13 research outputs found
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
- Author
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- The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group
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- ZZ Chong
- Publication venue
- Publication date
- 09/08/2008
- Field of study
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Continued efforts to translate diabetes cardiovascular outcome trials into clinical practice
- Author
- A Ceriello
- A Juutilainen
- AK Gitt
- Angelo Avogaro
- B Zinman
- BM Brenner
- BM Frier
- BM Scirica
- C Emerging Risk Factors
- C Emerging Risk Factors
- C Wanner
- CA Schneider
- CR Triggle
- CS Kwok
- D D’Alessio
- D Fitchett
- D Kirpichnikov
- E Ferrannini
- Enzo Bonora
- F Jiao
- F Paneni
- FA Laar Van de
- Gian Paolo Fadini
- Giorgio Sesti
- GP Fadini
- GP Fadini
- GP Fadini
- Group AC Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P et al.
- HN Ginsberg
- JA Dormandy
- JB Green
- JL Chiasson
- JR Ussher
- K Malmberg
- K Malmberg
- K Pyorala
- L Li
- LF Valenzuela-Garcia
- M Authors/Task Force
- M Hanefeld
- MA Pfeffer
- N Marx
- N Sattar
- OT Investigators
- P Gaede
- P Wang
- R Boussageon
- R Boussageon
- R Spiegel
- RA DeFronzo
- RK Ghosh
- RM Touyz
- RR Holman
- RR Wing
- S Singh
- SE Nissen
- SE Nissen
- SK Paul
- SK Paul
- SP Marso
- Stefano Del Prato
- T Wilke
- UK Prospective Diabetes Study (UKPDS) Group
- V Gyberg
- V Menon
- V Ritsinger
- WB White
- WX Li
- X Zhou
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial
- Author
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- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2018
- Field of study
Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline
Nanoparticles and potential neurotoxicity: focus on molecular mechanisms
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- Publication venue
- 'American Institute of Mathematical Sciences (AIMS)'
- Publication date
- 01/01/2018
- Field of study
Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial
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- Publication venue
- Publication date
- 01/01/2018
- Field of study
Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke
Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients
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- Zannad Faiez
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- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2017
- Field of study
BACKGROUN
Hepatic Carbohydrate Metabolism
- Author
- A Burchell
- A Gardemann
- A Giacca
- A Holstein
- A Mangia
- A Pocai
- A Valera
- A Valera
- A Xu
- AD Cherrington
- AD Cherrington
- AJ McCullough
- AM Fernandez
- AR Saltiel
- B Christ
- B Christ
- C Buettner
- C Pagano
- C Postic
- C Weigert
- C Weigert
- C Yu
- CL McTernan
- CM Steppan
- D Cai
- D Johnson
- D Raddatz
- D Raddatz
- DB Savage
- DK Sindelar
- DS Edgerton
- DT Duong
- E Bugianesi
- E Bugianesi
- E Ferrannini
- E Yagmur
- ED Muse
- EW Kraegen
- F Andreozzi
- F Stumpel
- F Tremblay
- G Bianchi
- G Buzzelli
- G Marchesini
- G Marchesini
- G Perseghin
- G Sesti
- G Toffolo
- GB Gregorio Di
- GF Lewis
- GF Lewis
- GM Reaven
- GS Hotamisligil
- H Inoue
- H Masuzaki
- H Masuzaki
- H Okamoto
- I Magnusson
- IA Leclercq
- J Friedman
- J Girard
- J Girard
- J Hirosumi
- J Radziuk
- J Tazawa
- JC Yoon
- JK Kim
- JM Fernandez-Real
- JM Hui
- JM Hui
- JM Way
- K Jungermann
- K Ozawa
- K Patel
- K Rittig
- KF Petersen
- KT Uysal
- KY Trinh
- M Fraenkel
- M Haluzik
- M Hoene
- M Krebs
- M Matsumoto
- M Roden
- M Shaheen
- M Simmgen
- M Wang
- MD Michael
- ME Allison
- MF White
- MJ Bahr
- MJ Muller
- MJ Pagliassotti
- MJ Yin
- MW Rajala
- MW Rajala
- N Barzilai
- N Houstis
- N Maeda
- NM Morton
- P Harle
- P Puigserver
- P Vannini
- PG McTernan
- R Basu
- R Dentin
- R Dentin
- R Desbriere
- R D’Alfonso
- R Suzuki
- R Taylor
- R Thieringer
- RK Hall
- RM O’Brien
- RR Pencek
- S Aleffi
- S Aytug
- S Boura-Halfon
- S Engeli
- S Furukawa
- S Gentile
- S Kaser
- S Kaser
- S Liangpunsakul
- S Metzger
- S Obici
- S Yakar
- S Yakar
- SE Shoelson
- SH Caldwell
- SH Mehta
- SJ Fisher
- SJ Pilkis
- SK Bethanis
- SK Fried
- SK Paulsen
- SM Rangwala
- SP Kim
- SY Lin
- T Ferre
- T Ferre
- T Kawaguchi
- T O’Connell
- T Tsutsumi
- T Yamauchi
- U Ozcan
- V Aguirre
- V Wallenius
- VT Samuel
- W Creutzfeldt
- W Nolte
- W Nolte
- X Dong
- Y Kotelevtsev
- Y Kruszynska
- Y Lin
- Y Shintani
- Y Sun
- YT Kruszynska
- Z Gao
- Z Li
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Management of diabetes in older adults
- Author
- A. Consoli
- A. Giaccari
- Abbatecola
- AMD – SID. Associazione Medici Diabetologi (AMD) – Società Italiana di Diabetologia (SID)
- American Diabetes Association
- American Diabetes Association
- American Diabetes Association
- American Diabetes Association
- Ashcroft
- Aubert
- Barnett
- Beckett
- Bethel
- Bo
- Bode
- Bonadonna
- Buffa
- Butler
- Campanelli
- Carstensen
- Catapano
- Centers for Disease Control and Prevention
- Chilton
- Chiniwala
- Crowley
- Crowley
- Cryer
- DeFronzo
- Dormandy
- Duarte
- E. Bonora
- Egan
- Engel
- Eurich
- F. Purrello
- FDA
- FDA
- FDA
- FDA
- Filion
- Fioretto
- Fralick
- G. Paolisso
- G. Sesti
- G. Vendemiale
- Gerstein
- Ghosh
- Giorda
- Giorda
- Giorda
- Green
- Gribble
- Halimi
- Hillier
- Holman
- Horsdal
- Huang
- Huang
- Hunter
- International Diabetes Federation
- Inzucchi
- Inzucchi
- Inzucchi
- James
- Johnston
- Johnston
- Josse
- Kalyani
- Karagiannis
- Karyekar
- Khalangot
- Kim
- Kimbro
- Kirkman
- Kosiborod
- Liatis
- Limongi
- Mamza
- Marchesini
- Marseglia
- Marso
- McCoy
- McGuire
- Mehta
- Mogensen
- Munshi
- N. Ferrara
- Neal
- Nelson
- Noale
- Osservatorio ARNO
- Pantalone
- Patel
- Pfeffer
- Pilotto
- Qi
- R. Antonelli Incalzi
- Riddle
- Roberts
- S. Maggi
- Scheen
- Schneider
- Schramm
- Scirica
- Scirica
- Searle
- Seufert
- Shih
- Shyangdan
- SID – SIGG. Società Italiana di Diabetologia (SID) – Società Italiana di Gerontologia e Geriatria
- Signorovitch
- Simpson
- Sinclair
- Sinclair
- Son
- Sonesson
- St-Onge
- Stafford
- Stratton
- UKPDS Group
- UKPDS Group
- Umezawa
- Wanner
- Watts
- White
- Wilcox
- World Health Organization
- Wu
- Xu
- Yu
- Zannad
- Zinman
- Zoungas
- Publication venue
- 'Elsevier BV'
- Publication date
- Field of study
Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients
- Author
- A A
- Abbott Jd
- Abdullah S
- Abib E Jr
- Ables Lr
- Abrantes Ja
- Acosta R
- Adams A
- Adams F
- Adroer Martori R
- Agafina As
- Agaiby Jm
- Aggarwala G
- Agraou B
- Aguilarsalinas Ca
- Ahmad A
- Ajala B
- Akdeniz B
- Akhtar N
- Akright L
- Aksentiev S
- Al-Zoebi A
- Alappat P
- Albert M
- Alfieri Ad
- Alhakim M
- Allaw Ma
- Alpizar-Salazar M
- Altafullah Im
- Alvarado Op
- Alvarez Ca
- Alvarez Jg
- Alvarez Ms
- Alvarez-Sala Walther La
- Alves AR Jr
- Alwine Lk
- Alzand B
- Amarenco P.
- Ambrovicova V
- Amerena J
- Andersen Jl
- Andersen Lt
- Anderson P
- Anderson Tj
- Andrassy P
- Andrei Ld
- Andreka P
- Angoulvant D
- Angun M
- Annamalai N
- Ansari Sh
- Anselmi M
- Antonicelli R
- Appel Kf
- Aracil Villar J
- Arain S
- Arambula Rm
- Araz M
- Arca M
- Arcanese Ml
- Arden C
- Areas Ca
- Ari H
- Ariani Mk
- Arif I
- Aroney C
- Aronson R
- Arstall M
- Arstila L
- Arya Kw
- Asamoah-Owusu N
- Askonen K
- Aslam Aa
- Assadourian A
- Assef V
- Atar S
- Auriel E
- Avaca H
- Averna M
- Avornyo Aa
- Avram Ri
- Axthelm C
- Ayesu K
- Aylward Pe
- Ayoub Jc
- Baar M
- Babapulle M
- Badat Ae
- Bailey Sr
- Bajaj H
- Bajcsi D
- Baker J
- Bakhai A
- Baldari D
- Ball Em
- Ballantyne Cm
- Ballyuzek M
- Balo T
- Banaszkiewicz K
- Bandeira e Farias FA
- Banerjee M
- Banik M
- Banyai M
- Baranova E
- Barbarash Ol
- Barbieri Ds
- Barettella Mb
- Barker Ba
- Barnum O
- Barreda Gonzalez Mj
- Barrera Cm
- Barrington P
- Baultrukonis D
- Bax Wa
- Bayat J
- Bayron Cj
- Bays He
- Beaudry P
- Beckett Pl
- Begg A
- Behmanesh B
- Behnke T
- Belenkiy Di
- Belicova M
- Bellido Guerrero D
- Bellingar B
- Beltran Lg
- Benacka J
- Benatar Jr
- Benczur B
- Benitez O
- Benjamin Sa
- Berenguer Ra
- Bergeron J
- Bergerot C
- Berk Mr
- Berli M
- Berlingieri Jc
- Bernard Jv
- Berrouschot J
- Bertolet Bd
- Bhindi R
- Bianco Ht
- Bijata-Bronisz R
- Bilz S
- Bittar Gd
- Bitzur R
- Bjasker Kr
- Blach E
- Black H
- Blagden Md
- Blaha V
- Blake G
- Blanco Coronado Jl
- Blaze K
- Blignault Sc
- Blokhin A
- Bloom Sa
- Bocek P
- Bod E
- Bogaard K
- Bogdanov E
- Bokern Mj
- Boman K
- Bonansea Tc
- Bonfanti Ja
- Bonner Jh
- Bonora E
- Boonyavarakul A
- Borer Js
- Botas Rodrigues J
- Botelho Rv
- Botella Serrano M
- Botero-Lopez R
- Botta Ce
- Bourgeois R
- Bourhaial H
- Boye A
- Boyett Be
- Brandon Dm
- Brar Hs
- Brauer C
- Bravo P
- Bredlau Ce
- Breedveld Rw
- Brenner H
- Breton Cf
- Bretton Em
- Brito Sanfiel Ma
- Broncel M
- Bronnum Schou J
- Brotons Cuixart C
- Broughton R
- Bruguera Cortada J
- Brunell R.
- Bruno Rl
- Budassi N
- Budoff Mj
- Bueno Diez M
- Bufka V
- Buganova I
- Bulanova N
- Buonanno M
- Burgess Lj
- Burnier M
- Burova N
- Busch Rs
- Busegeanu M
- Butuk Dj
- Buynak Rj
- Buysschaert I
- Bybee Ka
- Cabella Pr
- Cabezas Mc
- Caccavo A
- Calin A
- Calvo Gomez C
- Camp Ad
- Capiau L
- Caputo Rp
- Caramori Pr
- Carlier M
- Carlier Sg
- Carmena R
- Carnero Gs
- Carroll Pa
- Casabella Te
- Casaubon L
- Castro Montes Be
- Castro Ma
- Castro Nm
- Catano Js
- Caudmont S
- Cayla G
- Cech V
- Cecil Jt
- Cequier Fillat Ar
- Cerci R
- Ceska R
- Ceyhan C
- Cha Jy
- Chahin M
- Chakrabarti A
- Chambers Jd
- Chandna H
- Chang Ar
- Chang Kc
- Changlani M
- Chati Z
- Chaudhuri S
- Cheek Hb
- Chen J
- Chen Jc
- Cherlin Rs
- Chernyatina Ma
- Cheung Ss
- Chiang Ce
- Chilka S
- Chiong R
- Cho Br
- Cho Ys
- Chochinov Rh
- Chorin E
- Chouinard G
- Chueca Fernandez Je
- Chun H
- Cifkova R
- Ciomag Rm
- Civeira Murillo F
- Civeira F.
- Clark Gb
- Clark R
- Claudio J
- Clemens Pc
- Codutti Or
- Coetzer Tf
- Cohen Aj
- Cohen Ss
- Coisne D
- Collier Dj
- Colombo Hr
- Colquhoun D
- Colquhoun D
- Comlekci A
- Conde Dg
- Cone Cl
- Connelly T
- Connery L
- Contzen C
- Conway Jr
- Cools F
- Copaci I
- Corder Cn
- Corin A
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- Ueng Kc
- Uhliar R
- Ulla Mr
- Underberg Ja
- Updegrove Jd
- Uresin Ay
- Urhammer S
- Urina M
- Urina-Triana Ma
- Uusinarkaus Kt
- Vaca Ce
- Vahed Ya
- Valdez Lopez Hg
- Valtonen M
- Van Alem Ap
- van Beek E
- van Daele Me
- van de Borne P
- van de Wal Rm
- van de Wetering Ml
- van de Wiel A
- van der Meer P
- van der Walt E
- van der Zwaan Ct
- Van Gaal W
- van Hal Jm
- Van het Hof-Wiersma Jj
- van Kempen Ww
- Van Koningsbruggen P
- van Landegem P
- van Leendert Rj
- van Nieuwenhuizen E
- van Rossum P
- van Royen N
- van Zyl Lj
- Vannatta B
- Vanttinen E
- Varleta P
- Vazan A
- Vazquez-Tanus Jb
- Veenendaal A
- Vejar M
- Venereo Jm
- Venter Dj
- Verdeza C
- Vertes A
- Vervoort G
- Verwerft J
- Vesely J
- Vico Ml
- Viergever Ep
- Viklund J
- Vila Belmonte A
- Villaman-Bencosme Y
- Vinanska D
- Vincent J.
- Vincent S
- Vinyoles Bargallo E
- Violante Ortiz R
- Vishlitzky V
- Vishneva E
- Visser Rp
- Visseren F
- Vivekananthan K
- Vizel S
- Vlach Jj
- Vodnansky P
- Voehringer Hf
- Vogel Dr
- Vohnout B
- Vojacek J
- Volkova A
- Voller H
- von Engelhardt Cb
- von Hodenberg Ef
- Vora Kn
- Vora Sk
- Voros P
- Vrablik M.
- Vrkoc J
- Vukotic G
- Wadud K
- Wainstein J
- Wakefield Ph
- Wakeling J
- Walczak M
- Walczewska J
- Walukiewica P
- Wang D
- Wang E
- Wang G
- Wang Y
- Wasserburger B
- Waxler Ar
- Wayne Jd
- Weber D
- Weber K
- Wegner J
- Wei C
- Weigmann I
- Weinstein Dl
- Weiss R
- Welker Ja
- Welty F
- Wenetz Lm
- Wermuth S
- Wesson T
- West Sh
- Westerndorp I
- Wetzel T
- White H.
- Whitlock L
- Whitney Rt
- Wiggers H
- William M
- Williams Dg
- Williams M
- Willis Jg
- Willits Vl
- Winkelmann B
- Witt N
- Wittmann I
- Woehrle J
- Worner Diz F
- Wozniak I
- Wright R. S.
- Wronska D
- Wuerzner G
- Wychota K
- Xu P
- Xue L
- Yakusevich Vv
- Yang P
- Yang X
- Yao Lc
- Yared Z
- Yarows Sa
- Yigit Z
- Yoon J
- Yunis C.
- Zadra R
- Zaidman Cj
- Zamorano Gomez Jl
- Zannad F
- Zarandon Rb
- Zarich Sw
- Zateyshchikov D
- Zavaro Sh
- Zebrack Js
- Zeig S
- Zemek S
- Zemour G
- Zeng X
- Zeno Ml
- Zhang L
- Zhang X
- Zhang Y
- Zhao Y
- Zhou C
- Zhou Y
- Zhu Y
- Zidkova E
- Zieba B
- Zilahi Z
- Zoet-Nugteren Sk
- Zrazhevskiy K
- Zubek V
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2017
- Field of study
Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients