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Biomedical subjects

Isabelle Mahé

Publications and source records attributed to Isabelle Mahé.

At least 19 recordsLinked to original sources
PubMed2006

Effects of aspirin and clopidogrel on plasma brain natriuretic peptide in patients with heart failure receiving ACE inhibitors.

BACKGROUND: By inhibiting prostaglandins, aspirin may be deleterious in heart failure (HF) and/or may counteract angiotensin-converting enzyme (ACE) inhibitor efficacy. Conversely, clopidogrel has no effect on prostaglandin metabolism. AIM: To investigate the effect of aspirin and clopidogrel on brain natriuretic peptide (BNP) levels in HF patients treated with ACE inhibitors. METHODS: 36 patients with stable HF (65+/-13 years, 24 males/12 females, NYHA class II to IV, ejection fraction <40%, 13 with coronary disease, all treated with ACE inhibitors) were enrolled in this prospective, double-blind study and randomised to aspirin 325 mg/day or clopidogrel 75 mg/day for 14 days. BNP was determined at day 0 and day 14. RESULTS: 19 patients were randomised to aspirin and 17 to clopidogrel. Baseline characteristics were similar in both groups. BNP levels increased in the aspirin group from day 0 to day 14 (107+/-103 to 144+/-149 pg/ml, p=0.04) whereas clopidogrel had no effect (104+/-107 and 97+/-99 pg/ml respectively, p=0.61). CONCLUSION: This study demonstrates an adverse effect of aspirin 325 mg/day on BNP plasma levels in HF patients treated with ACE inhibitors. In contrast clopidogrel 75 mg/day had no effect.

Aged↗
PubMed2006

Antiarrhythmic drugs for maintaining sinus rhythm after cardioversion of atrial fibrillation: a systematic review of randomized controlled trials.

BACKGROUND: A variety of antiarrhythmic drugs have been used to prevent recurrence of atrial fibrillation after conversion to sinus rhythm. We performed a systematic review to determine the effect of long-term treatment with those drugs on death, embolisms, adverse effects, and atrial fibrillation recurrence. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library (all up to May 2005), and the reference lists of retrieved articles. We included randomized controlled trials that compared any antiarrhythmic against control (placebo or no treatment) or another antiarrhythmic, for more than 6 months. Postoperative atrial fibrillation was excluded. Two evaluators independently reviewed the retrieved studies and extracted all data. Disagreements were resolved by discussion. All results were calculated at 1 year of follow-up. RESULTS: Forty-four trials were included, with a total of 11 322 patients. Several class IA (disopyramide phosphate, quinidine sulfate), class IC (flecainide acetate, propafenone hydrochloride), and class III (amiodarone, dofetilide, sotalol hydrochloride) drugs significantly reduced recurrence of atrial fibrillation (number needed to treat, 2-9), but all increased withdrawals due to adverse effects (number needed to harm [NNH], 9-27) and all but amiodarone and propafenone increased proarrhythmia (NNH, 17-119). Class IA drugs, pooled, were associated with increased mortality compared with controls (Peto odds ratio, 2.39; 95% confidence interval, 1.03-5.59; P = .04; NNH, 109). No other antiarrhythmic showed a significant effect on mortality compared with controls. We could not analyze other outcomes because data were lacking. CONCLUSION: Class IA, IC, and III drugs are effective in maintaining sinus rhythm but increase adverse effects, and class IA drugs may increase mortality.

Anti-Arrhythmia Agents↗
PubMed2006

Comparative effect of aspirin and clopidogrel on arterial function in CHF.

BACKGROUND: By inhibiting prostaglandins, aspirin may be deleterious in congestive heart failure (CHF) and/or partially counteract the efficacy of angiotensin-converting enzyme inhibitors (ACEI). Conversely, clopidogrel has no effect on prostaglandin metabolism. The aim of this study was to prospectively investigate the effect of aspirin and clopidogrel on arterial functional properties in CHF patients treated with ACEI. METHODS: Forty-five patients with stable NYHA class II-IV CHF (64.0+/-15.5 years), ejection fraction <40%, were included in this prospective double-blind study and randomized to receive aspirin 325 mg/day or clopidogrel 75 mg/day for 14 days. Reflected wave assessed by radial applanation tonometry and pulse wave velocity (PWV) were measured at day 0 and day 14. RESULTS: Aspirin resulted in an increase in the augmentation index of the reflected wave (Delta=+3.5+/-5.2%, p=0.005) and the height above the shoulder of the reflected wave (Delta=+1.7+/-3.1 mm Hg, p=0.023), without statistically variation in PWV. Conversely, clopidogrel had no effect on the same parameters (p=0.512, p=0.677 and 0.801, respectively). Overall, variations in the augmentation index of reflected wave significantly differed when compared aspirin with clopidogrel (p=0.0261). CONCLUSION: This study demonstrates the existence of a negative effect of aspirin 325 mg/day when compared to clopidogrel 75 mg/day on arterial functional properties in CHF patients treated with ACEI.

Aged↗
PubMed2006

[Use and monitoring of vitamin K antagonists in everyday medical practice. French results of the international ISAM study of patients with nonvalvular atrial fibrillation].

INTRODUCTION: Bleeding complications of vitamin K antagonist (VKA) therapy are currently the most frequent iatrogenic event in France. OBJECTIVES: The aim of the ISAM study, an international longitudinal observational survey was to evaluate the use of VKA treatment and the quality of laboratory monitoring in everyday medical practice. METHODS: In France, a representative sample of general practitioners and cardiologists selected patients with nonvalvular atrial fibrillation who had been treated with VKA for at least 60 days during the past 12 months. Physicians and patients responded to standardized questionnaires collecting retrospective data for the previous year. RESULTS: Overall, 43 general practitioners and 20 cardiologists recruited 278 patients who completed questionnaires. INR was at least 2 for 264 patients during the study period. During the year preceding inclusion, INR had been within the target range (i.e., between 2.0 and 3.0) 59% of the time and above 3.0 27%. Physicians reported having giving approximately half their patients written recommendations about the VKA dosage regimen, but only 3% supplied a specific VKA information and monitoring booklet. Most patients (65%) reported receiving information on VKA therapy from their general practitioners, although 18% said they had not been informed about their treatment, 44% did not know their target INR, and 66% were unaware that bleeding events were a matter of concern. Finally, 45% of patients reported carrying a card indicating that they were taking VKA. CONCLUSION: Overall, these results show that better education of both physicians and patients could help to improve management, appropriate use and laboratory monitoring of VKA treatment.

Aged↗
PubMed2006

Effect of widely used combinations of antiretroviral therapy on liver CYP3A4 activity in HIV-infected patients.

AIMS: To evaluate the effects of combined antiretroviral drugs (HAART) on liver CYP3A4 activity using the [(14)C-N-methyl]-erythromycin breath test (ERMBT). METHODS: HIV-infected patients (31 women, 30 men) with mean (+/- SD) age of 38 +/- 9 years were enrolled and underwent complete clinical and laboratory evaluation. Patients were divided into five groups and were treated with two nucleoside analogues (NAs) and one of the following: nelfinavir alone (n = 13), any ritonavir-boosted protease inhibitor with (n = 8) or without (n = 13) nevirapine, nevirapine alone (n = 15), or a third NA (n = 12). Three or four ERMBTs were performed 7 days prior to (D-7) and at the beginning of treatment (D0), D14 (only for patients taking nevirapine) and on D28. RESULTS: Mean baseline liver CYP3A4 activity displayed high interindividual variability (47%) but low intraindividual variability (15%). Women had 30% higher ERMBT values than men [2.7 +/- 1.3 vs. 1.9 +/- 0.7; 95% confidence interval (CI) 20.5, 49.5; P = 0.003]. The ERMBT data correlated with body weight, alpha- and beta-globulins and alanin aminotransferases (0.10 < r(s) < 0.20; P < 0.01). Whereas nevirapine had no effect on liver CYP3A4 activity, nelfinavir-based and ritonavir-boosted drug regimens inhibited it by 69% (95% CI 64.7, 72.9; P = 0.005) and by 95% (95% CI 93.3, 96.7; P = 0.001), respectively. CONCLUSION: Evaluation of the effect of HAART on liver CYP3A4 activity may aid in preventing inappropriate treatment regimens in HIV-infected patients.

Adult↗
PubMed2006

Pharmacodynamics of a new ophthalmic mydriatic insert in healthy volunteers: potential alternative as drug delivery system prior to cataract surgery.

Cataract surgery requires a satisfactory degree of mydriasis throughout the entire operation. A phase I, open-labelled, randomised, cross-over trial was conducted in 18 healthy volunteers to compare mydriasis obtained with subsequent administration of phenylephrine 10% and tropicamide 0.5% eyedrops or a new insoluble-matrix retropalpebral ophthalmic insert containing 5.38 mg phenylephrine and 0.28 mg tropicamide. Phenylephrine serum concentrations were measured over 6 hr following each treatment administration. Secondary end-points included cardiovascular, general and local tolerance and quantification of bacterial colonisation of the conjunctiva and the cultured insert, respectively. When normalized to the pupil diameter after conventional treatment, the diameter achieved with the insert was 1.13 (95% confidence interval, 0.94-1.48, P=0.38). Moreover, standard eye drops provided faster effective mydriasis than the insert, starting 30 min. as compared to 90 min. upon treatment administration (P<0.01, repeated-measures ANOVA). Phenylephrine concentrations remained almost undetectable for both treatments and no change in heart rate or blood pressure were observed throughout the study. Only three superficial punctuate keratitis were diagnosed with the insert and two with the eye drops. No significant bacterial contamination of conjunctiva swab and cultured insert was observed. The new insoluble-matrix retropalpebral ophthalmic mydriatic insert produced similar but delayed effective and prolonged mydriasis as compared to the standard delivery system. In addition to its potential usefulness in patients undergoing cataract surgery, such new ophthalmic delivery system may be an advantage in children who need to undergo fundus photography due to the single administration and excellent tolerance as well.

Adolescent↗
PubMed2006

Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study.

BACKGROUND AND OBJECTIVES: Paracetamol (acetaminophen) has occasionally been reported to interact with warfarin. The primary end-point of this study was to investigate whether paracetamol initiation potentiates the anticoagulant effect of warfarin and the mechanism of the interaction. DESIGN AND METHODS: In a double-blind placebo-controlled, randomized, cross-over study, 20 patients on stable oral anticoagulant therapy with warfarin for at least 1 month were randomized to receive placebo or paracetamol 1g four times daily for 14 days. International Normalized Ratio (INR) and clotting factors activities were measured before the first administration and then on days 2, 4, 7, 9, 11,14. RESULTS: Mean INR rose rapidly after the start of paracetamol and was significantly increased within one week of paracetamol intake compared to placebo, p=0.0002. The INR values reached a mean maximum of 3.45+/-0.78 with paracetamol versus 2.66+/-0.73 with placebo (p=0.03), corresponding to a maximum increase from baseline of 1.20+/-0.62 with paracetamol versus 0.37+/-0.48 with placebo (p<0.001). Together with the rise in INR on paracetamol treatment there were significant reductions in the vitamin K-dependent clotting factors II, VII, IX and X. INTERPRETATION AND CONCLUSIONS: The most plausible hypothesis to explain the in vivo interaction is that paracetamol (or its metabolites) interfere with enzymes involved in vitamin K-dependent coagulation factor synthesis. Paracetamol at 4 g daily (a dose higher than that used in clinical practice) potentiates the anticoagulant response produced by warfarin. Clinicians should be aware of this clinically significant and underestimated interaction.

Acetaminophen↗
PubMed2005

Which treatment for patent foramen ovale in cryptogenic stroke?

The management of a patient with a cryptogenic stroke and a patent foramen ovale (PFO) depends on the existence of identifiable causes of stroke, on the PFO characteristics, on the characteristics of the patient, on the contraindications to antithrombotic therapy, and on the preference of the patient. There is no consensus on the management of a patient with a cryptogenic stroke and a PFO, but the algorithm presented in this article seems reasonable to these authors.

Journal Article↗
PubMed2005

Initiation of warfarin therapy in elderly medical inpatients: a safe and accurate regimen.

PURPOSE: Elderly patients are at high risk of over-anticoagulation when treated with warfarin, especially during treatment induction. We developed a simple low-dose regimen for starting warfarin therapy in elderly inpatients. The daily maintenance dosage is predicted from the international normalized ratio (INR) measured the day after the third daily intake of a 4-mg dose. We conducted a prospective multicenter study to evaluate the accuracy and safety of this regimen. METHODS: We studied 106 elderly (age >or=70 years) inpatients (mean [+/- SD] age, 85 +/- 6 years; range, 71 to 97 years) who had a target INR of 2.0 to 3.0. Accuracy in predicting the daily maintenance dose from INR value on day 3 was evaluated. RESULTS: The predicted daily maintenance warfarin dose (3.1 +/- 1.6 mg/d) correlated closely with the actual maintenance dose (3.2 +/- 1.7 mg/d; R(2) = 0.84). The predicted dose was equal to the actual dose in 77 patients (73%; 95% confidence interval [CI]: 64% to 81%) and within 1 mg in 101 patients (95%; 95% CI: 91% to 99%). The mean time needed to achieve a therapeutic INR was 6.7 +/- 3.3 days (median, 6.0 days); the mean time needed to achieve the maintenance dose was 9.2 +/- 4.5 days (median, 7.0 days). None of the patients had an INR >4.0 during this period. One fatal bleeding event was recorded in a patient with an INR in the therapeutic range. CONCLUSION: Our warfarin induction regimen was simple, safe, and accurate in predicting the daily maintenance warfarin dose in elderly hospitalized patients.

Age Factors↗
PubMed2005

Efficacy and safety of three ophthalmic inserts for topical anaesthesia of the cornea. An exploratory comparative dose-ranging, double-blind, randomized trial in healthy volunteers.

BACKGROUND: Cataract surgery requires prolonged anaesthesia, concomitant with permanent hydration and lubrication of the cornea, in order to provide a clear view of the operation area. AIMS: The primary objective of the study was to assess several formulae of a soluble ophthalmic insert: TOPICSERT [bupivacaine (Bupi) + hyaluronic acid (HA) or sodium hyaluronate] in terms of complete and long-lasting anaesthesia of the cornea. The hydration properties of HA were not assessed in this study. METHODS: In a prospective double-blind, cross-over, randomized study, with latin-square allocation of treatments, 16 healthy volunteers received a single dose of each formula (A, 1 mg Bupi and 0.1 mg HA; B, 0.5 mg Bupi and 0.1 mg HA; C, 1 mg Bupi and 0 mg HA, and D acting as a placebo) via the ocular route with 1 week of wash-out between each period. Corneal anaesthesia was measured using a Cochet-Bonnet esthesiometer. RESULTS: There was a statistically significant difference between treatments with regard to the main criterion (complete anaesthesia lasting at least 20 min) when general association statistics were used (Mantel-Haenzel test, P < 0.0001): 68.75% (n = 11) of subjects receiving treatment A, 37.5% (n = 6) receiving treatment B, and 87.5% (n = 14) on treatment C reached complete and satisfactory anaesthesia, while this was not achieved in any of the subjects receiving placebo. Ninety-five percent confidence intervals of the difference between treatments were as follows: treatment A vs. B (-0.03, 0.66), treatment A vs. C (-0.47, 0.10), treatment B vs. C (-0.84, - 0.16). Only the difference between B and C was statistically significant (adjusted probability by the method of Bonferroni, P < 0.001). When complete anaesthesia was reached, mean (+/-SD) duration of anaesthesia was as follows: 20.7 (+/-6.5), 15.3 (+/-11.4) and 24.7 (+/-7.6) min for treatments A, B, C, respectively. CONCLUSIONS: Bupivacaine 1 mg seems to be the efficient and safe dose. The value of hyaluronic acid as a corneal hydration agent and used in association with bupivacaine will be the subject of further studies.

Adjuvants, Immunologic↗
PubMed2004

Management of oral anticoagulant in clinical practice: a retrospective study of 187 patients.

Oral anticoagulant (OA) therapy is widely used in elderly patients because of the increase of indications with age (venous thromboembolism and atrial fibrillation). A particularity of France is to administer three different OAs (warfarin and more often fluindione or acenocoumarol). In an attempt to assess the particularities of managing all three OAs in elderly patients in clinical practice, we studied the modalities of anticoagulation of 187 consecutive OA therapy patients (mean age = 74.4 years) hospitalized in an Internal Medicine department (95 patients on OA at admission and 92 patients initiated on OA during hospitalization). Patients aged 75 years or older more often required a low dosage of OA than those aged younger than 75, irrespective of the OA (warfarin and more often fluindione or acenocoumarol). Ambulatory patients aged 75 years or older were more susceptible to receive acenocoumarol than were ambulatory patients younger than 75 years (respectively 30/67 vs 8/28, respectively), whereas fluindione was prescribed at the same frequency in ambulatory patients and hospitalized patients, regardless of age group (> or =75: 32/67; <75: 19/28). In hospitalized patients with OA induction, fluindione was prescribed as often in patients younger than 75 than in patients aged 75 years or older (40/47 vs 35/45, respectively). On admission, international normalized ratio was in the target range in 26 of the 95 patients (27.4%) and was >3 in 51 of the 95 patients (51.6%). OA therapy was stopped during hospitalization in 35 patients (36.8%). In conclusion, we have a picture of the practice of anticoagulation with three different OA therapies. Although it is usually recommended to prescribe long half-time OA therapy (2), it appears that short half-time therapy such as acenocoumarol still represents an important number of OA prescriptions in France, especially in ambulatory and elderly patients. International normalized ratio is not in the target range as often as expected in clinical practice, and elderly patients require specific modalities of OA therapy management, such as half dose initiation, use of long-half-life OA, and close monitoring.

Administration, Oral↗
PubMed2004

Effect of renal function on the pharmacokinetics of enoxaparin and consequences on dose adjustment.

The use of weight-adjusted enoxaparin dosage in patients with renal failure results in increased bleeding complications. The authors investigated the impact of patient-related factors such as renal function on the pharmacokinetics of enoxaparin. Anti-Xa activity was measured in the blood of 60 patients (74 +/- 10 years, body weight 72 +/- 15 kg, men 60%, creatinine clearance 56 +/- 24 mL/min) with acute coronary syndromes receiving subcutaneous administration of enoxaparin. A population-based approach with limited sampling strategy was used. A 1-compartment model with first-order absorption and elimination best fitted the data. The mean clearance (CL/F) and distribution volume (V/F) were 0.72 L/h and 6.65 L, respectively. V/F was influenced by body weight. CL/F was mainly related to the renal function, decreasing with increasing levels of serum creatinine, and lower in women than in men. The elimination half-life was thus estimated to be 6.4 and 9.2 hours in male and female patients, respectively. The final covariate submodel was then: [Equation included in full-text article]. Maximal anti-Xa activity was predicted to rise above 1.5 IU/mL in case of mild elevation of serum creatinine according to gender and body weight. Renal function is the main factor affecting enoxaparin pharmacokinetics. In patients with decreased renal function, enoxaparin dose should be adjusted on the basis of body weight, serum creatinine, and gender to reach a target anticoagulation level assessed by maximal anti-Xa activity in steady-state conditions.

Acute Disease↗
PubMed2004

D-dimer can predict survival in patients with chronic atrial fibrillation.

High mean levels of D-dimers (DD), markers of fibrin product and degradation, have been reported in patients with atrial fibrillation. In order to determine the predictive value of DD, 125 consecutive patients (mean age, 78 years) with chronic atrial fibrillation without acute disease were prospectively included. DD were quantified by Liatest at inclusion. Patients were followed for a mean duration of 2 years. DD and age at inclusion were significantly higher in patients who would die (n = 54) than in those who would not (n = 65). After multiple analysis of variance, age was not significantly related to prognosis (P = 0.36); low DD (P = 0.03) and oral anticoagulant therapy (P = 0.0192) were independently related to survival. In conclusion, a single determination of DD can strongly predict survival over the following 2 years. It may contribute to the risk stratification and perhaps to the choice of the antithrombotic therapy in high-risk patients with elevated DD.

Age Factors↗
PubMed2004

Does paracetamol potentiate the effects of oral anticoagulants?: a literature review.

Paracetamol (acetaminophen) is the analgesic and antipyretic therapy of choice for patients receiving oral anticoagulation. It is widely used by patients in both prescription and over-the-counter products, resulting in frequent co-prescription with oral anticoagulants, especially in elderly patients. Indeed, older patients are the most likely to receive this combination of drugs because indications for both oral anticoagulation and analgesic therapy increase with age. For many years reports have presented evidence both for and against the idea that paracetamol may potentiate the anticoagulant effect of oral anticoagulants, thus increasing haemorrhagic risk in patients receiving this combination of drugs. This issue has continued to be a matter of debate in recent publications. No clear practical conclusion can be drawn from the studies because of methodological bias and the lack of clinical relevance. No prospective, randomised study assessing the effect of paracetamol on the anticoagulant effect of oral anticoagulants as used in clinical practice (i.e. the types of patients and dosages used in clinical practice) are available in the literature. The implications are considerable since on the one hand, the ingestion of paracetamol may be a cause of altered anticoagulation in patients who regularly take oral anticoagulation and who may have a haemorrhagic risk factor; and on the other hand, paracetamol might be the analgesic drug of choice that can be used without the need for any restrictions in patients receiving oral anticoagulant drugs. A comprehensive search of Medline and EMBASE for studies and case reports from 1966-2002 was performed in order to review the available literature on the interaction between paracetamol and oral anticoagulant drugs. In conclusion, the potential interaction between oral anticoagulant drugs and paracetamol is an important unanswered question, due to the growing incidence of the concomitant use of these drugs and the possible bleeding implications. The association between paracetamol and the occurrence of excessive INR values remains controversial due to lack of prospective clinical studies assessing the effect of the prescription of paracetamol in patients receiving long-term oral anticoagulation in clinical conditions. Such a study is currently ongoing.

Acetaminophen↗
PubMed2003

Reduced thrombus cohesion in an ex vivo human model of arterial thrombosis induced by clopidogrel treatment: kinetics of the effect and influence of single and double loading-dose regimens.

OBJECTIVE: To compare the effects of clopidogrel on ex vivo thrombogenesis with those on ADP-dependent platelet aggregation, and to compare single and double loading-dose regimens. METHODS AND RESULTS: Step 1: Volunteers (n=12) received clopidogrel 75 mg/day for 8 days. ADP-induced platelet aggregation was measured in platelet-rich plasma (PRP). Thrombogenesis was measured in an ex vivo model. Clopidogrel produced rapid platelet inhibition, increasing up to day 5. Maximal intensity of platelet aggregation correlated with density of platelet thrombus, surface of collagen covered by platelets and thrombus cross-sectional surface (p<0.001). Step 2: On day 1, volunteers (n=60) randomly received clopidogrel 75 mg, a single 300-mg loading dose or two 300-mg loading doses separated by a 12-h interval. On day 2, all volunteers received clopidogrel 75 mg. Both loading dose regimens enhanced platelet inhibition at all time points (p<0.03 vs. clopidogrel 75 mg). After 3 h, the antiplatelet effect of a loading dose was substantial, and the mean decrease in dense thrombus surface was greater in the loading-dose groups than in the 75 mg group (p=0.041 for the single loading dose). Ex vivo, there were no significant differences between loading-dose groups. CONCLUSIONS: Clopidogrel reduces arterial thrombus cohesion by an effect that correlates with inhibition of ADP-induced platelet aggregation. A single 300-mg loading dose provides a rapid onset of such an antithrombotic effect, which was more significant at 24 h with the double loading dose.

Adult↗