patients) had been published by July 1992. All were placebo controlled trials. By July 1994, 8806 patients had been included in 18 indexed placebo controlled studies of prophylaxis or treatment. Only 462 patients had been in studies that compared ondansetron with other drugs, and there were no indexed comparative trials of treatment of nausea and vomiting. Roughly 2180 patients had been given placebo as prophylaxis and 440 had been given placebo when already experiencing postoperative nausea or vomiting. CONCLUSIONS: Around 2620 patients in the reviewed studies were denied existing drugs, which, though not completely effective or without side effects, do bring some relief from postoperative nausea and vomiting. Drug regulatory bodies should collaborate with drug companies to ensure better comparison of new with established drugs. This would avoid placebos being given to more than the fewest patients necessary to confirm effect and would allow doctors to be informed more quickly about relative efficacies.

Anesthesia Department, Hospital↗

PubMed1998

Perflenapent emulsion: a US contrast agent for diagnostic radiology--multicenter, double-blind comparison with a placebo. EchoGen Contrast Ultrasound Study Group.

PURPOSE: To evaluate perflenapent emulsion as a contrast agent for ultrasound (US) of the liver, kidneys, and vasculature. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled, multicenter trial of 151 patients was performed. Investigators and blinded readers compared sonograms obtained after intravenous administration of perflenapent emulsion (0.05 mL/kg) and of a placebo with baseline sonograms. RESULTS: Contrast enhancement occurred in 140 of 149 patients (94%) after perflenapent administration and in 12 patients (8%) after placebo administration (P < .001). Enhancement lasted 5.0-15.4 minutes with perflenapent and 0.1-1.7 minutes with the placebo (P < .001). Perflenapent enhanced or facilitated visualization of blood flow, abnormal structures, masses, and lesions in 138 of 147 patients (94%) versus 12 of 147 (8%) for the placebo (P < .001). Improved visualization assisted in the diagnosis in 105 of 143 perflenapent studies (73%) compared with five of 143 placebo studies (3%) (P < .001). Diagnostic information affected case management in 71 of 148 patients (48%) after perflenapent administration and in nine of 148 patients (6%) after placebo administration (P < .001). Adverse effects associated with perflenapent were few and mostly mild, occurred within 30 minutes, and resolved without treatment. CONCLUSION: Perflenapent emulsion is a safe and effective contrast agent for US of the liver, kidneys, and vasculature.

Adult↗

PubMed2005

Meta-analysis of the efficacy of ebastine 20 mg compared to loratadine 10 mg and placebo in the symptomatic treatment of seasonal allergic rhinitis.

BACKGROUND: Few randomized studies have compared the efficacy of ebastine and loratadine in the symptomatic treatment of seasonal allergic rhinitis (SAR). METHODS: A meta-analysis was performed on data from four randomized, double-blind, placebo-controlled, parallel-group clinical trials comparing the efficacy of ebastine 20 mg once daily versus loratadine 10 mg once daily in the symptomatic treatment of SAR symptoms. Primary efficacy variable was the mean change in the overall mean daily reflective total symptom score (TSS), i.e. the sum of five rhinitis symptom scores: nasal discharge, nasal congestion, nasal itching, sneezing and total eye symptoms (itchy/watery eyes) over the first 2 weeks of treatment compared to baseline. RESULTS: There were 2,089 patients in the population analyzed: 749, 739 and 601 patients in the ebastine 20 mg, loratadine 10 mg and placebo groups, respectively. Compared to baseline, overall mean daily reflective TSS over the first 2 weeks of treatment was -3.61 (35.4% reduction from baseline) in the ebastine group, -3.05 (29.0% reduction) in the loratadine group and -2.30 (22.7% reduction) in the placebo group. Statistically significant differences in the mean change from baseline were found when comparing ebastine and loratadine (p<0.001), ebastine and placebo (p<0.0001), and loratadine and placebo (p<0.0001). The global effect (i.e. the difference in overall mean daily reflective TSS over the first 2 weeks of treatment) of ebastine compared with loratadine over the first 2 weeks of treatment was -0.56 (95% confidence interval, CI, -0.86 to -0.26), and it was sustained during the whole (4-week) period studied. The global effects of ebastine and loratadine compared with placebo were -1.30 (95% CI, -1.61 to -0.99) and -0.74 (95% CI, -1.05 to -0.43), respectively. Secondary variables (reflective and snapshot individual symptom scores) showed the same trend. CONCLUSIONS: This meta-analysis confirms that ebastine 20 mg has a good efficacy profile, inducing a greater decrease from baseline in mean rhinitis symptom scores than loratadine 10 mg or placebo.

Adult↗

PubMed1987

Placebo effect and clinical trials in migraine therapy.

Migraine is a cyclical condition in which the cycles may occur or remit in an unpredictable fashion. The goal of prophylactic antimigraine therapy is to induce remission of an active cycle of migraine or to inhibit occurrence of individual headaches until the cycle remits for other reasons. The placebo effect probably takes advantage of these cycles. The placebo effect is significant and quite potent. The placebo effect may be divided into (1) the initial effect and (2) the continuing effect which is seen following a stabilization period. The initial placebo effect is dramatic with 62% of 188 subjects improving by 75% after 4 weeks of placebo. The continuing effect is demonstrated by occurrence of 75% further improvement in 28% of 282 subjects in 7 studies in which comparison of results after 4-12 weeks was made with a placebo stabilization period. The placebo effect is a very potent one and must be taken into account in designing and carrying out studies of migraine therapy.

Clinical Trials as Topic↗

PubMed1999

Both raloxifene and estrogen reduce major cardiovascular risk factors in healthy postmenopausal women: A 2-year, placebo-controlled study.

Currently raloxifene, a selective estrogen receptor modulator, is being investigated as a potential alternative for postmenopausal hormone replacement to prevent osteoporosis and cardiovascular disease. We compared the 2-year effects of raloxifene on a wide range of cardiovascular risk factors with those of placebo and conjugated equine estrogens (CEEs). Analyses were based on 56 hysterectomized but otherwise healthy postmenopausal women aged 54. 8+/-3.5 (mean+/-SD) years who entered this double-blind study and who were randomly assigned to raloxifene hydrochloride 60 mg/d (n=15) or 150 mg/d (n=13), placebo (n=13), or CEEs 0.625 mg/d (n=15). At baseline and after 6, 12, and 24 months of treatment, we assessed serum lipids, blood pressure, glucose metabolism, C-reactive protein, and various hemostatic parameters. Compared with placebo, both raloxifene and CEEs lowered the level of low density lipoprotein cholesterol by 0.53 to 0.79 mmol/L (all P<0.04) and lowered, at 24 months, the level of fibrinogen by 0.71 to 0.86 g/L (all P<0.05). The effects of raloxifene and CEEs did not differ significantly. In contrast to raloxifene, from 6 months on CEEs increased high density lipoprotein cholesterol by 0.25 to 0.29 mmol/L and reduced plasminogen activator inhibitor-1 antigen by 30.6 to 48.6 ng/mL (all P<0.02 versus both placebo and raloxifene). CEEs transiently increased C-reactive protein by 1.0 mg/L at 6 months (P<0.05 versus placebo) and prothrombin-derived fragment F1+2 by 0. 79 nmol/L at 12 months (P<0.001 versus placebo). Finally, from 12 months on, CEEs increased triglycerides by 0.33 to 0.56 mmol/L (all P<0.05 versus both placebo and raloxifene). Our findings suggest that in healthy postmenopausal women, raloxifene and estrogen monotherapy have similar beneficial effects on low density lipoprotein cholesterol and fibrinogen levels. These treatments differ, however, in their effects on high density lipoprotein cholesterol, triglycerides, and plasminogen activator inhibitor-1 and possibly in their effects on prothrombin fragment F1+2 and C-reactive protein.

Biomarkers↗

PubMed1991

Immediate postoperative aspirin improves vein graft patency early and late after coronary artery bypass graft surgery. A placebo-controlled, randomized study.

BACKGROUND: The efficacy of aspirin for prevention of thrombotic graft occlusion after coronary artery bypass grafting (CABG) depends both on the dosage and time window of administration. Early and late graft patency were therefore assessed in a prospective, double-blind, randomized, placebo-controlled trial of aspirin, 324 mg daily, given within 1 hour of CABG. METHODS AND RESULTS: Angiographic graft patency was determined at 1 week (231 patients) and 1 year (219 patients) after CABG. The early vein graft occlusion rate was 1.6% on aspirin and 6.2% on placebo (p = 0.004), and late graft occlusion rate was 5.8% on continued aspirin and 11.6% on placebo (p = 0.01). New graft occlusion between 1 week and 1 year was less common in patients on aspirin than on placebo (4.3% versus 7.4%, p = 0.013). The protective effect of aspirin against occlusion persisted in most subgroups of graft type, graft flow, diameter of recipient artery, location of grafted artery, and endarterectomy. Mean chest tube blood loss for the first 24 hours was 571 ml for the aspirin group and 563 ml for the placebo group. Red cell transfusion requirements were 902 ml in the aspirin group and 934 ml in the placebo group (p = NS). The reoperation rate was 4.8% in the aspirin group and 1% in the placebo group (p = 0.1). CONCLUSIONS: Immediate postoperative administration of aspirin (324 mg) improves early graft patency and, with continued usage, protects against further occlusion up to 1 year after CABG. Postoperative blood loss was similar in the two groups; however, aspirin was associated with a nonsignificant higher rate of reoperation.

Angiography↗

PubMed1997

Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with Integrilin in acute myocardial infarction. Results of a randomized, placebo-controlled, dose-ranging trial. IMPACT-AMI Investigators.

BACKGROUND: Platelet activation and aggregation may be key components of thrombolytic failure to restore and maintain perfusion in acute myocardial infarction. We performed a placebo-controlled, dose-ranging trial of Integrilin, a potent inhibitor of platelet aggregation, with heparin, aspirin, and accelerated alteplase. METHODS AND RESULTS: We assigned 132 patients in a 2:1 ratio to receive a bolus and continuous infusion of one of six Integrilin doses or placebo. Another 48 patients were randomized in a 3:1, double-blind fashion to receive the highest Integrilin dose from the first phase or placebo. All patients received accelerated alteplase, aspirin, and intravenous heparin infusion; all but two groups also received an intravenous heparin bolus. The highest Integrilin dose group from the nonrandomized phase and the randomized patients were pooled for analysis and compared with placebo-treated patients. The primary end point was Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow at 90-minute angiography. Secondary end points were time to ST-segment recovery, an in-hospital composite (death, reinfarction, stroke, revascularization procedures, new heart failure, or pulmonary edema), and bleeding variables. The highest Integrilin dose groups had more complete reperfusion (TIMI grade 3 flow, 66% versus 39% for placebo-treated patients; P = .006) and a shorter median time to ST-segment recovery (65 versus 116 minutes for placebo; P = .05). The groups had similar rates of the composite end point (43% versus 42% for placebo-treated patients) and severe bleeding (4% versus 5%, respectively). CONCLUSIONS: The incidence and speed of reperfusion can be enhanced when a potent inhibitor of the glycoprotein IIb/IIIa integrin receptor, such as Integrilin, is combined with accelerated alteplase, aspirin, and intravenous heparin.

Adult↗