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Biomedical subjects

Isabelle Mahé

Publications and source records attributed to Isabelle Mahé.

25 records · Page 2Linked to original sources

Aspirin alters arterial function in patients with chronic heart failure treated with ACE inhibitors: a dose-mediated deleterious effect.

BACKGROUND: By inhibiting prostaglandin synthesis, aspirin can interfere with both arterial functional and angiotensin-converting enzyme inhibitor (ACEI) properties and be deleterious in chronic heart failure (CHF). AIM: Our aim was to prospectively evaluate the effect of aspirin on arterial functional properties in CHF patients treated with ACEIs. METHODS AND RESULTS: Over three consecutive treatment periods of 7 days, 18 patients received placebo, followed by aspirin 100 mg/day, and then aspirin 325 mg/day. Single blind prospective assessment of reflected wave and time reflection by radial applanation tonometry; pulse wave velocity; blood pressure; thromboxane B2 (TxB2) and prostaglandins in plasma and urine was performed. Aspirin 325 mg/day induced a significant increase in augmentation index of reflected wave (P<0.0001 and P=0.0013 vs. placebo and aspirin 100 mg, respectively) and a significant decrease in reflected wave traveling times (P=0.0007 vs. placebo). Aspirin 100 mg/day produced a similar, though non-significant, trend in these parameters compared with placebo. Both aspirin treatments produced a statistically significant decrease in serum TxB2 (P<0.0001) but did not have an effect on the metabolite of prostaglandin I2 (P=0.136). CONCLUSION: This study demonstrates the existence of a dose-mediated deleterious effect of aspirin upon arterial functional properties in CHF patients treated with ACEI.

Adult↗

Risks versus benefits of NSAIDs including aspirin in myocarditis: a review of the evidence from animal studies.

NSAIDs, including aspirin (acetylsalicylic acid), are frequently used and effective in a broad variety of inflammatory diseases, i.e. rheumatic carditis and pericarditis. Myocarditis may constitute another suitable indication for NSAIDs in order to relieve the symptoms of the presumed viral infection or because pericardial effusion is often associated with this condition. However, concerns have been raised about their indiscriminate use in myocarditis. To clarify this issue, we conducted a systematic review of the literature concerning myocarditis, aspirin and NSAIDs. We examined five animal studies of NSAIDs (indomethacin and ibuprofen) and aspirin in coxsackievirus B3- and B4-induced myocarditis. These studies indicated a deleterious effect of NSAIDs and aspirin in this setting, demonstrating a 2- to 3-fold increase in inflammation, myocytes necrosis and even mortality when compared with placebo. This possible deleterious effect was more predominant when NSAIDs or aspirin were administered during the acute and subacute phases of myocarditis; however, it was still noted when NSAIDs were administered during the late phase of the disease (the effect of aspirin was not evaluated in late phase studies). According to these animal studies, such effect might be attributed to decreased viral clearance (possibly via interferon inhibition) and/or exaggerated cytotoxic response (via interleukin-2 or inhibition of suppressor cells factors) and/or coronary artery spasm. We found one animal study looking at autoimmune myocarditis and it did not demonstrate any beneficial or detrimental effect of aspirin. Moreover, recent data suggest that aspirin and NSAIDs may counteract part of the efficacy of ACE inhibitors and be deleterious in chronic heart failure. Taken together, these studies point to a possible deleterious effect of aspirin and NSAIDs in human myocarditis. In view of these animal studies and in the absence of controlled studies of aspirin or NSAIDs in human myocarditis, we do not recommend indiscriminate treatment with NSAIDs or high-dose aspirin in patients with myocarditis where there is no or minimal associated pericarditis.

Animals↗

Aspirin for the prevention of cardiovascular events in the elderly.

Aspirin (acetylsalicylic acid), the most widely used antiplatelet drug, is clinically effective for the prevention of vascular ischaemic events. Very few primary or secondary prevention trials address the benefit-risk ratio of aspirin in the elderly. In secondary prevention, it is generally accepted that the beneficial effect of aspirin in the general patient population, demonstrated by randomised controlled trials, can be extrapolated to the elderly. Elderly patients are at relatively high risk for the development of vascular disease and might also be expected to derive substantial benefit from regular aspirin administration. However, there is no consensus about the definition of elderly and no specific prospective trial conducted in elderly subjects is available. Retrospective studies in the elderly found that the benefit provided by aspirin in older patients was similar or increased compared with younger individuals. In primary prevention, the potential benefit of antiplatelet agents must be balanced against the risk of bleeding, which is higher in older patients. The risk-benefit trade-off from the use of low-dose aspirin in the elderly is not yet established and caution should be exercised when using aspirin in primary prevention. In conclusion, aspirin should only be given for primary and secondary prevention in the elderly after a comprehensive evaluation of an individual patient's thrombotic and haemorrhagic risk has been conducted.

Aged↗

Defining the role of calcium channel antagonists in heart failure due to systolic dysfunction.

Calcium channel antagonists (CCAs) may either be divided into the dihydropyridines (e.g. amlodipine, felodipine, isradipine, lacidipine, nilvadipine, nifedipine, nicardipine etc.), the phenylalkylamines (e.g. verapamil) and the benzothiazepines (e.g. diltiazem) according to their chemical structure, or into first generation agents (nifedipine, verapamil and diltiazem) and second generation agents (subsequently developed dihydropyridine-derivatives). Second generation CCAs are characterized by greater selectivity for calcium channels in vascular smooth muscle cells than the myocardium, a longer duration of action and a small trough-to-peak variation in plasma concentrations. Heart failure is characterized by decreased cardiac output resulting in inadequate oxygen delivery to peripheral tissues. Although the accompanying neurohormonal activation, leading to vasoconstriction and increased blood pressure, is initially beneficial in increasing tissue perfusion, prolonged activation is detrimental because it increases afterload and further reduces cardiac output. At the level of the myocyte, heart failure is associated with increased intracellular calcium levels which are thought to impair diastolic function. These changes indicate that the CCAs would be beneficial in patients with heart failure. There has been a strong interest and increasing experience in the use of CCAs in patients with heart failure. Despite potential beneficial effects in initial small trials, findings from larger trials suggest that CCA may have detrimental effects upon survival and cardiovascular events. However, this may not necessarily be a 'class b' effect of the CCAs as there is considerable heterogeneity in the chemical structure of individual agents. Clinical experience with different CCAs in patients with heart failure includes trials that evaluated their effects on hemodynamic parameters, exercise tolerance and on symptomatology. However, the most relevant results are those from randomized clinical trials that assessed mortality as the primary endpoint. First generation CCAs have direct negative inotropic effects and even sustained release formulations have not proved any beneficial effect upon survival. With second generation CCAs, some benefit on hemodynamic parameters has been observed but none on survival, alone or in combination with ACE inhibitors. It is noteworthy that although amlodipine had a neutral effect on morbidity and mortality in large, randomized, placebo-controlled trials in patients with heart failure, the drug was well tolerated. There is no specific indication for CCAs (first or second generation) in patients with systolic heart failure, alone or in combination with ACE inhibitors, but amlodipine may be a considered in the management of hypertension or coronary artery disease in patients with heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

Low molecular weight heparin for the prevention of deep venous thrombosis: a suitable monitoring in elderly patients?

Monitoring of anti-Xa activity (aXa) levels is not routinely required in patients receiving enoxaparine at prophylactic dosages, since aXa is supposed to stay below the manufacturer's recommended range in patients treated for venous thrombosis (0.5-1 IU/ml). In order to aXa in elderly subjects receiving prophylactic enoxaparin, 68 consecutive patients (mean age 82.5 +/- 10.7 years) hospitalized in a medical department receiving 4000 IU enoxaparin daily subcutaneously for the prevention of venous thromboembolic disease were studied. After the first injection of enoxaparin, the aXa of 57.4% patients was superior to 0.5 IU/ml while 69.4% had an aXa higher than 0.5 after 8.4 +/- 1.2 days. A negative relationship between aXa and body weight and a trend towards a positive correlation between aXa and age but not with creatinine clearance were noted. Our findings question the opportunity to monitor aXa in elderly patients receiving 4000 IU enoxaparin as antithrombotic prophylaxis.

Age Factors↗

[What are the criteria for evaluation and prevention of venous thromboembolism?].

Venous thromboembolism occurs frequently in both medical and surgical units. Although we possess the therapeutic means to prevent this condition, the question is how to assess the benefit induced by a treatment in relation to the haemorrhagic risk? The primary evaluation criteria and the evaluation method must be correctly chosen. While phlebography is the reference method for diagnosing deep venous thrombosis, the limitations associated with this method have led to the promotion of other diagnostic techniques, and clinical criteria or composite criteria are increasingly used. These different approaches--with their respective advantages and limitations--will be developed.

Hemorrhage↗