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dc.contributor.authorRidker, Paul M.pt_BR
dc.contributor.authorTardif, Jean Claudept_BR
dc.contributor.authorPolanczyk, Carisi Annept_BR
dc.contributor.authorSPIRE Cardiovascular Outcome Investigatorspt_BR
dc.date.accessioned2018-03-23T02:27:12Zpt_BR
dc.date.issued2017pt_BR
dc.identifier.issn0028-4793pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/173822pt_BR
dc.description.abstractBACKGROUND Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin– kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of −56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of –59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients. (Funded by Pfizer; SPIRE-1 and SPIRE-2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389.)en
dc.format.mimetypeapplication/pdf
dc.language.isoengpt_BR
dc.relation.ispartofThe New England journal of medicine. Boston. Vol. 376, no. 17 (Apr. 2017), p. 1527-1539pt_BR
dc.rightsOpen Accessen
dc.subjectAnticolesterolemiantespt_BR
dc.subjectPró-proteína convertase 9pt_BR
dc.subjectLDL-colesterolpt_BR
dc.subjectDoenças cardiovascularespt_BR
dc.subjectAnticorpos monoclonais humanizadospt_BR
dc.titleCardiovascular efficacy and safety of bococizumab in high-risk patientspt_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb001060046pt_BR
dc.type.originEstrangeiropt_BR


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