In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes

Abt, Markus

Ballantyne, Christie M.

Barter, Philip J.

Brumm, Jochen

Chaitman, Bernard R.

Colquhoun, David

Holme, Ingar M.

Kallend, David

Leiter, Lawrence A.

Leitersdorf, Eran

McMurray, John J. V.

Mundl, Hardi

Nicholls, Stephen J.

Olsson, Anders G.

Schwartz, Gregory G.

Shah, Prediman K.

Tardif, Jean-Claude

The dal-OUTCOMES Investigators

Wright, R. Scott

English

Schwartz G.G.

Olsson A.G.

Abt M.

Ballantyne C.M.

Barter P.J.

Brumm J.

Chaitman B.R.

Holme I.M.

Kallend D.

Leiter L.A.

Leitersdorf E.

McMurray J.J.

DE CATERINA, Raffaele

dal OUTCOMES Investigators

Archivio della Ricerca - Università di Pisa

Effects of dalcetrapib in patients with a recent acute coronary syndrome

Gregory G. Schwartz

Anders G. Olsson

Markus Abt

Christie M. Ballantyne

Philip J. Barter

Jochen Brumm

Bernard R. Chaitman

Ingar M. Holme

David Kallend

Lawrence A. Leiter

Eran Leitersdorf

John J.V. McMurray

Hardi Mundl

Stephen J. Nicholls

Prediman K. Shah

Jean-Claude Tardif

R. Scott Wright

Crossref

New England Journal of Medicine

Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome

University of Queensland eSpace

BackgroundIn observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes.MethodsWe randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation.ResultsAt the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P=0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (PConclusionsIn patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann-La Roche; dal-OUTCOMES ClinicalTrials.gov number, NCT00658515.).Gregory G. Schwartz, Anders G. Olsson, Markus Abt, Christie M. Ballantyne, Philip J. Barter, Jochen Brumm, Bernard R. Chaitman, Ingar M. Holme, David Kallend, Lawrence A. Leiter, Eran Leitersdorf, John J.V. McMurray, Hardi Mundl, Stephen J. Nicholls, Prediman K. Shah, Jean-Claude Tardif and R. Scott Wright for the dal-OUTCOMES Investigator

Schwartz, G.

Olsson, A.

Ballantyne, C.

Abt, M.

Barter, P.

Brumm, J.

Chaitman, B.

Holme, I.

Kallend, D.

Leiter, L.

Leitersdorf, E.

McMurray, J.

Mundl, H.

Nicholls, S.

Shah, P.

Tardif, J.

Wright, R.

Adelaide Research &amp; Scholarship

BACKGROUND: In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes.
METHODS: We randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation.
RESULTS: At the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P=0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (P
CONCLUSIONS: In patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann-La Roche; dal-OUTCOMES ClinicalTrials.gov number, NCT00658515.)

Schwartz, Gregory G

Olsson, Anders G

Ballantyne, Christie M

Barter, Philip J

Chaitman, Bernard R

Holme, Ingar M

Leiter, Lawrence A

McMurray, John J V

Nicholls, Stephen J

Shah, Prediman K

Wright, R Scott

Goldner, David

Lehigh Valley Health Network: LVHN Scholarly Works

Effects of dalcetrapib in patients with a recent acute coronary syndrome.

BACKGROUND: In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes.

METHODS: We randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation.

RESULTS: At the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P=0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (P<0.001 for both comparisons).

CONCLUSIONS: In patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann-La Roche; dal-OUTCOMES ClinicalTrials.gov number, NCT00658515.)

ZORA

Schwartz, G.G.

Olsson, A.G.

Ballantyne, C.M.

Barter, P.J.

Chaitman, B.R.

Holme, I.M.

Leiter, L.A.

McMurray, J.J.V.

Nicholls, S.J.

Shah, P.K.

Wright, R.S.

Enlighten

Arterioscler Thromb Vasc Biol

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Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease: the dal-VESSEL randomized clinical trial.

What is the optimal blood pressure in patients after acute coronary syndromes?: Relationship of blood pressure and cardiovascular events in the PRavastatin OR atorVastatin Evaluation and Infection Therapy-Thrombolysis In

BACKGROUND less thanbrgreater than less thanbrgreater thanIn observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes. less thanbrgreater than less thanbrgreater thanMETHODS less thanbrgreater than less thanbrgreater thanWe randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation. less thanbrgreater than less thanbrgreater thanRESULTS less thanbrgreater than less thanbrgreater thanAt the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P = 0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (Pandlt;0.001 for both comparisons). less thanbrgreater than less thanbrgreater thanCONCLUSIONS less thanbrgreater than less thanbrgreater thanIn patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann-La Roche; dal-OUTCOMES ClinicalTrials.gov number, NCT00658515.)</p

Schwartz, Gregory G,

Olsson, Anders,

Abt, Markus,

Ballantyne, Christie M,

Barter, Philip J,

Brumm, Jochen,

Chaitman, Bernard R,

Holme, Ingar M,

Kallend, David,

Leiter, Lawrence A,

Leitersdorf, Eran,

McMurray, John J V,

Mundl, Hardi,

Nicholls, Stephen J,

Shah, Prediman K,

Tardif, Jean-Claude,

Wright, R Scott,

Swepub

Background: In observational analyses, higher levels of high-density lipoprotein ( HDL ) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein ( CETP ) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes. Methods: We randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation. Results: At the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter ( 1.1 mmol per liter ), and the mean low-density lipoprotein ( LDL ) cholesterol level was 76 mg per deciliter ( 2.0 mmol per liter ). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events ( 71% of the projected total number ), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point ( cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P=0.52 ) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo ( P < 0.001 for both comparisons ). Conclusions: In patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. ( Funded by F. Hoffmann–La Roche; dal-OUTCOMES ClinicalTrials.gov number, NCT00658515. 

Tardif, Jean Claude

ACU Research Bank

http://www.zora.uzh.ch/75761/1/NEJMoa1206797.pdf

Effects of dalcetrapib in patients with a recent acute coronary syndrome

Abstract

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Full text

Available Versions

Archivio della Ricerca - Università di Pisa

Crossref

University of Queensland eSpace

Adelaide Research & Scholarship

Lehigh Valley Health Network: LVHN Scholarly Works

ZORA

Enlighten

Swepub

ACU Research Bank

Effects of dalcetrapib in patients with a recent acute coronary syndrome

Abstract

Similar works

Full text

Available Versions

Archivio della Ricerca - Università di Pisa

Crossref

University of Queensland eSpace

Adelaide Research &amp; Scholarship

Lehigh Valley Health Network: LVHN Scholarly Works

ZORA

Enlighten

Swepub

ACU Research Bank

Adelaide Research & Scholarship