Residual Inflammatory Risk On Treatment with PCSK9 Inhibition and Statin Therapy
Background—The combination of statin therapy and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition markedly lowers low-density lipoprotein cholesterol (LDL-C) and reduces cardiovascular event rates. Whether residual inflammatory risk as measured by on-treatment high sensitivity C-reactive protein (hsCRP) remains an important clinical issue in such patients is uncertain.
Methods—We evaluated residual inflammatory risk among 9,738 patients participating in the Studies of PCSK9 Inhibition and the Reduction of Vascular Events (SPIRE)-1 and -2 cardiovascular outcomes trials who were receiving both statin therapy and bococizumab, according to on-treatment levels of hsCRP (hsCRPOT) and LDL-COT measured 14 weeks after drug initiation. The primary endpoint was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death.
Results—At 14 weeks, the mean percent change in LDL-C among statin treated patients who additionally received bococizumab was -60.5% (95% CI -61.2 to -59.8; p<0.001; median change -65.4%) as compared to 6.6% (95% CI -1.0 to 14.1; p=0.09; median change 0.0%) for hsCRP. Incidence rates for future cardiovascular events for patients treated with both statin therapy and bococizumab according to on treatment levels of hsCRP <1, 1-3, and >3 mg/L were 1.96, 2.50, and 3.59 events per 100 person-years, respectively, corresponding to multivariable adjusted hazard ratios of 1.0, 1.16 (95% CI 0.81 to 1.66), 1.62 (95% CI 1.14 to 2.30) (p-trend=0.001) after adjustment for traditional cardiovascular risk factors and LDL-COT. Comparable adjusted hazard ratios for LDL-COT (<30, 30-50, >50 mg/dL) were 1.0, 0.87, and 1.21, respectively (p-trend=0.16). Relative risk reductions with bococizumab were similar across hsCRPOT groups (p-interaction=0.87).
Conclusions—In this post-hoc analysis of the SPIRE trials of bococizumab in a stable outpatient population, evidence of residual inflammatory risk persisted among patients treated with both statin therapy and PCSK9 inhibition.
- Received March 1, 2018.
- Revision received April 13, 2018.
- Accepted April 18, 2018.