Elsevier

Atherosclerosis

Volume 266, November 2017, Pages 158-166
Atherosclerosis

Cholesterol target value attainment and lipid-lowering therapy in patients with stable or acute coronary heart disease: Results from the Dyslipidemia International Study II

https://doi.org/10.1016/j.atherosclerosis.2017.08.013Get rights and content

Highlights

  • LDL-C target attainment extremely low for very high-risk CHD and ACS patients.

  • Statin dosages not maximized, with scarce use of combination therapies.

  • Under-treatment of hyperlipidemia on a global scale.

Abstract

Background and aims

Low-density lipoprotein cholesterol (LDL-C) is a major contributor to cardiovascular disease. In the Dyslipidemia International Study II (DYSIS II), we determined LDL-C target value attainment, use of lipid-lowering therapy (LLT), and cardiovascular outcomes in patients with stable coronary heart disease (CHD) and those suffering from an acute coronary syndrome (ACS).

Methods

DYSIS II included patients from 18 countries. Patients with either stable CHD or an ACS were enrolled if they were ≥18 years old and had a full lipid profile available. Data were collected at a physician visit (CHD cohort) or at hospital admission and 120 days later (ACS cohort).

Results

A total of 10,661 patients were enrolled, 6794 with stable CHD and 3867 with an ACS. Mean LDL-C levels were low at 88 mg/dl and 108 mg/dl for the CHD and ACS cohorts respectively, with only 29.4% and 18.9% displaying a level below 70 mg/dl. LLT was utilized by 93.8% of the CHD cohort, with a mean daily statin dosage of 25 ± 18 mg. The proportion of the ACS cohort treated with LLT rose from 65.2% at admission to 95.6% at follow-up. LLT-treated patients, who were female, obese, or current smokers, were less likely to achieve an LDL-C level of <70 mg/dl, while those with type 2 diabetes, chronic kidney disease, or those taking a higher statin dosage were more likely.

Conclusions

Few of these very high-risk patients achieved the LDL-C target, indicating huge potential for improving cardiovascular outcome by use of more intensive LLT.

Introduction

Cardiovascular disease, including both ischemic coronary heart disease (CHD) and stroke, has become the leading cause of death worldwide [1]. Ischemic heart disease arises from occlusion of the coronary arteries, which results in reduced blood flow to the heart, damage to the cardiac tissue, and, potentially, death. Arterial occlusion is most often caused by the gradual accumulation of lipoproteins and foam cells in the vessel wall, initiating an inflammatory cascade and a build up of atherosclerotic plaque. Acute coronary syndrome (ACS) is a severe and life-threatening clinical manifestation of cardiovascular disease, which is characterized by a sudden reduction in blood flow to the heart as a result of plaque rupture.

The benefits of LDL-C lowering via statin treatment, especially early after an ACS, have been established [2], [3], [4], [5], [6], [7]. Despite the evidence of the benefits to patients with stable and acute CHD of lowering this type of cholesterol, attainment of the recommended LDL-C levels is not well characterized [8]. Several reports from the Dyslipidemia International Study (DYSIS) assessed achievement of LDL-C targets in statin-treated patients, and reported attainment of a level of <70 mg/dl ranging from 14% to 40% for the very high-risk patients [9], [10], [11], [12]. Furthermore, in EUROASPIRE IV, a cross-sectional study of European patients with a first or recurrent coronary event, just 17.5% of patients on a low/moderate-intensity lipid-lowering therapy (LLT) regimen and 26.6% of patients on a high-intensity LLT regimen had an LDL-C level of <70 mg/dl [13]. However, no other international studies have assessed the rates of LDL-C target value attainment in both stable and acute CHD patients. Thus, DYSIS II was carried out to assess the frequency and predictors of LDL-C target achievement in multiple regions across the globe. Treatment with statin and non-statin LLT was also documented, and outcomes were compared across regions to provide insight into the management of stable CHD and ACS in various parts of the world.

Section snippets

Study design

DYSIS II was a multinational, multicenter, prospective observational study of lipid profiles, lipid target value attainment, and LLT in patients with stable CHD and in patients being hospitalized for an ACS event. From 2012 to 2013, patients were enrolled from eighteen countries in Asia (Hong Kong, India, South Korea, the Philippines, Singapore, Thailand, Taiwan, and Vietnam), Europe (France, Greece, Germany, Ireland, and Italy), and the Middle East (Egypt, Jordan, Lebanon, Saudi Arabia, and

Patient characteristics

A total of 10,661 patients were enrolled in DYSIS II, 6794 in the CHD cohort and 3867 in the ACS cohort.

The mean age of the CHD patients was 65.3 ± 10.8 years and 79.1% were male (Table 1). More than half of the patients had hypertension (70.1%) or a history of ACS (69.8%). The majority of the CHD cohort was being treated with LLT at the time of the physician visit (6370; 93.8%). These patients were more likely to be obese or have hypertension or type 2 diabetes mellitus.

The mean age of the ACS

Discussion

DYSIS II showed that less than a third of the patients with stable CHD had an LDL-C level below 70 mg/dl, despite all being at very high cardiovascular risk. For the patients being hospitalized due to an ACS, the proportion was even lower, with only approximately a quarter of those known to be at very high risk prior to the ACS having attained this target. Although use of LLT was widespread and was improved after hospitalization for an ACS, the intensity of such therapy was only moderate in

Conflict of interest

A.K.G. received honoraria from Merck &Co., Inc. for contributions to the DYSIS study. M. H. reports that his institution received funding for recruitment and biostatistics for the DYSIS registry. J.F. received grants and personal fees from Amgen, Merck & Co., Inc., and Sanofi. G.M.D.F. received speaker's fee from Merck & Co., Inc., and Amgen. W.A. received honorarium from Merck & Co., Inc. At the time of the study, A.V. was a full-time employee of Rutgers University, which received grant

Financial support

This work was supported by Merck & Co., Inc., Kenilworth, NJ, USA.

Authors' contributions

M.H. performed statistical analysis; B.A., L.D.B., V.A. and C.B. handled funding and supervision; A.K.G. acquired the data; A.K.G., J.F., B.A., P.B., D.L., and L.D.B. conceived and designed the research; D.L and A.K.G drafted the manuscript; all authors contributed to the interpretation of the data and made critical revisions to the manuscript. All authors approve the final version of the manuscript.

Acknowledgments

The authors explicitly thank Larry Liu, Hiremagalur Parthasarathy Balaji, and Sameh Wajih from Merck & Co, Inc., as well as Michel Hermans, Moises Elisaf, Mohammed Sobhy, Samer Kabbani, Saud Al Sifri, Bryan Yan, JPS Sawhney, Rody Sy, and Yang-Soo Jang for their scientific contributions. The authors would also like to thank the DYSIS II investigators for their contribution to the successful completion of this study.

The authors also thank Joan Minguet and Katherine Smith, from IPPMed Spain, and

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