Mišićne nuspojave statina

Cilj istraživanja Inhibitori 3-hidroksi-3-metilglutaril-koenzim A-reduktaze ili statini su revolucionarni lijekovi u liječenju kardiovaskularnih bolesti, smanjuju morbiditet i mortalitet od kardiovaskularnih bolesti za oko 25%. Deseci milijuna pacijenata diljem svijeta sada primaju statine za liječenje hiperkolesterolemije. Ovo istraživanje daje pregled patofiziologije, epidemiologije i kliničkih obilježja mišićnih nuspojava statina jer je i mali postotak od desetaka milijuna pacijenata velik, a navedene nuspojave mogu negativno utjecati na kvalitetu života, ali i na odnos prema tom potencijalno životno važnom lijeku. Materijal i metode Izveden je sveobuhvatan pregled baza podataka PubMed, Cochrane, te akademskog izdavača časopisa u otvorenom obliku Scientific Research i portala znanstvenih časopisa Republike Hrvatske Hrčak za članke koji se odnose na kardiovaskularnu primarnu prevenciju i nuspojave statina. Pojmovi za pretragu uključuju kardiovaskularne bolesti i svaki od sljedećih pojmova zasebno: primarna prevencija, terapija statinima, nuspojave statina, mijalgija, miopatija, rabdomioliza i koenzim Q10. Literatura je selektivno pregledana dajući prednost kliničkim mišljenjima, meta-analizama i velikim randomiziranim kontroliranim ispitivanjima. Rezultati Statini se dobro toleriraju, ali mogu se pojaviti zabrinjavajuće mišićne nuspojave. Opservacijske studije procjenjuju da oko 10% korisnika statina razvijaju mišićne nuspojave koje variraju od prolaznih povećanja kreatin kinaze do teških slučajeva rabdomiolize (1). Dok je kobna rabdomioliza rijedak događaj (0,15 umrlih na milijun propisanih recepata), štetne mišićne manifestacije poput mialgije i miozitisa su mnogo češće, a procjenjena pojavnost je 1-7% (2). Predloženi mehanizmi za navedene nuspojave uključuju smanjenu razinu koenzima Q10 i izoprenoida te poremećaj funkcije mitohondrija u miocitima. Rizik od nuspojava povećava bilo koja varijabla koja podiže koncentraciju statina u serumu, a ključne su: doza statina, karakteristike pacijenta (starija dob, ženski spol, niski indeks tjelesne mase, učestala konzumacija alkohola, povećana tjelesna aktivnost) i istodobno liječenje s inhibitorima citokroma P450 (3, 4). U jednoj meta-analizi, koja je sintetizirala kolektivne podatke o nuspojavama uočenim u prospektivnim randomiziranim kliničkim ispitivanjima, atorvastatin je bio povezan s najvećim rizikom od nuspojava, a fluvastatin s najmanjim rizikom (5). Zaključak Mogućnosti za liječenje statinima kod pacijenta kod kojih se pojavljuju nuspojave su prebacivanje na niže doze, nesvakodnevno doziranje statina s dugotrajnim djelovanjem, kao što su rosuvastatin i atorvastatin i terapija nestatinskim lijekovima. Zaključno, mišićne nuspojave statina su značajan klinički problem, ali mogle bi se spriječiti u mnogim slučajevima predviđajući moguće interakcije lijekova.Objectives The 3-hydroxy-3-methylglutary coenzyme A reductase inhibitors or statins have revolutionized the management of cardiovascular disease, they decrease cardiovscular disease morbidity and mortality by about 25%. Tens of millions of patients worldwide now receive statins for hypercholesterolemia. This research reviewed the pathophysiology, epidemiology, clinical features, and management of statin-related myopathy becouse even a small percentage of tens of millions of patients is a large number, and statin myopathy can adversely affect both quality of life and adherence to this potentially life-saving treatment. Material and Methods It's been performed a comprehensive review of Pubmed, Cohrane, Scientific Research and Hrčak databases for articles relating to cardiovascular primary prevention and statin side effects. Search Terms included cardiovascular disease and each of the following terms separately: primary prevention, statin therapy, statin side effects, myalgia, myopathy, rhabdomyolisis and coenzyme Q10. The literature has been selectively reviewed giving precedence to clinical reviews, meta-analysis and large-scale randomised controlled trials. Results Statins are well tolerated but side effects that concern skeletal muscle may arise. Observational studies estimate that about 10% of statin users develop statin-related muscle side effects which ranges from transient increases in creatine kinase to severe cases of rhabdomyolysis (1). While fatal rhabdomyolisis is rare event (0,15 deaths per million of prescriptions), deleterious muscle manifestations such as myalgia and myositis are much more common, with an estimated occurrence of 1-7% (2). Proposed mechanisms for listed adverse effects include depletion of coenzyme Q10 and isoprenoids and mitochondrial dysfunction in myocytes. Any variable that increases the serum concentration of the statin may increase the risk of myopathy, and the key variables are the statin dose, the patient characteristics (older age, female gender, low body mass index, severe alcohol consumption, increased physical activity) and concomitant treatment with certain cytochrome P450 inhibitors (3, 4). In one meta-analysis that was intended to synthesize the collective adverse events data observed in prospective randomized clinical trials atorvastatin was associated with the greatest risk of adverse events and fluvastatin with the least risk (5). Conclusion Management options for statin intolerant patients include statin switching, especially to low-dose, non-daily doses of long-acting statins, such as rosuvastatin and atorvastatin, and other non-statin lipid-loering agents. In conclusion, statin-revated muscle adverse events are a significant clinical problem, but they could be prevented in many cases by anticipating possible drug-drug interactions