[Compared with atorvastatin at the dose of 10 mg per day rosuvastatin was more effective to reach an LDL goal of < 1.00 g/l in high cardiovascular risk patients (ARIANE study)]. / A la dose identique de 10 mg/j, la rosuvastatine est plus efficace que l'atorvastatine pour atteindre l'objectif de LDL-cholestérol < 1,00 g/l chez les patients à haut risque cardiovasculaire (étude ARIANE).

Many patients at high cardiovascular risk still fail to achieve recommended LDL-C goals. Showing evidence of a difference between two statins at the same dose can significantly contribute to selecting the most appropriate strategy to reduce cardiovascular risk in these patients. ARIANE study was a randomized, open-label comparative study. 844 patients at high cardiovascular risk were recruited by primary care cardiologists in France. They were randomized to receive once-daily dose of 10 mg of rosuvastatin or atorvastatin. The primary objective of this study was to compare the efficacy of rosuvastatin with that of atorvastatin in achieving an LDL-C goal of < 1.00 g/1 at 12 weeks. High cardiovascular risk was defined by either history of cardiovascular event, or a type IIa or IIb dyslipidemia associated with more than 2 other cardiovascular risk factors or 2 risk factors and a 10-year coronary risk > 20% based on Framingham score. 790 patients were available for intention-to-treat analysis. At 12 weeks, LDL-C goal was reached by 211 of the 411 patients treated with rosuvastatin (51.3%) and 119 of 379 patients treated with atorvastatin (31.4%), the difference being statistically significant (p < 0.0001). Both treatments were well tolerated. Adverse events were equally observed in the 2 groups, one patient in the rosuvastatin group showed a CK elevation without clinical consequence. The risk profile for the patients in this study matched that which, in 2005, had led to the Afssaps lowering the LDL-C target below 1.00g/l. The doses of the two statins compared here correspond to the doses most commonly used in day-to-day clinical practice. The greater efficacy of rosuvastatin versus atorvastatin at the same dose demonstrated here confirms previous data. Therefore, in high risk patients treated by primary care cardiologists, rosuvastatin allows a significantly greater proportion to reach the LDL-C goal of < 1.00 g/l compared to atorvastatin at the same dose. However, many patients remain not at goal.

[Treatment with statins in general medicine: dosage and effectiveness. Results of the observational study STATIMED]. / Traitements par statines en médecine générale: posologie et atteinte des objectifs. Résultats de l'observatoire STATIMED.

Using a retrospective study in general medicine, we observed the rates of achieving targets for LDL-cholesterol as recommended by the French Agency for the Safety of Health care Products (AFSSAPS) in 2000, according to the types of statin prescribed and the dosages used. Out of 64 961 individuals treated with a statin between 31 July 2001 and 1 August 2002, we identified 22 065 patients treated with monotherapy, having had an LDL-cholesterol level performed at least 6 weeks after starting treatment or after changing statin or dosage, and no longer than 6 months before the start of our study in the other cases. In primary prevention, 81.9% of patients attained their objectives. The success rates became less impressive with increasing levels of cardiovascular risk: 95.6%, 86.9%, 72.0% and 56.3% for 0, 1, 2 and 3 or more risk factors respectively (p < 0.0001). For secondary prevention, the targets were only met for 62.8% of patients. In total, only 77.8% of the entire sample met their targets. For each type of statin, higher doses were used for patients with higher cardiovascular risk, but the percentage of patients reaching their LDL-cholesterol targets diminished. In conclusion, under the current conditions of managing lipid risk, the LDL-cholesterol targets are not sufficiently met. Extrapolating from the data obtained in this study, about 300 000 patients in France require better management than recommended in the 2000 AFSSAPS guidelines.

[Aspects of acute renal failure during cardiovascular investigations and procedures which require the administration of iodine contrast medium. Literature review]. / Facteurs d'insuffisance rénale aiguë au cours des explorations et interventions cardiovasculaires nécessitant l'administration d'un produit de contraste iodé.

The increase in the number of diagnostic and interventional procedures in cardiovascular pathology brings with it more and more frequently the risk of impaired renal function due to the use of iodine contrast media. As these are often older patients with many cardiovascular risk factors, this risk is confounded by the general risk associated with these procedures. The evaluation of acutely impaired renal function in clinical practice is difficult because it essentially relies on the measurement of plasma creatinine or the calculation of its clearance, which are not perfect indicators and are also susceptible to errors of interpretation. The evaluation of the prognostic value of plasma creatinine variations is difficult because of the disparity of indications, procedures and patients. In all the available studies, and even accounting for their imperfections, this deterioration in renal function, even if transient, nevertheless seems to represent an important prognostic factor during the procedures and in the months that follow. Due to these restrictions, the evaluation of preventive measures for renal damage during diagnostic and interventional procedures is very imprecise, particularly as to the choice of contrast medium and the systematic use of certain pharmacological agents. Hydration, which would seem to be the easiest and most certain precaution, is not necessarily applicable in all cases, especially when left ventricular function is impaired.

[The best of clinical pharmacology in 2002]. / L'essentiel de 2002 en pharmacologie clinique et thérapeutique.

The results of several large therapeutic cardiovascular trials were reported in 2002. The LIFE study concluded that losartan is superior compared to atenolol in terms of prevention of cardiovascular morbidity and mortality, the benefit being for CVA without changing the incidence of myocardial infarction. The OPTIMAAL study stated the disappointing results of post-infarct losartan. The IONA study represents a first demonstration with nicorandil of benefit not only in angina crises but equally on cardiac morbidity and mortality. The HPS study confirms the benefit of a statin in secondary prevention but for the first time, no matter what the initial level of LDL-cholesterol. Finally in the LIPS study, it is reported that statins reduce major cardiovascular events after coronary angioplasty. The year 2002 was marked elsewhere by imagination after the publication of the RAVEL study on coated stents delivering anti-proliferative drugs in order to avoid coronary restenosis. Three drugs were the subject of work confirming their potential significance in cardiovascular pathology: a) ezetimibe, representing a new class of cholesterol lowering drugs with which the association with statins seems especially synergic, b) nesiritide recombinant type B natriuretic peptide, whose significance was confirmed in acute cardiac insufficiency. c) levosimendan (calcium sensitisor) which moreover can be a significant treatment in cardiac decompensation as suggested by the LIDO study with a follow up of 180 days. By contrast, omapatrilate did not confirm its potential superiority over ACE inhibitors in the treatment of cardiac insufficiency. Some encouraging data were reported in 2002 in the field of therapeutic angiogenesis as much at the myocardial level as in lower limb arteritis. Finally, 2002 was marked by the publication of the WHI study which intensified suspicions regarding hormonal substitution treatment, confirming the advantage of not only secondary but perhaps primary cardiovascular prevention.

[The best of 2001. Clinical pharmacology]. / L'essentiel de 2001 en pharmacologie clinique.

In the field of cardiovascular pharmacology the year 2001 has been marked by the demonstration of the clinical significance of new anti-thrombotics and by the interesting results with anti-endothelins. Whereas the failure of oral antiGPIIb-IIIa has been confirmed, melagatran (an anti-thrombin administered orally) and pentasaccharide (a new subcutaneous anti-Xa) have proved their efficacy in the prevention of venous thromboembolic disease compared to low molecular weight heparins, with an acceptable incidence of unwanted effects. Anti-endothelins under development have variable mechanisms of action from one drug to another. Their efficacy in cardiac insufficiency, pulmonary artery hypertension and arterial hypertension is suggested by clinical studies investigating small population; a more important study in decompensated cardiac insufficiency has not however shown a reduction of the morbidity and mortality with one of these drugs. The clinical significance of angiotensin II receptor antagonists has been confirmed for the indications which they share with ACE inhibitors (cardiac insufficiency, prevention of diabetic nephropathy). However, there are not enough comparative trials for these indications between these two classes in order to draw conclusions about the equivalence or superiority of one or the other. Of help elsewhere has been a re-interpretation of the mode of action of arterial wall drugs, and the inflammatory theory of atherosclerosis, putting the accent for example on the reduction of C reactive protein with a statin, or on the anti-inflammatory effect of aspirin. However, one study has not shown any benefit in giving a short course of corticosteroids in unstable angina. A very prominent event in the year 2001 remains the withdrawal of cerivstatin due to fatal rhabdomyolysis. The consequences go far beyond this drug, as its withdrawal justifies a fresh examination of the risk-benefit ratio for all the statins, with the probable corollary of a halt in the escalation of prescriptions. In this context, the new ezetimibe-type cholesterol absorption inhibitors could be a future solution.

[The best in 2000 on clinical pharmacology]. / L'essentiel de 2000 en pharmacologie clinique.

The year 2000 provided many new articles in clinical pharmacology and therapeutics in the different fields of cardiology. The authors present some of them in this review. In the field of prevention, the statins were the object of complementary studies showing their value in high cardiovascular risk patients with benefits not only in the reduction of coronary but also cerebrovascular events. These benefits are maintained at long-term. The debate about the value of Vitamin E is still on-going with divergent results (HOPE, SPACE studies...). The absence of secondary coronary prevention by post-menopausal hormone replacement therapy seems to be confirmed. The arrhythmogenic risk of neuroleptic drugs is of increasing concern. New data also suggests the possibility of a venous thromboembolic risk. The NSAIDs are an important factor in the first episode of cardiac failure. The risk of thromboembolism with the 3rd generation of contraceptives has been confirmed. Some data has been published about the safety of drugs used in cardiology: the haemorrhagic risk of LMW heparin in renal failure and of aspirin, even at low doses, drug interactions, aspirin-ACE inhibitors interaction. Future perspectives include the potential value of vasopeptidase inhibitors, of cerebral natriuretic peptide and of therapeutic approaches to induce angiogenesis in ischaemic heart disease (gene therapy, recombining factors).

[The best of coronary artery disease in 1999]. / L'essentiel de 1999 dans la maladie coronaire.

Despite the (modest) regression observed in the MONICA study, coronary artery disease remains the leading cause of mortality in industrialised countries and it is worryingly progressive in emerging countries. Therapeutic progress has been considerable but only a small number of coronary patients benefit from it. The techniques are costly and justify efforts to improve selection of high risk patients. The results of the VA-HIT study, which demonstrated the importance of HDL cholesterol level in prevention, now raise the question of the optimal treatment of these patients and that of the association of fibrates and statins. The value of ACE inhibitors in the HOPE study in coronary artery disease was outstanding. In parallel, the efficacy of Mediterranean diet has been confirmed in secondary prevention as that of supplements of omega-3 fatty acids in the GISSI-Prevenzione study. When reference anti-anginal agents are ineffective in the most resistant forms of coronary artery disease, other classes of drugs have been shown to be effective in association. Finally, the theory of inflammation and infection of atherosclerosis has found new indirect arguments, whereas angiogenesis and vasculogenesis have been confirmed as the main leaders in the future treatment of coronary artery disease.

[Electron microscopic comparison of the antithrombotic potential of 2 low osmolality iodine contrast media in percutaneous transluminal coronary angioplasty]. / Comparison en microscopie électronique du potentiel antithrombogène de deux produits de contraste iodés de basse osmolalité au cours de l'angioplastie coronaire transluminale percutanée.

The antithrombogenic potentials of two low osmolality iodine contrast media, ioxaglate (Iox), an ionic product, and iopamidol (Iop), a non-ionic product, were compared in a multicentre, randomised, double-blind study in 64 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) by scanning electron microscopy for the presence of thrombotic material on the guiding catheter (GC) and guide wires (GW). The procedure was strictly standardised: stable angina, type A coronary lesions; aspirin administration (at least 300 mg the day before and on the day of angioplasty); heparinisation (10000 IU at the beginning of the procedure); same GCs (Marathon Baxter 8F), same GWs (Veriflex USCI 0.014). The tips of the catheters and guide wires were scanned by an electronic microscope in a double-blind protocol. The scores for the number of erythrocytes (RBCs), platelets (PLs) and constituted thrombi (THi) were; thickness scored from 0 to 3, the % surface covered and an index of volume combining these two parameters. The clinical and angiographic characteristics of the 2 groups were strictly comparable. The time that the GCs and GWs were in the circulation were 30.0 +/- 2.3 vs 32.6 +/- 3.0 minutes for the former, and 18.6 +/- 1.8 vs 17.1 +/- 1.4 minutes for the later in the Iox and Iop groups, respectively (NS). An angiographic filling defect was not observed in any of the patients in the Iox group and in 4 patients (13%) in the Iop group (NS). The number of thrombotic elements observed on the GCs (RBCs, PLs, THi) was negligible in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acceptability and efficacy of two associations of paracetamol with a central analgesic (dextropropoxyphene or codeine): comparison in osteoarthritis.

A double-blind randomized parallel group trial was undertaken to compare the acceptability and efficacy of 2 forms of analgesic treatment, DI-Antalvic (Houde Laboratories, Puteaux, France) (30 mg dextropropoxyphene and 400 mg paracetamol per capsule) and Efferalgan-Codeine (UPSA Laboratories, Rueil Malmaison, France) (30 mg codeine and 500 mg paracetamol per tablet) prescribed for 1 week at doses of 6 capsules/day and 6 tablets/day, respectively, in 141 outpatients with active osteoarthritis of the knee or hip. The principal aim of the trial was concerned with acceptability, with efficacy as its secondary aim. The principal trial criterion was defined as overall assessment of acceptability by the patient at the end of the trial (success or failure) or by treatment dropouts because of an adverse effect (failure). Comparability of the groups was confirmed before any treatment regarding the physical characteristics of the patients, characteristics of osteoarthritis, and the initial level of pain and functional consequences of pain. Results show that the analgesic efficacy of the treatment was similar, but that the acceptability of Efferalgan-Codeine was significantly worse than that of DI-Antalvic: 53% failure with Efferalgan-Codeine versus 29% failure with DI-Antalvic (P = .005). Other trials of the same type would seem necessary (comparison of lower doses, other types of pain) before being able to generally extrapolate such findings.

Safety and efficacy of once-daily carvedilol vs twice-daily labetalol in mild to moderate hypertension.

A multicenter, randomized, double-blind, parallel-group trial of 8 weeks' duration was designed to compare the efficacy and safety of once-daily carvedilol with that of twice-daily labetalol in patients with essential hypertension. A total of 61 patients (13 women and 48 men) aged 26-64 years (mean +/- SEM = 49.6 +/- 1.3 years) were enrolled. All patients had mild to moderate hypertension, defined as diastolic blood pressure (DBP) of 95-114 mm Hg at the end of a 1- to 2-week single-blind placebo period. In all, 30 patients received carvedilol (25 mg once daily) and 31 received labetalol (200 mg twice daily). The initial dose could be doubled for both treatment groups at day 29 if the DBP was greater than 90 mmHg on days 28 and 29. Hemodynamic parameters, including supine and standing DBP, systolic blood pressure (SBP), and heart rate (HR), were measured and safety was evaluated at baseline and at days 14, 28, and 56 at the end of the dosing interval. In all, 3 patients on carvedilol and 4 patients on labetalol required upward dose titration after 1 month. At the end of the trial, 26 of 30 carvedilol-treated patients and 27 of 31 labetalol-treated patients (87% of each group) had a supine DBP of less than or equal to 90 mm Hg. On day 56, mean decreases in supine DBP, SBP, and HR in the carvedilol group were 18.5 and 23.4 mm Hg and 11 beats/min, respectively, from baseline values of 101.6 and 163.8 mm Hg and 80 beats/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiological effects of intravenous nicaïnoprol, a new antiarrhythmic agent, in 11 patients.

Nicaïnoprol, a new class 1 antiarrhythmic drug was given intravenously in a dose of 2 mg kg-1 of body weight (two patients) and 3 mg kg-1 of body weight (nine patients), and the clinical, electrocardiographic and electrophysiological effects were studied. Fifteen minutes after the end of drug administration, the PR interval was prolonged by 24.4% (P less than 0.001), and the QTc by 3.9% (P less than 0.01). The prolongation of QRS duration (+6%) was not significant. There was a slight (-3.9%) but non-significant decrease of the heart rate, with no alteration in sinus node function. Alteration of atrial conduction and atrioventricular (AV) conduction were due to an increase in the PA interval (+57.4%, P less than 0.05), the AH interval (+10.9%, NS) and the HV interval (+43.8%, P less than 0.01). The anterograde Wenckebach cycle length increased by 11% (P less than 0.01). The effective and functional atrial refractory periods increased respectively by 4.5% and 11.4% (P less than 0.05), and the effective refractory period of the AV node increased by 11.2% (P less than 0.05). None of the other electrophysiological variables changed significantly. A non-significant drop in blood pressure was noted between the second minute following injection (-9.4%) and the 15th minute (-3.4%), and two patients complained of dizziness; one of these two patients reported a heat flush with an oral burning. In conclusion, nicaïnoprol seems to possess the electrophysiological properties of some other class I antiarrhythmic drugs, and is clinically well tolerated.

[Neurinoma of the posterior cerebral fossa and mitral valve prolapse. Possible association and study of possible peri-operative consequences on rhythm]. / Neurinome de la fosse cérébrale postérieure et prolapsus valvulaire mitral. Association possible et recherche d'éventuelles conséquences rythmiques péri-opératoires.

27 patients with an acoustic neurinoma were submitted to a complete cardiological survey oriented towards the detection of mitral valve prolapse (2D echo) and ECG signs of a particular risk of arrhythmia (standard ECG and continuous Holter monitoring). 9 of these 27 patients presented MVP, but none of them presented any serious ventricular arrhythmias. The corrected QT interval was significantly longer in patients without MVP. The frequency of the association of MVP and acoustic neurinoma can not be explained simply by the female predominance of the series and its should be interpreted with reservation in the absence of a control series. The absence of pre-operative arrhythmia does not exclude the potentiating role of MVP in the development of certain cases of unexplained post-operative death.

[Pure arrhythmic form of the pre-infarction syndrome or spasm responsible for myocardial necrosis]. / Syndrome prémonitoire à forme rythmique pure ou spasme responsable d'une nécrose myocardique.

A 74 years old man was admitted as an emergency for syncopal attacks due to recurrent ventricular fibrillation (VF). These attacks were observed at the height of myocardial ischaemia as shown by ST elevation in Leads II, III and RV without associated anginal pain. Inferior myocardial infarction occurred during recurrent VF on the 4th day; the outcome was favourable. Coronary angiography was performed on the 10th day and showed double vessel disease; ergometrine (0.2 mg) induced anginal pain and ST elevation in Leads II, III and AVF. A good clinical result was obtained by calcium antagonists with an 18 months follow-up. Coronary spasm, documented in this case by the ergometrine provocation test, is now recognised as a cause of resting angina, effort angina and also some cases of myocardial infarction. This report suggests that coronary spasm may also induce apparently isolated severe ventricular arrhythmias without associated chest pain, which raises the question as to whether arrhythmias induced by spasm could play a primary role in aggravating myocardial ischaemia, leading to myocardial infarction.

[Associated coronary and carotid atheroma. Implications and current role of indications for double surgery]. / Athérome coronarien et carotidien associés. Implications et place actuelle d'une double indication chirurgicale.

Coronary insufficiency is responsible for part of the peri-operative mortality of carotid surgery and it is by far the principal long term cause of death. Conversely, cerebral vascular accidents due to extra-cranial carotid stenosis compromise the results of myocardial revascularisation operations less than coronary insufficiency itself. Patients who require double surgery can be recognised on the basis of the clinical findings. The essential indication for this surgery is double clinical instability. Apart from these patients, the group of patients at high risk still need to be defined. Strictly preventative coronary and carotid surgery seem to be less justified, particularly as the currently available prophylactic measures and medical treatments appear to achieve a relative improvement in the long term prognosis of these patients with multiple vessel disease.

[Rest and exercise angina caused by spasm of the left coronary artery. Apropos of a case with angiographically normal coronary arteries]. / Angor de repos et d'effort par spasme du tronc coronaire gauche. A propos d'un cas à artères coronaires angiographiquement normales.

A 42 year old woman presented with resting and effort angina. During an attack of chest pain, ST-T wave depression was recorded in the anterior chest leads. Coronary angiography showed spontaneous spasm of the left main stem, relieved by nitrate derivatives. The coronary arteries were angiographically normal between attacks of angina. Thallium 201 myocardial scintigraphy showed anterior wall hypofixation at maximal effort. A good therapeutic result was obtained with calcium antagonists. The site of coronary spasm is the special feature of this case, which may be grouped with other rare reported cases of spontaneous spasm or spasm on effort. We confirm that spasm-induced myocardial ischaemia may cause ST depression on the surface ECG.