• Je něco špatně v tomto záznamu ?

Long-term Tolerability of Ticagrelor for the Secondary Prevention of Major Adverse Cardiovascular Events: A Secondary Analysis of the PEGASUS-TIMI 54 Trial

MP. Bonaca, DL. Bhatt, T. Oude Ophuis, PG. Steg, R. Storey, M. Cohen, J. Kuder, K. Im, G. Magnani, A. Budaj, P. Theroux, C. Hamm, J. Špinar, RG. Kiss, AJ. Dalby, FA. Medina, F. Kontny, PE. Aylward, EC. Jensen, P. Held, E. Braunwald, MS. Sabatine,

. 2016 ; 1 (4) : 425-32.

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, randomizované kontrolované studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19001380

IMPORTANCE: In the PEGASUS-TIMI 54 trial, treatment with ticagrelor reduced the incidence of cardiovascular death, myocardial infarction, or stroke by 15% to 16% among stable patients compared with placebo. However, more patients prematurely discontinued treatment with ticagrelor than with placebo. OBJECTIVE: To investigate the reasons and timing of discontinuation of treatment with ticagrelor among stable patients prior myocardial infarction. DESIGN, SETTING, AND PARTICIPANTS: In the PEGASUS-TIMI 54 trial, 21 162 stable outpatients with prior myocardial infarction were randomly assigned to 90 mg of ticagrelor twice daily, 60 mg of ticagrelor twice daily, or placebo, with all of the patients receiving a low dose of aspirin. These participants were followed up for a median of 33 months (study start date: October 2010; completion date: December 2014). Discontinuation of treatment was evaluated by treatment arm, cause, and timing. This analysis was initiated in May 2015. MAIN OUTCOME AND MEASURE: Discontinuation of treatment. RESULTS: Over 33 months, 32%, 29%, and 21% of patients receiving 90 mg of ticagrelor, 60 mg of ticagrelor, and placebo, respectively, discontinued treatment (P < .001). Discontinuation of treatment due to an adverse event occurred in 19%, 16%, and 9% of patients, respectively (P < .001). The most frequent adverse events leading to discontinuation of treatment were bleeding (with Kaplan-Meier event rates of 7.8%, 6.2%, and 1.5% of patients, respectively; P < .001) and dyspnea (6.5%, 4.6%, and 0.8% of patients, respectively; P < .001). Eighty-six percent of bleeding events that led to the discontinuation of treatment with ticagrelor were nonmajor, and 86% of adverse events due to dyspnea that led to discontinuation of treatment with ticagrelor were mild or moderate in severity. The discontinuation rates are annualized for patients who received 90 mg of ticagrelor twice daily (hazard ratio [HR], 2.00 [95% CI, 1.84-2.16] for the first year; HR, 1.12 [95% CI, 1.00-1.26] for the second and third years) and patients who received 60 mg of ticagrelor twice daily (HR, 1.59 [95% CI, 1.46-1.73] for the first year; HR, 1.18 [95% CI, 1.06-1.32] for the second and third years) compared with patients who received placebo. CONCLUSIONS AND RELEVANCE: When initiated among stable patients with prior myocardial infarction, discontinuation of treatment with ticagrelor was driven primarily by nonserious adverse events occurring primarily early after randomization. For patients completing 1 year of treatment, the subsequent discontinuation rate was low. These data demonstrate how adverse events considered "nonserious" by traditional trial criteria may have an effect on quality of life and, thus, may precipitate the discontinuation of treatments and underscore the need for patient education and counseling on the timing and nature of adverse effects with the aim of improving adherence when appropriate. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01225562.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19001380
003      
CZ-PrNML
005      
20200121111400.0
007      
ta
008      
190107s2016 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1001/jamacardio.2016.1017 $2 doi
035    __
$a (PubMed)27438319
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Bonaca, Marc P $u TIMI Study Group, Brigham and Women's Hospital Heart and Vascular Center, Boston, Massachusetts.
245    10
$a Long-term Tolerability of Ticagrelor for the Secondary Prevention of Major Adverse Cardiovascular Events: A Secondary Analysis of the PEGASUS-TIMI 54 Trial / $c MP. Bonaca, DL. Bhatt, T. Oude Ophuis, PG. Steg, R. Storey, M. Cohen, J. Kuder, K. Im, G. Magnani, A. Budaj, P. Theroux, C. Hamm, J. Špinar, RG. Kiss, AJ. Dalby, FA. Medina, F. Kontny, PE. Aylward, EC. Jensen, P. Held, E. Braunwald, MS. Sabatine,
520    9_
$a IMPORTANCE: In the PEGASUS-TIMI 54 trial, treatment with ticagrelor reduced the incidence of cardiovascular death, myocardial infarction, or stroke by 15% to 16% among stable patients compared with placebo. However, more patients prematurely discontinued treatment with ticagrelor than with placebo. OBJECTIVE: To investigate the reasons and timing of discontinuation of treatment with ticagrelor among stable patients prior myocardial infarction. DESIGN, SETTING, AND PARTICIPANTS: In the PEGASUS-TIMI 54 trial, 21 162 stable outpatients with prior myocardial infarction were randomly assigned to 90 mg of ticagrelor twice daily, 60 mg of ticagrelor twice daily, or placebo, with all of the patients receiving a low dose of aspirin. These participants were followed up for a median of 33 months (study start date: October 2010; completion date: December 2014). Discontinuation of treatment was evaluated by treatment arm, cause, and timing. This analysis was initiated in May 2015. MAIN OUTCOME AND MEASURE: Discontinuation of treatment. RESULTS: Over 33 months, 32%, 29%, and 21% of patients receiving 90 mg of ticagrelor, 60 mg of ticagrelor, and placebo, respectively, discontinued treatment (P < .001). Discontinuation of treatment due to an adverse event occurred in 19%, 16%, and 9% of patients, respectively (P < .001). The most frequent adverse events leading to discontinuation of treatment were bleeding (with Kaplan-Meier event rates of 7.8%, 6.2%, and 1.5% of patients, respectively; P < .001) and dyspnea (6.5%, 4.6%, and 0.8% of patients, respectively; P < .001). Eighty-six percent of bleeding events that led to the discontinuation of treatment with ticagrelor were nonmajor, and 86% of adverse events due to dyspnea that led to discontinuation of treatment with ticagrelor were mild or moderate in severity. The discontinuation rates are annualized for patients who received 90 mg of ticagrelor twice daily (hazard ratio [HR], 2.00 [95% CI, 1.84-2.16] for the first year; HR, 1.12 [95% CI, 1.00-1.26] for the second and third years) and patients who received 60 mg of ticagrelor twice daily (HR, 1.59 [95% CI, 1.46-1.73] for the first year; HR, 1.18 [95% CI, 1.06-1.32] for the second and third years) compared with patients who received placebo. CONCLUSIONS AND RELEVANCE: When initiated among stable patients with prior myocardial infarction, discontinuation of treatment with ticagrelor was driven primarily by nonserious adverse events occurring primarily early after randomization. For patients completing 1 year of treatment, the subsequent discontinuation rate was low. These data demonstrate how adverse events considered "nonserious" by traditional trial criteria may have an effect on quality of life and, thus, may precipitate the discontinuation of treatments and underscore the need for patient education and counseling on the timing and nature of adverse effects with the aim of improving adherence when appropriate. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01225562.
650    _2
$a adenosin $x škodlivé účinky $x analogy a deriváty $x terapeutické užití $7 D000241
650    _2
$a dyspnoe $x chemicky indukované $7 D004417
650    _2
$a krvácení $x chemicky indukované $7 D006470
650    _2
$a lidé $7 D006801
650    _2
$a infarkt myokardu $x prevence a kontrola $7 D009203
650    _2
$a antagonisté purinergních receptorů P2Y $7 D058921
650    _2
$a kvalita života $7 D011788
650    12
$a sekundární prevence $7 D055502
650    _2
$a cévní mozková příhoda $x prevence a kontrola $7 D020521
650    _2
$a ticagrelor $7 D000077486
655    _2
$a časopisecké články $7 D016428
655    _2
$a randomizované kontrolované studie $7 D016449
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Bhatt, Deepak L $u TIMI Study Group, Brigham and Women's Hospital Heart and Vascular Center, Boston, Massachusetts.
700    1_
$a Oude Ophuis, Ton $u Department of Cardiology, CWZ Hospital, Nijmegen, the Netherlands.
700    1_
$a Steg, P Gabriel $u Département Hospitalo Universitaire FIRE, AP-HP, Hôpital Bichat, Paris, France4Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
700    1_
$a Storey, Robert $u Department of Cardiovascular Science, University of Sheffield, Sheffield, England.
700    1_
$a Cohen, Marc $u Cardiovascular Division, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark, New Jersey.
700    1_
$a Kuder, Julia $u TIMI Study Group, Brigham and Women's Hospital Heart and Vascular Center, Boston, Massachusetts.
700    1_
$a Im, Kyungah $u TIMI Study Group, Brigham and Women's Hospital Heart and Vascular Center, Boston, Massachusetts.
700    1_
$a Magnani, Giulia $u TIMI Study Group, Brigham and Women's Hospital Heart and Vascular Center, Boston, Massachusetts.
700    1_
$a Budaj, Andrzej $u Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland.
700    1_
$a Theroux, Pierre $u Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada.
700    1_
$a Hamm, Christian $u Department of Cardiology, Kerckhoff Heart Center, Bad Nauheim, Germany10University of Giessen, Giessen, Hesse, Germany.
700    1_
$a Špinar, Jindrich $u Internal Cardiology Department, University Hospital and Medical Faculty, Brno, Czech Republic.
700    1_
$a Kiss, Robert G $u Department of Cardiology, Military Hospital, Budapest, Hungary.
700    1_
$a Dalby, Anthony J $u South African Cardiology Clinical Trials Group, Milpark Hospital, Johannesburg, South Africa.
700    1_
$a Medina, Felix A $u Departamento de Clínicas Médicas, Hospital Nacional Cayetano Heredia, San Martin de Porres, Lima, Peru.
700    1_
$a Kontny, Frederic $u Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.
700    1_
$a Aylward, Philip E $u South Australian Health and Medical Research Institute, Flinders University, Adelaide, Australia.
700    1_
$a Jensen, Eva C $u AstraZeneca Research and Development, Mölndal, Sweden.
700    1_
$a Held, Peter $u AstraZeneca Research and Development, Mölndal, Sweden.
700    1_
$a Braunwald, Eugene $u TIMI Study Group, Brigham and Women's Hospital Heart and Vascular Center, Boston, Massachusetts.
700    1_
$a Sabatine, Marc S $u TIMI Study Group, Brigham and Women's Hospital Heart and Vascular Center, Boston, Massachusetts18Deputy Editor, JAMA Cardiology.
773    0_
$w MED00191356 $t JAMA cardiology $x 2380-6591 $g Roč. 1, č. 4 (2016), s. 425-32
856    41
$u https://pubmed.ncbi.nlm.nih.gov/27438319 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20190107 $b ABA008
991    __
$a 20200121111737 $b ABA008
999    __
$a ok $b bmc $g 1364077 $s 1039503
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2016 $b 1 $c 4 $d 425-32 $i 2380-6591 $m JAMA cardiology $n JAMA Cardiol $x MED00191356
LZP    __
$a Pubmed-20190107

Najít záznam

Citační ukazatele

Možnosti archivace