1059
KLINICKÁ341804001074588109168189242288347
FARMAKOLOGIE709804001074291138211265312372415474533554598
A13288040010753
FARMACIE1403804001074191138210265316336380
/18298040010732
Klin190680400107446583131
Farmakol2057804001074278105179220258305325
Farm.2402804001074178104179195
2025;39(1):14-212617804001074487128172185229271295335352367404443472511550
/32128040010732
www.klinickafarmakologie.cz4568804001076513320121425327329234035839843647950254457164568672477179183988990895196610061045
201838020012657115
PŮVODNÍ341200012660132201274348422456
PRÁCE818200012661124196256314
Lipid341360010629478199138
lowering49536001062968127158194212253293
with80336001065875107149
inclisiran:9673600106165791123141173190225267308324
a1306360010638
single-center13593600106314889128159192220256288329362394430
experience180436001063068103135171188220261296328
from214836001062864105159
Slovakia232336001063061100137174209227267
baseline34362001095195131177199220270316
values.68362001094387109158204240260
The96762001094596142
ORION-11133620010962111134197257287328
study148562001093667116168211
showed172062001093686136202247299
a343760010943
15–19%40976001094687133175216288
reduction72076001092974126176217249270320370
after111376001094370103147177
11313760010946
dose1382760010950100136182
of158676001095076
inclisiran168576001092171112133154189210240284334
and34390001094494146
a515900010943
19–25%58490001094788137179226297
reduction90690001093075128178219252273323374
after130690001094470104149179
21511900010946
administrations158390001094496171193244265301332362406343104001093153104157193
over563104001095195142173
150763104001094789137
days,927104001095297140177198
but11521040010952104136
none13151040010951103155202
of1544104001095179
the1649104001093183130
reductions180610400109307713118234311800109407293143194229
reached596118001093075118159209255307
statistical927118001093566111140161196227248289333355
significance.1306118001093556107157178205229269314364405449468
In1798118001092171
the1893118001093080126
ORION-33431320010961109130191250279322
study,680132001093565113163204219
in913132001092170
the997132001092978122
open-label1134132001094999144193221243285335380401
continuation1549132001094087136165185233281324352372421470
of343146001095077
ORION-1,4451460010963113135199260290331346
the817146001093080126
decrease969146001095197139169215259295341
was13361460010966111147
only15091460010949100122165
by1700146001095294
6.31820146001094766115
%19471460010972
and343160001094496149
14.3518160001094790109159
%6901600010972
in789160001092173
the888160001093182129
group1044160001095182133184237
transitioning1308160001093061106158194216247269320372394445498
from1832160001092758109187
PCSK9-mAbs3431740010948100146194241272348403455491
(11).858174001092668105125142
In1024174001092272
the1120174001093080126
ORION-912701740010962111134197257287334
study1628174001093667116168211
monitoring18631740010975125343188001095173104154185208259311
patients681188001095298128150197249279317
with1025188001096790121172
HeFH,12241880010959107153212232
the1483188001093081128
reduction1638188001093076130181223256278329381
was3432020010966110146
17.251420200109478697145
%6712020010971
compared767202001094189165217261291336388
to1180202001093079
placebo,1285202001095173117157202254304322
but16332020010951101132
again,1790202001094495138159210229
it343216001092151
was4162160010966110146
not5842160010950100130
significant736216001093556107157178205229269314364393
(12).1151216001092668108132149
In1322216001092172
contrast,1416216001094089139169198242278309328
the1766216001093080126
reduction19132160010930753432300010951101142174195245296
in664230001092172
the761230001093080126
ORION-109132300010962111134197257287329371
studies1310230001093566116168189235271
was16062300010967111147
25.61778230001094693111158
%19472300010972
compared343244001094089165216260290335387
to750244001093079
placebo,849244001095173117157202254304322
while11912440010967117138160205
in1416244001092172
the1508244001092979125
ORION-1116532440010962111134197257287328366
study,343258001093565114165207221
it580258001092050
was6452580010966109143
18.6804258001094587106152
%.966258001097191
All107225800109547596
results1183258001092973109157178207243
were14422580010965109138183
consistent1640258001094088137172192227257300350379
with343272001096789120171
findings540272001092651102154176226278314
from880272001092758108185
studies1091272001093667118170192238275
involving1392272001092172115165187232254305356
PCSK917752720010948101147197244
antibodies,343286001094597129151205258313335383421442
which8172860010968121144187239
also1088286001094467105157
observed12772860010951105143191223271318373
a16822860010944
similar1758286001093759138161184229261
decrease343300001095196138167213256292338
(13).700300001092567108131148
Monoclonal4833140010975127180232275297350402448471
antibodies982314001094497128150204256311333381418
(mAbs)14283140010927102160214251275
against1731314001094598144166218255288
PCSK93433280010949103149199247
reduce616328001093077130181223268
Lp(a)911328001094396123165189
levels1127328001092168113158181218
by1371328001095295
approximately1493328001094497150181232274296373418449495343342001092164
20–30433342001094691140185231
%6753420010972
(16).772342001092668110134151
In948342001092272
large104634200109216494144190
clinical126234200109406182132153194238260
studies1547342001093667116168189235270
such1843342001093685126176
as343356001094480
FOURIER4493560010944106165215238283332
with807356001096688119169
evolocumab1002356001094689139161212254304380424476
and1493356001094494146
ODYSSEY16653560010963124171215258303354
OUTCOMES3433700010964126174227290366413461
with838370001096891123176
alirocumab,104837000109446890122174218270348395449468
a15503700010945
reduction1629370001093078132184227262284337390
of343384001095179
about450384001094598151204235
25714384001094796
%8233840010973
in924384001092274
major10263840010978123146199230
adverse1284384001094599145191223261309
CV16213840010954109
events1758384001094792138191222261
(MACE)343398001092698155207252279
was6483980010967112149
noted8233980010951102132178231
(26,1081398001092671117137
27).1244398001094793119137
In1407398001092273
the1506398001093182129
ODYSSEY16613980010963125172217261306357
OUTCOMES3434120010962121167217277350395440
study,800412001093566116167211225
patients1042412001095296125147192243272309
with1368412001096688118168
recent1553412001092974116160211240
acute1810412001094484134164209
coronary343426001094192123174226271302349
syndrome719426001093782134188218269347395
had1141426001095196149
LDL-C13174260010943105150172229
levels1573426001092269114160183219
close1819426001094164115152200
to343440001093079
1.8448440001094762110
mmol/L5704400010975151202224256300
and895440001094495146
Lp(a)1067440001094395121162186
levels1279440001092268111156178214
≥15194400010954
13.71585440001094687106152
mg/dL,17484400010976127159207251271
which3434540010966117138178228
were5964540010966111141186
associated807454001094379114165206227270300345397
with1228454001096788118168
a14214540010943
significant1489454001093657107158179205229270314364394
clinical190745400109416283343468001094970110153174
benefit533468001095096146191217241270
from819468001092656104179
alirocumab101346800109436485114162203252326369420
therapy.1448468001093079124153196247288303
In1767468001092170
contrast,1853468001094088137343482001093059104139170189
patients551482001095296126147192243272309
with879482001096688118168
LDL-C10674820010942102145166222
around1308482001094373122173223274
1.81601482001094661109
mmol/L17224820010975150200222254297
but3434960010951102132
Lp(a)498496001094294120161185
<13.7mg/dL7064960010953111151170215302353384432475
showed1204496001093585135201246298
no15254960010950100
reduction1648496001093075127176217249270320371
in343510001092172
MACE4415100010973129180224
with691510001096789119170
alirocumab,88651000109446687117167209259335379431449
whereas13615100010967118164195240284320
patients1707510001095296126148194245275312
with343524001096789120170
higher539524001095172124174221251
LDL-C8165240010943104148169225
levels1067524001092268112157179215
consistently1308524001094190141177199234266311362392414457
benefited179152400109529915019734353800109265080125177
from546538001092656106182
alirocumab75353800109436586116165207256332375427
treatment,1205538001093060105149178254300350380399
regardless1629538001093075127170200251272318354390
of343552001094976
Lp(a)438552001094394120161185
levels642552001092167110154176212
(28).873552001092570116140157
In483566001092274
our5845660010951102133
study,744566001093769120173218234
we10055660010968114
found1146566001092778130182235
a14085660010945
significant1479566001093759111163185213238281326378409
interindividual1915566001092173343580001093178110133186240263309333386439485508
variation885580001094491122146192223246298352
in1271580001092174
Lp(a)1379580001094498126169195
reduction,1608580001093078132184228262285337390411
ranging343594001092974124174196246297
from659594001092657106182
08605940010946
%9175940010971
to1008594001092978
58.331106594001094692111160204
%.1321594001097292
In1432594001092272
patients1523594001095196125146192242272309
with1851594001096688118168
elevated343608001094568114158202232277330
Lp(a)699608001094294121162186
levels911608001092268111157179215
>11516080010954
501217608001094793
mg/dL13216080010976128160208251
(n1598608001092674
=16986080010954
5),177860800109467188
the1892608001093081127
reduction343622001092975126176217249270320370
in730622001092171
levels817622001092167110155177212
after1045622001094370103148177
adding1239622001094394146167217268
inclisiran1523622001092171112133154189210240284334
was18736220010966110146
more3436360010975124154199
pronounced557636001095181130180230279329369413465
compared1038636001094088163214258287332383
to1437636001093078
patients1531636001095195124145190240269305
with1852636001096687117167
normal3436500010950100130206249271
Lp(a)638650001094394120161185
levels:847650001092167110155177212231
16.661102650001094688108155202
±13286500010954
5.71406650001094765110
%15286500010971
vs.162365000109447999
15.471746650001094787105152195
±19656500010954
5.4343664001094664111
%,465664001097191
which5816640010966117138178228
may8346640010975119160
explain1019664001094588140162205226276
and1320664001094393145
align148966400109446586137187
with1701664001096688118168
the1893664001093080126
findings343678001092650100152173223274309
from676678001092656106181
the881678001093080125
aforementioned1030678001094370120150195270316367396417467518563615
ODYSSEY16696780010962123169212256300350
OUTCOMES3436920010962121167218278351396441
study.810692001093667117168211227
The1062692001094596142
exact1230692001094588132173205
mechanism14616920010975121163213256307328363439
by1925692001095194
which3437060010968120142184236
PCSK96067060010949103150201249
inhibitors882706001092173125147200223254305336374
reduce1283706001093077131182225271
Lp(a)1581706001094396124166191
levels1799706001092269114160183220
remains343720001092975150194215265300
unclear.6657200010949100140162207251280296
Current9737200010952100130160205256285
hypotheses1280720001095091143194224274320356401437
include1739720001092171112133183234280
increased343734001092170111140185228263308359
clearance718734001094061106149178222271312356
of1089734001095076
Lp(a)1180734001094393119160183
particles1379734001095094123156176216237282318
through1713734001092979108157206256306
LDL3437480010944106151
receptors520748001093178121167220252303334372
(LDL-R),919748001092670132177199251277295
increased1241748001092274116147194239276324378
clearance1646748001094163111156187232284327373
of343762001095179
Lp(a)450762001094497125168193
via671762001094468113
other812762001095182134182214
receptors1054762001093077121167221253304335374
(LDL-R-related1456762001092670132178200252283315362385431462509563
protein343776001095181131161205227277
1,642776001094660
cluster724776001094062111147178222252
differentiation99877600109517299128174204249300329350393423444494545
receptor1564776001093075116161213243292322
36,1908776001094692111
Toll-like213862001094692115137167191213257303
receptor246762001093177120166220251302333
2,282762001094767
scavenger292062001093779125169215267320367398
receptor334562001093077120166219251301332
B1,370462001095094110
and213876001094597150
plasminogen231576001095376121158236259311363416464516
receptors),285876001093077121167221252303335373397415
as330076001094582
well3409760010968115138160
as359676001094582
reduced3705760010930772138900010951100141186238
production,239990001095181131182232273305326376427446
secretion,286890001093581123152197228249299349368
or326090001094979
assembly336290001094479115160236287310353
of373890001094976
apo(a)2138104001094395145172212236
(29).2393104001092671116141158
hsCRP2278118001095087141190240
has2546118001095095132
been27051180010952100147199
shown2932118001093687139206258
to3218118001093080
be3326118001095299
a34531180010944
reliable3524118001093077100122167220243290
marker21381320010974118147190234264
of2419132001094976
underlying2511132001094999150196226248291313363414
systemic2941132001093679115146191266287328
inflammation,328613200109207097121164239314357387408458508528
a21381460010943
strong219714600109366696145195246
and2459146001094393144
independent2619146001092171122167218264314365411461490
predictor3126146001095080125177198238270319349
of3492146001094875
future3584146001092576106155185230
CV21381600010952104
events2259160001094588133183213250
in2526160001092171
individuals2614160001092171123144188210261311355376412
with3043160001096587118168
and3228160001094393144
without3389160001096688118168218268299
established37051600010944802138174001092974126148169205255301353
CV25081740010952105
disease.2630174001095072107153197233279298
Measurement29451740010972118162198247277322398444494524
of3487174001094875
hsCRP3580174001094985137185234
can2138188001094186138
aid2303188001094466119
physicians24491880010952104147184206248270315366403
in2879188001092273
assessing2980188001094380117164201238260312364
CV33721880010952106
risk350618800109295289132
and3666188001094395148
monitoring21382020010976128180203235286317340392445
therapeutic2611202001093082130161207261309361393415458
interventions3097202001092173104151182230277329360383435487524
(30).3649202001092672120146165
Although2138216001095679110162214266318370
PCSK925362160010949103150200249
inhibition2813216001092173125148201224256278330382
does32232160010952103151189
not34402160010950102134
reduce36022160010929761301812138230001094188
CRP22552300010954104156
levels2439230001092270116163187225
in2693230001092174
clinical279623000109416487140163206253276
studies,3101230001093770122176199247286307
including3437230001092174117141193247270323377
ORION-1,21382440010962112136199260291333349
-2,251224400109287191
and2628244001094495147
-7,280124400109277081
preclinical2907244001095283129171193215266288330375397
studies3330244001093567118170192239275
have3631244001095094138183
provided2138258001095284135180204257305359
substantial2525258001093688141179212258310341364410433
evidence2986258001094691114168215268311357
for3372258001092678110
a35102580010944
relationship358325800109307710014617720021382720010950102139191214267
between24332720010952100132202249297349
PCSK928102720010949103150200249
and3087272001094496149
inflammation,3264272001092173101126172249326372403426477530550
as2138286001094583
well22502860010969117141164
as2444286001094483
the2556286001093184133
impact27182860010922101156203246281
of3028286001095180
PCSK931382860010949105153204254
inhibition3422286001092175128151206229262285338392
on21383000010949101
the2263300001093081128
overall2415300001095093139170215237259
inflammatory2698300001092273100125169245321366397446477524
process3246300001095283133175221257294
(31).3564300001092672114135152
In3741300001092173
our21383140010950102134
study,2300314001093669121174219236
we25643140010967114
observed27063140010951104142190222270316371
an3105314001094496
average3229314001094488135167213266313
hsCRP3571314001095087142192243
reduction2138328001092976128179221254276326378
of2538328001094976
14.82636328001094789109158
±28163280010953
8.72891328001094667114
%,3018328001097192
but31323280010951102133
significant3287328001093658109160182210235276321372403
interindividual37123280010921722138342001092974103125175226247290312363412456477
differences263234200109507198127172202247297338382418
were30663420010965110140185
present.3267342001095181126161207257286306
Based3589342001094892128173225
on21383560010950102
the2268356001093081128
sample2424356001093682159212235282
size,273435600109365898145164
it2926356001092153
is3007356001092157
difficult3092356001095174102133158200251274305
to3425356001093080
predict3533356001095283130183205247281
the2138370001093082129
effect2295370001094674105153196229
of2552370001095078
inclisiran2658370001092173115138160197219250296348
on30343700010950102
hsCRP3164370001095087141191241
levels;3433370001092269114160183220239
we37003700010967114
rather2138384001092974105156202233
assume2395384001094379116166242289
that2707384001093081126156
it2886384001092152
was29623840010966111147
influenced313338400109217299124174221272314359412
by3569384001095194
the3686384001093081128
titrated213839800109305283113158188234287
statin2442398001093668113143165216
levels2676398001092168112157180216
or2910398001094980
the3008398001093080127
interaction3153398001092172102148178223265298319370421
of3592398001095077
the3687398001093080127
PCSK921384120010948101147197244
inhibition2407412001092172123145197220251273323375
pathways2806412001095197127178244289332368
themselves,3199412001093080127204240287309354400436457
but36804120010951103134
further2138426001092678109142193240271
studies2436426001093667118171193239276
are2739426001094474120
needed2887426001095096144196243296
to3210426001093080
demonstrate3317426001095198174225277313345375420451497
this2138440001093081103139
effect.2298440001094573103150192225246
In2278454001092171
terms2365454001093074104180215
of2596454001094975
side2687454001093657107153
effects,2856454001094572101146188219256275
our3147454001094999129
study3292454001093566115166209
showed3517454001093685135201245297
slightly213846800109355677128177206227270
higher2424468001094970121170216245
rates2685468001092973102146182
of2883468001094975
local2974468001092171112155176
reactions3166468001092974117158189210260310345
compared35264680010941891642152592138482001092974125
to2278482001093078
the2372482001092978123
clinical251148200109406081130151191234255
studies2782482001093565114165186230266
ORION-3,30634820010962110132194254283327345
-9,342348200109287490
-10,3528482001092868110128
and3671482001094392143
-112138496001092869107
(14).2270496001092668110134151
When24474960010976127173223
assessing2696496001094379115161197232254304355
adverse3076496001094495139184214251297
effects,3398496001094673103148190222259279
we37024960010967112
found2138510001092676126176228
that2387510001092979123152
mild2560510001097597118169
burning27505100010951102131182203253304
occurred3075510001094990130180209240285337
in3432510001092172
38.233524510001094792112161207
%37435100010971
of2138524001094975
total2228524001092977107150171
administrations2414524001094393167188237257292322351394423443492542576
during3006524001095098127148197247
therapy.3269524001092978123152195245287301
In3586524001092170
studies36715240010936661152138538001095172117153
ORION-3,23125380010962111134197257287332350
-9,268253800109287591
-10,2794538001092869111129
and2944538001094393145
-11,3109538001092869107121
the3251538001093080125
prevalence3397538001095181126170214235281331372417
of2138552001094975
injection222955200109217192137178210230280330
site257455200109365786131
reactions2720552001093074117158189210259310344
was30805520010966109145
3–173240552001094692133172
%34235520010971
(15).3510552001092567107131148
The3673552001094596141
aforementioned2138566001094572124156203281329382413435487539587641
UK28065660010960111
real-world2944566001093178123146176246297329352405
registry3376566001093178131154191223254301
reported370556600109307721385800010951102132165209261
only24155800010950100122165
125965800010946
patient2658580001095196125146192242272
(1.3294658000109266883131
%)3088580001097295
with3199580001096688118168
a33835800010944
moderate34435800010975125177222252296326371
injection213859400109216990134174205225273322
site247459400109355584127
reaction,2616594001092972115154185205253302320
while29515940010964113134154198
the3164594001092977121
German33005940010957102131204247295
study3610594001093464112162204
reported2138608001092975126177207240284336
524936080010946
patients2558608001095195125146191242271308
(32885608001092570
%)2966608001097195
(16,17).3079608001092668110129170210236253
In3350608001092272
our3441608001094999129
study,3588608001093667117168211226
we21386220010966111
did2275622001095072123
not24236220010950100130
observe25786220010950102138183213260304
any2908622001094393135
moderate30686220010975125177223253297326371
or3464622001095080
severe3569622001093682125170200245
reactions.2138636001093077123165199221273325362383
In2548636001092274
studies2649636001093769121174197244282
ORION-9,29586360010964115139204266298346364
-10,3349636001092871115135
and3511636001094496150
-11,3688636001092871110126
other2138650001094979129175205
types2360650001093075127173209
of2586650001094976
reported2679650001092974126177207239284336
side3032650001093556108153
effects3202650001094572102147189221258
occurred3477650001094990130180209240285337
with2138664001096688118168
similar2325664001093657132153175218248
frequency2592664001092656102153203249299340385
in2996664001092171
both30866640010951102132182
groups3287664001095080129180231267
(14).3573664001092568109133150
In3742664001092172
real-world2138678001092975118140169236285315337388
studies,2546678001093667116168189235270290
fewer2856678001092672138183213
side3089678001093657108153
effects3263678001094572101147188221257
(4–63540678001092670118168
%)3719678001097195
were21386920010966110139184
reported,2337692001093074125175205237281332350
which27036920010966116136176225
were29446920010966110139184
of3143692001094975
a32346920010943
similar3292692001093656130151172215244
nature:3552692001094992121170199244262
myalgia,21387060010975117161182233254298317
dizziness,2476706001095172111153174224270306341361
headache,2858706001095096140191234275325371389
and3269706001094393145
fatigue,3435706001092671100121172222268286
in3742706001092172
addition2138720001094497150172203224276328
to2492720001093081
the2599720001093182129
previously2754720001095384130174197248300336358403
mentioned31837200010977124175206228279331378431
mild3641720001097698120173
injection213873400109217294141183216238288340
site250473400109365888134
reaction2664734001093076121162195216267319
(15).3009734001092669110135153
In3188734001092273
our32877340010950101132
study,3445734001093667118170214230
we37017340010967113
monitored21387480010976127178200230280311357409
the2573748001093081128
above2727748001094396147191236
symptoms2989748001093680158210241290367403
in3418748001092172
5.93516748001094765111
%36397480010972
of3737748001095077
administrations,2138762001094497174196248269306338368413444466517569605625
with2790762001096890121172
a29897620010944
maximum30607620010976121165188265316393
duration34807620010951102133178209231282334
of2138776001094976
up22387760010949101
to2362776001093079
242465776001094690
hours.25797760010950100150180216236
In2839776001092171
the2934776001093080126
German30837760010958105135211254305
study3411776001093667117168211
with3646776001096688118168
PCSK93934620010949102149198246
mAbs,4206620010976133186222242
most4475620010976127164195
side469762001093658110157
effects488062001094673104151193226264
(74517062001092673114
%)529762001097296
were5420620010967113144190
also393476001094365100150
reported410376001093075127177207240285337
in445976001092171
patients454976001095296126147192243272309
without487776001096688118168218268298
concurrent519576001094089139180230259290335385415
lipid-lowering39349000109214292114164193215264329374403424474524
therapy.447390001093079124154197248289304
Although479390001095475105154204253303353
the516190001093079124
etiology53019000109447495144166215266309
is3934104001092156
not40081040010950100130
always4156104001094465132176217253
known,4427104001094294144210261280
for4725104001092676106
example,4849104001094588132207258280326344
in5211104001092272
the5301104001092979125
case5444104001094185120166
of3934118001094976
myalgia40261180010975116161182233254297
symptoms,4340118001093579155206236285361396415
it4772118001092151
is4839118001092156
important4911118001092196148198228261305355385
to5312118001093079
listen540711800109214277108153203
to3934132001093181
patients4042132001095399130152200252283321
to4390132001093182
arrive4499132001094475107129175221
at4747132001094576
an4850132001094597
optimal49741320010950104136158236281304
tailored530513200109307699121173204251305
treatment3934146001093059103147176250296346375
plan4325146001095072115165
to4505146001093078
minimize4599146001097596145166240261300345
individual4959146001092171122142186207258307350371
ASCVD53461460010955100151204264
risk393416000109295186128
(17).4083160001092567107133150
Adherence42531600010955106156201231277327368412
to4685160001093079
therapy4784160001093080126156200251293
was50971600010967111146
similar5263160001093657132153175218248
to5531160001093079
that3934174001093080123153
in4106174001092171
clinical419717400109406182132153194238260
studies,4476174001093566116167189234270289
and4785174001094393145
we49491740010966111
observed50791740010950101137183213259304356
therapy54541740010930801263934188001093074126168
interruption4128188001092172102147177208258310341362412463
in4617188001092172
only47141880010950101123166
149061880010946
patient4978188001095296126148194245274
after5278188001094471104149179
the5483188001093080127
first393420200109265080116147
dose40982020010951101137182
of4297202001095076
inclisiran,4390202001092171112133154190211240284334353
but47602020010952102132
not49092020010950100130
due50562020010951100146
to5219202001093078
adverse5314202001094495139184214250296
effects.3934216001094572102147189221258277
Furthermore,4229216001094492121154204250280355405435481499
liver474621600109214286130160
tests4924216001093074110141178
after5120216001094369103147177
starting5315216001093566111140173194244295
treatment3934230001093059104148177252298349378
with4328230001096688118168
inclisiran4512230001092171112133154189210239283333
were48612300010966111141186
comparable5063230001094089164216260289333385407452
to5531230001093079
baseline3934244001095195131177199220270316
levels.4269244001092167110154176212231
In4074258001092170
conclusion,4159258001094088137177198246281301350399418
consistent4592258001094087137171191226256299349377
with4985258001096586115164
clinical516425800109406181130150190233254
trials543325800109295879122142177
and3934272001094393145
other4098272001094979129175205
studies4322272001093566116167189234270
in4611272001092171
real4701272001093075118140
clinical486027200109406182133154194238260
practice,5139272001095181125166198219260304322
our54802720010950100130
findings393428600109264998148168217267301
support4250286001093584134184234263295
that4560286001092978120149
inclisiran4724286001092170110130150185205234277326
has5065286001094991126
a52062860010943
favorable5264286001092669110158187230280301346
safety3934300001093680107152183228
profile4183300001095181131157181203248
and4453300001094393144
can4619300001094084134
be4774300001095298
an4893300001094494
effective5008300001094572102148189221242286331
means53603000010975121164215250
of3934314001095076
achieving4036314001094384134156201245267317368
LDL-C44303140010943103146167223
target4679314001093074104155201231
values4936314001094388109159205241
in5203314001092171
patients5300314001095196125147192243273310
at3934328001094475
very4036328001094491122169
high4232328001095173126177
CV44363280010954108
risk,457132800109305389133155
which47533280010968120142184236
we50163280010968114
achieved5157328001094587138160208252298352
in5536328001092273
63.43934342001094589106151
%40953420010970
of4179342001094974
patients,4267342001095193122142186235263298317
compared4598342001094087160210253281325375
to4987342001093077
050783420010945
%51333420010970
with5217342001096586115163
LDL-C5395342001094199141161215
>39343560010954
2.63999356001094666113
mmol/L41233560010975150200222254297
based4439356001095195131177229
on46873560010949100
inclusion4806356001092171112133183218239289339
criteria.516435600109417092122167197218262281
Limitations3934381001475990192223266328370401469538588
This4074398001094597119156
study4257398001093667118171215
has4499398001095195132
several4658398001093683127173204249271
limitations,4957398001092143119142173218249271322374410430
most54153980010975126163195
of3934412001094977
which40364120010966117139181232
are4293412001094373120
characteristic4437412001094192136166211253286332362385421453475516
of4978412001095077
observational50804120010949102139185216263308339361412463507530
studies.3934426001093668119171194240278298
The4260426001094597144
study4431426001093668119172216
is4675426001092157
based4760426001095197133180234
on50214260010950101
information5150426001092172100151182259304335357408460
reported3934440001092976128180211244290343
by4304440001095195
patients,4426440001095196127149195247277315335
and4788440001094495147
we49624400010967113
did5102440001095173125
not52544400010950101132
measure541344000109751221673934454001093789121169
drug4132454001095284138192
(or4353454001092676108
metabolite)44904540010978126159206261315339362394442468
concentrations.4987454001094193146190237291323355402434457510563601623
Therefore,3934468001094596143173219247297328374393
we43444680010966112
cannot4473468001094185136187237268
exclude4758468001094589129151201253299
the5075468001092980126
possibility52194680010951102139175197248271293315345391
that3934482001093081125156
in4117482001092172
some4216482001093687163210
patients,4453482001095197127149195247277315335
the4815482001093081128
varying4970482001094388119165188239291
changes5288482001094091136187238285322
in3934496001092173
LDL-C,40354960010942104149171228250
particularly4313496001095197128162184226278300345376399444
after4785496001094371106152183
the4996496001093081129
second5152496001093684126177229282
and5461496001094496149
subsequent3934510001093686138175222274325372423453
injections441151000109217295141184217239289341377
of4812510001094977
inclisiran,4913510001092172114136158194216246291342362
may52995100010975120162
have54855100010950953934524001094491
been40535240010952101150202
due42845240010951103151
to4464524001093081
non-adherence45745240010950103156187233286339387418466518561608
to5210524001093182
accompanying53205240010945871291802593934538001095196147190212263315
lipid-lowering427553800109214395118170200224274341387418441491543
therapy.4844538001093081127158203255298314
The5184538001094597144
cohort5353538001094090142192223257
was39345520010966110145
also4096552001094365101151
highly4264552001094971122172194237
heterogeneous4518552001094995126171201251302348398444495545581
and5116552001094393144
included5277552001092171112134184235281333
patients39345660010953100132155204257289328
with4291566001096992125178
various4498566001094591123147200253291
diagnoses,4818566001095376122176229282320369408429
albeit5276566001094568123172196228
at5533566001094577
very3934580001094388119165
high4117580001095072123174
CV43095800010952105
risk,443258000109295288130152
on46025800010950101
different4720580001095173100131177208254305335
baseline5073580001095196132178201223274320
lipid-541158000109214395117169199
-lowering3934594001092851102169215245268319370
therapies.4322594001093081127158203255278324361381
Finally,4721594001094466116161183205249265
in5004594001092172
this5094594001093080102138
study,5250594001093668118170214230
we54985940010966112
did3934608001095173125
not40776080010950101132
distinguish4227608001095173109141163214265316338374425
between4670608001095299130200246293344
patients5032608001095297127149196247277315
taking5365608001093075119142193245
a39346220010945
statin4008622001093770117149172225
and4263622001094497152
those4444622001093184137175224
receiving4697622001093078122170194240264317371
combination5097622001094294173228251305351383406459513
therapy3934636001093184133165212266311
with4276636001096892124178
a44846360010944
statin4559636001093670117149172226
and4815636001094598152
ezetimibe.4997636001094789137170194273296351400421
This54486360010946100124162
factor3934650001092672113146196227
may41806500010975120162
have4361650001095095138183
influenced456465000109217299124174221272314360412
the4995650001093081128
interpretation514265000109217210214817923226330934038541643839346640010949101
of4060664001094976
the4161664001093081128
results,4313664001093076113163185216254274
although461266400109436697147198249301352
the4989664001093081127
primary5141664001095182105181225256302
aim5468664001094466142
of3934678001095078
this4039678001093082104141
study4207678001093668120173217
was44526780010967112149
to4629678001093080
highlight4737678001095072125176199221273325356
the5121678001093081128
fact5277678001092672114148
that5453678001093081126157
the3934692001093081128
addition4089692001094396148170201223274326
of4442692001094977
inclisiran4546692001092172114136158194216247292343
to4916692001093080
the5023692001093081128
initially517869200109217294125147192214236280
initiated548569200109217395393470600109305296127172225
lipid-lowering418670600109214395118170200224275341387418441492543
therapy4756706001093081128159204256299
led5082706001092168121
to5230706001092979
a53367060010944
more54077060010975126157203
pronounced3934720001095284135188239291344386433486
reduction4448720001093077131183225259282334386
in4862720001092173
LDL-C49637200010944106151173231
and5222720001094496149
Lp(a).5399720001094397124167192211
Despite39347340010960106143194216247292
the4244734001092979126
study‘s4387734001093667117169212234268
limitations,4673734001092142118140170215245267317368403423
our5114734001094999130
data5261734001095195125169
provide54487340010951811313934748001094366118165
valuable4118748001094388110161205257280327
insights4464748001092172108130181233263301
into4783748001092273103153
the4955748001092980127
effectiveness5101748001094573103150192225247292337389435472509
of3934762001094976
inclisiran4027762001092071111133154190211241285335
and4379762001094393144
the4540762001093079125
management46827620010974118168212263308383429480509
of5209762001094875
patients5301762001095195125146192242272309
in3934776001092172
real4027776001092975120142
clinical419077600109416385136158199244266
practice4477776001095282127169202224265311
in4809776001092172
Slovakia.4902776001094466117161206249273317337