Público alvo: leigo e técnico.
Nos estudos científicos mais sérios, um porcentual de 5% a 20% dos pacientes em uso das várias formas de estatina apresentam fraqueza e dores musculares, cãimbras às vezes severas, artralgias (dores nas juntas) e, em muitos casos, elevação da enzima CPK no sangue.
A sequência usual do médico nestes casos é de troca por outra estatina, talvez até 3 diferentes em sequência e, permanecendo os sintomas, passar para outro tipo de remédio que possa atuar sobre as gorduras elevadas no sangue. Ezetimibe tem sido um candidato quase natural nestes casos.
Na última edição do JAMA (periódico científico do Colégio Americano de Medicina, altamente considerado em todo o mundo), temos a publicação do primeiro estudo randomizado e controlado em pessoas que tiveram problemas musculares com pelo menos duas estatinas distintas. A solução passa pelo uso de uma nova classe de agentes biológicos, ditos inibidores de PCSK9 (em inglês: “protein convertase subtilisin/kexin type 9 inhibitors”).
Os resultados mostraram boa tolerância e redução significativa dos níveis de colesterol no curto prazo, faltando demonstrar agora, em estudos futuros, a redução de episódios cardiovasculares sérios, como angina e infarto do miocárdio.
A seguir o resumo do artigo principal, publicado na data de hoje. Será que o tempo das estatinas estará chegando ao fim?
Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance The GAUSS-3 Randomized Clinical Trial
Steven E. Nissen, MD; Erik Stroes, MD, PhD; Ricardo E. Dent-Acosta, MD et al
IMPORTANCE Muscle-related statin intolerance is reported by 5% to 20% of patients.
OBJECTIVE To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab.
DESIGN, SETTING, AND PARTICIPANTS Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks.
INTERVENTIONS Phase A: atorvastatin (20 mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily).
MAIN OUTCOME AND MEASURES Coprimary end points were the mean percent change in LDL-C level from baseline to the mean of weeks 22 and 24 levels and from baseline to week 24 levels.
RESULTS Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3
[SD, 67.9] mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72] mg/dL). For the mean of weeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, −16.7% (95% CI, −20.5% to −12.9%), absolute change, −31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, −54.5% (95% CI,
−57.2% to −51.8%); absolute change, −106.8 mg/dL (P < .001). LDL-C level at week 24 with ezetimibe was 181.5 mg/dL; mean percent change, −16.7% (95% CI, −20.8% to −12.5%); absolute change, −31.2 mg/dL and with evolocumab was 04.1 mg/dL; mean percent change, −52.8% (95% CI, −55.8% to −49.8%); absolute change, −102.9 mg/dL (P < .001). For the mean of weeks 22 and 24, between-group difference in LDL-C was −37.8%; absolute difference, −75.8 mg/dL. For week 24, between-group difference in LDL-C was
−36.1%; absolute difference, –71.7 mg/dL. Muscle symptoms were reported in 28.8% of
ezetimibe-treated patients and 20.7% of evolocumab-treated patients (log-rank P = .17). Active study drug was stopped for muscle symptoms in 5 of 73 ezetimibe-treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%).
CONCLUSIONS AND RELEVANCE Among patients with statin intolerance related to
muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety.
TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01984424