[State of unmet medical needs in France in 2006: necessity of reinforcing research effort].

Leem (French Pharmaceutical Companies) realized an inventory of unmet medical needs in 2006 in France for 12 pathologies. All of them are considered as national public health priorities by the law of August 9th, 2004. Allied to the epidemiological projections, analyses concerned various stages and/or pathology forms, impact of guidelines in clinical practice, therapeutic strategies, marketed therapeutics and pharmacological products in an advanced phase of clinical development.

[Lifestyle and cardiovascular risk].

This paper describes the relation between lifestyle and cardiovascular risk globally and for each lifestyle risk factor. In 3 large studies (Interheart, HALE project and the Nurses' health study), four risk factors have been identified: smoking, diet, low level of exercise and low or no alcohol consumption. Prevention of atherosclerotic diseases can be obtained by smoking cessation, diet modifications aimed at lowering body weight and having a Mediterranean style diet, continuing lifelong physical activity such as walking more than two hours a week.

Clinical significance of renal function in hypertensive patients at high risk: results from the INSIGHT trial.

Background: Increasing evidence suggests renal involvement in hypertension-related cardiovascular and cerebrovascular complications. To assess this role of renal function in more detail, we studied the evolution of renal function and the relationship of renal function with mortality and morbidity in the Intervention as a Goal in Hypertension Treatment (INSIGHT) study.

Methods: The INSIGHT study was a double-blind, randomized, multicenter trial in patients with hypertension and at least 1 additional cardiovascular risk factor.

Effects of nifedipine GITS and diuretics in isolated systolic hypertension--a subanalysis of the INSIGHT study.

Aims: This study tested the effects on cardiovascular outcomes of treatments based on nifedipine gastrointestinal therapeutic system (GITS) compared with the diuretic combination co-amilozide in a pre-specified subset of patients with isolated systolic hypertension (ISH) enrolled in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study.

Major Findings: Of 6321 randomized patients, 1498 (23.7%) had ISH with a baseline mean BP of 173/88 mmHg in both treatment groups.

Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.

Background: The utility of N-terminal proBNP (NT-proBNP) to predict the occurrence of death and hospitalization was prospectively evaluated in the COPERNICUS study, which enrolled patients with an ejection fraction <25% and symptoms of chronic congestive heart failure at rest or on minimal exertion.

Methods And Results: Baseline plasma concentrations of NT-proBNP were measured in a subgroup of 814 men and 197 women with symptoms at rest or on minimal exertion who were enrolled in the COPERNICUS study and were randomized to placebo (n=506) or carvedilol (n=505). Values of NT-proBNP were markedly increased despite the requirement that patients be euvolemic before the start of treatment (mean+/-SD, 3235+/-4392 pg/mL; median, 1767 pg/mL).

Influence of pretreatment systolic blood pressure on the effect of carvedilol in patients with severe chronic heart failure: the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study.

Objectives: We sought to evaluate the influence of pretreatment systolic blood pressure (SBP) on the efficacy and safety of carvedilol in patients with chronic heart failure (CHF).

Background: Although beta-blockers reduce the risk of death in CHF, there is little reported experience with these drugs in patients with a low pretreatment SBP, who may respond poorly to beta-blockade.

Methods: We studied 2,289 patients with severe CHF who participated in the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.

NT-proBNP in severe chronic heart failure: rationale, design and preliminary results of the COPERNICUS NT-proBNP substudy.

Background: Neither profiles nor prognostic value of cardiac N-terminal proBNP (NT-proBNP) have been prospectively evaluated in a sufficient number of patients with severe chronic heart failure (CHF) treated with carvedilol or placebo.

Methods: Baseline and follow-up plasma concentrations of NT-proBNP were measured in the European part of the COPERNICUS Trial. This study enrolled patients with an ejection fraction <25% and symptoms of CHF at rest or on minimal exertion, equally randomized to placebo or carvedilol.

[Aldosterone and its antagonists in heart failure].

Unlabelled: THE ROLE OF ALDOSTERONE: Aldosterone is the key hormone in salt-water homeostasis. In heart failure, it participates in the appearance and maintenance of signs of congestion. Predominantly synthesised in the glomerular area of the cortico-adrenal glands, extra adrenal production areas have recently been identified notably in the brain, the heart and the large artery trunks.

Outcomes with nifedipine GITS or Co-amilozide in hypertensive diabetics and nondiabetics in Intervention as a Goal in Hypertension (INSIGHT).

To investigate the impact of treatment on cardiovascular mortality and morbidity, we assessed outcomes in patients with hypertension and diabetes who received co-amilozide or nifedipine in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension. Participants had to be 55 to 80 years of age, with hypertension (> or =150/95 or > or =160 mm Hg) and at least one additional cardiovascular risk factor. Patients received 30 mg nifedipine once daily or co-amilozide (25 mg hydrochlorothiazide and 2.

[Critical reading for studies on antithrombotic medications in acute coronary syndromes].

Numerous studies of anti-thrombotic medications in the treatment of acute coronary syndromes have been published in the past few years. The "technical" quality of these studies is usually good. However, the critical reader must focus on the potential use of the observed differences for his patient.

The Framingham prediction rule is not valid in a European population of treated hypertensive patients.

Background: Stratification of population groups according to cardiovascular risk level is recommended for primary prevention.

Objective: To assess whether the Framingham models could accurately predict the absolute risk of coronary heart disease (CHD) and stroke in a large cohort of middle-aged European patients with hypertension, and rank individual patients according to actual risk.

Design: A prospective cohort study comparing the actual risk with that predicted by either the Framingham equations or models derived from the INSIGHT study.

[Reassessment of drugs].

The usefulness of a product can vary considerably over the course of time. Nothing is more arduous than to have to re-evaluate a medication but nothing is more necessary. The Legal Information of market authorization can become obsolete and necessitate a re-evaluation, a harmonisation with the products of the same therapeutic class, in short, a re-writing.

[Role of drugs in therapeutic strategies].

When a medication receives an authorization for the release onto the market, it is necessary to determine the place that it will occupy in the therapeutic strategies with 2 regulatory steps: The Commission de la transparence (Commission for Transparency) gives an opinion on the target population, the placing in the therapeutic strategies, the level of medical benefit for patient, the restriction or not to hospital usage, and the inclusion in the national medical insurance reimbursement scheme for the medications that are not reserved to hospitals. The second step is the passage before the Comité économique du médicament (Medical Economics Committee) that fixes the price of re-emboursement of the product. The place that the medication will occupy depends on the expectations of the doctors, and through them the patients, and the promotional efforts of the pharmaceutic industry.

[Hospital mortality in cardiology. Analysis of deaths occurring in the Federation of Cardiology of a university hospital center].

The aim of this study was to examine the nature of cardiovascular deaths occurring in a University Hospital. All the hospital files of 1999 of the Federation of Cardiology of Henri Mondor Hospital, Creteil, of patients who died in the department or after transfer to the intensive care unit or cardiac surgery department, were analysed. Myocardial ischaemia was the leading cause of death, occurring either in the acute phase of transmural infarction or in patients with chronic cardiac failure.

What is the relevance of the HOPE study in general practice?

The unique findings from the HOPE (Heart Outcomes Prevention Evaluation) study strongly support extending the use of the angiotensin-converting enzyme (ACE) inhibitor ramipril as a preventive agent for patients at high risk of cardiovascular events with normal left ventricular function. In addition, ramipril provides significant benefit in diabetic patients. These findings will impact on how ramipril is used in primary care, where ACE inhibitors are currently underprescribed.

Effect of carvedilol on survival in severe chronic heart failure.

Background: Beta-blocking agents reduce the risk of hospitalization and death in patients with mild-to-moderate heart failure, but little is known about their effects in severe heart failure.

Methods: We evaluated 2289 patients who had symptoms of heart failure at rest or on minimal exertion, who were clinically euvolemic, and who had an ejection fraction of less than 25 percent. In a double-blind fashion, we randomly assigned 1133 patients to placebo and 1156 patients to treatment with carvedilol for a mean period of 10.

Altered baroreflex gain during voluntary breathing in chronic heart failure.

Background: We assessed the behavior of the baroreflex (BR) gain in chronic heart failure (CHF) patients using the spectral analysis method during application of a forcing stimulus, i.e. respiration.

Costs for acute myocardial infarction in a tertiary care centre and nationwide in France.

Objective: We compared the estimated costs of coronary interventions from our hospital's cost accounting system with data from the French Diagnosis Related Group (DRG) cost database, taking the perspective of our hospital.

Design: Cost data on hospital resources used by patients hospitalised for acute myocardial infarction (MI), with and without complications, including deceased patients, were collected in a tertiary care university hospital located in Paris, France. The data were collected using the hospital's cost accounting system and then compared with the estimates provided by the DRG reimbursement schedule for similar conditions.

Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT).

Background: The efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established. We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension.

Methods: We did a prospective, randomised, double-blind trial in Europe and Israel in 6321 patients aged 55-80 years with hypertension (blood pressure > or = 150/95 mm Hg, or > or = 160 mm Hg systolic).

Study on COgnition and Prognosis in the Elderly (SCOPE): baseline characteristics.

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multi-centre, prospective, randomized, double-blind, parallel-group study. The primary objective of SCOPE is to assess the effect of the angiotensin II type 1 (AT1) receptor blocker, candesartan cilexetil 8-16 mg once daily, on major cardiovascular events in elderly patients (70-89 years of age) with mild hypertension (DBP 90-99 and/or SBP 160-179 mmHg). The secondary objectives of the study are to test the hypothesis that antihypertensive therapy can prevent cognitive decline (as measured by the Mini Mental State Examination, MMSE) and dementia, and to assess the effect of therapy on total mortality, myocardial infarction (MI), stroke, renal function, and hospitalization.

[Results of large-scale clinical trials and medical practice].

The results of large scale clinical trials are part of the scientific data on which medical and, in particular therapeutic decisions, are base; very concordant data may even be used to define appropriate or inappropriate prescribing behaviour in the context of recommendations or references of good medical practice. Large scale clinical trials, however, have limitations inherent to their method; they give a mean result observed in an average population. The true question is to know if the therapeutic benefit proved in a therapeutic trial will be observed in a given individual in the future.

Influence of diabetes and type of hypertension on response to antihypertensive treatment.

The aim of our investigation was to determine whether the presence of additional risk factors or type of hypertension (diastolic or isolated systolic) influences blood pressure (BP) response to treatment. The International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study is a double-blinded outcome comparison of calcium channel blockade with diuretics in high-risk patients aged 55 to 80 years. Dynamic randomization between nifedipine once daily and hydrochlorothiazide/amiloride was performed to ensure that approximately equal numbers of patients in the 2 groups had each of the major cardiovascular risk factors.

Effects of bradykinin on coronary blood flow and vasomotion in transplant patients.

Objectives: To evaluate the effects of exogenous bradykinin on coronary epicardial and microcirculatory tone in transplant patients (HTXs), and to compare them with the effects of acetylcholine.

Background: Coronary endothelial dysfunction has been reported to occur early after heart transplantation, most notably when acetylcholine was the endothelium-function marker used. The effects of bradykinin on coronary vasomotion are unknown in HTXs.

Stimulation of bradykinin B(1) receptors induces vasodilation in conductance and resistance coronary vessels in conscious dogs: comparison with B(2) receptor stimulation.

Background: Constitutive bradykinin B(1) receptors have been identified in dogs; however, their physiological implications involving the coronary circulation remain to be determined. This study examined, in conscious dogs, the coronary response to des-Arg(9)-bradykinin (a B(1) receptor agonist) and the mechanisms involved.

Methods And Results: Eleven dogs were instrumented with a left ventricular micromanometer, a circumflex coronary catheter, a cuff occluder, a Doppler flow probe, and ultrasonic crystals to measure coronary blood flow velocity (CBFv) and coronary diameter (CD).