Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Lancet. 2010 Aug 14;376(9740):517-23. doi: 10.1016/S0140-6736(10)60935-X.

Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial.

Collaborators (792)

Topol EJ, Bhatt DL, Bousser MG, Fox KA, Cohen E, Creager MA, Despres JP, Easton JD, Hamm CW, Montalescot G, Pearson TA, Steg PG, Gaudin C, Job B, Murphy JH, Slatylak-Cheek S, Ansari K, Klayman G, Frye R, Harrington R, Imbs JL, Lee K, Kastrati A, Knopman DS, McCarthy C, Buyse M, Brass LM, Schömig A, Salloum IM, Cannata R, Cross J, Strzelecki M, Prcela L, Juran N, Bruce A, Pasca N, Del Valle M, Sarver W, Gamble T, Fleckenstein C, Mrazek K, Brown S, Brennan D, Balog C, Zito T, Brennan T, Terry D, Piontkowski S, Stewart D, Neale S, Pratt A, Pepoy M, Albuquerque A, Lara JF, Askari A, Baranowski B, Bartel T, Basart DC, Bashian G, Lima AF, Belli G, Bordalo e Sa AL, Brener S, Busch EW, Campbell E, Chhatriwalla A, Christofferson R, Ciccone A, Dahl T, Farkkila MA, Gonzales IF, Haude M, Held C, Kaminska A, Menon V, Mikulik R, Neau JP, Nederkoorn PJ, Okay T, Opala G, Orlova IA, Pasierski TJ, Peng GS, Plomaritoglou A, Ronaszeki A, Rossi ML, Sas K, Shields R, Sila C, Sitar J, Siva A, Stam J, Sweeney P, Syvanne M, Sztriha L, Thomas G, Urbanek K, Van Belle E, Vavuranakis M, Baptista MV, Vojtisek P, Yoon J, Fernando C, Roberto P, Alberto V, Sebastián A, León L, Astrid L, Alejandro U, Alfredo L, Luis L, Alberto C, Arturo RA, Carlos C, Hugo R, Julio V, Andrés A, Ignacio M, Miguel U, Juan S, Carlos J, Edgar H, Ruxandra DD, Vinereanu D, Vintila M, Cristina P, Lacramioara PD, Denilson A, Alvaro A, Ana A, Ge J, Van Cleemput J, Boxho G, De Deyn P, Eddy V, Frank N, Thissen JP, Van Gaal L, Liénart F, Ides C, Scheen A, Muyldermans L, Thoeng J, Geraedts J, Hasenbroekx MC, El allaf D, Dendale P, Van Mieghem W, Cools F, Degaute JP, Renkin J, Chenu P, Vandermotte M, Descamps O, De Wolf L, Tamás F, Gábor KR, László U, László C, Attila V, Péter- D, István- K, Zoltán- J, György- P, András- G, Károly- N, Gábor- W, János- N, András- N, Kim Y, Han K, Lee K, Nam M, Seo H, Bae HJ, Kim Y, Jeong MH, Ferrari E, Bassand JP, Paillard F, Cottin Y, Ben Ahmed F, Danchin N, Charpentier G, Marechaud R, Duly-Bouhanick B, Charbonnel B, Ziegler O, Moulin P, Taminau D, Gabreau T, Borys JM, Crassard I, Pinel JF, Boulliat J, Ellie E, Rosolacci T, Decombe R, Abenhaim N, Fonteny R, Medvedowsky A, Mongin G, Mansour M, Lucas C, Mahagne MH, Steg G, Montalescot G, Demarcq JM, Roynard JL, Gacem K, Martelet M, Galley D, Genest M, Jean M, Touze E, Abhay M, Kumar AP, Sanjay K, Parag S, Sanjay C, Rajeev G, Belousov Y, Shestakova M, Butrova S, Egorova I, Chazova I, Ageev F, Glezer M, Parfenov V, Suslina Z, Skoromets A, Yakusevich V, Khrustalev O, Mkrtchian V, Blokhin A, Gorokhovskaya G, Zrazhevsky K, Zateyshchikov D, Kostenko V, Stryuk R, Bart B, Gratsiansky N, Vishnevsky A, Leslie B, Ranjit M, Robert C, Richard D, Adam A, Geraint J, David M, John R, Cliff S, David B, David S, Gerry S, Jonathan T, Tony W, John W, Philip W, Yuk-ki W, Marcus F, Gary F, Damian M, Malcolm M, John P, Robaayah Z, Hian SK, Bin KN, Mohamad WB, Haron KH, Amir K, Felix M, Mario C, Juan U, Michael GJ, Sharyl MB, Allen A, James A, Irfan A, Alexander A, Christie B, Heather G, Susan B, Neville B, Nancy B, Jeffrey B, Robert B, Timothy B, John C, James B, Harish C, Lambert C, Brett IJ, Michael C, Thomas D, Kathleen C, Anthony C, Steven K, James C, Gregory C, Berge D, Bhuvaneswari D, Drake D, Joshua D, Michael D, Peter D, Margaret D, Michael D, Daniel E, William E, Raymond E, William F, Paul F, Alan F, Raul G, Alan G, James G, Wilford GF, John G, Santosh G, Anne G, Jerome G, Bradley G, Jerry G, Dinesh G, Wayne H, Robert H, Paul H, Kathie H, John H, Peter H, Robert H, Ali I, Mark J, Kumar R, Peter K, Kerry K, Roy K, Ronald K, Roger K, Nelson K, Michael K, Mark K, German L, Michael L, Todd H, James L, Jon L, Roberta L, Barry M, Scott W, Anthony M, Edward T, Paul M, William B Jr, Thomas R, Jerry M, Joseph M 3rd, Patrick M, Kin NK, Fernando O, Barry P, Zorba P, Kiritkumar P, Thomas P, Candice P, Daniel P, Stewart P, Rakesh P, Campbell JH, Patrick R, Daniel U, Andrew RR, Sanjeev R, Michele R, Kenneth R, Lee RT, Brenda R, Jeffrey R, David R, Kenneth R, John R, Lon L, Lori R, Nectana P, Nectana P, James S, Roger M, John F, James N, Suguna M, David C, Stephen J, Scott B, Wager M, Frank S, Kenneth S, Charles B, John S, Shaukat S, Robert H, David S, William S, Mohammed S, Scott S, Elias K, Savala GM, Bozena S, Greg S, Khaled Z, David S, Danny S, Raul T, Georges T, Robert W, Gary Y, Louis G, James C, Kenneth C, Tim F, Barry G, Intekhab A, Priscilla H, Robert M, Thomas M, Richard C, Joseph O, Karen O, Timothy S, Christopher S, Michael T, Paul T, Mark T, Douglas Z, Dorothy B, Perminder B, Christine K, Bruce C, Mark C, Warren F, Glenn G, John A, Mark HE, Barry H, Victor H, Cynthia H, Alan J, William J, Diane K, Judith K, DeRen H, Kenneth L, Sandip M, Abdullah N, Peter N, Michael P, Ernesto R, Michael S, Matthew S, John S, Catherine V, Garo G, Daniel D, John A, Souvik S, Michael A, Marc R, Richard B, Bret H, Sunil G, Jet H, Allan B, James F, Thomas V, John C, Julio R, Kamelesh P, Eric D, Dean K, Parag P, Joseph H, Andrew S, Marc C, Paul M, Todd S, Anthony F, Jeffrey K, Terry F, Sharon J, James B, Darren M, Gordon C, Scott K, Odilon A, Anne R, Stephen N, Jeffrey S, Neal W, Levin ER, David B, Michael S, Ulrich S, David K, Martin M, Saravanan K, Greg F, Stuart Z, Gary H, Janet S, Alexander M, Robert G Jr, Alan H, Robert O, John B, Karunaratne HB, David H, Edward K, McGrew F 3rd, Peter R, Stephen C, Wayne L, Harold G, Jeffrey Q, Peter C, Hans N, Michael M, Witoon WA, Nizar D, Vibhuti S, Robert R, John H, Kirk P, Hal K, Ahmad H, Abayomi O, Deborah S, David T, William S, David G, Michael L, Donald C, Thomas R, Jonathan L, Joseph K, Lemont M, Charles W, Kenneth M, Raymond K, Philip W, Leo E, Renee S, Barney B, Bernard E, Edward S, Littlejohn T 3rd, James Z, Robert L, Mahmoud A, Mehar A, Albert C, Kurt D, Stephen G, David K, John M, William P, Diane Z, Harry C, Steve K, Rodney I, James H, John M, Gregory M, Kevin A, Joseph G, Allan E, Victor E, Robert F, David H, Robert S, Robert S, Douglas D, Haroonur R, Mark H, Michael GC, Scott J, Kabir Y, Evan S, Bobby K, Robert V, Tyler WL, David K, Russell S, Martin S, Eric H, Bruce J, Stanley D, Edward K, Michael S, McLaughlin MA, Bassem M, Bassem M, James H, Raye B, Rohit A, William F, Carlos I, Rodney H, Addison T, Joseph R, Veita B, Scott C, Ira F, Charles E, Herbert HW, David D, Alex A, Robert B, Richard D, Waenard M, Stanley S, Purushotham K, Satyaprakash M, David SZ, Muhammad K, Henry L, Brian S, Dharmendra P, Garnett RJ, Shealy NL, John S, Bret W, Matthew F, Bernard M, Venkata C, Vinay S, Jeff H, James K, David H, William P, Kenneth P, Jeffrey R, Ronnie A, Joseph B, Teosar B, Laurie B, James C, Sammy C, Christian C, Richard G, Kenneth G, Irving G, Irene H, William H, Ashiqul I, Campbell J, Simon K, Lau DC, Garry M, David M, Robert P, Lew P, David SJ, Gérald T, Yaw TB, Garth V, Anthony WD, Paul W, Jafna C, Lawrence L, Remo Z, Jacques B, Keith B, Ariane M, Robert C, Ashfaq S, Anthony W, Petr P, Stephen P, Paul P, Daniel S, Eric SA, Peter K, Milan G, Keith K, Hiren D, Louis Y, Dennis R, Leo B, Andrew P, Pierre A, Ronald G, Victor G, Luis M, Luis C, Patrícia C, Vasco S, Manuel M, José S, Carlos C, Maria S, Dinis M, Rita D, Miguel R, João L, Sum CF, Tan RS, Chang HM, Chen C, Chan BP, John DA, Andrew J, Lindsay RB, Petrus VT, Christian BD, Jeffrey K, Landman L, Dudley K, Hoosain LG, Deepak L, Kathleen C, Shirley M, Soraya C, Juan GP, Alberto MH, Luis AS, Lluis M, Miquel V, Xavier F, María AN, Enrique M, Jaume R, Javier OA, Jordi J, Elisa C, Francisco G, Exuperio D, Dolores JM, Héctor B, Eduardo de T, Ramón GJ, Fernando WD, Vicente B, Norberto AO, Enrique P, Ramón G, Bartolomé B, Pedro de PV, Anna S, Olga C, Miguel RL, Joaquín S, Vivencio B, José A, Carlos C, Víctor L, Arturo FC, Francisco B, Jan O, Anders OG, Mikael D, Tage S, Anders W, Peter N, Rebecca UG, Lena B, Jörg T, Peter B, Augusto G, Alain G, Philippe L, Hans R, Juan R, Hugo S, Tiziano M, Kurt L, Habib H, Samir K, Habib G, Fayçal H, Habiba D, Amel M, Riadh G, Chokri M, Mahbouba FA, Hakan K, Hasan I, Candeger Y, Sazi I, Bascil TN, Aytekin O, Mustafa B, Murat E.

Author information

  • 1Scripps Translational Science Institute, La Jolla, CA 92037, USA. etopol@scripps.edu

Abstract

BACKGROUND:

Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant would improve major vascular event-free survival.

METHODS:

This double-blind, placebo-controlled trial was undertaken in 974 hospitals in 42 countries. 18,695 patients with previously manifest or increased risk of vascular disease were randomly assigned to receive either rimonabant 20 mg (n=9381) or matching placebo (n=9314). Randomisation was stratified by centre, implemented with an independent interactive voice response system, and all study personnel and participants were masked to group assignment. The primary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke, as determined via central adjudication. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00263042.

FINDINGS:

At a mean follow-up of 13.8 months (95% CI 13.6-14.0), the trial was prematurely discontinued because of concerns by health regulatory authorities in three countries about suicide in individuals receiving rimonabant. All randomised participants were analysed. At the close of the trial (Nov 6, 2008), the composite primary endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 364 (3.9%) patients assigned to rimonabant and 375 (4.0%) assigned to placebo (hazard ratio 0.97, 95% CI 0.84-1.12, p=0.68). With rimonabant, gastrointestinal (3038 [33%] vs 2084 [22%]), neuropsychiatric (3028 [32%] vs 1989 [21%]), and serious psychiatric side-effects (232 [2.5%] vs 120 [1.3%]) were significantly increased compared with placebo. Four patients in the rimonabant group and one in the placebo group committed suicide.

INTERPRETATION:

The premature termination of this trial has important lessons for drug development. A drug that was being marketed for weight loss, but being tested for improving cardiovascular outcomes, induced a level of serious neuropsychiatric effects that was deemed unacceptable by regulatory authorities, and both the drug and the trial were abruptly terminated.

FUNDING:

Sanofi-Aventis.

Copyright 2010 Elsevier Ltd. All rights reserved.

Comment in

PMID:
20709233
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk