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Valutazione comparativa degli effetti di statine e inibitori di PCSK9 sul colesterolo LDL e sul rischio di eventi cardiovascolari

Questo studio ha raffrontato l'efficacia degli inibitori PCSK9 e delle statine in termini di riduzione del rischio di eventi cardiovascolari maggiori confrontando i risultati dei trial FOURIER (su evolocumab) e SPIRE (su bococizumab) con i risultati della metanalisi del CTT sulle statine. Le due classi di ipolipemizzanti sembrano avere effetti notevolmente simili a parità di riduzione assoluta del colesterolo LDL e a parità di durata della terapia, risultati confermati dalle evidenze derivanti dagli studi di randomizzazione mendeliana.

Reduction of low density lipoprotein-cholesterol and cardiovascular events with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and statins: an analysis of FOURIER, SPIRE, and the Cholesterol Treatment Trialists Collaboration

Ference BA, Cannon CP, Landmesser U, Lüscher TF, Catapano AL, Ray KK.

Eur Heart J 2018;39:2540-2545

Treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors reduce low density lipoprotein cholesterol (LDL-C) by approximately 45–60%, whether used alone or in combination with a statin. Two large cardiovascular outcomes trials have now reported that lowering LDL-C with a PCSK9 inhibitor when added to treatment with a statin reduces the risk of major cardiovascular events. We sought to compare the efficacy of PCSK9 inhibitors and statins for reducing the risk of cardiovascular events by comparing the results of the FOURIER and SPIRE trials with the results of the Cholesterol Treatment Trialists (CTT) meta-analysis of statin trials.

In the FOURIER trial, 27 564 patients with cardiovascular disease and LDL-C levels above 1.8 mmol/L (70 mg/dL) on statin therapy were randomized to either 140 mg every 2 weeks (or 420 mg monthly) of evolocumab subcutaneously or matching placebo.3 At 48 weeks, treatment with evoloculmab reduced LDL-C by 59%, from a baseline level of 2.4 mmol/L (92 mg/dL) to 0.78 mmol/L (30 mg/dL). Using the CTT method of imputation for missing values, this translated into a 1.4 mmol/L (53.4 mg/dL) absolute difference in LDL-C between the two treatment groups. After a median follow-up of 26 months (2.2 years), treatment with evolocumab reduced the incidence of the composite primary cardiovascular endpoint of cardiovascular death (CVD), myocardial infarction (MI), stroke, coronary revascularization, or hospitalization for unstable angina by 15%, from 11.3 to 9.8% (hazard ratio 0.85, 95% CI: 0.79–0.92, P < 0.001). The key secondary endpoint of CVD, MI, or stroke was reduced by 20%, from 7.4 to 5.9% (HR 0.80, 95% CI: 0.73–0.88, P < 0.001). When measured per mmol/L reduction in LDL-C, treatment with evolocumab reduced the risk of the primary outcome by 11.0% (HR 0.89, 95% CI: 0.84–0.94) per mmol/L reduction in LDL-C, and reduced the key secondary endpoint by 14.7% (HR 0.85, 95% CI: 0.80–0.91) per mmol/L reduction in LDL-C. The magnitude of this effect appears to be slightly less than the 22% reduction in risk (HR 0.78, 95% CI: 0.76–0.80) per mmol/L reduction in LDL-C during treatment with a statin as reported by CTT collaboration (P for difference = 1.6 × 10−5 for primary outcome; P = 0.015 for secondary outcome)...

Eur Heart J 2018;39:2540-2545