Can LDL-cholesterol targets be achieved in a population at high risk? Results of the non-interventional study ACT II

Abstract:

Objective:

Lowering low-density lipoprotein cholesterol (LDL-C) levels can reduce vascular clinical endpoints in outcome studies. Despite this evidence, previous cross-sectional analyses reported a mean LDL-C target attainment of <50%. This non-interventional, longitudinal study aimed to asses the rate of target attainment by intensified LDL-C lowering therapy in a high-risk population under routine medical care.

Design:

This was an open-label, non-interventional, observational, non-comparative longitudinal study.

Methods:

A total of 1682 outpatients at high cardiovascular risk, not at LDL-C target despite statin therapy, were documented. Treating physicians administered an intensified therapy at their discretion. In all, 794 patients completed all the examinations at baseline after 3 and 12 months. The achieved LDL-C reductions was evaluated based on expert consensus reflecting the 2007 guidelines issued by the European Society of Cardiology (ESC) on cardiovascular disease prevention.

Registration:

www.clinicaltrials.gov, identification number NCT 01381679

Results:

In the study, 40.3% achieved the individual LDL-C target of <1.8 mmol/L (70 mg/dl) or <2.5 mmol/L (100 mg/dl); 73% received a simvastatin/ezetimibe fixed-dose combination; 3% received add-on ezetimibe and 23% statin therapy at maintained or increased doses; 1% received no drug treatment at all. LDL-C declined after 12 months by −31.0% (ratio 0.69, 95% CI 0.67–0.71, p < 0.001), triglycerides by −11.8% (ratio 0.88, 95% CI 0.85–0.91, p < 0.01) and high-density lipoprotein cholesterol (HDL-C) increased by 11.9% (ratio 1.12, 95% CI 1.10–1.14, p < 0.01).

Conclusion:

Intensified therapy was effective, but target attainment was still low at 40.3% or 13.9% with regard to the new 2011 guidelines issued by the European Atherosclerosis Society (EAS) and the ESC on dyslipidemias. Enhanced screening of LDL-C levels and the use of statins at highest tolerated dose and concomitant combination therapy is recommended in order to achieve LDL-C targets outlined by current guidelines. Limitations include the design as a non-interventional study. However, this study reflects real life conditions.

Keywords::

• Cholesterol
• Ezetimibe
• Guidelines
• Statins
• Target attainment

Transparency

Declaration of funding

The study was funded by Merck, Sharp & Dohme (known as Merck & Co in the US).

Declaration of financial/other relationships

D.L. and C.F. are employees of Merck, Sharp and Dohme (MSD) and own stock in the company. B.E. is a consultant and serves on speakers’ bureaus for MSD. K.P. is a statistical consultant for MSD. O.T. is a paid speaker for MSD, AstraZeneca, Takeda and Eli Lilly. M.P. has served on speakers’ bureaus and is a consultant for MSD Austria. H.D. declares no conflict of interest.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors would like to thank the ACT II study group and Claudia Adler, Karl Boegl, and Philippe Brudi from Merck, Sharp & Dohme for the initiation and continued support of this study.