J Lefebvre

Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Quebec, Canada

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Publications (43)106.66 Total impact

  • No preview · Conference Paper · Jan 2015
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    ABSTRACT: Blood pressure (BP) control is frequently difficult to achieve in patients with predominantly elevated systolic BP. Consequently, these patients frequently require combination therapy including a thiazide diuretic such as hydrochlorothiazide (HCTZ) and an agent blocking the renin-angiotensin-aldosterone system. Current clinical practice usually limits the daily dose of HCTZ to 25 mg. This often leads to the necessity of using additional antihypertensive agents to control BP in a high proportion of patients. To compare the efficacy of two doses of losartan (LOS)⁄HCTZ combinations in patients with uncontrolled ambulatory systolic hypertension after six weeks of treatment with LOS 100 mg⁄HCTZ 25 mg (LOS100⁄HCTZ25). Following a two- to four-week washout period, subjects with a mean clinic sitting systolic BP of 160 mmHg or higher and a mean ambulatory daytime systolic BP (MDSBP) of 135 mmHg or higher on LOS100⁄HCTZ25 (n=105; 33 women and 72 men) were randomly assigned to receive LOS 150 mg⁄HCTZ 25 mg (group 1; n=53) or LOS 150 mg⁄HCTZ 37.5 mg (LOS150⁄HCTZ37.5, group 2; n=52). The primary end point was the difference in MDSBP reductions. At the end of the six-week treatment period, the respective additional decreases in MDSBP were 1.2 mmHg (P=0.335) on LOS 150 mg⁄HCTZ 25 mg and 5.6 mmHg (P<0.0001) on LOS150⁄HCTZ37.5 (difference of 4.4 mmHg; P=0.011). Daytime systolic ambulatory BP goal (lower than 130 mmHg) achievement tended to be higher (25% versus 17%; P=0.313) with LOS150⁄HCTZ37.5, while it was significantly higher (65% versus 43%; P=0.024) for mean daytime diastolic BP (lower than 80 mmHg). No deleterious metabolic changes were observed. In patients with uncontrolled systolic ambulatory hypertension receiving LOS100⁄HCTZ25, increasing both HCTZ and LOS dosages simultaneously to LOS150⁄HCTZ37.5 may be an effective strategy that does not affect metabolic parameters.
    Full-text · Article · Oct 2010 · The Canadian journal of cardiology
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    ABSTRACT: Stress dipyridamole technetium-99(m) sestamibi single photon emission computed tomographic imaging was used to study myocardial perfusion in 1116 hypertensive patients without known coronary artery disease (CAD). The test confirmed the presence of CAD in 28.9% of patients. As expected, patients with diabetes mellitus (DM) had a significantly higher prevalence of myocardial perfusion abnormalities (35.9% vs 23.9%; odds ratio, 1.79; 95% confidence interval [CI], 1.38-2.33; P<.0001) and high-risk myocardial imaging (16.4% vs 10.6%; odds ratio, 1.67; 95% CI, 1.18-2.37; P=.004) than those without DM. Odd ratios further increased, again as expected, with dyslipidemia (2.19; 95% CI, 1.54-3.12; P<.0001), peripheral arterial disease (2.61; 95% CI, 1.77-3.85; P<.0001), microalbuminuria (3.03; 95% CI, 1.91-4.82; P<.0001), and abnormal electrocardiographic findings (3.06; 1.68; 95% CI, 2.08-4.48; P<.0001). This large cohort study showed that more than 1 of 4 treated hypertensive patients have subclinical CAD. These study data should be clinically helpful in selecting hypertensive patients who are the most suitable candidates to screen for the presence of CAD.
    Preview · Article · Dec 2007 · Journal of Clinical Hypertension
  • Y Lacourcière · J Lefebvre · L Poirier · C Côté · M Dumont
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    ABSTRACT: Objective: Essential hypertension and other atherogenic factors increase the risk of silent coronary artery disease (CAD). Its early detection may improve medical intervention and outcome. We studied the prevalence and severity of silent CAD and the impact of other atherogenic risk factors on abnormal myocardial perfusion in treated asymptomatic hypertensive patients. Methods: A number of 1116 patients (579 males, 537 females, aged 66.3 10 years) were prospectively investigated with stress dipyridamole Tc-99m sestamibi SPECT imaging and pharmacological stimulation using dipyridamol. Myocardial images along with summed stress (SSS) and summed rest (SRS) scores were assessed by 2 blinded observers. The difference between scores, the summed difference score (SDS), represented the severity of myocardial ischemic abnormality. Results: The prevalence of silent CAD was 28.9% in our hypertensive population. Overall myocardial perfusion abnormalities were significantly (p < 0.0001) more prevalent in hypertensives with diabetes (35.9%) and other risk factors. Moreover, patients with hypertension and diabetes versus hypertensives without diabetes had a greater incidence of high risk myocardial imaging (16.5% vs. 10.6%; OR 1.67; 95% Cl (1.18, 2.37); p = 0.004). The frequency of silent ischemia was further increased when hypertension and diabetes were combined with other cardiovascular risk factors such as dyslipidemia (37.4%), peripheral artery disease (40.5%), abnormal ECG at rest (41.8%) and microalbuminuria (48.8%) (all p-values < 0.0001 vs. hypertension alone plus the respective risk factor). Conclusion: Silent ischemia is a frequent problem in asymptomatic hypetensive patients. The risk to have a myocardial perfusion abnormality is tripled in those patients when diabetes, microalbuminuria and abnormal ECG are present.
    No preview · Article · Dec 2007 · Journal of Hypertension
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    ABSTRACT: Aims: Nebivolol is a β1-adrenergic receptor antagonist with vasodilating properties used in the treatment of hypertension. It is administered as a racemic mixture (D- and L-nebivolol) and is highly metabolized by the cytochrome P-450 2D6 (CYP2D6). The purpose of this study was to determine the role of CYP2D6 phenotypes on the efficacy and tolerability of nebivolol during chronic administration to patients with essential hypertension. Methods: Two hundred and eighteen patients were genotyped and phenotyped for CYP2D6 activity, allowing to find and match 14 poor metabolizers (PMs) with 23 extensive metabolizers (EMs). Patients took rac-nebivolol 5 mg daily for 12 weeks. Blood pressure (BP), heart rate, adverse events, plasma levels of the two enantiomers D- and L-nebivolol and their corresponding hydroxymetabolites were assessed. Results: The metabolic disposition of nebivolol was enantioselective and highly influenced by CYP2D6 phenotypes. Mean steady-state plasma concentrations of D- and L-nebivolol were 10- and 15-fold greater in PMs than in EMs, respectively (P < 0.0001). Despite these differences in the pharmacokinetics of nebivolol, EMs and PMs displayed similar BP responses. Mean reductions in sitting systolic and diastolic BPs were -11/-10 ± 9/4 mmHg in EMs and -11/-9 ± 10/5 mmHg in PMs. Side-effects were mild to moderate and not different between groups. Conclusion: Polymorphisms in the gene encoding CYP2D6 significantly influenced the metabolism of nebivolol, but not its antihypertensive efficacy and tolerability. The similar clinical response between EMs and PMs could be explained by the contribution of active hydroxylated metabolites of nebivolol to its antihypertensive actions in EMs.
    Preview · Article · Jun 2007 · British Journal of Clinical Pharmacology
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    Yves Lacourcière · Luc Poirier · Jean Lefebvre
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    ABSTRACT: The present study investigated whether initiating therapy with a combination of losartan (L) and hydrochlorothiazide (HCTZ) allows for faster blood pressure (BP) control and fewer medications than the usual stepped-care approach in patients with stage 2 or 3 hypertension and ambulatory systolic hypertension. Patients with a mean daytime systolic ambulatory BP (ABP) of 135 mmHg or higher were randomly assigned to receive L 50 mg plus HCTZ 12.5 mg titrated to L 100 mg plus HCTZ 25 mg versus HCTZ 12.5 mg plus atenolol 50 mg. Amlodipine 5 mg was then added, if needed, to achieve a BP goal of less than 130 mmHg. Treatment titration was based on ABP. Significantly more patients randomly assigned to L/HCTZ (63.5%) than stepped-care (37.5%; P=0.008) achieved the primary end point (daytime systolic BP of less than 130 mmHg). Initial L/HCTZ induced significantly greater decreases in ABP during each 24 h period after six weeks of therapy. Although reductions in systolic and diastolic ABP were not statistically different at the end of the study, ABP reduction was significantly greater (P<0.001) with the L/HCTZ-based regimen. Twice as many patients in the L/HCTZ group achieved the goal ABP with no more than two drugs (30.0% versus 14.7%; P=0.03). Moreover, tolerability was significantly better (P=0.006) in the L/HCTZ group, with a 40.0% incidence of adverse events, versus 65.6% in the stepped-care group. Initiating antihypertensive therapy with the combination of L/HCTZ in patients with stage 2 or 3 hypertension and ambulatory systolic hypertension reaches a target BP faster in a higher proportion of patients, with fewer adverse events and less need for a third drug regimen than the conventional stepped-care approach.
    Preview · Article · May 2007 · The Canadian journal of cardiology
  • C Cote · M Dumont · J Lefebvre · L Poirier · Y Lacourciere

    No preview · Article · Mar 2007 · Journal of Nuclear Cardiology
  • Y. Lacourcière · J. Lefebvre · C. Côté · M. Dumont

    No preview · Article · Jul 2006 · Journal of Nuclear Cardiology
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    ABSTRACT: Coronary artery disease (CAD) is the leading cause of morbidity and mortality in hypertensive and diabetic patients. Early diagnosis of CAD and identification of high-risk subgroups, followed by appropriate therapy, may therefore enhance survival. To prospectively establish the prevalence of silent CAD in asymptomatic patients with essential hypertension (EH), and to establish to what extent type 2 diabetes mellitus (DM) modifies the prevalence and severity of silent CAD in these patients. The study population consisted of 543 patients 45 years of age and older with EH (n=321) or EH with type 2 DM (n=222), without typical angina or known CAD, selected according to criteria defined by the American Diabetes Association. All patients underwent dipyridamole stress and rest 99mtechnetium sestamibi myocardial single-photon emission computed tomography imaging. The stress and rest myocardial images were divided into 20 segments and blindly scored by two experienced observers. The summed stress score and summed rest score were obtained by adding the scores of the 20 segments of the stress and rest sestamibi images, respectively. The difference between the summed stress score and the summed rest score was defined as the summed difference score, representing reversible ischemia. There was a significant difference (P=0.001) between the percentage of EH patients with (41.4%) and without (27.7%) DM, with regard to abnormal summed stress scores. Moreover, hypertensive, diabetic patients had a significantly greater incidence of moderate to severe ischemia (P=0.011). In addition, a significantly greater proportion of hypertensive patients with DM showed reversible ischemia compared with EH patients without DM (39.6% versus 24.6%; P<0.0001). Proteinuria and dyspnea were significant predictors of silent ischemia in EH patients with DM. In this high-risk population screened according to the American Diabetes Association criteria with dipyridamole sestamibi myocardial single-photon emission computed tomography imaging, the prevalence of silent ischemia was 28% in EH patients. It is noteworthy that the prevalence (41%) and severity of silent ischemia were significantly greater in EH patients with DM.
    No preview · Article · Feb 2006 · The Canadian journal of cardiology

  • No preview · Article · Aug 2005 · Journal of Nuclear Cardiology
  • C. Ĉté · M. Dumont · J. Lefebvre · L. Poirier · Y. Lacourcière

    No preview · Article · Jul 2005 · Journal of Nuclear Cardiology
  • Yves Lacourciere · Luc Poirier · Jean Lefebvre
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    ABSTRACT: More than one drug is often needed in treating patients with the systolic form of hypertension. The efficacy of 2 types of antihypertensive combination therapy on 24-hour blood pressure profile was compared in patients who have elevated systolic blood pressure (SBP) both in clinic (>150mmHg) and during daytime ambulatory monitoring (>135mmHg). Eligible patients (n=121; 40F/81M) were randomized to received a once daily morning regimen with either Losartan (L) 50 mg plus hydrochlorothiazide (H) 12.5 mg (Group 1; n=60) or H 12.5 mg (Group 2; n=61). If the target SBP (mean daytime ambulatory ≤ 135 mm Hg) was not achieved after 6 weeks of treatment, drug regimens were titrated up to L 100 mg plus H 25 mg or to H 12,5 mg plus Atenolol 50 mg for an additional 6-week period. Amlodipine 5 mg was then added as a third drug in combination for a further 6 weeks in non responders of each group. Clinic and ambulatory BP were measured after 6, 12 and 18 weeks. Daytime ambulatory systolic/diastolic BP were comparable in Group 1 (152.6/87.0 mmHg) and Group 2 (154.3/89.0 mmHg) at baseline. Average decreases were −9.8/−4.4, −16.0/−8.0 and −22.3/−11.3 mmHg in Group 1 and −2.2/−0.1, −12.3/−8.1 and −20.1/−12.0 mmHg in Group 2, after 6, 12 and 18 weeks, respectively. All reductions were significant (p
    No preview · Article · May 2005 · American Journal of Hypertension
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    ABSTRACT: Am J Hypertens (2005) 18, 66A–67A; doi:10.1016/j.amjhyper.2005.03.183 P-165: Comparative effects of lercanidipine, amlodipine and hydrochlorothiazide on 24-hour ambulatory blood pressure and leg edema in confirmed ambulatory hypertensive patients Jean Lefebvre1, Luc Poirier1 and Yves Lacourcière11Hypertension Research Unit, Centre Hospitalier Universitaire de Québec, Ste-Foy, QC, Canada.
    No preview · Article · Apr 2005 · American Journal of Hypertension

  • No preview · Article · Mar 2005 · Journal of Nuclear Cardiology

  • No preview · Article · Jan 2005 · Journal of Nuclear Cardiology
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    Jean Lefebvre · Luc Poirier · Yves Lacourcière
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    ABSTRACT: To review and comment on methods used to assess the duration of action of antihypertensive drugs. A MEDLINE search (1966-June 2000) using key terms such as trough-to-peak ratio and ambulatory blood pressure monitoring was conducted. An article was considered for this review if it pertained to the assessment of the duration of action of antihypertensive drugs. Special attention was given to articles dealing with methodologic aspects. Antihypertensive drugs with a long duration of action are thought to provide better therapeutic coverage against hypertensive complications compared with that of short-acting agents. Measuring blood pressure at the end of the dosing interval may be a way to assess the duration of action of a drug. However, the use of high doses of a short-acting agent to obtain sufficient effect when at trough concentrations can potentially cause dose-related adverse effects at the peak time, contributing to nonadherence to therapy and thus to adverse outcomes. To alleviate this problem, the US Food and Drug Administration (FDA) has conceptualized the trough-to-peak (T:P) ratio. Although this arithmetic index has since been widely used to characterize the duration and safety of blood pressure control achieved by antihypertensive agents, several methodologic flaws limit its interpretation in the clinic. Ambulatory blood pressure monitoring (ABPM) is a more reliable approach to assess the duration of action and outcome of antihypertensive therapy. Different methodologic approaches exist to evaluate the duration of action of antihypertensive drugs. Although the T:P ratio has been suggested by the FDA, it is difficult to establish a fair comparison among various antihypertensive agents based solely on this index. Treatment evaluation based on ABPM may be preferable to those guided by T:P because ABPM is more reproducible and is now established as a predictor of cardiovascular risk.
    Preview · Article · Jun 2002 · Annals of Pharmacotherapy
  • Y Lacourcière · L Poirier · J Lefebvre
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    ABSTRACT: Ambulatory blood pressure (ABP) monitoring has contributed significantly to the diagnosis, prognosis and treatment of hypertension. However, most of the published reviews have not focused on the 24 h efficacy of conventional and new antihypertensive agents as measured by ABP monitoring. To discuss the importance of 24 h blood pressure control, and to review the antihypertensive efficacy of conventional antihypertensive agents and of angiotensin II type I receptor (AT1R) blockers as assessed by ABP monitoring. The 24 h antihypertensive efficacy of the different classes of agents was reviewed based on clinical, randomized, double-blind trials published in peer review journals. These trials were mainly performed in the authors' research unit but were performed in other centres as well. Most antihypertensive agents provided 24 h ABP control. However, in the authors' experience, hydrochlorothiazide, some angiotensin converting enzyme inhibitors and low dosages of the calcium antagonist diltiazem did not permit satisfactory blood pressure reduction as assessed by ABP monitoring in truly hypertensive patients. AT1R blockers and especially those of the new generation characterized by tight and long lasting AT1-receptor binding produced adequate 24 h ABP control and continued effectiveness during the high risk early morning hours.
    No preview · Article · Oct 2000 · The Canadian journal of cardiology
  • L. Poirier · J. Lefebvre
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    ABSTRACT: Objectives: To evaluate the efficacy of Nebivolol (N), a beta-blocking agent, in hypertensive patients classified as extensive metabolizers (EM) or non-extensive metabolizers (non-EM) based on phenotype for cytochrome 2D6.
    No preview · Article · Jun 2000 · American Journal of Hypertension
  • L. Poirier · J. Lefebvre · F. Archambault
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    ABSTRACT: Objectives: To compare the antihypertensive efficacy of Irbesartan, an angiotensin receptor antagonist, and Enalapril, an angiotensin-converting enzyme inhibitor, in patients aged 65 years and over with grade I and II essential hypertension.
    No preview · Article · Jan 2000
  • J. Lefebvre · J. Turgeon · L. Poirier
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    ABSTRACT: There is increasing evidence that polymorphism of ACE gene is associated with diabetic nephropathy (GENEDIABStudy). Since hypertension plays important and independant role in the development of diabetic complications, it is worth measuring the occurrence of ACE polymorphism in hypertensives with type 2 diabetes. Objective: To evaluate the association of ACE Insertion/Deletion (I/D) polymorphism with ambulatory hypertension in patients with or without type 2 diabetes mellitus (DM).
    No preview · Article · Jan 2000

Publication Stats

273 Citations
106.66 Total Impact Points


  • 1992-2010
    • Centre hospitalier de l'Université de Montréal (CHUM)
      Montréal, Quebec, Canada
  • 1992-2007
    • Laval University
      • Faculty of Pharmacy
      Québec, Quebec, Canada
  • 2006
    • Centre Hospitalier de Laval
      Лаваль, Pays de la Loire, France
  • 2005
    • CHU de Québec
      Quebec City, Quebec, Canada
  • 2002-2005
    • Centre Hospitalier Universitaire de Québec (CHUQ)
      Québec, Quebec, Canada
  • 1996
    • Centre Hospitalier Le Vinatier
      Брон, Rhône-Alpes, France