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

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

Abstract

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

Method:
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.

Results:
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.

Conclusions:
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.

Citation

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. https://doi.org/10.1136/heartjnl-2018-314253

• 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
• DOI: https://doi.org/10.1136/heartjnl-2018-314253
• Keywords: Cardiovascular disease; LDL-cholesterol; sub-optimal response; population; cohort
• Public URL: https://nottingham-repository.worktribe.com/output/1513636
• Publisher URL: https://heart.bmj.com/content/early/2019/04/16/heartjnl-2018-314253
• Contract Date: Feb 1, 2019