Association between an acute, drug-induced decrease in high-density lipoprotein cholesterol levels and risk of cardiovascular events

Abstract

BACKGROUND AND OBJECTIVE: The literature describing the long-term effect of an acute, drug-induced decrease in high-density lipoprotein cholesterol (HDL-C) and cardiovascular (CV) risk is limited. We aimed to further explore this potential association.

METHODS: A retrospective cohort study was conducted using the Clinical Practice Research Datalink (CPRD) between 2006 and 2014. The study enrolled patients who initiated statin therapy for a short term, to identify patients with an acute, short-term decrease in HDL levels rather than to assess sustained treatment. HDL-C measurements were assessed within 9 months before and after statin initiation and patients were followed up for up to 5 years for CV events, comparing those with a decrease in HDL-C with those with constant HDL-C levels. The primary composite endpoint of major adverse cardiac events (MACE) was defined as CV death, myocardial infarction, revascularisation, and hospitalised ischaemic stroke. We estimated crude and propensity score weighted 5-year cumulative risk differences and hazard ratios (HR) comparing both groups.

RESULTS: A total of 17,543 patients (HDL-C decrease group, n = 6454; HDL-C constant group, n = 11,089) were included in the study. The 5-year cumulative incidence of MACE in the HDL-C constant cohort was 5.91%. The corresponding risk differences for HDL-C decrease versus the constant group was 1.23% (95% confidence interval [CI] 0.28-2.18) and the HR was 1.20 (95% CI 1.04-1.39). This was mainly driven by an increased risk in ischaemic stroke (HR 1.44, 95% CI 1.08-1.90) and CV death (HR 1.23, 95% CI 0.93-1.63).

CONCLUSION: Patients with a short-term, drug-induced decrease in HDL-C had a moderately increased long-term risk of CV events compared with those with constant HDL-C levels.

TRIAL REGISTRATION NUMBER: 207595 (GlaxoSmithKline Trial registry; https://www.gsk-studyregister.com/).