Article Text

other Versions

Download PDFPDF
Original research article
Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease
  1. Ralph Kwame Akyea,
  2. Joe Kai,
  3. Nadeem Qureshi,
  4. Barbara Iyen,
  5. Stephen F Weng
  1. Division of Primary Care, University of Nottingham, Nottingham, UK
  1. Correspondence to Dr Stephen F Weng, Primary Care Stratified Medicine (PRISM), Division of Primary Care, University Park Campus, University of Nottingham, Nottingham NG7 2RD, UK ; stephen.weng{at}


Objective To assess low-density lipoprotein cholesterol (LDL-C) response in patients after initiation of statins, and future risk of cardiovascular disease (CVD).

Methods Prospective cohort study of 165 411 primary care patients, from the UK Clinical Practice Research Datalink, who were free of CVD before statin initiation, and had at least one pre-treatment LDL-C within 12 months before, and one post-treatment LDL-C within 24 months after, statin initiation. Based on current national guidelines, <40% reduction in baseline LDL-C within 24 months was classified as a sub-optimal statin response. Cox proportional regression and competing-risks survival regression models were used to determine adjusted hazard ratios (HRs) and sub-HRs for incident CVD outcomes for LDL-C response to statins.

Results 84 609 (51.2%) patients had a sub-optimal LDL-C response to initiated statin therapy within 24 months. During 1 077 299 person-years of follow-up (median follow-up 6.2 years), there were 22 798 CVD events (12 142 in sub-optimal responders and 10 656 in optimal responders). In sub-optimal responders, compared with optimal responders, the HR for incident CVD was 1.17 (95% CI 1.13 to 1.20) and 1.22 (95% CI 1.19 to 1.25) after adjusting for age and baseline untreated LDL-C. Considering competing risks resulted in lower but similar sub-HRs for both unadjusted (1.13, 95% CI 1.10 to 1.16) and adjusted (1.19, 95% CI 1.16 to 1.23) cumulative incidence function of CVD.

Conclusions Optimal lowering of LDL-C is not achieved within 2 years in over half of patients in the general population initiated on statin therapy, and these patients will experience significantly increased risk of future CVD.

  • lipoproteins and hyperlipidemia
  • epidemiology
  • electronic medical records

Statistics from


  • Contributors SFW, BI, JK and NQ were involved in the design and planning of the study. RKA conducted the main statistical analysis and wrote the first draft of the manuscript. All authors contributed to the interpretation of the data, writing of the manuscript and critical revisions. SFW is guarantor.

  • Funding The research was funded and supported by the University of Nottingham.

  • Competing interests NQ is a member of the NICE Familial Hypercholesterolaemia Guideline Development Group (CG71) and NICE Lipid Modification Guidelines Group (CG181). SW is a member of the Clinical Practice Research Datalink (CPRD) Independent Scientific Advisory Committee (ISAC) and previously held an NIHR-SPCR career launching fellowship award. The remaining authors have no competing interests.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles