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

Abstract

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.

Keywords: electronic medical records; epidemiology; lipoproteins and hyperlipidemia.

Figure 1

Venn diagram showing the incident CVD events recorded in each database used to ascertain CVD outcomes: primary care data (CPRD) 16 080; secondary care data (HES) 9834; mortality registry (ONS) 4350. The overlap of incident CVD events in the three datasets are also indicated: 713 in all three databases. CVD, cardiovascular disease; CPRD, Clinical Practice Research Datalink; HES, Hospital Episode Statistics; ONS, Office for National Statistics.

Figure 2

The cumulative incidence curve demonstrated that patients with a sub-optimal LDL-C response to statin therapy were associated with a higher risk of CVD events than patients with an optimal response during the follow-up period, with an adjusted HR of 1.22 (95% CI 1.19 to 1.25). Adjusted for age and baseline LDL-cholesterol level. CVD, cardiovascular disease; HR, hazard ratio; LDL-C, low-density lipoprotein cholesterol.