Elsevier

Thrombosis Research

Volume 183, November 2019, Pages 124-130
Thrombosis Research

Full Length Article
Cardiovascular event rates and trajectories of LDL-cholesterol levels and lipid-lowering therapy in patients with atherosclerotic cardiovascular disease: A population-based cohort study

https://doi.org/10.1016/j.thromres.2019.09.034Get rights and content

Highlights

  • 10,772 patients with atherosclerosis, statin use, and LDL ≥ 1.8 mmol/L were studied.

  • The cardiovascular event rate was 62.7 per 1000 person-years.

  • 97% of statin users were on high-intensity therapy at the end of follow-up.

  • 25% of patients achieved LDL levels ≤1.8 mmol/L at the end of follow-up.

Abstract

Background

An understanding of cardiovascular event rates and low-density lipoprotein cholesterol (LDL-C) levels and trajectories in patients with atherosclerotic cardiovascular disease is needed to evaluate treatment goals and adherence to guidelines.

Methods

We conducted a population-based cohort study in the North and Central Denmark Regions. Patients with prevalent atherosclerotic cardiovascular disease (myocardial infarction, non-hemorrhagic stroke, or peripheral artery disease) during 2006–2009 were identified. All patients received lipid-lowering therapy (statins or ezetimibe) and had LDL-C levels ≥1.8 mmol/L at baseline (January 1, 2010). We followed patients for 6 years until a primary composite outcome of cardiovascular death, myocardial infarction, non-hemorrhagic stroke, hospitalization for unstable angina, or coronary revascularization. Additionally, we characterized changes in LDL-C levels and use of statins during follow-up.

Results

The study included 10,772 patients (median age 69.2 years, 60.4% male). The overall event rate for the primary outcome was 62.7 (95% confidence interval: 59.2–66.2) per 1000 person-years. This event rate was higher among men than among women and increased with age and baseline LDL-C levels. Approximately 25% of patients with LDL-C measurements during follow-up achieved LDL-C levels below 1.8 mmol/L. Of the approximately two-thirds of patients using statins at the end of follow-up, nearly all patients (97%) received high-intensity therapy.

Conclusions

In this population of patients with atherosclerotic cardiovascular disease, we found high cardiovascular event rates, which increased with baseline LDL-C levels. Although most patients were on high-intensity statin therapy at end of follow-up, only one-quarter reached the guideline-recommended target LDL-C level ≤ 1.8 mmol/L.

Introduction

Atherosclerotic cardiovascular disease currently accounts for the majority of deaths in most parts of the world [1]. Within the realm of cardiovascular disease, coronary heart disease and stroke are the number 1 and number 3 causes of death, accounting for 42% and 35% of global cardiovascular mortality, respectively [1]. Based on data from the National Health and Nutrition Examination Survey (NHANES), a series of surveys conducted in the United States during 2009–2010, an estimated 16.2 million Americans (7.2% of the population) have prevalent atherosclerotic cardiovascular disease [1,2].

Treatment of this disease includes therapies aimed at reducing the level of low-density lipoprotein cholesterol (LDL-C) to prevent recurrent cardiovascular events [3,4]. However, despite the potential for reducing LDL-C levels pharmacologically, EUROASPIRE IV, an observational study conducted across Europe, suggested that 80% of patients with established coronary heart disease do not achieve LDL-C levels <1.8 mmol/L [5].

It was shown recently that non-statin lipid-lowering therapy, including the cholesterol reuptake inhibitor ezetimibe and the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, when added to statin therapy, further reduce the risk of cardiovascular events in populations with established atherosclerotic cardiovascular disease [[6], [7], [8]].

Cardiovascular event rates are often higher among patients with atherosclerotic disease included in population-based registries than among those observed in randomized clinical trials [9]. Thus, to evaluate the potential benefit of new preventive therapies, it is essential to examine cardiovascular event rates encountered outside a trial environment, in a routine clinical setting. In addition, it is important to understand the current quality of care in patients with established atherosclerotic cardiovascular disease. Such analyses will allow for identification of high-risk patients who may benefit from newer cholesterol-lowering therapies.

We examined real-world estimates of cardiovascular event rates in a secondary prevention population at very high cardiovascular risk. We also reported patterns of statin use and trajectories of LDL-C levels during 6 years of follow-up in this population.

Section snippets

Design, setting, and data sources

We conducted a population-based cohort study of patients with prevalent atherosclerotic cardiovascular disease in the North and Central Denmark Regions (population ~1.8 million inhabitants or about one-third of the total Danish population) [10]. The Danish National Health Service provides tax-supported health care, ensuring unfettered access to general practitioners and hospitals for all Danish residents. The unique central personal registry number assigned to each Danish citizen at birth and

Results

We identified a total of 10,722 individuals (median age 69.2 years, 60.4% male) with prevalent atherosclerotic cardiovascular disease (Table 1). About one-third (36%) were included based on MI, 39% based on NS, and 24% based on PAD. At baseline, only 2% used ezetimibe and 99% used statins. Among statin users, 16% were receiving high-intensity statin therapy. Almost half of patients (43%) had an LDL-C measurement ≥2.5 mmol/L and 6% had an LDL-C level ≥ 4.0 mmol/L. The median LDL-C level was

Cumulative risk and event rates

The overall event rate for the composite primary outcome including cardiovascular death was 62.7 (95% CI: 59.2–66.2) per 1000 person-years and 43.9 (95% CI: 42.1–45.8) per 1000 person-years excluding cardiovascular death (Table 2). The overall event rate for the composite secondary outcome including cardiovascular death was 49.6 (95% CI: 46.5–52.7) per 1000 person-years, and 33.8 (95% CI: 32.2–35.4) per 1000 person-years excluding cardiovascular death. Event rates for the primary outcome were

LDL-C levels and lipid-lowering therapy during follow-up

Throughout follow-up, approximately 75% of patients had LDL-C measurements each year. The proportion of patients achieving the guideline-recommended LDL-C level (below 1.8 mmol/L) increased from 19% at the end of first year of follow-up to 25% at the end of the fourth year of follow-up and remained at this level until the end of follow-up. Thus, by the end of follow-up, 75% of patients had not reached the guideline-recommended LDL-C level of <1.8 mmol/L, with 44% having an LDL-C level between

Discussion

In this population-based cohort study of patients with prevalent atherosclerotic cardiovascular disease, we reported event rates and cumulative incidences for composite cardiovascular outcomes in a setting similar to cardiovascular outcome trials of PCSK9 inhibitors, such as the FOURIER trial [7]. Event rates for both the primary and secondary outcomes increased with increasing baseline LDL-C levels and were substantially higher in subgroups of patients with previously diagnosed diabetes or

Contributors

J. Sundbøll, A.P. Larsen, and H.T. Sørensen contributed to the conception of the work. J. Sundbøll and A.P. Larsen contributed to the design of the work. J. Sundbøll and K. Veres contributed to the acquisition of data for the work. J. Sundbøll, K. Veres, and A.P. Larsen contributed to the analysis and interpretation of data. J. Sundbøll drafted the manuscript. All authors critically revised the manuscript and gave final approval and agreed to be accountable for all aspects of work, ensuring

Acknowledgements

This study was supported by an institutional research grant from Amgen to Aarhus University. All authors had full access to the study data and had final responsibility for the decision to submit for publication. APL is an employee of Amgen AB, Denmark.

Declaration of competing interest

None.

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