[Transcatheter Aortic Valve Implantation versus surgical aortic valve replacement in intermediate-risk patients with severe symptomatic aortic stenosis]. / L'étude clinique du mois. PARTNER-2 : TAVI versus chirurgie dans les risques intermédiaires de sténose aortique sévère symptomatique.

Aortic valve stenosis (AS) is the most commonly operated valvular heart disease in developed countries. Aortic valve replacement is the sole effective treatment of symptomatic patients. PARTNER-1 (Placement of AoRtic TraNscathetER Valves) has recently proved the efficacy of percutaneous aortic valve replacement (TAVI : Transcatheter Aortic Valve Implantation) in patients at high surgical risk, or inoperable. In the present article, we report and discuss the results of the PARTNER-2 study in intermediate risk patients. Data from PARTNER-2 confirmed those of PARTNER-1 with a similar rate of combined events (death or disabling stroke) in the TAVI and surgical groups. At 2 years, the Kaplan-Meier event rates were 19.3% in the TAVI group and 21.1% in the surgery group, with a hazard ratio in the TAVI group of 0.89. The non inferiority analysis was validated with a p inferior to 0.001. In the transfemoral-access cohort, TAVI resulted in a lower rate of death or disabling stroke than surgery (p = 0.05), whereas, in the transthoracic access cohort, outcomes were similar in the two groups. Finally, TAVI was associated with lower rates of new onset atrial fibrillation, acute renal failure, and severe bleeding, whereas surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation.

La sténose aortique est la valvulopathie la plus fréquemment opérée dans les pays industrialisés. Le remplacement valvulaire aortique est le seul traitement efficace dans les formes sévères symptomatiques. L'étude PARTNER-1 (Placement of AoRtic TraNscathetER Valves/Mise en place de valves aortiques transcathéters) a récemment prouvé l'efficacité du remplacement valvulaire aortique par voie percutanée (TAVI: Transcatheter Aortic Valve Implantation) chez les patients à haut risque chirurgical ou inopérables. Dans cet article, nous rapportons et discutons les résultats de l'étude PARTNER-2 réalisée chez les patients à risque intermédiaire. PARTNER-2 confirme les données observées dans PARTNER-1, avec un critère d'évaluation principal [taux d'événements combinés, décès ou accident vasculaire cérébral (AVC) invalidant] similaire dans les deux groupes (TAVI versus chirurgie). A deux ans, l'incidence de ce critère primaire était de 19,3 % dans le groupe TAVI versus 21,1 % dans le groupe chirurgie, soit un risque relatif de 0,89 dans le groupe TAVI. L'analyse de non-infériorité était validée (p inf�rieur a 0,001). Le TAVI par voie transfémorale était associé à un plus faible taux de décès ou d'AVC invalidant que la chirurgie (p = 0,05), tandis que, dans l'approche transthoracique, le pronostic des patients était similaire dans les deux groupes. Finalement, le TAVI était associé à une incidence moindre de fibrillation auriculaire de novo, d'insuffisance rénale aiguë, et d'hémorragies sévères, tandis que l'avantage de la chirurgie se traduisait par moins de fuites paravalvulaires et de complications vasculaires.

[Fibrillation, an epidemic in the elderly?]. / La fibrillation auriculaire: une épidémie du troisième âge?

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. In its non valvular form, it appears as a disorder of the aged. Surprisingly, its incidence and prevalence have constantly been on the rise over the last decades to the extent that some authors nowadays call this phenomenon an "emerging epidemic". The reasons for that proliferation are not entirely elucidated. Obesity, which has simultaneously and similarly increased in frequency, might have played a significant role. AF is frequently pauci-symptomatic in the aged and can easily go unrecognized. Yet, it entails a higher mortality rate, carries a significant risk of thrombo-embolic events, in particular strokes, and may lead to heart failure. We shall briefly review the current epidemiologic aspects of AF and evoke the possible role of obesity. We shall then discuss the therapy of this disorder with a particular attention to the new oral anticoagulants.

[My pet, a safeguard for my health]. / Mon chien, gardien de ma santé?

For some of us, to possess a pet, and particularly a dog, can be the source of great satisfaction. Recently, the opinion has prevailed that pet ownership provides significant beneficial effects in terms of prevention of cardiovascular diseases and could even improve survival after a coronary event. The American Heart Association has recently summoned some experts to express their view on this matter and their group has issued an official statement. We thought it useful to summarize their publication: it is properly cautious and will surely prompt further research; it will also comfort dog owners in their belief that their pet can indeed, in difficult times, be a resourceful helpmate.

[Atherosclerosis: a complex disease]. / L'athérosclérose: une maladie complexe.

Atherosclerosis is a complex disease resulting from an interaction between environmental risk factors (diet, smoking habit, lack of exercise, stress) and a favourable genetic profile. In the recent past, the analysis of the genetic factors involved has considerably progressed. A significant number of genetic variants associated with the various phenotypes of atherosclerosis or its risk factors have been identified. Each, taken individually, only exerts a modest influence, but as a group, they play a significant role, albeit as yet not precisely quantified, in the aetiology of atherosclerosis. The individual response to various therapies prescribed in atherosclerosis can also be significantly influenced by genetic factors. In the next future, genetics and pharmacogenetics will represent major determinants of our approach to the prevention and individualized treatment of atherosclerosis and its complications.

[Cardiovascular prevention: could the polypill reduce the risk of clinical inertia and poor compliance?]. / Prévention cardio-vasculaire: la "polypill", une solution pour vaincre l'inertie clinique et le manque d'observance?

The concept of "polypill" for cardiovascular prevention was introduced in 2003 in a landmark paper of the British Medical Journal. A model based on results provided by evidence-based medicine suggested that a "polypill", that contains a statin, three blood pressure lowering drugs (each at half standard dose), aspirin and folic acid, would result in an 80% reduction in the incidence of coronary and cerebrovascular events, while being associated with a good tolerance profile and offering a favourable cost-effectiveness ratio. The present paper aims at presenting the new advances dealing with this new paradigm in cardiovascular prevention. We will present the progresses of the "polypill" concept since 2003, the results of a first controlled clinical trial, the pharmaceutical feasibility for routine clinical use and the potential pharmaco-economical impacts of such a strategy. The "polypill" may offer a solution to avoid physician's clinical inertia and reduce patients's lack of compliance, two drawbacks in the field of cardiovascular prevention.

[The top ten major advances in heart disease and stroke research in 2008: a compilation of the AHA]. / Les 10 contributions les plus significatives de la littérature cardiologique en 2008: une sélection de l'American Heart Association.

Following the tradition, the AHA has compiled a list of the top 10 major advances in heart disease and stroke research in 2008. As always, the choice was rather eclectic. There were, to start with, a series of papers providing objective data to validate several programs of public health, prevention, or good practice promotion that the AHA has initiated, or encouraged. Then came the results of some recent clinical trials which may prompt a change in clinical habits, or even in international guidelines related to cardio- or cerebro-vascular disease. Finally, the AHA identified new areas of research which, even if they are still in their early development, show significant promise for the future of medicine.

[The top ten major advances in heart disease and stroke research in 2007: a selection of the American Heart Association]. / Les 10 contributions les plus significatives de la littérature cardiologique en 2007: une sélection de l'American Heart Association.

The AHA has released its annual selection of the 10 top major advances in heart disease and stroke research for 2007. This list is very interesting. It contains papers on genetics which present the newly introduced genome-wide association studies of different common diseases, including coronary artery disease. The results of investigations carried out on cardiomyocytes derived from adult mouse spermatogonial stem-cells are mentioned. The value of angioplasty in chronic stable coronary artery disease is reassessed as is the need for mouth to mouth ventilation in resuscitation manoeuvres for cardiac arrest. The effectiveness and safety of drug-eluting stents in routine clinical practice is demonstrated and the merit of bivaluridin for the treatment of patients with a STEMI infarct is described. The improvement in quality of care provided by a statewide system for coronary revascularisation is outlined. Finally, two papers are devoted to epidemiological issues: one demonstrates that a reduced sodium intake lowers not only blood pressure, but also the risk of clinical cardiovascular disease outcomes; the second stresses that hypertension and prehypertension are often undiagnosed in the pediatric population.

[The 2006 American Heart Association selection of the "top ten advances in heart disease and stroke research"]. / Les 10 contributions les plus significatives en littérature cardiologique en 2006: Une Sélection De L'américan Heart Association.

The American Heart Association (AHA) has once again released its "top ten research advances in heart disease and stroke" for the past year. A place of choice is devoted to stroke as well as to pediatric cardiology and to prevention of heart disease in childhood and adolescence. As is the case every year, reading the selected articles is rich of enlightment and the source of a good many thoughts.

[The 2005 AHA selection of the "top ten advances in heart disease and stroke research"]. / Les dix contributions les plus significatives de 2005 en littérature cardiologique: la selection annuelle de l'American Heart Association ("top ten").

The American Heart Association has once again released its "top ten" research advances in heart disease and stroke for the past year. As always, the choice is rather heterogeneous. Besides the quality of the selected contributions, it also reflects some areas of concern which primarily interest the Unites States, or the support that the AHA wishes to bring to some particular research programmes; Reading this list is however always rich of enlightment for anyone working in the field.

[Aspirin and cardiovascular prevention: last minute information]. / Aspirine et prévention cardiovasculaire, dernière minute: prise en charge des effets secondaires gastro-duodénaux.

Just a few days after the publication in this journal of a review on aspirin and cardiovascular prevention, a significant article appeared in the international literature; it provides new information and deserves a brief presentation. This paper is concerned with patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding. After the ulcers had healed and after eradication of Helicobacter pylori had, if necessary, been achieved, 320 patients were randomly assigned to receive either 75 mg of clopidogrel daily or 80 mg of aspirin daily + 20 mg of esomeprazole twice daily. Recurrent ulcer bleeding occurred in 13 of the 161 patients assigned to receive clopidogrel and in 1 of the 159 who received aspirin plus esomeprazole. The cumulative incidence of recurrent bleeding during the 12 months of follow up was 8.6% in the clopidogrel group and 0.7% in the aspirin-esomeprazole group (p = 0.001). These findings do not support a current American recommendation that patients with major gastrointestinal intolerance of aspirin should be given clopidogrel instead.

[The "top" of cardiology literature in 2004: an annual selection of the American Heart Association]. / Le "gratin" de la littérature cardiologique en 2004: une sélection annuelle de l'American Heart Association.

The American Heart Association has once again released its top ten research advances in heart disease and stroke for the past year. As always, the selection is assorted. It contains very pointed, at times preliminary, research, as well as major clinical trials; it also reports findings that seem of particular interest for an American audience or come as a support for a special programme proposed by the association. Reading these ten abstracts is, however, invariably rich of enlightenment, and stimulation for everyone.

[Medication of the month. Adalat Oros 60 mg]. / Le médicament du mois. L'Adalat Oros 60 mg.

The release of Adalat Oros 60 on the Belgian market was justified since it has been clearly demonstrated that the dosage of 60 mg significantly increases the proportion of responders to nifedipine monotherapy. This gives us the opportunity to briefly review the history of nifedipine and to describe the original and ingenious galenic controlled-release formulation known as Oros (Gastrointestinal Therapeutic System, or GITS in the anglo-saxon world). Cleary, nifedipine is a potent calcium antagonist the action of which is now smooth and devoid of the usual ups and downs observed with the regular capsules, even in their Retard form. These abrupt changes in plasma concentrations, with the subsequent variations in heart rate and blood pressure, were dangerous and bothersome. Oros allows plasma concentrations of nifedipine to plateau for at least 24 hours after oral administration. This reduces the incidence of side-effects which remain those classically attributable to calcium antagonists (i.e.: flushes, headaches); interestingly, they tend to appear early after treatment initiation which allows to easily ascribe them to the drug and to quickly assess tolerance. The INSIGHT trial compared the effects on nifedipine Oros to those of a classical diuretic combination (hydrochlorothiazide-amiloride) in 6321 hypertensives who had at least one additional risk factor for cardiovascular disease. The rate of the primary outcome (a composite of cardiovascular death, myocardial infarction, heart failure, stroke) was similar in the two treatment groups, but nifedipine was superior among the subgroup of diabetics. Substudies suggested that nifedipine slows the progression of atherosclerotic lesions (carotid and coronary arteries), preserves renal function, and prevents the development of new diabetes.

[Clinical study of the month. REVERAL and PROVE-IT: confirmation of the concept " the lower, the better" for cholesterol therapy in patients with coronary heart disease]. / L'étude clinique du mois. REVERSAL et PROVE-iT: confirmation du concept "the lower, the better" dans le traitement de l'hypercholestérolemie chez le patient coronarien.

Statins, as compared to placebo, have proven their efficacy in reducing cardiovascular events in patients with or without cardiovascular disease and in a large range of cholesterol levels. Two new head-to-head randomised trials comparing intensive treatment with atorvastatin 80 mg/day with moderate treatment with pravastatin 40 mg/day were recently completed. The mechanistic "Reversing Atherosclerosis with Aggressive Lipid Lowering" (REVERSAL) trial randomised 502 patients with stable coronary disease. Atorvastatin 80 mg (leading to a mean LDL cholesterol of 79 mg/dl) was superior to pravastatin 40 mg (mean LDL of 110 mg/dl) in terms of limiting the progression of atheroma assessed with the use of intravascular ultrasonography after 18 months of follow up (p = 0.02). These differences may be related to the greater reduction in atherogenic lipoprotein (-46% versus -26%, p < 0.001) and C-reactive protein (-36% versus -5%, p < 0.001) in patients treated with atorvastatin as compared to pravastatin. In the clinical "Pravastatin or Atorvastatin Evaluation and Infection Therapy" (PROVE-IT) trial, 4162 patients with acute coronary syndromes were randomised to either atorvastatin 80 mg or pravastatin 40 mg and followed for a mean of 24 months. Again, atorvastatin (mean LDL of 62 mg/dl) was superior to pravastatin (mean LDL of 95 mg/dl), resulting in a 16% percent lower risk of the primary end point, a composite of major cardiovascular events (p = 0.005). Thus, both REVERSAL and PROVE-IT support the concept "the lower, the better". However, they do not allow to disentangle the independent and interdependent effects of statins on LDL cholesterol and the process of arterial inflammation. What so ever, the results suggest that the target LDL cholesterol level may be lower than recommended in the current guidelines in high-risk patient so that a sea change in the prevention and management of atherosclerotic vascular disease may occur very soon.

[The top ten advances in heart disease and stroke research for 2003: a selection from the American Heart Association]. / Le "gratin" de la littérature cardiologique en 2003: une sélection de l'American Heart Association.

Since 1996, the American Heart Association (AHA) publishes, with its year-end report, the list of "The Ten Top Advances in Heart Disease and Stroke Research". These milestones include the results of some major clinical trials, new medications, guidelines published during the past year, and innovative research work that can be very preliminary, but contains promising data for the years to come. It is not without interest to read the list of publications or presentations that were selected; one can indeed imagine that these contributions were, over the past twelve months, among the most significant in our specialty and that some of them will indeed exert a considerable influence on the practice of cardiology in the future. It is with pleasure that we observe that some of these publications were already analysed in our journal during 2003.

[Aspirin: recent advances in cardiovascular prevention]. / L'aspirine: acquisitions récentes en prévention cardiovasculaire.

More than a century after being launched onto the market, aspirin still remains a fascinating drug, both for its demonstrated antalgic, antipyretic, antiinflammatory and antithrombotic properties and, also, for newer, yet conjectural, applications mentioned in recent publications. The role of aspirin, as an irreversible COX-1 inhibitor and antiplatelet agent, is well elucidated and established. Our purpose is to review the value of aspirin for primary and secondary prevention of ischemic cardiovascular events. The clinician constantly has to manage a trade off between the protective effects of aspirin and its possible hemorrhagic, notably gastrointestinal, side-effects. The Task Force of the ESC recommends the use of doses no higher than 75-100 mg/d. New antiplatelet agents (thienopyridin derivatives), which have a totally different mode of action, have been introduced and were compared with aspirin. Although clopidogrel may be slightly superior to the latter, according to the European experts: "the size of any additional benefit is statistically uncertain and the drug has not been granted a claim, of superiority". Economical considerations reinforce this view. Clopidogrel is undoubtedly a good alternative when aspirin is contra-indicated, poorly tolerated, or not efficacious. Resistance to aspirin and resistance to clopidogrel have been described. In some high-risk patients, the combined use of aspirin and clopidogrel is deemed justified.

[Interheart: nine risk factors predict nine out of ten myocardial infarctions]. / L'étude clinique du mois. "INTERHEART": la preuve par 9. Neuf facteurs de risque prédisen neuf infarctus du myocarde sur dix.

INTERHEART is a standardised case-control study of acute myocardial infarction in 52 countries representing every inhabited continent. 15152 cases and 14820 controls were enrolled. Collectively, 9 factors accounted for 90% of myocardial infarctions in men and 94% in women. These factors were 6 risk factors (dyslipidaemia characterized by high apoB/apoA1 ratio, smoking, hypertension, diabetes mellitus, abdominal obesity and stressful psychosocial factors) and 3 protective factors (daily consumption of fruits and vegetables, regular alcohol consumption, and regular physical activity). These findings suggest that interventions targeting these 9 factors have the potential to prevent most premature cases of myocardial infarction and that these strategies should be implemented worldwide.

[Clinical study of the month. The CHARM study]. / L'étude clinique du mois. L'étude CHARM.

In parallel, randomized, double-blind, controlled clinical trials, candesartan (titrated to 32 mg once daily) was compared to placebo in 3 distinct populations: 1) patients with symptomatic heart failure (SHF) and left ventricular ejection fraction (LVEF) 40% or less who were not receiving an ACE inhibitor because of previous intolerance (CHARM-Alternative); 2) patients with SHF and LVEF 40% or less who were currently receiving an ACE inhibitor (CHARM-Added); 3) patients with SHF and LVEF higher than 40% (CHARM-Preserved). The primary outcome for the overall programme (CHARM-Overall) was all-cause mortality. For the component trials, it was a composite of cardiovascular death and hospital admission for CHF. Analysis was by intention to treat. In CHARM-Overall (placebo, n = 3796; candesartan, n = 3803; mean follow-up; 37.7 months), candesartan induced a 1.6% absolute reduction in all-cause mortality (unadjusted HR: 0.91; 95% CI 0.83-1.00; p = 0.055). In a prespecified analysis with covariate adjustment, this was statistically significant (HR: 0.90; 95% CI 0.82-0.94; p = 0;032). A highly significant reduction in the combined incidence of cardiovascular death and CHF hospital admission (HR: 0.84; 95% CI 0.77-0.91; p < 0.0001) was noted as well as a reduction of the number of patients developping a new diabetes (6% vs 7.4%: p = 0.02). In CHARM-Alternative, there were 1013 patients on candesartan and 1015 on placebo and the mean follow-up was 33.7 months. The combined incidence of cardiovascular death and CHF hospitalization was reduced by 23% (p = 0.0004). In CHARM-Added, 1276 patients received candesartan and 1272, placebo; mean follow-up was 41 months. The benefit induced by candesartan on the primary endpoint was 15% (p = 0.011). In those two studies the two components of the primary endpoint were significantly reduced. Candesartan was beneficial in all prespecified subgroups, including patients concomitantly treated by beta-blockers. In CHARM-Preserved (candesartan, n = 1514; placebo, n = 1509; mean follow-up: 36.6 months), neither the composite endpoint, nor cardiovascular death were reduced, but the number of admissions for heart failure was reduced. The clinical implications of these important results are discussed.