Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

HPS3/TIMI55–REVEAL Collaborative Group

doi:10.1056/nejmoa1706444

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

HPS3/TIMI55–REVEAL Collaborative Group

Genomforskning og Molekylær Biomedicin

448 Citationer (Scopus)

Abstract

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of −18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo.

Originalsprog	Engelsk
Tidsskrift	The New England Journal of Medicine
Vol/bind	377
Udgave nummer	13
Sider (fra-til)	1217-1227
Antal sider	11
ISSN	0028-4793
DOI	https://doi.org/10.1056/nejmoa1706444
Status	Udgivet - 28 sep. 2017

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@article{d39b8daffd0f4175b3f2dc34e50a2015,

title = "Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease",

abstract = "BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of −18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo.",

keywords = "Aged, Anticholesteremic Agents/adverse effects, Atherosclerosis/complications, Cholesterol/blood, Cholesterol Ester Transfer Proteins/antagonists & inhibitors, Coronary Disease/epidemiology, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Incidence, Kaplan-Meier Estimate, Male, Medication Adherence, Middle Aged, Oxazolidinones/adverse effects",

author = "Louise Bowman and Hopewell, {Jemma C} and Fang Chen and Karl Wallendszus and William Stevens and Rory Collins and Wiviott, {Stephen D} and Cannon, {Christopher P} and Eugene Braunwald and Emily Sammons and Landray, {Martin J} and Steen Stender and {HPS3/TIMI55–REVEAL Collaborative Group}",

year = "2017",

month = sep,

day = "28",

doi = "10.1056/nejmoa1706444",

language = "English",

volume = "377",

pages = "1217--1227",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "13",

}

TY - JOUR

T1 - Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

AU - Bowman, Louise

AU - Hopewell, Jemma C

AU - Chen, Fang

AU - Wallendszus, Karl

AU - Stevens, William

AU - Collins, Rory

AU - Wiviott, Stephen D

AU - Cannon, Christopher P

AU - Braunwald, Eugene

AU - Sammons, Emily

AU - Landray, Martin J

AU - Stender, Steen

AU - HPS3/TIMI55–REVEAL Collaborative Group

PY - 2017/9/28

Y1 - 2017/9/28

N2 - BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of −18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo.

AB - BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of −18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo.

KW - Aged

KW - Anticholesteremic Agents/adverse effects

KW - Atherosclerosis/complications

KW - Cholesterol/blood

KW - Cholesterol Ester Transfer Proteins/antagonists & inhibitors

KW - Coronary Disease/epidemiology

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Female

KW - Humans

KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use

KW - Incidence

KW - Kaplan-Meier Estimate

KW - Male

KW - Medication Adherence

KW - Middle Aged

KW - Oxazolidinones/adverse effects

U2 - 10.1056/nejmoa1706444

DO - 10.1056/nejmoa1706444

M3 - Journal article

C2 - 28847206

SN - 0028-4793

VL - 377

SP - 1217

EP - 1227

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 13

ER -

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

Abstract

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