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Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease

Akyea, Ralph; Kai, Joe; Qureshi, Nadeem; Iyen, Barbara; Weng, Stephen


Clinical Assistant Professor in Primary Care

Stephen Weng


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

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

84,609 (51.2%) patients had sub-optimal LDL-cholesterol 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 to optimal responders, the hazard ratio (95% CI) for incident CVD was 1.17 (1.13–1.20) and 1.22 (1.19–1.25) after adjusting for age and baseline untreated LDL-cholesterol level. Considering competing risks resulted in lower but similar sub-hazards ratios for both unadjusted 1.13 (1.10–1.16) and adjusted cumulative incidence function, 1.19 (1.16–1.23) of CVD.

Optimal lowering of LDL-cholesterol is not achieved within two years in over half of patients in the general population initiated on statin therapy, and these patients will experience significantly increased risk of future cardiovascular disease.


Akyea, R., Kai, J., Qureshi, N., Iyen, B., & Weng, S. (2019). Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease. Heart, 105(13), 975-981.

Journal Article Type Article
Acceptance Date Jan 29, 2019
Online Publication Date Apr 15, 2019
Publication Date Apr 15, 2019
Deposit Date Feb 1, 2019
Publicly Available Date Jun 20, 2019
Journal Heart
Print ISSN 1355-6037
Electronic ISSN 1468-201X
Publisher BMJ Publishing Group
Peer Reviewed Peer Reviewed
Volume 105
Issue 13
Pages 975-981
Keywords Cardiovascular disease; LDL-cholesterol; sub-optimal response; population; cohort
Public URL
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