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In spite of optimization and simplification of arterial hypertension (AH) treatment, achieving blood pressure (BP) control is still challenging, with most patients requiring combination treatment to achieve target BP. Due to the multifactorial effect of AH, additional prevention of hypertension-mediated end-organ damage and the maintenance of vascular integrity achieved by antihypertensive medications in addition to the BP-lowering effect are beneficial for the optimal reduction of cardiovascular (CV) risk. The aim of VICTORY II, a multicenter, open, prospective clinical study with 100 patients included in the active phase was to assess the safety and the efficacy of single-pill combinations (SPC) of amlodipine/valsartan (Wamlox®) and amlodipine/valsartan/hydrochlorothiazide (Valtricom®) in naïve or previously treated but uncontrolled patients with grade 2 or 3 AH. All patients with grade 2 AH started the treatment with the SPC of amlodipine/valsartan 5 mg/80 mg, which if necessary could be up-titrated step by step to the final option – the SPC of amlodipine/valsartan/hydrochlorothiazide 10/160/12.5 mg to achieve the target levels of BP. Patients with grade 3 AH started the treatment with the SPC of amlodipine/valsartan 5 mg/160 mg, which could be up-titrated step-by-step to the SPC of amlodipine/valsartan/hydrochlorothiazide 10/160/25 mg if necessary to achieve the target levels of BP. In addition to achieving the target office BP in 90% of the patients after 16 weeks of therapy, the amlodipine/valsartan-based treatments also decreased the prevalence of albuminuria and the central aortic pressure, improved vessel elasticity, and exerted a positive effect on the vascular endothelial function through its effect on the markers involved in the endothelial function., Unatoč optimizaciji i pojednostavnjenju liječenja arterijske hipertenzije (AH), postizanje kontrole arterijskoga tlaka (AT) i dalje je izazov, a većini je bolesnika potrebno kombinirano liječenje da bi postigli ciljnu kontrolu AT-a. Zbog višefaktorskog učinka AH-a, uz smanjenje vrijednosti AT-a, dodatna prevencija oštećenja ciljnih organa te održavanje vaskularnog integriteta postignuta antihipertenzivima korisni su za optimalno smanjenje kardiovaskularnog (KV) rizika. Cilj multicentričnog, otvorenog, prospektivnog kliničkog ispitivanja VICTORY II u 100 bolesnika uključenih u aktivnu fazu bio je procijeniti sigurnost i djelotvornost fiksnih kombinacija amlodipina/valsartana (Wamlox®) i amlodipina/valsartana/ hidroklorotiazida (Valtricom®) u prethodno neliječenih ili prethodno liječenih bolesnika s AH-om 2. ili 3. stupnja u kojih nije postignuta kontrola vrijednosti AT-a. Svi bolesnici s AH-om 2. stupnja započeli su liječenje fiksnom kombinacijom amlodipina/ valsartana 5 mg / 80 mg, koja se po potrebi mogla titrirati naviše korak po korak do konačne opcije – fiksne kombinacije amlodipina/valsartana/hidroklorotiazida 10/160/12,5 mg kako bi se postigle ciljne vrijednosti AT-a. Bolesnici s AH-om 3. stupnja započeli su liječenje fiksnom kombinacijom amlodipina/valsartana 5 mg / 160 mg, koja se po potrebi mogla titrirati naviše korak po korak do fiksne kombinacije amlodipina/valsartana/hidroklorotiazida 10/160/25 mg kako bi se postigle ciljne vrijednosti. Uz postizanje ciljne vrijednosti AT-a mjerena u ordinaciji, u 90 % bolesnika nakon 16 tjedana liječenja, terapije na bazi kombinacije amlodipina/valsartana također su smanjile prevalenciju albuminurije i centralnoga aortalnog tlaka, poboljšale elastičnost krvnih žila i pokazale pozitivan učinak na funkciju vaskularnog endotela putem svojeg djelovanja na markere uključene u funkciju endotela.

Arterijska hipertenzija (AH) vodeći je uzrok kardiovaskularnog (KV) morbiditeta i mortaliteta diljem svijeta. Unatoč brojnim različitim preporukama i mjerama za probir i liječenje AH-a, postizanje ciljnih vrijednosti arterijskoga tlaka (AT) i dalje je izazov u kliničkoj praksi. Glavni cilj pri liječenju bolesnika s AH-om i dalje je maksimalno smanjenje rizika od fatalnih i nefatalnih KV komplikacija, cerebrovaskularnih komplikacija i kronične bolesti bubrega. Da bi se taj cilj postigao, potrebno je sniziti AT na ciljne razine. Osim promjena životnoga stila, potrebni su i učinkoviti antihipertenzivni lijekovi. Ispitivanje VICTORY II provedeno je u svrhu procjene djelotvornosti i sigurnosti primjene fiksnih kombinacija amlodipina/valsartana i amlodipina/valsartana/hidroklorotiazida u jednoj tableti za postizanje ciljnih vrijednosti AT-a u bolesnika s novodijagnosticiranim i nekontroliranim AH-om 2. ili 3. stupnja. U ovo multicentrično, otvoreno, prospektivno kliničko ispitivanje bilo je uključeno ukupno 100 bolesnika. Svi bolesnici s AH-om 2. stupnja započeli su liječenje fiksnom kombinacijom amlodipina/valsartana u jednoj tableti od 5 mg/80 mg, koja se po potrebi mogla titrirati naviše, korak po korak do završne opcije, tj. do fiksne kombinacije amlodipina/valsartana/hidroklorotiazida 10/160/12,5 mg u jednoj tableti kako bi se postigle ciljne vrijednosti AT a. Bolesnici s AH-om 3. stupnja započeli su liječenje fiksnom kombinacijom amlodipina/valsartana 5/160 mg u jednoj tableti, koja se po potrebi mogla titrirati naviše, korak po korak, do fiksne kombinacije amlodipina/valsartana/hidroklorotiazida 10/160/25 mg u jednoj tableti kako bi se postigle ciljne razine AT-a. Rezultati ispitivanja VICTORY II pokazali su da fiksne kombinacije amlodipina/valsartana i amlodipina/valsartana/hidroklorotiazida u jednoj tableti učinkovito smanjuju AT u bolesnika s AH-om 2. ili 3. stupnja te da imaju dobar profil podnošljivosti., Hypertension is the leading cause of cardiovascular (CV) morbidity and mortality worldwide. In spite of many different recommendations and actions related to screening and management of hypertension, reaching target levels of blood pressure (BP) is still a challenge in clinical practice. The main goal of treating patients with hypertension remains the maximum reduction in the risk of fatal and non-fatal CV complications, cerebrovascular complications, and chronic kidney disease. To achieve this goal, it is necessary to lower BP to target levels. In addition to lifestyle changes, effective antihypertensive medication is needed. The VICTORY II study was performed to assess the efficacy and safety of the use of single-pill combinations (SPCs) of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide in achieving the target level of BP in newly diagnosed or uncontrolled patients with grade 2 or 3 arterial hypertension. A total of 100 patients were enrolled in this multicenter, open, prospective clinical study. All patients with grade 2 hypertension started the treatment with SPC of amlodipine/valsartan, 5 mg/80 mg, which if necessary could be up titrated step-by-step to the final option, i.e. SPC of amlodipine/valsartan/ hydrochlorothiazide 10/160/12.5 mg, to achieve target levels of BP. Patients with grade 3 hypertension started the treatment with SPC of amlodipine/valsartan 5 mg/160 mg, which could be up-titrated step-by-step to SPC of amlodipine/valsartan/hydrochlorothiazide 10/160/25 mg if necessary to achieve target levels of BP. The results of the VICTORY II study showed that SPCs of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide effectively reduce BP in patients with grade 2 or 3 hypertension and have a good tolerability profile.

Kardiovaskularne (KV) bolesti i dalje su vodeći uzrok morbiditeta i mortaliteta u svijetu i u Sloveniji. Prema preporukama Europskih smjernica za prevenciju kardiovaskularnih bolesti u kliničkoj praksi, smanjenje razine LDL kolesterola primjenom statina ključno je za prevenciju KV događaja. Brojna klinička ispitivanja i godine iskustva dokazuju djelotvornost terapije statinima. Unatoč tomu, oni se još uvijek premalo uporabljuju u kliničkoj praksi ili se primjenjuju u neadekvatnim dozama. U tromjesečnome neintervencijskom ispitivanju FROZEN praćena je klinička djelotvornost svih doza Krkina rosuvastatina (Roswera®). Rezultati su pokazali da su bolesnici s visokim ili vrlo visokim rizikom od KV događaja nedovoljno liječeni te su imali manje izglede za postizanje ciljnih razina LDL kolesterola nego oni s umjerenim rizikom. Liječenje je ocijenjeno sigurnim i učinkovitim tijekom razdoblja praćenja u bolesnika s umjerenim, visokim i vrlo visokim rizikom od KV a., Cardiovascular (CV) diseases remain the leading cause of morbidity and mortality in the world and in Slovenia. According to the recommendations of the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice, reducing LDL-cholesterol levels, especially with statins, is essential for prevention of CV events. A number of clinical studies and years of experience demonstrate the efficacy of statin therapy. Nevertheless, they are still rarely used in clinical practice or are used at insufficient doses. The clinical efficacy of all doses of Krka’s rosuvastatin (Roswera®) was monitored in FROZEN, a three-month non-interventional study. The results showed that patients at high or very high risk of a cardiovascular event were undertreated and were less likely to reach target LDL-C levels than moderate-risk patients. Treatment was evaluated as safe and effective during the follow-up period in patients at a moderate, high, and very high CV risk.

Endotelna disfunkcija najranija je vaskularna abnormalnost, a uključena je u sve faze kardiovaskularnog kontinuuma. Osim sposobnosti snizivanja arterijskoga tlaka, antihipertenzivni lijekovi u idealnom slučaju trebaju imati dodatna svojstva zaštite endotela. Čini se da među inhibitorima angiotenzin-konvertaze perindopril ima najsnažnije protektivne učinke na endotel. Amlodipin je dobro poznat po svojemu ateroprotektivnom učinku. Klinički dokazi pokazuju da perindopril i amlodipin pojedinačno mogu usporiti progresiju kardiovaskularne bolesti, uz dugoročne blagotvorne učinke liječenja na mortalitet. Taj je učinak jači i širi ako se oba lijeka primjenjuju zajedno. Važnim se doima rano propisivanje perindoprila i amlodipina jer se većina koristi od liječenja obama lijekovima događa u ranim ili srednjim fazama kardiovaskularnog kontinuuma. Klinički dokazi također podupiru blagotvorni učinak na vaskularni endotel kakav pruža trojna kombinacija perindoprila i amlodipina s indapamidom., Endothelial dysfunction is the earliest vascular abnormality and it is involved in all stage of the cardiovascular continuum. Antihypertensive compounds should ideally have additional endothelial protective properties beyond their ability to reduce blood pressure. Among angiotensinconverting enzyme inhibitors, perindopril appears to have the greatest endothelial protective effects. Amlodipine is well known for its atheroprotective effect. Clinical evidence has shown that perindopril and amlodipine could individually interrupt and slow the progression of cardiovascular disease with long-term beneficial effects of treatment on mortality. The effect is enhanced and broadened if both agents are used together. Early prescription of perindopril and amlodipine appears to be important, as most of the treatment benefits of both agents occur in the early or middle stages of the cardiovascular continuum. Clinical evidence also supports the beneficial effect on the vascular endothelium offered by the triple combination of perindopril and amlodipine with indapamide.

Arterijska je hipertenzija glavni uzrok kardiovaskularnih bolesti kao što su infarkt miokarda, ishemijski moždani udar, zatajivanje srca, bubrežna insuficijencija i drugi klinički događaji. Stoga je, uz primjerene promjene životnih, navika potrebno učinkovito liječenje antihipertenzivima kako bi se bolesnicima ne samo ublažili simptoma nego i pružila kardiovaskularna zaštita. Studija TANDEM provedena je kako bi se procijenile učinkovitost i sigurnost monoterapije telmisartanom (Tolura®) i kombinacije fiksne doze telmisartana i hidroklorotiazida (Tolucombi®) u odraslih bolesnika s arterijskom hipertenzijom. U ovoj neintervencijskoj postautorizacijskoj studiji učinkovitosti i sigurnosti sudjelovala su ukupno 1234 pacijenata. Pacijenti su liječeni monoterapijom telmisartanom ili kombinacijom fiksne doze telmisartana i hidroklorotiazida jednom na dan tijekom četiri mjeseca. Studija je pokazala da Tolura® i Tolucombi® znatno smanjuju sistolički i dijastolički arterijski tlak (p < 0,0001) te da ih hipertenzivni bolesnici dobro podnose., Arterial hypertension represents the main cause of cardiovascular disorders, such as myocardial infarction, ischemic stroke, heart failure, renal insufficiency, and other clinical events. Therefore, an effective antihypertensive pharmacotherapy is clearly needed, in addition to proper lifestyle changes, in order to provide not only symptomatic relief but also cardiovascular protection. The TANDEM study was undertaken to evaluate the efficacy and safety of telmisartan monotherapy (Tolura®) and the fixed-dose combination of telmisartan/hydrochlorothiazide (Tolucombi®) in adult hypertensive patients. A total of 1,234 patients were enrolled in this non-interventional post-authorization efficacy and safety study. Patients were treated with telmisartan monotherapy or the fixed-dose combination of telmisartan/hydrochlorothiazide once daily for four months. The study demonstrated that Tolura® and Tolucombi® reduce systolic and diastolic blood pressure significantly (p

Tijekom 65 godina svojega postojanja Krka je iz maloga farmaceutskog laboratorija prerasla u jednu od vodećih generičkih farmaceutskih tvrtki u svijetu. Krkini se inovativni generički lijekovi s dodanom vrijednosti razvijaju primjenom našega vlastitog znanja i umijeća. Time se osiguravaju ključne prednosti u odnosu prema konkurentskim proizvodima, koje su rezultat razvoja novih tehnologija primijenjenih u proizvodnji djelatnih tvari i farmaceutskih oblika. Pri planiranju naše ponude lijekova uvijek pažljivo pratimo najčešće bolesti u modernome svijetu. Omogućujemo liječnicima i bolesnicima odabir širokog raspona pakiranja, jačina i kombinacija u jednoj tableti. Terapijska se ekvivalentnost Krkinih proizvoda s originalnim lijekovima dokazuje u in vivo istraživanjima bioekvivalencije. Rezultati mnogobrojnih kliničkih istraživanja pokazuju da su naši lijekovi učinkoviti i dobro podnošljivi u svakodnevnoj kliničkoj praksi., In its 65-year history, Krka has grown from a small pharmaceutical laboratory to become one of the leading generic pharmaceutical companies in the world. Krka’s innovative, added-value generic medications are developed using the company’s own know-how. This ensures that they hold certain key advantages over competitor products, resulting from the development of new technologies used in the production of active ingredients and dosage forms. When planning our product portfolio, we closely monitor the most common diseases in the modern world. We allow doctors and patients to choose from a wide variety of packaging, strengths, and single-pill combinations. The therapeutic equivalence of our medications with the originator’s medications is demonstrated by in vivo bioequivalence studies. The results of numerous clinical studies show that our medications are effective and well-tolerated by patients in clinical practice.

Dokazano je da statini smanjuju kardiovaskularni pobol i smrtnost u primarnoj i sekundarnoj prevenciji kardiovaskularnih bolesti. No liječenje statinima još uvijek nije optimalno jer većina pacijenata ne postiže najveće moguće pozitivne učinke ovakve preventivne strategije. Krka ima širok raspon statina koji su iscrpno testirani. Studije donose jasne i opsežne dokaze o dobrobiti primjene atorvastatina (Atoris®) irosuvastatina (Roswera®) u primarnoj i sekundarnoj prevenciji, uključujući uspješno liječenje ukupnoga lipidnog profila, postizanje ciljne razine lipida, prevencije ozbiljnih ishemijskih ishoda u pacijenata s akutnim koronarnim sindromom, preventivne pleiotropne učinke i dobar sigurnosni profil. Kliničke studije na Krkinim statinima važan su doprinos boljem liječenju hiperlipidemije u različinim skupinama pacijenata., Statins have been proven to reduce cardiovascular morbidity and mortality in primary and secondary prevention of cardiovascular disease. However, statin treatment is still not optimal, with the majority of patients not achieving the maximum benefits of this preventive strategy. Krka offers a wide range of statins that have been extensively studied. The studies have provided clear and conclusive evidence about the benefits of atorvastatin (Atoris®) and rosuvastatin (Roswera®) in primary and secondary prevention patients, including effective management of the total lipid profile, achievement of target lipid levels, prevention of severe ischemic outcomes in patients with acute coronary syndrome, protective pleiotropic effects and a good safety profile. Clinical studies with Krka’s statins represent an important contribution to a better management of hyperlipidemia in different groups of patients

Krka ima više od 25 godina iskustva u proizvodnji visokokvalitetnih lijekova koji djeluju na renin-angiotenzin-aldosteronski sustav (RAAS) te je postala jedan od vodećih proizvođača takvih lijekova u Europi. Otkad je prvi put uvela lijek koji djeluje na RAAS, Krka provodi međunarodna klinička istraživanja kako bi pratila učinkovitost i sigurnost svojih proizvoda unutar opsega primjene, omogućila liječnicima da steknu vlastito iskustvo o njihovom korištenju te dokazala njihovu učinkovitost i sigurnost u kliničkoj praksi. Uz podatke iz istraživanja opisanih u ovom članku, izložit ćemo i dvadesetpetogodišnji doprinos Krkinih lijekova koji utječu na RAAS u liječenju arterijske hipertenzije., Krka has over 25 years of experience in the production of high-quality medicines acting on the renin-anigotensin-aldosterone system (RAAS) and has become one of the leading producers of them in Europe. Since its first introduction of a medicine acting on RAAS it has been performing international clinical studies in order to monitor the efficacy and safety of its products within the scope of the doctrine, enable doctors to gain their own experience with them, and prove their efficacy and safety in clinical practice. With the findings of the studies described in this article, we would like to present the contribution of Krka’s RAAS-acting medicines in the treatment of hypertension in over 25 years.

Povišeni arterijski tlak (AT) vodeći je globalni čimbenik rizika za kardiovaskularne bolesti i kronične bubrežne bolesti. Stoga su uz promjene u životnome stilu očito potrebni i djelotvorni antihipertenzivni lijekovi kako bi se pacijentima pružilo ne samo ublaživanje simptoma nego i kardiovaskularna zaštita. Kliničko ispitivanje VICTORY provedeno je kako bi se procijenila djelotvornost i sigurnost monoterapije valsartanom (Valsacor®) i liječenja kombinacijom fiksnih doza (KFD) valsartana i hidroklorotiazida (Valsacombi®) u širokoj populaciji bolesnika s blagom do umjerenom arterijskom hipertenzijom. Ukupno je 365 pacijenata bilo uključeno u šesnaestotjedno međunarodno, multicentrično, otvoreno, prospektivno ispitivanje. Pacijenti su počeli liječenje s 80 mg valsartana na dan, što se zatim moglo titrirati do 320 mg dnevno ili kombinirati s hidroklorotiazidom KFD kako bi se postigla ciljna vrijednost AT-a. Rezultati kliničkog ispitivanja VICTORY pokazali su da valsartan i KFD valsartana i hidroklorotiazida djelotvorno smanjuju AT u bolesnika s blagom do umjerenom arterijskom hipertenzijom te imaju vrlo dobar profil podnošljivosti., Raised blood pressure (BP) is the leading global risk factor for cardiovascular disease and chronic kidney disease. Thus, in addition to lifestyle changes effective antihypertensive medication is clearly needed to provide not only symptomatic relief but also cardiovascular protection. The VICTORY trial was performed to assess the efficacy and safety of valsartan monotherapy (Valsacor®) and therapy with the fixed-dose combination (FDC) of valsartan and hydrochlorothiazide (Valsacombi®) in a broad population of patients with mild to moderate arterial hypertension. A total of 365 patients were enrolled in this 16-week, international, multicentre, open-label, prospective trial. The patients started the treatment with 80 mg valsartan daily, which could be up-titrated to 320 mg daily or combined with hydrochlorothiazide (HCTZ) in a fixed-dose combination to achieve target BP. The results of the VICTORY trial showed that valsartan and the FDC of valsartan and hydrochlorothiazide effectively reduce BP in patients with mild to moderate arterial hypertension, and have a very good tolerability profile.

Dislipidemija je povezana s najvećim rizikom za srčano-žilne bolesti u populaciji. Od raznih preventivnih postupaka, dokazi iz randomiziranih kontroliranih studija podržavaju važnost agresivnog smanjenja vrijednosti lipida koje se najsnažnije postiže uporabom statina. Kliničke studije su pokazale da čak i malo smanjenje LDL kolesterola ima važan klinički učinak. No, usprkos jasnim dokazima korisnosti terapije statinima, ti lijekovi se i dalje nedovoljno koriste ili se primjenjuju u nedostatnim dozama. Većina pacijenata s dislipidemijom liječi se najnižim dozama, a liječnici vrlo rijetko propisuju najviše doze. Da bi se potpomoglo zatvaranje tog terapijskog jaza, Krka je priredila širok spektar jačina rosuvastatina, uključujući dvije doze srednje jačine od 15 mg i 30 mg. Te jačine omogućuju individualnu prilagodbu liječenja te postizanje željene razine lipida u većeg broja pacijenata., Dyslipidemia is associated with the highest population attributable risk for cardiovascular disease. Of various cardiovascular preventive therapies, the evidence from randomised controlled studies supporting the importance of aggressive lipid lowering is the most robust for statins. Clinical studies have shown that even a small reduction of LDL cholesterol has an important clinical effect. However, despite clear evidence of the benefits of statin therapy, these drugs are still underused or underdosed. The majority of patients with dyslipidemia are treated with the lowest doses, and doctors use the highest doses only very rarely. To help close the therapeutic gap, Krka has made available a wide range of rosuvastatin dosage strengths, including two intermediate strengths of 15 mg and 30 mg. These enable treatment to be individually adjusted and result in more patients reaching target lipid levels.

Adherence of patients to therapy has in the past years been identified as one of the major factors influencing blood pressure (BP) control in treated population. The use of fixed dose combinations improves ad- herence, and consequentially increases the rate of BP control. The fixed dose combination of perindopril and indapamide deserves special attention because of the large-scale outcome trials which have shown its advantages beyond blood pressure lowering as well as improved cardiovascular prognosis. The results of the clinical trials have also been confirmed in daily clinical practice. With its fixed dose combination of perindopril and indapamide Krka offers the opportunity of individualized therapy either for start or for continuation of antihypertensive treatment.

Patients with established cardiovascular disease (CVD) are the ones that are most commonly considered for therapeutic intervention in order to prevent progression of the disease. In contrast, patients without manifested CVD and at increased risk are often left untreated, even though they would have the greatest benefits from early risk reduction in terms of CVD prevention. According to the recently published European CVD prevention guidelines, the reduction of LDL cholesterol must be of prime concern in the prevention of CVD. With potent statins, such as rosuvastatin, we can achieve meaningful reductions of LDL cholesterol levels and, consequently, reduce an individual’s total CVD risk. On the basis of a large clinical study with rosuvastatin, prevention of major cardiovas- cular events in patients who are estimated to have a high risk was added to statin labels. A post hoc analysis of this clinical study which included only patients considered to be at high risk, showed that patients with a 10-year Framingham risk score of >20% or an estimated SCORE risk of >5% had statistically significant reductions, 50% and 43%, respectively, in the risk of MI, stroke, or cardiovascular death when treated with rosuvastatin compared with patients treated with placebo. Rosuvastatin also has established benefits in other high-risk patients, such as patients with diabetes and hypertension. Long-term compliance with statin therapy is critical for its efficacy in patients at high risk. With long-term statin treatment we can achieve greater reductions of the CVD risk and an even more pro- nounced regression of atherosclerotic plaques.

Među 67 analiziranih čimbenika visoki arterijski tlak (AT) identificiran je kao glavni čimbenik rizika za smrtni ishod i invalidnost. Kontrola vrijednosti AT-a još je uvijek daleko od razine koja bi bila nužna za smanjenje kardiovaskularnog rizika, a liječenje bolesnika s arterijskom hipertenzijom i dalje je izazov u svakodnevnoj kliničkoj praksi. Smanjenje učestalosti kardiovaskularnih događaja tijekom liječenja perindoprilom potkrepljuje koncept dodatnih zaštitnih kardiovaskularnih učinaka perindoprila i uz snizivanje vrijednosti AT-a. Učinkovita kontrola AT-a, kao što je to dokazano u kliničkim studijama s Krkinim perindoprilom i njegovim ksnim kombinacijama doza s indapamidom i amlodipinom, zajedno s dobrom podnošljivošću i pogodnim jednodnevnim doziranjem, u pacijenata dovodi do pozitivnog učinka na ustrajnost liječenja, što je ključan korak prema postizanju ciljnih vrijednosti AT-a., High blood pressure has been identified as the leading risk factor, among 67 studied, for death and disability. Blood pressure control is still far from what would be necessary to reduce the cardiovascular risk. The treatment of hypertensive patients remains a challenging issue in daily clinical practice. The reduction in cardiovascular events with perindopril supports the concept of cardiovascular protective effects of perindopril beyond blood pressure lowering. Effective blood pressure con- trol, as demonstrated in clinical studies with Krka’s perindopril and its sed-dose combinations with indapamide and amlodipine, together with good tolerability and convenient once-daily dosing, have a positive impact on patients’ adherence to the treatment – which is a crucial step towards reaching the blood pressure targets.

Tijekom prošlih šest desetljeća Krka je postala jedna od vodećih generičkih farmaceutskih tvrtki u svijetu. Naše inovativne generičke lijekove, tj. generičke lijekove s dodanom vrijednosti, razvijamo sami koristeći se vlastitim znanjem i umijećem. Time se osiguravaju ključne prednosti pred konkurentnim lijekovima zahvaljujući razvoju novih tehnologija primjenjivanih u proizvodnji aktivnih supstancija i farmaceutskih oblika. Lijekovi za liječenje kardiovaskularnih bolesti čine ključni dio među Krkinim lijekovima koji se propisuju na recept. Nudimo širok raspon kardiovaskularnih lijekova dostupnih u različitim oblicima, kombinacijama fiksnih doza i inovativnih jačina, što liječnicima omogućuje optimalno liječenje bolesnika. Terapijska ekvivalentnost Krkinih proizvoda s originalnim lijekovima dokazuje se u in vivo studijama bioekvivalencije. Rezultati mnogobrojnih kliničkih studija dokazali su da su naši lijekovi klinički dokazani, učinkoviti i dobro podnošljivi u svakodnevnoj kliničkoj praksi., In the past six decades, Krka has emerged as one of the leading generic pharmaceutical companies in the world. Our innovative generics, i.e. value-added generic medicines, are developed using the company’s own know-how. This ensures that our products hold certain key advantages over competitor products, resulting from the development of new technologies used in the production of active ingredients and dosage forms. Our key therapeutic area in prescription pharmaceuticals is cardiovascular medicines. We offer a wide range of cardiovascular medicines, available in a variety of different dosage forms, fixed-dose combinations and innovative strengths, which enable doctors to optimize the treatment of their patients. The therapeutic equivalence of Krka’s product with the originator’s product is demonstrated by in vivo bioequivalence studies. The results of numerous clinical studies have shown that our medicines are clinically proven, effective, and well tolerated by patients in real clinical practice.

Koronarna bolest srca (KBS) predstavlja vodeći uzrok smrti diljem svijeta. Nažalost, iznenadna srčana smrt je za mnoge pojedince prvi manifestacija KBS. Prevencija idealno počinje primarnom intervencijom u osoba s povećanim rizikom od kardiovaskularnih bolesti (KVB), ali bez klinički manifestne bolesti. Usmjerena je na zbrinjavanje čimbenika rizika, koji uključuju dislipidemiju i artrijsku hipertenziju, koji su odavno utvrđeni kao važni promjenjivi kardiovaskularni (KV) čimbenici rizika. Međutim, postupci primarne prevencije su još uvijek nedovoljni i ne mogu pružiti optimalnu zaštitu od razvoja KVB. Napori u sekundarnoj prevenciji, gdje zbrinjavanje KV čimbenika rizika postaje još važnije, usmjereni su na prevenciju daljnje progresije bolesti koja može dovesti do ponovne pojave KV događaja, pa čak i smrti. Tijekom proteklog desetljeća, klinička dobrobit hipolipemika i antihipertenzivnih lijekova u smislu smanjenja KV rizika je utvrđena u brojnim randomiziranim kontroliranim istraživanjima. Statini su jedina skupina hipolipemika koji poboljšavaju kliničke ishode u bolesnika sa i bez KVB. Oni dokazano smanjuju KV pobol i smrtnost, kao i potrebu za intervencijama na koronarnim arterijama. Dokazi o djelotvornosti perindoprila u smanjenju pojavnosti KV slučaja su dobro utemeljeni. Rezultati studije EUROPA u bolesnika sa stabilnom KBS pružaju jasne dokaze o djelotvornosti perindoprila u sekundarnoj prevenciji. Mogućnosti liječenja zasnovane na dokazima, poput statina i inhibitora angiotenzin konvertirajućeg enzima bi mogle pomoći u smanjenju faktora rizika kod bolesnika sa KVB, a time i osigurati odgovarajuću zaštitu od daljnje progresije ove bolesti., Coronary heart disease (CHD) is the leading cause of death worldwide. Unfortunately, sudden cardiac death is for many individuals the first manifestation of CHD. Prevention ideally begins with primary interventions in persons at increased risk for cardiovascular disease (CVD) but without clinically manifested disease. It is aimed at managing risk factors, including dyslipidemia and hypertension, which have long been established as important modifiable cardiovascular (CV) risk factors. However, primary prevention practices are still inadequate and may provide suboptimal protection against the development of CHD. Efforts in secondary prevention, where the management of CV risk factors becomes even more crucial, are focused on the prevention of further progression of the disease which can result in recurrence of the CV event or even death. Over the past decade, the clinical benefit of lipid-lowering and antihypertensive medicines in terms of CV risk reduction has been established in numerous randomised controlled trials. Statins are the only lipid-lowering medicines which improve clinical outcomes in patients with and without CVD. They have been shown to reduce CV morbidity and mortality as well as the need for coronary artery interventions. Evidence of the efficacy of perindopril in reducing the incidence of CV events is well established. The findings of the EUROPA study in patients with stable CHD provided clear evidence of the efficacy of perindopril in secondary prevention in patients with stable CHD. Evidence-based treatment options, such as statins and angiotensin-converting enzyme inhibitors, could help reduce risk factors in CHD patients and, consequently, provide adequate protection against further progression of the disease.

Telmisartan je dugodjelujući, snažan, vrlo selektivan antagonist AT1 receptora angiotenzina II. Omogućuje preciznije i potpunije blokadu djelovanja angiotenzina II od ACE inhibitora. Telmisartan je već etabliran kao učinkovit antihipertenzivni lijek s jednokratnim doziranje koji se primjenjuje kod različitih skupina hipertenzivnih bolesnika. Dobro je podnošljiv i učinkovit antihipertenzivkoji nudi cjelovitu 24-satnu kontrolu arterijskog tlaka čak i u slučaju izostanka doze. Iako je učinkovitost blokatora angiotenzinskih receptora (ARB) potvrđena u različitih tipova bolesnika, telmisartan je trenutno jedini ARB s jasnim dokazima i indikacijom za uporabu za smanjenje rizika od kardiovaskularnih događaja., Telmisartan is long-acting, potent, highly selective angiotensin II subtype 1 (AT1) receptor antagonist. It provides a more specific and complete blockade of the actions of angiotensin II than ACE inhibitors. Telmisartan has already been established as an effective once- daily blood-pressure-lowering drug in different types of patients. It is a well-tolerated and effective antihypertensive therapy, which offers full 24 h control of blood pressure even in the event of a missed dose. Nevertheless that the efficacy of angiotensin receptor blockers (ARBs) in different type of patients were confirmed, telmisartan is currently the only ARB with clear evidence and indication for usage in cardiovascular event risk reduction.

Akutni koronarni sindromi predstavljaju vodeći uzrok smrtnosti i jedan su od glavnih razloga bolničkog prijma u razvijenim zemljama. Zbog visoke stope smrtnosti i ponovnog infarkta, akutni koronarni sindromi predstavljaju veliki problem javnog zdravstva. Klopidogrel ima čvrstu bazu dokaza koja podupire njegovu uporabu kao učinkovitog i dobro podnošljivog antitrombocitnog lijeka za sekundarnu prevenciju ishemijskih događaja kod bolesnika s različitim kardiovaskularnim stanjima, uključujući akutni koronarni sindrom, pa je sveprisutan u kardiološkoj praksi. Nekoliko velikih studija utvrdilo je važnost klopidogrela kod terapije infarkta miokarda bez i sa elevacijom ST-segmenta te kod perkutane koronarne intervencije, gdje je registrirano smanjenje smrtnosti, reinfarkta i neželjenih kardioloških ishoda. Zyllt® (Krkin klopidogrel) također ima formiranu bazu dokaza od mnogih postautorizacijskih kliničkih studija koje potvrđuju njegovu djelotvornost i sigurnost. Ove studije pružaju značajne rezultate i veliku bazu podataka, koja nije dostupna kod bilo kojeg drugog generičkog klopidogrela., Acute coronary syndromes are the leading cause of mortality and one of the main reasons for hospital admissions in the developed nations. Due to high rates of mortality and reinfarction, acute coronary syndromes represent a major public health concern. Clopidogrel has a strong evidence base supporting its use as an effective and well-tolerated antiplatelet agent for the secondary prevention of ischemic events in patients with various cardiovascular conditions, including acute coronary syndrome, and is ubiquitous in cardiology practice. Landmark studies have established the importance of clopidogrel in the treatment of non-ST and ST-segment elevation myocardial infarction and in percutaneous coronary interventions, where it was shown to reduce death, reinfarction, and adverse cardiac events. Zyllt® (Krka’s clopidogrel) also has an established evidence base from many post-authorisation clinical studies demonstrating its efficacy and safety. These studies yielded important results and an extensive database, which is not available for any other generic clopidogrel.

Dislipidemija je jedan od najvažnijih i najčešćih promjenjivih čimbenika rizika za kardiovaskularne bolesti (KVB). Postoji mnogo različitih hipolipemika, ali do današnjeg dana statini su i dalje ostali jedini lijekovi koji dokazano smanjuju kardiovaskularnu smrtnost i morbiditet u bolesnika sa i bez utvrđene KVB. To je razlog zašto oni su postali temeljna teraoija u smjernicama. U posljednjih nekoliko godina, smjernice za zbrinjavanje dislipidemije i prevenciju KVB predlažu još više smanjenje ciljnih vrijednosti razine lipida. Bile su prihvaćene na temelju rezultata iz kliničkih studija, uključujući i rezultate iz meta-analiza, što pokazuje da je daljnje sniženje LDL kolesterola rezultiralo dobrobitima, bez novih ili neočekivanih neželjenih nuspojava. Nadalje, kliničke studije su pokazale da čak i malo smanjenje LDL kolesterola ima značajan klinički učinak i da svakim 1% smanjenjem razine LDL kolesterola smanjuje i relativan rizik od velikih manifestacija koronarne bolesti srca za oko 1%. Unatoč poznatim prednostima postizanja ciljnih razina lipida, većina bolesnika, posebice u sekundarnoj prevenciji, ih ne postiže. Statini se obično propisuju u manjim dozama, a često se ne titriraju porastom doze do postizanja terapijskih ciljeva. Posjedovanje cjelovitog asortimana doza može biti jedan od pristupa za poboljšanje uspješnosti u postizanju ciljnih razina lipida u zbrinjavanju hiperlipidemije. To bi moglo pomoći u poboljšanju kliničkih ishoda i pružanju maksimalnih koristi za bolesnike od liječenja statinima za bolesnike., Dyslipidemia is one of the most important and common modifiable risk factors for cardiovascular disease (CVD). There are many different types of lipid lowering medicines, but till this date statins have remained the only medicines proven to reduce cardiovascular mortality and morbidity in patients with and without established CVD. This is why they have become the mainstay of therapeutic guidelines. In recent years, guidelines for the management of dyslipidemia and on CVD prevention have mandated even lower target lipid levels. These were accepted based on the results from clinical studies, including the results of meta-analyses, which demonstrated that further lowering of LDL cholesterol produced additional benefits, without new or unexpected safety issues. Moreover, clinical studies have shown that even a small reduction of LDL cholesterol has a significant clinical effect and that every 1% reduction in the LDL cholesterol level reduces the relative risk for major coronary heart disease events by approximately 1%. Despite the known benefits of reaching target lipid levels, the majority of patients, especially in secondary prevention, are not reaching them. Statins are usually prescribed at lower doses and often not up-titrated to achieve the therapeutic goals. Having a complete range of doses can be one of the approaches to improve the success rate in reaching target lipid levels in the management of hyperlipidemia. It could help improve clinical outcomes and provide maximum benefits of statin treatment for the patients.

Elevated blood pressure (BP) is one of the most important risk factors for cardiovascular (CV) morbidity and mortality, and BP lowering is associated with reduction of coronary events. Despite this, less than one-third of hypertensive patients in Europe have adequate BP control. Improvement of the rates of adequate BP control and thereby a reduction of CV morbidity and mortality, currently represent a major challenge in the daily clinical practice. Many patients require two or more antihypertensives to achieve guideline-recommended BP targets. Findings from different studies have demonstrated that the fixed-dose combination (FDC) perindopril/amlodipine is an effective and well tolerated treatment in patients uncontrolled with monotherapy, and in patients inadequately managed on another combination therapy. The perindopril/amlodipine FDC provides good rates of BP control in daily clinical practice. These good rates of BP control could be explained by the synergistic mode of action of the two components, leading to enhanced BP lowering and reduced si- de effects, which may have a positive impact on treatment adherence. Krka’s perindopril/amlodipine FDC is available in the full range of doses, providing a flexible and effective treatment of hypertension.

Arterijska hipertenzija (AH) predstavlja najveći pojedinačni čimbenik rizika koji doprinosi globalnoj smrtnosti. Usprkos stalnom poboljšanju liječenja, samo jedna trećina liječenih bolesnika ima dostignite željene vrijednosti arterijskog tlaka (AT). Novija klinička istraživanja navode da pristup korištenja monoterapije za kontrolu AH vjerojatno neće biti uspješan kod mnogih bolesnika. Stoga prednost ima kombinirana terapija, temeljem činjenice da AH doprinose višestruki čimbenici, a postizanje kontrole AT sa samo jednim lijekom koje djeluje preko jednog mehanizma vjerojatno neće biti dostatno. Kombiniranjem lijekova u odgovarajućoj dozi smanjuje se doza pojedinačnih komponenti i učestalost nuspojava te se poboljšava suradljivost bolesnika. Temeljem dokaza iz studije Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure-Lowering Arm kombinacija inhibitora angiotenzin konvertirajućeg enzima (ACE) i blokatora kalcijevih kanala (CCB) predstavlja liječenje izbora kod AH. Kombinacija perindoprila i amlodipina jedini je oblik liječenja kombinacijom ACE inhibitora i CCB koje je dokazalo da zadovoljava primarni cilj antihipertenzivne terapije, tj. cjelokupnom smanjenju pobola i smrti povezanog s AH. Krka je trenutno jedina generička tvrtka koja nudi fiksnu kombinaciju perindoprila i amlodipina i tako omogućava učinkovito liječenje prilagođeno pojedinačnim potrebama bolesnika i liječnika., Hypertension is currently the biggest single risk factor contributing to global death. Despite the constantly improving treatments, only one third of patients who are treated have a normalisation of blood pressure (BP). Recent clinical trials suggest that the approach of using monotherapy for the control of hypertension is not likely to be successful in most patients. Combination therapy is preferred, based on the fact that multiple factors contribute to hypertension and achieving control of BP with a single agent acting through one particular mechanism may not be possible. Combining the medicines makes them available in a convenient dosing format and lowers the dose of individual components, thus reducing the side effects and improving compliance. Based on evidence from the Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure-Lowering Arm (ASCOT-BPLA), the combination of an angiotensin-converting enzyme (ACE) inhibitor with a calcium channel blocker (CCB) is one of the preferred therapeutic options. The combination perindopril-amlodipine is the only treatment among ACE inhibitor and CCB combinations that has been demonstrated to meet the primary objective of antihypertensive therapy, that is, overall reduction of hypertension-related death and morbidity. Krka is now the only generic company offering a fixed combination of perindopril and amlodipine and thus enabling effective treatment tailored to the individual needs of patients and physicians.

U nedavno objavljenim europskim smjernicama uvedena je nova klasifikacija bolesnika u četiri kategorije rizika te su preporučene čak i niže ciljne razine lipida za pacijente s vrlo visokim rizikom. U svjetlu činjenice da oko polovice europskih pacijenata koji su liječeni hipolipemicima ne postižu ciljne razine lipida prema smjernicama Europskog kardiološkog društva iz 2007. godine, nove ciljne razine lipida se mogu shvatiti kao veći izazov. Uporabom "jačih" statina, poput rosuvastatina ili atorvastatina, u primjerenim dozama, može se udovoljiti zahtjevima novih europskih preporuka., Recently issued European guidelines introduced new classification of patients into 4 risk categories and mandated even lower target lipid levels for patients at very high risk. In the light of the fact that about half of patients in Europe receiving lipid-lowering therapy were not reaching target lipid levels as set in the 2007 European Society of Cardiology guidelines, new target lipid levels may be seen as an even greater challenge. However by using potent statins such as rosuvastatin or atorvastatin and in appropriate doses, the requirements of the new European recommendations can be met.

Čimbenike rizika čine stanja ili navike koje povećavaju rizik nastanka bolesti. Čimbenici rizika, poput arterijske hipertenzije, pušenja, povišene vrijednosti kolesterola i dijabetesa, značajno doprinose razvoju kardiovaskularnih bolesti koje su vodeći uzrok smrtnosti i pobola u industrijaliziranim zemljama. Inhibitori angiotenzin konvertirajućeg enzima smanjuju rizik od kardiovaskularnih događaja kod pacijenata sa svim razinama rizika. Brojne kliničke studije su već dokazale učinkovitost i sigurnost ramiprila u liječenju hipertenzije. Rezultati studije HOPE su već ukazali na jasne vaskularne i metaboličke prednosti terapije ramiprila. Ove prednosti su dosljedne bez obzira na prisutne čimbenike rizika bolesnika ili primjenu dodatnih liječenja. Kliničke studije Krkinog ramiprila su potvrdile njegovu učinkovitost u postizanju ciljnih razina arterijskog tlaka i ukazale na dodatne koristi kod visokorizičnih bolesnika., Risk factors are conditions or habits that increase the risk of developing a disease. Risk factors such as hypertension, smoking, high cholesterol and diabetes contribute significantly to the development of cardiovascular diseases. Cardiovascular diseases are the major cause of mortality and morbidity in industrialised countries. Angiotensin-converting enzyme inhibitors reduce the risk of cardiovascular events in patients at all levels of risk. Numerous clinical studies have already proved the efficacy and safety of ramipril in hypertension treatment. The results of the HOPE study also demonstrated clear vascular and metabolic benefits of ramipril therapy. These benefits were consistent regardless of the patients’ risk factors or additional treatments. Clinical studies with Krka’s ramipril confirmed its efficacy in achieving target blood pressure levels and demonstrated its various additional benefits in high-risk patients.

Kardiovaskularne bolesti (KVB) su i dalje vodeći uzrok globalnog mortaliteta te uzrokuju gotovo polovicu smrti u Europi. Istraživanja pokazuju da dislipidemija predstavlja jedan od najznačajnijih čimbenika rizika koji doprinose razvoju KVB. U kolovozu 2011. god. Europsko kardiološko društvo i Europsko društvo za aterosklerozu objavili su nove smjernice za liječenje pacijenata s dislipidemijama, koje snižene razine LDL kolesterola i dalje smatraju primarnim ciljem liječenja. Smjernice preporučaju propisivanje terapije statinima do najviše moguće doze ili najviše podnošljive doze kako bi se dosegla ciljna razina LDL kolesterola. Nekoliko kliničkih studija potvrdilo je učinkovitost i sigurnost atorvastatina u kliničkoj praksi kod širokog spektra bolesnika. Studija Anglo Scandinavian Cardiac Outcomes Trial – Lipid-Lowering Arm (ASCOT-LLA) je ukazala da smanjenje velikih kardiovaskularnih događaja primjenom atorvastatina može omogućiti dugoročnu dobrobit na ukupnu smrtnost. Krka je posvećena kontinuiranoj procjeni učinkovitosti i sigurnosti svojih proizvoda., Cardiovascular disease (CVD) still remains the leading cause of global mortality and causes nearly half of all deaths in Europe. Research shows that among many risk factors contributing to the development of CVD, dyslipidemia is one of the most significant. In August 2011, the European Society of Cardiology and the European Atherosclerosis Society released new guidelines for the management of patients with dyslipidemias, which consider low LDL cholesterol levels still as the primary treatment target. The guidelines recommend physicians prescribe statin therapy up to the highest dose possible or the highest tolerable dose to reach the target LDL cholesterol level. Several clinical studies confirmed the efficacy and safety of atorvastatin in clinical practice in a wide range of patients. The Anglo Scandinavian Cardiac Outcomes Trial – Lipid-Lowering Arm (ASCOT-LLA) has demonstrated that reductions in major cardiovascular events with atorvastatin may contribute to long-term benefits on all-cause mortality. Krka is dedicated to continuously evaluate the efficacy and safety of its products.