[Are there any differences in the cardiovascular tolerance between classical NSAIDs and coxibs?]. / Y a-t-il des différences de tolérance cardiovasculaire entre AINS classiques et coxibs?

Three placebo-controlled studies have demonstrated deleterious cardiovascular (CV) effects of rofecoxib, celecoxib, and pare/valdecoxib. It remains to be determined whether this CV toxicity is specific to coxibs, or shared with all non-steroidal anti-inflammatory drugs (NSAIDs). Seven meta-analyses show that, in comparison with non-specific NSAIDs, the risk of thrombotic CV accident is increased with rofecoxib and celecoxib, but not with valdecoxib or lumiracoxib. Concerning the risk of thrombotic CV accident, seven of the ten observational studies which have evaluated the risk have found an increased risk for the non-specific NSAIDs in comparison with non-exposed subjects. The seven observational studies, which evaluated the risk of coxibs, have all found an increased risk with rofecoxib, and two with celecoxib. Three studies out of six have shown on increase of risk with rofecoxib and one study out of five with celecoxib. Two of the three studies, which have compared rofecoxib with celecoxib, have found on increased risk with rofecoxib. Concerning the risk of arterial hypertension, aedemas or congestive cardiac insufficiency, a meta-analysis and a randomised trial have shown a deleterious effect of rofecoxib in comparison with celecoxib and non-specific NSAIDs. Two studies have shown a deleterious effect of the non-selective NSAIDs and three a deleterious effect of rofecoxib in comparison with non-exposed subjects. Three studies have demonstrated a deleterious effect of rofecoxib in comparison with non-specific NSAIDs. No study has shown any deleterious effect of celecoxib in comparison with subjects non-exposed or exposed to non-specific NSAIDs. These studies suggest that all the NSAIDs, specific or not, increase the CV and renal risk. This risk seems variable from a compound to another one and must be evaluated, for each patient, according to the susceptibility and associated risk factors. While waiting for other long-term controlled studies, the available data show the existence of a risk of CV secondary effect linked to the class of NSAIDs, specific (coxibs) or not.

[How to watch over a patient treated with a NSAID in relation to the cardiovascular and renal risk?]. / Comment surveiller un patient traité par AINS en ce qui concerne le risque cardiovasculaire et rénal?

Despite the cardiovascular risk attributable to the NSAIDs, these drugs are among the most prescribed treatments in the world. Recently to manage this risk during chronic inflammatory rheumatisms a surveillance plan has been developed based on a decision algorithm. Given that the arterial thrombotic risks (myocardial or cerebral) are observed essentially during long-term treatments, two types of situation have been envisaged, short-term treatments and long-term treatments. Before any short-term NSAID prescription (less than one month), the cardio-renal risk should be evaluated. A pre-therapeutic check-up should include the search for risk factors and the treatment surveillance should imply a clinical and biological check-up carried out after 2 to 3 weeks of treatment. Before any long-term NSAID prescription (more than one month), the arterial thrombotic risk (cardiac or cerebral) should be evaluated and the patient's history determined. Pre-therapeutic check-up and surveillance should be carried out and reconsidered at least every three months. In the case of high risk the advice of a cardiologist or a nephrologist should be obtained and drastic therapeutic measures taken. There are cases where the prescription of NSAIDs or coxibs is possibly not recommended.

[Which information should be given to the patient concerning the cardiovascular and renal risk of the NSAIDs?]. / Quelles informations délivrer au patient sur le risque cardiovasculaire et rénal des AINS?

OBJECTIVE: Patient information is a topical subject. The aim of this review is to present the rare studies concerning the degree of patient information on the cardiovascular and renal risks of the non-steroidal anti-inflammatory drugs and to suggest some recommendations on this subject. METHODOLOGY: After analysis of the literature (Medline search - January 2006), a series of recommendations has been drown up following discussion among experts from different specialties (clinical epidemiology rheumatology cardiology nephrology gastroenterology). RECOMMENDATIONS: It appears necessary to warn all patients of the potential risk of hyperkolemia, renal insufficiency and/or hydrosodium retention (decompensation of an arterial hypertension or a cardiac insufficiency), especially subjects who present risk factors such as age over 75 years, a dehydration, a pre-existing renal disorder etc. Concerning the risk of arterial thrombotic incident (coronary or cerebral), it is important to indicate that this risk is rare and seems to be observed particularly during prolonged treatments and at high dose.

[Are there any differences in the cardiovascular tolerance between classical NSAIDs and coxibs?]. / Y a-t-il des différences de tolérance cardiovasculaire entre AINS classiques et coxibs?

Three placebo-controlled studies have demonstrated deleterious cardiovascular (CV) effects of rofecoxib, celecoxib, and pare/valdecoxib. It remains to be determined whether this CV toxicity is specific to coxibs, or shared with all non-steroidal anti-inflammatory drugs (NSAID). Seven meta-analyses show that, in comparison with non-specific NSAIDs, the risk of thrombotic CV accident is increased with rofecoxib and celecoxib, but not with valdecoxib or lumiracoxib. Concerning the risk of thrombotic CV accident, seven of the ten observational studies which have evaluated the risk, have found an increased risk for the non-specific NSAID in comparison with non-exposed subjects,. The seven observational studies, which evaluated the risk of coxibs, have all found an increased risk with rofecoxib, and two with celecoxib. Three studies out of six have shown an increase of risk with rofecoxib and one study out of five with celecoxib. Two of the three studies, which have compared rofecoxib with celecoxib, have found an increased risk with rofecoxib. Concerning the risk of arterial hypertension, oedemas or congestive cardiac insufficiency, a meta-analysis and a randomised trial have shown a deleterious effect of rofecoxib in comparison with celecoxib and non-specific NSAID. Two studies have shown a deleterious effect of the non-selective NSAID and three a deleterious effect of rofecoxib in comparison with non-exposed subjects. Three studies have demonstrated a deleterious effect of rofecoxib in comparison with non-specific NSAID. No study has shown any deleterious effect of celecoxib in comparison with subjects non-exposed or exposed to non-specific NSAID. These studies suggest that all the NSAID, specific or not, increase the CV and renal risk. This risk seems variable from a compound to another one and must be evaluated, for each patient, according to the susceptibility and associated risk factors. While waiting for other long-term controlled studies, the available data show the existence of a risk of CV secondary effect linked to the class of NSAID, specific (coxibs) or not.

[How to watch over a patient treated with a NSAID in relation to the cardiovascular and renal risk?]. / Comment surveiller un patient traité par AINS en ce qui concerne le risque cardiovasculaire et rénal?

Despite the cardiovascular risk attributable to the NSAIDs, these drugs are among the most prescribed treatments in the world. Recently to manage this risk during chronic inflammatory rheumatisms a surveillance plan has been developed based on a decision algorithm. Given that the arterial thrombotic risks (myocardial or cerebral) are observed essentially during long-term treatments, two types of situation have been envisaged, short-term treatments and long-term treatments. Before any short-term NSAID prescription (less than one month), the cardio-renal risk should be evaluated. A pre-therapeutic check-up should include the search for risk factors and the treatment surveillance should imply a clinical and biological check-up carried out after 2 to 3 weeks of treatment. Before any long-term NSAID prescription (more than one month), the arterial thrombotic risk (cardiac or cerebral) should be evaluated and the patient's history determined. Pre-therapeutic check-up and surveillance should be carried out and reconsidered at least every three months. In the case of high risk, the advice of a cardiologist should be obtained and drastic therapeutic measures taken. There are cases where the prescription of NSAIDs or coxibs is possibly not recommended.

[Which information should be given to the patient concerning the cardiovascular and renal risk of the NSAIDs?]. / Quelles informations délivrer au patient sur le risque cardiovasculaire et rénal des AINS?

OBJECTIVE: Patient information is a topical subject. The aim of this review is to present the rare studies concerning the degree of patient information on the cardiovascular and renal risks of the non-steroidal anti-inflammatory drugs and to suggest some recommendations on this subject. METHODOLOGY: After analysis of the literature (Medline search - January 2006), a series of recommendations has been drawn up following discussion among experts from different specialties (clinical epidemiology, rheumatology, cardiology, nephrology, gastroenterology). RECOMMENDATIONS: It appears necessary to warn all patients of the potential risk of hyperkalemia, renal insufficiency and/or hydrosodium retention (decompensation of an arterial hypertension or a cardiac insufficiency), especially subjects who present risk factors such as age over 75 years, a dehydration, a pre-existing renal disorder, etc. Concerning the risk of arterial thrombotic incident (coronary or cerebral), it is important to indicate that this risk is rare and seems to be observed particularly during prolonged treatments and at high dose.

Aggregates of endothelial microparticles and platelets circulate in peripheral blood. Variations during stable coronary disease and acute myocardial infarction.

INTRODUCTION: Activated endothelial cells on the surface of atherosclerotic plaques can shed membrane microparticles (MPs) with procoagulant potential. We have investigated whether circulating endothelial MPs could bind platelets, form aggregates, and be involved in thrombus formation during acute myocardial infarction (AMI). PATIENTS/METHODS AND RESULTS: We first assessed the in vitro formation of aggregates comprising endothelial MPs and platelets by incubating supernatants of activated endothelial cells in culture with freshly isolated platelets. Endothelial MP-platelets (EMP-P) aggregates were characterized by flow cytometry using antibodies to specific markers of endothelial cells and of platelets. Identical EMP-P aggregates were detected in vivo in the peripheral blood of healthy individuals, of patients with stable coronary disease (SCD), and of patients with AMI. The levels of EMP-P aggregates were significantly higher in patients with SCD than in controls (16.7+/-1.8/microl versus 7.1+/-0.3/microl, P<0.0002). In contrast, the levels of EMP-P aggregates in the first hours of AMI were significantly lower than in controls and in SCD, both before primary angioplasty (2.5+/-0.7/microl) and 2 h after reperfusion (1.7+/-0.3 microl) (P<0.0001 versus healthy controls and versus SCD). However, 48 h after the onset of AMI, the levels of EMP-P aggregates (14.7+/-1.8/microl) had returned to values close to those observed in SCD. CONCLUSIONS: Endothelial MPs can bind to platelets and form aggregates. The enumeration of those aggregates in peripheral blood shows significant differences between the various groups of patients tested. This new test can help in the evaluation of the level of endothelial cell activation and the damages created by chronic atherosclerosis.

Different effects of mibefradil and amlodipine on coronary vessels and during beta-adrenergic stimulation in conscious dogs.

Coronary effects of Ca -channel blockers mibefradil and amlodipine were compared in conscious dogs. Ten dogs were instrumented for measurement of aortic and left ventricular pressures, circumflex coronary blood flow velocity (CBFv), and coronary diameter (CD). A permanent catheter was implanted in the circumflex coronary artery. At doses having no systemic effects (7.5-150 micro g/kg), mibefradil and amlodipine increased CBFv and CD dose dependently. At the same dose, mibefradil increased less CBFv than amlodipine. However, for a similar increase in CBFv induced by amlodipine, mibefradil increased CD more. BAY K8644, an L-type Ca -channel agonist, prevented the CBFv and CD responses to amlodipine, but minimally affected the coronary responses to mibefradil. Intracoronary isoproterenol (6 ng/kg) increased LV dP/dt max, CBFv, and CD. Amlodipine markedly altered these responses, while mibefradil did not affect LV inotropic response and slightly altered CBFv response to isoproterenol. Thus, in conscious dogs, both mibefradil and amlodipine exert coronary vasodilation, with different patterns on coronary conductance and resistance vessels and during beta-adrenergic stimulation. These differences could be related to their actions on different Ca channels.

Reduced coronary vasodilator responses to amlodipine in pacing-induced heart failure in conscious dogs: role of nitric oxide.

1. This study examined whether NO is involved in the in-vivo coronary vasodilator effects of amlodipine (a calcium channel blocker) and whether heart failure (HF) alters the coronary responses to amlodipine. 2. Nine conscious dogs were chronically instrumented to measure circumflex coronary blood flow (CBF) and coronary diameter (CD). Drugs were administered directly into the circumflex artery through an indwelling catheter to avoid systemic changes. HF was induced by right ventricular pacing (240 b.p.m., 3 weeks). 3. Compared with control (C), in HF, coronary responses to acetylcholine (1 - 10 ng kg(-1)) were reduced while responses to nitroglycerin (0.1 - 0.5 microg kg(-1)) were unchanged. In C, amlodipine (30 - 150 microg kg(-1)), increased dose-dependently CBF and CD. After LNA (a NO synthase inhibitor, 2 mg kg(-1)), amlodipine produced less increases in CBF and CD (+121+/-26 ml min(-1) and +76+/-35 microm versus +196+/-40 ml min(-1) and +153+/-39 microm respectively for 150 microg kg(-1) amlodipine alone, both P<0.05). In HF, the coronary responses to amlodipine were reduced (150 microg kg(-1) of amlodipine increased CBF and CD +121+/-23 ml min(-1) and +77+/-21 microm respectively, both P<0.05). After LNA, the CBF responses to amlodipine tended to be reduced (+94+/-19 ml min(-1) at 150 microg kg(-1)) but CD responses were significantly reduced (+41+/-16 microm, P<0.05). The supplementation with L-arginine did not enhance the coronary responses to amlodipine. 4. These results indicate that, in conscious dogs, NO participates in the coronary responses to amlodipine and in HF, the coronary responses to amlodipine are reduced, which is related to a reduced NO production.