Beta-Blockers: Drugs that Prolong Survival

Beta-blokatori (β-B) imaju veliko značenje u liječenju kardiovaskularnih bolesti zbog svoje sposobnosti blokiranja nepovoljnoga neurohumoralnog učinka vrlo složene β-adrenergične stimulacije. Od otkrića propranolola, 1964. g., stvoreno je više farmakološki različitih β-B. β-B imaju antiishemijska svojstva i rabe se u svim stadijima ishemijske bolesti srca, s izuzetkom vazospastične angine pektoris. Produžavaju život u bolesnika nakon preboljelog infarkta miokarda i imaju posebno povoljan učinak na ishod u bolesnika sa zatajivanjem srca (ZS), stoga su trenutačno jedna od temeljnih skupina lijekova u terapiji ZS-a. Imaju antiaritmijska svojstva i služe za uobičajenu kontrolu frekvencije klijetki u bolesnika s kroničnom fibrilacijom atrija. Indicirani su u liječenju arterijske hipertenzije, posebno uzimajući u obzir određena pridružena klinička stanja. Rabe se u liječenju bolesnika s opstruktivnom kardiomiopatijom, prolapsom mitralnog zalistka, disekcijom aorte, Marfanovim sindromom, Fallotovom tetralogijom, a i u nekih nekardiovaskularnih bolesti (npr. migrena, esencijalni tremor, glaukom). Ispravno primijenjeni β-B su sigurni lijekovi, dokazano iznimno vrijedni i korisni u mnogim segmentima kardiovaskularnog kontinuuma.Beta blockers (β-B) have an important role in the treatment of cardiovascular diseases because of their ability to block adverse neurohumoral effect of very complex β-adrenergic stimulation. Since the discovery of propranolol in 1964, more pharmacologically different β-B have been discovered. β-B have anti-ischemic properties and are used in all stages of ischemic heart disease, with the exception of vasospastic angina pectoris. They prolong life in patients after myocardial infarction and they have particularly beneficial effect on the outcome in patients with heart failure (HF). They are, therefore, one of the main classes of drugs in the treatment of HF. They have antiarrhythmic properties and are used as a common treatment to control ventricular frequency in patients with chronic atrial fibrillation. They are indicated in the treatment of arterial hypertension, especially taking into account certain associated clinical conditions. They are used in the treatment of patients with obstructive cardiomyopathy, mitral valve prolapse, aortic dissection, Marfan syndrome, tetralogy of Fallot, and are also used in some non-cardiovascular diseases (e.g. migraine, essential tremor, glaucoma). When properly used β-B are safe drugs and have proved extremely valuable and useful in many segments of the cardiovascular continuum

Beta-Blockers: Drugs that Prolong Survival

Beta-blokatori (β-B) imaju veliko značenje u liječenju kardiovaskularnih bolesti zbog svoje sposobnosti blokiranja nepovoljnoga neurohumoralnog učinka vrlo složene β-adrenergične stimulacije. Od otkrića propranolola, 1964. g., stvoreno je više farmakološki različitih β-B. β-B imaju antiishemijska svojstva i rabe se u svim stadijima ishemijske bolesti srca, s izuzetkom vazospastične angine pektoris. Produžavaju život u bolesnika nakon preboljelog infarkta miokarda i imaju posebno povoljan učinak na ishod u bolesnika sa zatajivanjem srca (ZS), stoga su trenutačno jedna od temeljnih skupina lijekova u terapiji ZS-a. Imaju antiaritmijska svojstva i služe za uobičajenu kontrolu frekvencije klijetki u bolesnika s kroničnom fibrilacijom atrija. Indicirani su u liječenju arterijske hipertenzije, posebno uzimajući u obzir određena pridružena klinička stanja. Rabe se u liječenju bolesnika s opstruktivnom kardiomiopatijom, prolapsom mitralnog zalistka, disekcijom aorte, Marfanovim sindromom, Fallotovom tetralogijom, a i u nekih nekardiovaskularnih bolesti (npr. migrena, esencijalni tremor, glaukom). Ispravno primijenjeni β-B su sigurni lijekovi, dokazano iznimno vrijedni i korisni u mnogim segmentima kardiovaskularnog kontinuuma.Beta blockers (β-B) have an important role in the treatment of cardiovascular diseases because of their ability to block adverse neurohumoral effect of very complex β-adrenergic stimulation. Since the discovery of propranolol in 1964, more pharmacologically different β-B have been discovered. β-B have anti-ischemic properties and are used in all stages of ischemic heart disease, with the exception of vasospastic angina pectoris. They prolong life in patients after myocardial infarction and they have particularly beneficial effect on the outcome in patients with heart failure (HF). They are, therefore, one of the main classes of drugs in the treatment of HF. They have antiarrhythmic properties and are used as a common treatment to control ventricular frequency in patients with chronic atrial fibrillation. They are indicated in the treatment of arterial hypertension, especially taking into account certain associated clinical conditions. They are used in the treatment of patients with obstructive cardiomyopathy, mitral valve prolapse, aortic dissection, Marfan syndrome, tetralogy of Fallot, and are also used in some non-cardiovascular diseases (e.g. migraine, essential tremor, glaucoma). When properly used β-B are safe drugs and have proved extremely valuable and useful in many segments of the cardiovascular continuum

Disadvantages of Current LDL-cholesterol Lowering and the Role of PCSK9 Inhibitors.

LDL kolesterol (LDL-K) snažan je nezavisni čimbenik kardiovaskularnog (KV) rizika na koji je moguće utjecati. Statini su danas terapija izbora u postizanju ciljnih vrijednosti LDL-K-a. Iako su u kontroliranim kliničkim ispitivanjima dokazano učinkoviti i sigurni, u praksi se često susrećemo s nepodnošenjem statina, a u značajnog dijela bolesnika i nepostizanjem ciljnih vrijednosti LDL-K-a unatoč maksimalnim dozama. U bolesnika s visokim i vrlo visokim KV rizikom i preostala eulipemijska farmakoterapija često nije dostatna. Inhibitori PCSK9 (PCSK9-I) novi su, revolucionarni lijekovi s potentnim učinkom na LDL-K. Brzi razvoj PCSK9-I-a započeo je 2003. godine otkrićem mutacije gena PCSK9 u bolesnika s porodičnom hiperkolesterolemijom. Produkt tog gena, enzim proprotein konvertaza subtilizin/keksin tip 9 (PCSK9) ima važnu ulogu u regulaciji ekspresije LDL receptora i u metabolizmu kolesterola. Istraživanjima na životinjama dokazano je da inaktivacija gena PCSK9 gena snizuje LDL-Ks regresijom aterosklerotskih promjena aorte. Heterozigoti i homozigoti s inaktivirajućom mutacijom gena PCSK9 imaju niske vrijednosti LDL-K-a i manju pojavnost ateroskleroze. Među različitim skupinama PCSK9-I-a, snažan razvoj doživjela su monoklonska protutijela (alirokumab, evolokumab i bokocizumab). Klinička ispitivanja treće faze porodične i primarne hiperkolesterolemije sa statinskom intolerancijom ili rezistencijom pokazala su snažan povoljan učinak alirokumaba i evolokumaba na LDL-K (sniženje od 60 %), uz visoku sigurnost i dobru podnošljivost. OSLER studija s evolokumabom dokazala je i povoljne učinke na ishode KV-a. U tijeku je više kliničkih pokusa različitih PCSK9-I-a, u kojima se prati njihov učinak na pobol i smrtnost zbog KV-a. Pozitivni rezultati tih studija potvrdili bi veliki potencijal PCSK9-I-a u boljoj prevenciji i liječenju KV bolesti.LDL cholesterol (LDL-C) is a strong independent cardiovascular (CV) risk factor that can be easily influenced. Today, statins are the therapy of choice for the achievement of target LDL-C values. Although controlled clinical trials have demonstrated their effectiveness and safety, in practice we are often met with statin intolerance as well as a failure to achieve target LDL-C values in a significant portion of the patients despite maximal doses. In patients with high and very high CV risk, other antilipemic pharmacotherapy is often also insufficient. PCSK9 inhibitors (PCSK9-I) are new revolutionary drugs with a potent effect on LDL-C. The rapid development of PCSK9-I began in 2003 with the discovery of a PCSK9 gene mutation in patients with familial hypercholesterolemia. The product of this gene, proprotein convertase subtilisin/kexin type 9 (PCSK9), has an important role in the expression of LDL receptors and cholesterol metabolism. Animal models demonstrated that inactivation of the PCSK9 gene lowers LDL-C with regression of atherosclerotic changes in the aorta. Heterozygotes and homozygotes with the inactivation mutation of PCSK9 have lower LDL-C values and lower incidence of atherosclerosis. Among the various groups of PCSK9-I, monoclonal antibodies saw strong development (alirocumab, evolocumab, bococizumab). Phase 3 clinical trials on familial and primary hypercholesterolemia with statin intolerance or resistance have demonstrated a strong positive effect of alirocumab and evolocumab on LDL-C values (a reduction of 60%), with high safety and good tolerability. The OSLER study on evolocumab also demonstrated positive effects on CV outcomes. Multiple clinical trials on PCSK9-I are currently monitoring their effect on CV morbidity and mortality. Positive results from these studies would confirm the great potential of PCSK9-I for better prevention and treatment of CV diseases

Beta-Blockers: Drugs that Prolong Survival

Beta-blokatori (β-B) imaju veliko značenje u liječenju kardiovaskularnih bolesti zbog svoje sposobnosti blokiranja nepovoljnoga neurohumoralnog učinka vrlo složene β-adrenergične stimulacije. Od otkrića propranolola, 1964. g., stvoreno je više farmakološki različitih β-B. β-B imaju antiishemijska svojstva i rabe se u svim stadijima ishemijske bolesti srca, s izuzetkom vazospastične angine pektoris. Produžavaju život u bolesnika nakon preboljelog infarkta miokarda i imaju posebno povoljan učinak na ishod u bolesnika sa zatajivanjem srca (ZS), stoga su trenutačno jedna od temeljnih skupina lijekova u terapiji ZS-a. Imaju antiaritmijska svojstva i služe za uobičajenu kontrolu frekvencije klijetki u bolesnika s kroničnom fibrilacijom atrija. Indicirani su u liječenju arterijske hipertenzije, posebno uzimajući u obzir određena pridružena klinička stanja. Rabe se u liječenju bolesnika s opstruktivnom kardiomiopatijom, prolapsom mitralnog zalistka, disekcijom aorte, Marfanovim sindromom, Fallotovom tetralogijom, a i u nekih nekardiovaskularnih bolesti (npr. migrena, esencijalni tremor, glaukom). Ispravno primijenjeni β-B su sigurni lijekovi, dokazano iznimno vrijedni i korisni u mnogim segmentima kardiovaskularnog kontinuuma.Beta blockers (β-B) have an important role in the treatment of cardiovascular diseases because of their ability to block adverse neurohumoral effect of very complex β-adrenergic stimulation. Since the discovery of propranolol in 1964, more pharmacologically different β-B have been discovered. β-B have anti-ischemic properties and are used in all stages of ischemic heart disease, with the exception of vasospastic angina pectoris. They prolong life in patients after myocardial infarction and they have particularly beneficial effect on the outcome in patients with heart failure (HF). They are, therefore, one of the main classes of drugs in the treatment of HF. They have antiarrhythmic properties and are used as a common treatment to control ventricular frequency in patients with chronic atrial fibrillation. They are indicated in the treatment of arterial hypertension, especially taking into account certain associated clinical conditions. They are used in the treatment of patients with obstructive cardiomyopathy, mitral valve prolapse, aortic dissection, Marfan syndrome, tetralogy of Fallot, and are also used in some non-cardiovascular diseases (e.g. migraine, essential tremor, glaucoma). When properly used β-B are safe drugs and have proved extremely valuable and useful in many segments of the cardiovascular continuum

Cardiovascular Safety of Oral Antidiabetic Drugs.

Hrvatska pripada skupini europskih zemalja s visokim kardiovaskularnim rizikom i rastućom prevalencijom šećerne bolesti tipa 2 (DMT2). Prema podatcima Nacionalnog registra osoba sa šećernom bolešću (CroDiab registar), u Hrvatskoj je 2014. godine bilo evidentirano ukupno 254 296 osoba oboljelih od dijabetesa starijih od 18 godina (7,9 %). DMT2 je, uz hipertenziju i hiperlipidemiju, jedan od vodećih čimbenika kardiovaskularnog rizika. Glavne regulatorne agencije za lijekove, potaknute štetnim kardiovaskularnim učincima rosiglitazona u RECORD studiji i kasnijim metaanalizama, zahtijevaju za sve antidijabetike kliničke pokuse o utjecaju na kardiovaskularne ishode i dokaze o sigurnosti. U procjeni učinka antidijabetika na kardiovaskularni rizik važna je gornja granična vrijednost dvostranog intervala pouzdanosti od 95 % (95 % CI) za procijenjeni omjer rizika. Svi antidijabetici s gornjom granicom omjera rizika 1,3 zahtijevaju dodatne sigurnosne provjere. Kardiovaskularna sigurnost oralnih antidijabetika posebno je važna u bolesnika sa zatajivanjem srca. S obzirom na veliki broj antidijabetika na tržištu, odluka o optimalnom liječenju DMT2 treba ovisiti o svim individualnim karakteristikama bolesnika i procijenjenom kardiovaskularnom riziku.Croatia belongs to a group of European countries with a high cardiovascular risk and growing prevalence of diabetes mellitus type 2 (DMT2). According to data of the National Diabetes Registry (CroDiab registry), a total of 254,296 individuals aged >18 suffering from diabetes were registered in 2014 (7.9%). Along with hypertension and hyperlipidemia, DMT2 is one of the leading cardiovascular risk factors. Prompted by adverse cardiovascular effects of rosiglitazone, demonstrated in the RECORD study and subsequent meta-analyses, the main drug regulatory agencies require clinical trials of the effect on cardiovascular outcomes and safety evidence for all antidiabetic drugs. On assessing the effects of antidiabetic drugs on cardiovascular risk, the two-sided confidence interval upper borderline value of 95% (95% CI) is highly relevant for the estimated risk ratio. Additional safety testing is required for all antidiabetic drugs with the risk ratio upper limit ≥1.3. Cardiovascular safety of oral antidiabetic drugs is of special importance in patients with heart failure. Considering the great number of antidiabetic drugs on the market, decision on optimal DMT2 therapy should be made in dependence of specific characteristics of each individual patient and cardiovascular risk assessment