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• Genètica/Mesures dels lípids
• Teràpies farmacològiques futures
• Articles relacionats amb discontinuitat de tt
Novel genes in LDL metabolism
• L’heretabilitat dels nivells de LDL colesterol és de 40-50%.
• La primera alteració genètica es va descobrir amb l’alteració del
LDL-receptor en HF.
• Genomic wide Association studies (GWAS) han permès identificar
més de 157 locis associats a alteracions de nivells lipídics en
plasma. (30 amb nivells de LDLque explicarien un 12-15% de les
variacions de LDL )
GWAS/Seqüenciació exoma
• Resumeix les troballes més recents de “Genomic Wide association studies” (GWAS), la seqüenciació de l’exoma de pacients amb hipercolesterolèmia familiar assenyalen nous gens en el metabolisme del colesterol-LDL.
• El loci per ABCT (ATP-binding cassette transporter G5 i G8), Niemann-Pick C1-like protein 1, sortilin-1, ABO grup sanguini glicosiltranferases i d’altres s’associen amb nivells de LDL i malaltia coronària.
• La descoberta de nous gens mitjançant el GWAS permetrà millorar la comprensió dels mecanismes metabòlics de les LDL i identificar noves dianes terapèutiques.
GWAS/Seqüenciació exoma
• En pacients amb hipercolesterolèmia familiar
• En HF homozigota s’ha trobat una variant de la lipasa àcida
lisosomal A
• La LIPA comportaria malaltia autosomica recessiva que acumularia
lípids hepàtics i esplènics i comportaria malaltia coronària precoç.
• Altres nous gens implicats inclourien el gen insulin-induced, patatin-
like fosfolipasa... Aquestes troballes encara han de correlacionar-se
amb estudis funcionals per a confirmar el paper en el LDL-colesterol
metabolisme
Sachdeva.&et&al.,&American&Heart&Journal&157&(2009)&
50%!of!people!!w h o &h a v e &a &c a r d i o v a s c u l a r &e v e n t &h a v e &n o rm a l &L D L RC &l e v e l s &
Riesgo!cardiovascular!residual
4&
Mora&S.&et&al.,&CirculaI on&119&(2009)&2396R2404&
Fewer&LDL&ParI cles&Lower!Risk!
More&LDL&ParI cles&Higher!Risk!
LDLRC&&&115&mg/dL&&&&&&OK!LDLRP&&&1200&nmol/L&&&&↑!
LDLRC&&&115&mg/dL&&&&OK!LDLRP&&&800&nmol/L&&&OK!
Lipoproteínas,!más!allá!de!la!concentración
6&
Patrón frecuente Trastornos metabólicos
Mallol R. et al., Journal of Lipid Research, 2015
Liposcale lípidos parUculas tamañoVLDL LDL HDL
Test!avanzado!de!lipoproteínas!por!RMN:!Liposcale
Atherosclerosis
• Fàrmacs que augmenten HDL han fracassat en la reducció
de risc cv en pacients DM2
• Avaluant quantitativament HDL en pacients en diferents tts
(fenofibrat vs niacina/laropiprant) no hi ha diferències
significatives.
• Conclusió: niacina o fenofibrat, no reverteixen les anomalies
en HDL en DM2 encara que modifiquen la composició de les
HDL de forma diferent.
IMPROVE-IT
MÈTODES
• N:18.144, SCA 10 dies
• 25%dones, 27%DM
• LDL 50-100/50-125mg/dL
• S40 vs S40+E10
• Objectiu: compost de mort cardiovascular, IAM no fatal, ictus no fatal, àngor inestable rehospitalitzant, revasc.>30d
• Seguiment: 6 anys
RESULTATS
• LDL 53.7 vs 69.5 (p<0.001)
• KM objectiu primari 32.7% S40E10 vs 34.7% S40.
• Events adversos similars en ambdos grups
• Subgrup de DM.
IMPROVE-IT
• Afegir ezetimibe a una estatina redueix 24% la LDL amb gran seguretat i escassos AE.
• Redueix risc cv amb corba que inicia separació a partir de l’any de la randomització
• NNT 50, nivells de partida de LDL baixos.
• 48% abandonaments (simva 80, llarg seguiment, càncer...)
• La reducció d’events és consistent amb la previsible amb estatines a igual reducció.
ODYSSEY LONG TERM
• N:2341 alt risc cardiovascular,
LDL>70 + tt amb estatines
• Alirocumab 150mg/14d vs
placebo 2:1.
• Objectiu primari: LDL
24setmanes.
• DURADA 78 SETMANES
• LDL 62% (p<0.001)
• Aliro/LDL 48mg/dL (80%<70)
• Placebo/LDL 119mg/dL (8%)
• Efecte mantingut (52%)
• Discontinuaren 28 vs 25%
• EAs: locals, 5.9 vs 4.2%
• Mialgia 5.4% vs 2.9%
• Neurocognitius 1.2% vs 0.5%
• Oftalmològics 2.9 vs 1.9%
• Anàlisi post-hoc: descens
d’events majors cv 1.7 vs 3.3%
(HR 0.52) p0.02.
ODYSSEY LONG TERM
• El descens de LDL fou clarament significatiu novament amb tt
no estatínic
• Els efectes adversos no van relacionar-se amb nivells de LDL
més baixos
• Altres paràmetres lipídics com lp(a) i triglicèrids i
apolipoproteïna B també van reduir-se.
Aliro Pcbo
Safety and efficacy of evolocumab
• N: 4465
• Aleatoritzats 2:1
• Evolocumab 140/set. o
240/mes, vs placebo
• Seguiment 11mesos
• LDL 61%
• Mantingut
• 73% <70mg/dL vs 3.8%.
Articles
1474 www.thelancet.com Vol 386 October 10, 2015
We assessed the safety, pharmacokinetics, and
pharmacological eff ects of ISIS-APO(a)Rx in healthy
volunteers.
MethodsStudy design and participantsThis randomised, placebo-controlled, double-blind,
phase 1 study was done at the PAREXEL Clinical
Pharmacology Research Unit (Harrow, Middlesex, UK).
We tested ascending doses of ISIS-APO(a)Rx in healthy
adults, aged 18–65 years, with body-mass index (BMI)
less than 32∙ 0 kg/m² and Lp(a) concentration of
25 nmol/L (100 mg/L) or more. To be included, women
had to not be pregnant and not lactating and either
surgically sterile (eg, tubal occlusion, hysterectomy,
bilateral salpingectomy, bilateral oophorectomy) or
postmenopausal, whereas men had to be surgically
sterile, abstinent, or, if engaged in sexual relations of
childbearing potential, must have been using an
acceptable contraceptive method during treatment and
for at least 30 days (single-dose groups) or 12 weeks
(multi-dose groups) after the last dose. Further exclusion
Figure 1: Mechanism by which ISIS-APO(a)Rx suppresses apo(a) protein synthesis
A ubiquitous intracellular ribonuclease RNase H1 recognises the RNA:DNA duplex formed when ISIS-APO(a)Rx binds to the complementary apo(a) mRNA sequence
and cleaves the target, thereby reducing apo(a) protein and preventing generation of Lp(a) particles. TG=triglyceride. PL=phospholipid. FC=free cholesterol.
CE=cholesteryl ester. KIV=kringle IV repeats. KV=kringle V repeat. OxPL=oxidizsed phospholipid. apo(a)=apolipoprotein(a). apoB- 100=apolipoprotein B-100.
This fi gure was adapted from Albers JJ et al 10 with permission.
ISIS-APO(a)Rx
Newly synthesised LDL
apo(a)
Mature
Lp(a)
particle
s-s
PLTG
FC
CE
LPA gene apo(a) mRNA
TranscriptionRNase H1
degrades
apo(a) mRNA
No apo(a)
produced
Antisense oligonucleotide
(single stranded, DNA-like)
apo(a)
apoB-100
KIV1
KIV2
KIV3KIV
4
KIV5KIV
6KIV7KIV
8KIV
9KIV
10
KV
OxPLP
apoB-100
apoB-100
KIV1
KIV2
KIV3KIV
4
KIV5KIV
6 KIV7 KIV
8KIV
9KIV
10
KV
OxPL
OxPL
P
.....................................................................................................................................................................................
.....................................................................................................................................................................................
CLINICAL RESEARCHPrevention and epidemiology
Negative stat in-related news stories decrease
stat in persistence and increase myocardial
infarction and cardiovascular mortality:
a nationwide prospective cohort study
Sune Fallgaard Nielsen and Børge Grønne Nordestgaard*
Department of Clinical Biochemistry, 54M1, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen,
Herlev Ringvej 75, DK-2730 Herlev, Denmark
Received 10 June 2015; revised 22 September 2015; accepted 6 November 2015
A im We tested the hypothesis that statin-related newsstories, cardiovascular disease, diabetes, statin dose, calendar year,
and socio-demographic status are associated with early statin discontinuation. We also examined frequency and con-
sequences of early statin discontinuation.
Met hods
and result s
From the entireDanish population, westudied 674 900 individuals aged 40 or older who were initiated on statin ther-
apy in 1995–2010, and followed them until 31 December 2011. Individuals on statins increased from , 1%in 1995 to
11%in 2010, while early statin discontinuation increased from 6%in 1995 to 18%in 2010. The odds ratios for early
statin discontinuation vs. continued use were 1.09 (95%confidence interval, 1.06–1.12) for negative statin-related
newsstories,1.04 (1.02–1.07) per increasingcalendar year,1.04 (1.02–1.06) per increasingdefined dailydoseof statin,
1.05 (1.03–1.06) for malesex,1.13 (1.11–1.15) for livingincities,1.67 (1.63–1.71) for other ethnicity thanDanish,0.92
(0.90–0.94) for positive statin-related news stories, 0.73 (0.72–0.74) for baseline cardiovascular disease, and 0.91
(0.90–0.93) for baseline diabetes. During follow-up, the hazard ratios for individuals with vs. without early statin dis-
continuation were 1.26 (1.21–1.30) for myocardial infarction and 1.18 (1.14–1.23) for death from cardiovascular
disease.
Conclusion Early statin discontinuation increased with negativestatin-related newsstories, calendar year, statin dose, malesex, liv-
ing in cities, and with other ethnicity than Danish, while the opposite wastrue for positive statin-related newsstories
and for baselinecardiovascular disease and diabetes. Earlystatin discontinuation wasalso associated with increased risk
of myocardial infarction and death from cardiovascular disease.- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -Keywords Statin compliance † Myocardial infarction † Death from cardiovascular disease † Statin-related news stories
Introduct ion
Although statinsareconsideredamongthesafest drugs,1–3initiation
on statin therapy may lead to side effects ranging from very rare
rhabdomyolysis to less rare and milder symptoms of muscle aches
and other forms of discomfort4–9 leading potentially to early dis-
continuation of statin therapy.10Morethan 90%of themilder symp-
tomsoccur duringthefirst 6monthsfrominitiation of statin therapy
or from up-titration of the statin dose.11 Exposure to negative and
positivestatin-relatednewsstoriesduringthisearlyphasemayplaya
role for the patient in the decision to continue or discontinue statin
therapy beyond the first dispense. This may especially be true for
the patient without ahistory of cardiovascular disease or diabetes,
and who previously considered him- or herself to be in good
cardiovascular health. Additionally,asstatin usereacheswidespread
population level use, statinsarebeingprescribed to individualsof di-
verse health and socio-demographic status, individualswho maydif-
fer from the participants recruited into major statin trials.12–19
* Correspondingauthor. Tel: + 45 3868 3297, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
European Heart Journal
doi:10.1093/eurheartj/ehv641
European Heart Journal Advance Access published December 1, 2015 European Heart Journal Advance Access published December 1, 2015
by
gu
est on D
ecember 1
4, 2
015
http
://eurh
eartj.ox
ford
jou
rnals.o
rg/
Do
wn
load
ed fro
m
.....................................................................................................................................................................................
.....................................................................................................................................................................................
CLINICAL RESEARCHPrevention and epidemiology
Negative statin-related news stories decrease
statin persistence and increase myocardial
infarction and cardiovascular mortality:
a nationwide prospective cohort study
Sune Fallgaard Nielsen and Børge Grønne Nordestgaard*
Department of Clinical Biochemistry, 54M1, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen,
Herlev Ringvej 75, DK-2730 Herlev, Denmark
Received 10 June 2015; revised 22 September 2015; accepted 6 November 2015
Aim We tested the hypothesis that statin-related newsstories, cardiovascular disease, diabetes, statin dose, calendar year,
and socio-demographic statusare associated with early statin discontinuation. We also examined frequency and con-
sequences of early statin discontinuation.
Met hods
and result s
From the entireDanish population, westudied 674900 individualsaged 40 or older who were initiated on statin ther-
apy in 1995–2010, and followed them until 31 December 2011. Individualson statins increased from , 1%in 1995 to
11%in 2010, while early statin discontinuation increased from 6%in 1995 to 18%in 2010. The odds ratios for early
statin discontinuation vs. continued use were 1.09 (95%confidence interval, 1.06–1.12) for negative statin-related
newsstories,1.04 (1.02–1.07) per increasingcalendar year,1.04 (1.02–1.06) per increasingdefined dailydoseof statin,
1.05(1.03–1.06) for malesex,1.13(1.11–1.15) for livingincities,1.67(1.63–1.71) for other ethnicity thanDanish,0.92
(0.90–0.94) for positive statin-related news stories, 0.73 (0.72–0.74) for baseline cardiovascular disease, and 0.91
(0.90–0.93) for baseline diabetes. During follow-up, the hazard ratios for individuals with vs. without early statin dis-
continuation were 1.26 (1.21–1.30) for myocardial infarction and 1.18 (1.14–1.23) for death from cardiovascular
disease.
Conclusion Early statin discontinuation increased with negativestatin-related newsstories, calendar year, statin dose, malesex, liv-
ing in cities, and with other ethnicity than Danish, while the opposite wastrue for positive statin-related newsstories
and for baselinecardiovascular diseaseand diabetes.Earlystatindiscontinuationwasalso associated with increased risk
of myocardial infarction and death from cardiovascular disease.- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -Keywords Statin compliance † Myocardial infarction † Death from cardiovascular disease † Statin-related newsstories
Introduct ion
Althoughstatinsareconsideredamongthesafest drugs,1–3initiation
on statin therapy may lead to side effects ranging from very rare
rhabdomyolysis to less rare and milder symptoms of muscle aches
and other forms of discomfort4–9 leading potentially to early dis-
continuation of statin therapy.10Morethan90%of themilder symp-
tomsoccur duringthefirst 6monthsfrominitiation of statin therapy
or from up-titration of the statin dose.11 Exposure to negative and
positivestatin-relatednewsstoriesduringthisearlyphasemayplaya
role for the patient in the decision to continue or discontinue statin
therapy beyond the first dispense. This may especially be true for
the patient without ahistory of cardiovascular disease or diabetes,
and who previously considered him- or herself to be in good
cardiovascular health.Additionally,asstatin usereacheswidespread
population level use,statinsarebeingprescribed to individualsof di-
versehealth and socio-demographic status, individualswho maydif-
fer from the participants recruited into major statin trials.12–19
* Correspondingauthor. Tel: + 45 3868 3297, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
European Heart Journal
doi:10.1093/eurheartj/ehv641
European Heart Journal Advance Access published December 1, 2015 European Heart Journal Advance Access published December 1, 2015
by
guest o
n D
ecember 1
4, 2
01
5http
://eurh
eartj.ox
ford
journ
als.org
/D
ow
nlo
aded
from
.....................................................................................................................................................................................
.....................................................................................................................................................................................
CLINICAL RESEARCHPrevention and epidemiology
Negative stat in-related news stories decrease
stat in persistence and increase myocardial
infarction and cardiovascular mortality:
a nationwide prospective cohort study
Sune Fallgaard Nielsen and Børge Grønne Nordestgaard*
Department of Clinical Biochemistry, 54M1, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen,
Herlev Ringvej 75, DK-2730 Herlev, Denmark
Received 10 June 2015; revised 22 September 2015; accepted 6 November 2015
A im We tested the hypothesis that statin-related newsstories, cardiovascular disease, diabetes, statin dose, calendar year,
and socio-demographic status are associated with early statin discontinuation. We also examined frequency and con-
sequences of early statin discontinuation.
Met hods
and result s
From the entireDanish population, westudied 674 900 individuals aged 40 or older who were initiated on statin ther-
apy in 1995–2010, and followed them until 31 December 2011. Individuals on statins increased from , 1%in 1995 to
11%in 2010, while early statin discontinuation increased from 6%in 1995 to 18%in 2010. The odds ratios for early
statin discontinuation vs. continued use were 1.09 (95%confidence interval, 1.06–1.12) for negative statin-related
newsstories,1.04 (1.02–1.07) per increasingcalendar year,1.04 (1.02–1.06) per increasingdefined dailydoseof statin,
1.05 (1.03–1.06) for malesex,1.13 (1.11–1.15) for livingincities,1.67 (1.63–1.71) for other ethnicity thanDanish,0.92
(0.90–0.94) for positive statin-related news stories, 0.73 (0.72–0.74) for baseline cardiovascular disease, and 0.91
(0.90–0.93) for baseline diabetes. During follow-up, the hazard ratios for individuals with vs. without early statin dis-
continuation were 1.26 (1.21–1.30) for myocardial infarction and 1.18 (1.14–1.23) for death from cardiovascular
disease.
Conclusion Early statin discontinuation increased with negativestatin-related newsstories, calendar year, statin dose, malesex, liv-
ing in cities, and with other ethnicity than Danish, while the opposite wastrue for positive statin-related newsstories
and for baselinecardiovascular disease and diabetes. Earlystatin discontinuation wasalso associated with increased risk
of myocardial infarction and death from cardiovascular disease.- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -Keywords Statin compliance † Myocardial infarction † Death from cardiovascular disease † Statin-related news stories
Introduct ion
Although statinsareconsideredamongthesafest drugs,1–3initiation
on statin therapy may lead to side effects ranging from very rare
rhabdomyolysis to less rare and milder symptoms of muscle aches
and other forms of discomfort4–9 leading potentially to early dis-
continuation of statin therapy.10Morethan 90%of themilder symp-
tomsoccur duringthefirst 6monthsfrominitiation of statin therapy
or from up-titration of the statin dose.11 Exposure to negative and
positivestatin-relatednewsstoriesduringthisearlyphasemayplaya
role for the patient in the decision to continue or discontinue statin
therapy beyond the first dispense. This may especially be true for
the patient without ahistory of cardiovascular disease or diabetes,
and who previously considered him- or herself to be in good
cardiovascular health. Additionally,asstatin usereacheswidespread
population level use, statinsarebeingprescribed to individualsof di-
verse health and socio-demographic status, individualswho maydif-
fer from the participants recruited into major statin trials.12–19
* Correspondingauthor. Tel: + 45 3868 3297, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
European Heart Journal
doi:10.1093/eurheartj/ehv641
European Heart Journal Advance Access published December 1, 2015 European Heart Journal Advance Access published December 1, 2015
by
gu
est on D
ecember 1
4, 2
015
http
://eurh
eartj.ox
ford
jou
rnals.o
rg/
Do
wn
load
ed fro
m
.....................................................................................................................................................................................
.....................................................................................................................................................................................
CLINICAL RESEARCHPrevention and epidemiology
Negative statin-related news stories decrease
statin persistence and increase myocardial
infarction and cardiovascular mortality:
a nationwide prospective cohort study
Sune Fallgaard Nielsen and Børge Grønne Nordestgaard*
Department of Clinical Biochemistry, 54M1, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen,
Herlev Ringvej 75, DK-2730 Herlev, Denmark
Received 10 June 2015; revised 22 September 2015; accepted 6 November 2015
Aim We tested the hypothesis that statin-related newsstories, cardiovascular disease, diabetes, statin dose, calendar year,
and socio-demographic statusare associated with early statin discontinuation. We also examined frequency and con-
sequences of early statin discontinuation.
Met hods
and result s
From the entireDanish population, westudied 674900 individualsaged 40 or older who were initiated on statin ther-
apy in 1995–2010, and followed them until 31 December 2011. Individualson statins increased from , 1%in 1995 to
11%in 2010, while early statin discontinuation increased from 6%in 1995 to 18%in 2010. The odds ratios for early
statin discontinuation vs. continued use were 1.09 (95%confidence interval, 1.06–1.12) for negative statin-related
newsstories,1.04 (1.02–1.07) per increasingcalendar year,1.04 (1.02–1.06) per increasingdefined dailydoseof statin,
1.05(1.03–1.06) for malesex,1.13(1.11–1.15) for livingincities,1.67(1.63–1.71) for other ethnicity thanDanish,0.92
(0.90–0.94) for positive statin-related news stories, 0.73 (0.72–0.74) for baseline cardiovascular disease, and 0.91
(0.90–0.93) for baseline diabetes. During follow-up, the hazard ratios for individuals with vs. without early statin dis-
continuation were 1.26 (1.21–1.30) for myocardial infarction and 1.18 (1.14–1.23) for death from cardiovascular
disease.
Conclusion Early statin discontinuation increased with negativestatin-related newsstories, calendar year, statin dose, malesex, liv-
ing in cities, and with other ethnicity than Danish, while the opposite wastrue for positive statin-related newsstories
and for baselinecardiovascular diseaseand diabetes.Earlystatindiscontinuationwasalso associated with increased risk
of myocardial infarction and death from cardiovascular disease.- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -Keywords Statin compliance † Myocardial infarction † Death from cardiovascular disease † Statin-related newsstories
Introduct ion
Althoughstatinsareconsideredamongthesafest drugs,1–3initiation
on statin therapy may lead to side effects ranging from very rare
rhabdomyolysis to less rare and milder symptoms of muscle aches
and other forms of discomfort4–9 leading potentially to early dis-
continuation of statin therapy.10Morethan90%of themilder symp-
tomsoccur duringthefirst 6monthsfrominitiation of statin therapy
or from up-titration of the statin dose.11 Exposure to negative and
positivestatin-relatednewsstoriesduringthisearlyphasemayplaya
role for the patient in the decision to continue or discontinue statin
therapy beyond the first dispense. This may especially be true for
the patient without ahistory of cardiovascular disease or diabetes,
and who previously considered him- or herself to be in good
cardiovascular health.Additionally,asstatin usereacheswidespread
population level use,statinsarebeingprescribed to individualsof di-
versehealth and socio-demographic status, individualswho maydif-
fer from the participants recruited into major statin trials.12–19
* Correspondingauthor. Tel: + 45 3868 3297, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
European Heart Journal
doi:10.1093/eurheartj/ehv641
European Heart Journal Advance Access published December 1, 2015 European Heart Journal Advance Access published December 1, 2015
by
guest o
n D
ecember 1
4, 2
01
5http
://eurh
eartj.ox
ford
journ
als.org
/D
ow
nlo
aded
from
.....................................................................................................................................................................................
.....................................................................................................................................................................................
CLINICAL RESEARCHPrevention and epidemiology
Negative stat in-related news stories decrease
stat in persistence and increase myocardial
infarction and cardiovascular mortality:
a nationwide prospective cohort study
Sune Fallgaard Nielsen and Børge Grønne Nordestgaard*
Department of Clinical Biochemistry, 54M1, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen,
Herlev Ringvej 75, DK-2730 Herlev, Denmark
Received 10 June 2015; revised 22 September 2015; accepted 6 November 2015
A im We tested the hypothesis that statin-related newsstories, cardiovascular disease, diabetes, statin dose, calendar year,
and socio-demographic status are associated with early statin discontinuation. We also examined frequency and con-
sequences of early statin discontinuation.
Met hods
and result s
From the entireDanish population, westudied 674 900 individuals aged 40 or older who were initiated on statin ther-
apy in 1995–2010, and followed them until 31 December 2011. Individuals on statins increased from , 1%in 1995 to
11%in 2010, while early statin discontinuation increased from 6%in 1995 to 18%in 2010. The odds ratios for early
statin discontinuation vs. continued use were 1.09 (95%confidence interval, 1.06–1.12) for negative statin-related
newsstories,1.04 (1.02–1.07) per increasingcalendar year,1.04 (1.02–1.06) per increasingdefined dailydoseof statin,
1.05 (1.03–1.06) for malesex,1.13 (1.11–1.15) for livingincities,1.67 (1.63–1.71) for other ethnicity thanDanish,0.92
(0.90–0.94) for positive statin-related news stories, 0.73 (0.72–0.74) for baseline cardiovascular disease, and 0.91
(0.90–0.93) for baseline diabetes. During follow-up, the hazard ratios for individuals with vs. without early statin dis-
continuation were 1.26 (1.21–1.30) for myocardial infarction and 1.18 (1.14–1.23) for death from cardiovascular
disease.
Conclusion Early statin discontinuation increased with negativestatin-related newsstories, calendar year, statin dose, malesex, liv-
ing in cities, and with other ethnicity than Danish, while the opposite wastrue for positive statin-related newsstories
and for baselinecardiovascular disease and diabetes. Earlystatin discontinuation wasalso associated with increased risk
of myocardial infarction and death from cardiovascular disease.- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -Keywords Statin compliance † Myocardial infarction † Death from cardiovascular disease † Statin-related news stories
Introduct ion
Although statinsareconsideredamongthesafest drugs,1–3initiation
on statin therapy may lead to side effects ranging from very rare
rhabdomyolysis to less rare and milder symptoms of muscle aches
and other forms of discomfort4–9 leading potentially to early dis-
continuation of statin therapy.10Morethan 90%of themilder symp-
tomsoccur duringthefirst 6monthsfrominitiation of statin therapy
or from up-titration of the statin dose.11 Exposure to negative and
positivestatin-relatednewsstoriesduringthisearlyphasemayplaya
role for the patient in the decision to continue or discontinue statin
therapy beyond the first dispense. This may especially be true for
the patient without ahistory of cardiovascular disease or diabetes,
and who previously considered him- or herself to be in good
cardiovascular health. Additionally,asstatin usereacheswidespread
population level use, statinsarebeingprescribed to individualsof di-
verse health and socio-demographic status, individualswho maydif-
fer from the participants recruited into major statin trials.12–19
* Correspondingauthor. Tel: + 45 3868 3297, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
European Heart Journal
doi:10.1093/eurheartj/ehv641
European Heart Journal Advance Access published December 1, 2015 European Heart Journal Advance Access published December 1, 2015
by
gu
est on D
ecember 1
4, 2
015
http
://eurh
eartj.ox
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CLINICAL RESEARCHPrevention and epidemiology
Negative statin-related news stories decrease
statin persistence and increase myocardial
infarction and cardiovascular mortality:
a nationwide prospective cohort study
Sune Fallgaard Nielsen and Børge Grønne Nordestgaard*
Department of Clinical Biochemistry, 54M1, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen,
Herlev Ringvej 75, DK-2730 Herlev, Denmark
Received 10 June 2015; revised 22 September 2015; accepted 6 November 2015
Aim We tested the hypothesis that statin-related newsstories, cardiovascular disease, diabetes, statin dose, calendar year,
and socio-demographic statusare associated with early statin discontinuation. We also examined frequency and con-
sequences of early statin discontinuation.
Met hods
and result s
From the entireDanish population, westudied 674900 individualsaged 40 or older who were initiated on statin ther-
apy in 1995–2010, and followed them until 31 December 2011. Individualson statins increased from , 1%in 1995 to
11%in 2010, while early statin discontinuation increased from 6%in 1995 to 18%in 2010. The odds ratios for early
statin discontinuation vs. continued use were 1.09 (95%confidence interval, 1.06–1.12) for negative statin-related
newsstories,1.04 (1.02–1.07) per increasingcalendar year,1.04 (1.02–1.06) per increasingdefined dailydoseof statin,
1.05(1.03–1.06) for malesex,1.13(1.11–1.15) for livingincities,1.67(1.63–1.71) for other ethnicity thanDanish,0.92
(0.90–0.94) for positive statin-related news stories, 0.73 (0.72–0.74) for baseline cardiovascular disease, and 0.91
(0.90–0.93) for baseline diabetes. During follow-up, the hazard ratios for individuals with vs. without early statin dis-
continuation were 1.26 (1.21–1.30) for myocardial infarction and 1.18 (1.14–1.23) for death from cardiovascular
disease.
Conclusion Early statin discontinuation increased with negativestatin-related newsstories, calendar year, statin dose, malesex, liv-
ing in cities, and with other ethnicity than Danish, while the opposite wastrue for positive statin-related newsstories
and for baselinecardiovascular diseaseand diabetes.Earlystatindiscontinuationwasalso associated with increased risk
of myocardial infarction and death from cardiovascular disease.- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -Keywords Statin compliance † Myocardial infarction † Death from cardiovascular disease † Statin-related newsstories
Introduct ion
Althoughstatinsareconsideredamongthesafest drugs,1–3initiation
on statin therapy may lead to side effects ranging from very rare
rhabdomyolysis to less rare and milder symptoms of muscle aches
and other forms of discomfort4–9 leading potentially to early dis-
continuation of statin therapy.10Morethan90%of themilder symp-
tomsoccur duringthefirst 6monthsfrominitiation of statin therapy
or from up-titration of the statin dose.11 Exposure to negative and
positivestatin-relatednewsstoriesduringthisearlyphasemayplaya
role for the patient in the decision to continue or discontinue statin
therapy beyond the first dispense. This may especially be true for
the patient without ahistory of cardiovascular disease or diabetes,
and who previously considered him- or herself to be in good
cardiovascular health.Additionally,asstatin usereacheswidespread
population level use,statinsarebeingprescribed to individualsof di-
versehealth and socio-demographic status, individualswho maydif-
fer from the participants recruited into major statin trials.12–19
* Correspondingauthor. Tel: + 45 3868 3297, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
European Heart Journal
doi:10.1093/eurheartj/ehv641
European Heart Journal Advance Access published December 1, 2015 European Heart Journal Advance Access published December 1, 2015
by
guest o
n D
ecember 1
4, 2
01
5http
://eurh
eartj.ox
ford
journ
als.org
/D
ow
nlo
aded
from
.....................................................................................................................................................................................
.....................................................................................................................................................................................
CLINICAL RESEARCHPrevention and epidemiology
Negative statin-related news stories decrease
statin persistence and increase myocardial
infarction and cardiovascular mortality:
a nationwide prospective cohort study
Sune Fallgaard Nielsen and Børge Grønne Nordestgaard*
Department of Clinical Biochemistry, 54M1, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen,
Herlev Ringvej 75, DK-2730 Herlev, Denmark
Received 10 June 2015; revised 22 September 2015; accepted 6 November 2015
Aim We tested the hypothesis that statin-related newsstories, cardiovascular disease, diabetes, statin dose, calendar year,
and socio-demographic statusare associated with early statin discontinuation. We also examined frequency and con-
sequences of early statin discontinuation.
Met hods
and result s
From the entireDanish population, westudied 674900 individualsaged 40 or older who were initiated on statin ther-
apy in 1995–2010, and followed them until 31 December 2011. Individualson statins increased from , 1%in 1995 to
11%in 2010, while early statin discontinuation increased from 6%in 1995 to 18%in 2010. The odds ratios for early
statin discontinuation vs. continued use were 1.09 (95%confidence interval, 1.06–1.12) for negative statin-related
newsstories,1.04 (1.02–1.07) per increasingcalendar year,1.04 (1.02–1.06) per increasingdefined dailydoseof statin,
1.05(1.03–1.06) for malesex,1.13(1.11–1.15) for livingincities,1.67(1.63–1.71) for other ethnicity thanDanish,0.92
(0.90–0.94) for positive statin-related news stories, 0.73 (0.72–0.74) for baseline cardiovascular disease, and 0.91
(0.90–0.93) for baseline diabetes. During follow-up, the hazard ratios for individuals with vs. without early statin dis-
continuation were 1.26 (1.21–1.30) for myocardial infarction and 1.18 (1.14–1.23) for death from cardiovascular
disease.
Conclusion Early statin discontinuation increased with negativestatin-related newsstories, calendar year, statin dose, malesex, liv-
ing in cities, and with other ethnicity than Danish, while the opposite wastrue for positive statin-related newsstories
and for baselinecardiovascular diseaseand diabetes.Earlystatindiscontinuationwasalso associated with increased risk
of myocardial infarction and death from cardiovascular disease.- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -Keywords Statin compliance † Myocardial infarction † Death from cardiovascular disease † Statin-related newsstories
Introduct ion
Althoughstatinsareconsideredamongthesafest drugs,1–3initiation
on statin therapy may lead to side effects ranging from very rare
rhabdomyolysis to less rare and milder symptoms of muscle aches
and other forms of discomfort4–9 leading potentially to early dis-
continuation of statin therapy.10Morethan90%of themilder symp-
tomsoccur duringthefirst 6monthsfrominitiation of statin therapy
or from up-titration of the statin dose.11 Exposure to negative and
positivestatin-relatednewsstoriesduringthisearlyphasemayplaya
role for the patient in the decision to continue or discontinue statin
therapy beyond the first dispense. This may especially be true for
the patient without ahistory of cardiovascular disease or diabetes,
and who previously considered him- or herself to be in good
cardiovascular health.Additionally,asstatin usereacheswidespread
population level use,statinsarebeingprescribed to individualsof di-
versehealth and socio-demographic status, individualswho maydif-
fer from the participants recruited into major statin trials.12–19
* Correspondingauthor. Tel: + 45 3868 3297, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
European Heart Journal
doi:10.1093/eurheartj/ehv641
European Heart Journal Advance Access published December 1, 2015 European Heart Journal Advance Access published December 1, 2015
by
guest o
n D
ecember 1
4, 2
01
5http
://eurh
eartj.ox
ford
journ
als.org
/D
ow
nlo
aded
from
.....................................................................................................................................................................................
.....................................................................................................................................................................................
CLINICAL RESEARCHPrevention and epidemiology
Negative stat in-related news stories decrease
stat in persistence and increase myocardial
infarction and cardiovascular mortality:
a nationwide prospective cohort study
Sune Fallgaard Nielsen and Børge Grønne Nordestgaard*
Department of Clinical Biochemistry, 54M1, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen,
Herlev Ringvej 75, DK-2730 Herlev, Denmark
Received 10 June 2015; revised 22 September 2015; accepted 6 November 2015
A im We tested the hypothesis that statin-related newsstories, cardiovascular disease, diabetes, statin dose, calendar year,
and socio-demographic status are associated with early statin discontinuation. We also examined frequency and con-
sequences of early statin discontinuation.
Met hods
and result s
From the entireDanish population, westudied 674 900 individuals aged 40 or older who were initiated on statin ther-
apy in 1995–2010, and followed them until 31 December 2011. Individuals on statins increased from , 1%in 1995 to
11%in 2010, while early statin discontinuation increased from 6%in 1995 to 18%in 2010. The odds ratios for early
statin discontinuation vs. continued use were 1.09 (95%confidence interval, 1.06–1.12) for negative statin-related
newsstories,1.04 (1.02–1.07) per increasingcalendar year,1.04 (1.02–1.06) per increasingdefined dailydoseof statin,
1.05 (1.03–1.06) for malesex,1.13 (1.11–1.15) for livingincities,1.67 (1.63–1.71) for other ethnicity thanDanish,0.92
(0.90–0.94) for positive statin-related news stories, 0.73 (0.72–0.74) for baseline cardiovascular disease, and 0.91
(0.90–0.93) for baseline diabetes. During follow-up, the hazard ratios for individuals with vs. without early statin dis-
continuation were 1.26 (1.21–1.30) for myocardial infarction and 1.18 (1.14–1.23) for death from cardiovascular
disease.
Conclusion Early statin discontinuation increased with negativestatin-related newsstories, calendar year, statin dose, malesex, liv-
ing in cities, and with other ethnicity than Danish, while the opposite wastrue for positive statin-related newsstories
and for baselinecardiovascular disease and diabetes. Earlystatin discontinuation wasalso associated with increased risk
of myocardial infarction and death from cardiovascular disease.- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -Keywords Statin compliance † Myocardial infarction † Death from cardiovascular disease † Statin-related news stories
Introduct ion
Although statinsareconsideredamongthesafest drugs,1–3initiation
on statin therapy may lead to side effects ranging from very rare
rhabdomyolysis to less rare and milder symptoms of muscle aches
and other forms of discomfort4–9 leading potentially to early dis-
continuation of statin therapy.10Morethan 90%of themilder symp-
tomsoccur duringthefirst 6monthsfrominitiation of statin therapy
or from up-titration of the statin dose.11 Exposure to negative and
positivestatin-relatednewsstoriesduringthisearlyphasemayplaya
role for the patient in the decision to continue or discontinue statin
therapy beyond the first dispense. This may especially be true for
the patient without ahistory of cardiovascular disease or diabetes,
and who previously considered him- or herself to be in good
cardiovascular health. Additionally,asstatin usereacheswidespread
population level use, statinsarebeingprescribed to individualsof di-
verse health and socio-demographic status, individualswho maydif-
fer from the participants recruited into major statin trials.12–19
* Correspondingauthor. Tel: + 45 3868 3297, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
European Heart Journal
doi:10.1093/eurheartj/ehv641
European Heart Journal Advance Access published December 1, 2015 European Heart Journal Advance Access published December 1, 2015
by
gu
est on D
ecember 1
4, 2
015
http
://eurh
eartj.ox
ford
jou
rnals.o
rg/
Do
wn
load
ed fro
m