Are we getting to lipid targets in real life?
Niki Katsiki1,2, Dimitri P . Mikhailidis1, Vasilis G. Athyros3, Apostolos I. Hatzitolios2, Asterios Karagiannis3,
In this issue of Archives of Medical Science a Hungarian group reports
on lipid goal achievement in 12,317 high risk patients . This analysis
considers the treatment of dyslipidemia between 2004 and 2008 and also
compares the performance of general practitioners (GPs) and specialists
(9,508 and 2,809 patients, respectively). During this period the percentage
of patients “on target” for low density lipoprotein-cholesterol (LDL-C)
increased from 14% to 32% and 20% to 43% when treated by GPs and
specialists, respectively. In contrast, there was no significant improvement
in high density lipoprotein-cholesterol (HDL-C) or triglyceride (TG) levels.
The conclusion was that “more attention needs to be paid to changing
treatment of patients to achieve target levels”. This includes an increased
use of combination therapy.
The authors  attribute the improvement in lipid management between
2004 and 2008 to the application of up-to-date consensus recom men -
dations. More specifically, information was provided to physicians via
journals, scientific meetings and country-level coordinators.
We previously conducted 4 pilot best-practice implementation
enhancement programmes aimed at improving risk factor control [2-5].
Physicians from Hospitals or Health Centres recruited patients with
metabolic syndrome (MetS) (628 patients, the SAGE-METS [Standardized
arrangement for a guideline driven treatment of the metabolic syndrome]
study) , diabetes mellitus (DM) (578 patients, the INDEED [Initiative for
a new Diabetes therapeutic approach in a Mediterranean country] study)
, hypertension (697 patients, the IMPULSION [Implementation of
guidelines for the management of arterial hypertension] study)  or
dyslipidemia (1127 patients, the IMPROVE-dyslipidemia [Implementation
of strategy for the management of overt dyslipidemia] study) .
Participating physicians attended educational programmes related to
current guidelines for MetS, DM, hypertension, dyslipidemia, overt
cardiovascular disease (CVD), obesity and nutrition [2-5]. The physicians
were motivated to participate as part of their continuing medical education
program. Patients were also motivated by supplying them with a brochure
that included instructions to help them achieve treatment goals.
Corresponding author:Corresponding author:
Dimitri P . Mikhailidis
Department of Clinical
Biochemistry (Vascular Disease
Royal Free Hospital Campus
University College London
University College London
London, United Kingdom
E-mail: mikhailidis @ad.com
1Department of Clinical Biochemistry (Vascular Disease Prevention Clinics), Royal Free
Hospital Campus, University College London Medical School, University College London,
London, United Kingdom
21stPropedeutic Department of Internal Medicine, AHEPA University Hospital, Aristotle
University of Thessaloniki, Thessaloniki, Greece
32ndPropedeutic Department of Internal Medicine, Hippokration Hospital, Medical School,
Aristotle University of Thessaloniki, Thessaloniki, Greece
4Department of Hypertension, Chair of Nephrology and Hypertension, Medical University
of Lodz, Lodz, Poland
Submitted: Submitted: 27 August 2010
Accepted: Accepted: 4 September 2010
Arch Med Sci 2010; 6, 5: 639-641
Copyright © 2010 Termedia & Banach
Arch Med Sci 5, October / 2010
Niki Katsiki, Dimitri P . Mikhailidis, Vasilis G. Athyros, Apostolos I. Hatzitolios, Asterios Karagiannis, Maciej Banach
The prevalence of dyslipidemia was reduced
from 79 to 24% in the SAGE-METS study , from
76 to 12% in the INDEED study , from 59.7 to
53.6% in the IMPULSION study  and from 100 to
21% in the IMPROVE-dyslipidemia study . The
greatest reduction in LDL-C levels (31.6%) was
observed in patients with dyslipidemia (IMPROVE-
dyslipidemia study) . Triglyceride levels were
significantly reduced in all patient populations
(p from < 0.002 to < 0.0001 for all comparisons).
High density lipoprotein-cholesterol levels increased
in all studies (p < 0.0001) except for the IMPULSION
study where the rise was not significant.
All these studies [1-5] highlight the importance
of continuous education of medical practitioners.
Mark et al.  reported a higher percentage
of patients achieving LDL-C targets when treated
by specialists compared with those followed up by
GPs (43% vs. 32%, respectively; p < 0.0001 by our
calculations). In our studies [2-5] the performance
of specialists and GPs was not compared.
Mark et al.  suggested that the high percentage
of Hungarian patients on a statin may be at least
partly attributed to available generic agents which
are more affordable. The impact of this effect is
likely to increase as more statins (and other lipid-
lowering drugs) become generic. These authors 
also specified that the use of combination therapy
(e.g. statin plus ezetimibe) contributed to better
goal achievement. This interpretation is in
agreement with community-based studies that
showed a significantly improved outcome in lipid
targets following the addition of ezetimibe to
a statin [6, 7]. Overall, a meta-analysis (n = 5,039)
concluded that ezetimibe co-administration with
a statin provides significant additional lipid-lowering
effect (a further 23.6% reduction in LDL-C levels;
p < 0.0001), allowing more patients to achieve
LDL-C target values . Similar results were
obtained in another recent meta-analysis . Higher
doses of statins represent another therapeutic
option, although this may be associated with an
increased risk of adverse effects .
Although reduction of LDL-C remains the primary
goal for lipid-lowering interventions, other targets
(e.g. HDL-C and TG) may also be important [11-13].
In this context, non-HDL-C has also been proposed
as a marker of residual CVD risk [14, 15]. Another
potential therapeutic goal would be apolipoprotein
(apo) A and B levels or their ratio [14, 16-18]. The
advantage when using non-HDL-C, apo A and/or
apo B is that these markers can be measured in the
nonfasting state [14, 16, 17]. However, there is no
definitive evidence showing that raising HDL-C
levels in patients on statins will result in
a significant reduction in vascular events [19, 20].
Similarly, it is not absolutely clear if TG levels
(fasting or non-fasting) are independent predictors
of vascular risk [17, 21-24]; however TG, besides
LDL-C and C-reactive protein (CRP), seems to be
predictors of cardiovascular events especially in
patients with acute coronary syndromes [12, 25].
The role of “over the counter (OTC)” statins [26,
27] in achieving LDL-C goals is controversial [28-30].
Limitation of OTC statins include the fact that many
countries have not approved this process, the dose
allowed to be prescribed by the pharmacist is low
(e.g. 10 mg simvastatin in the UK) and the cost has
to be paid by the patient [26, 27].
Finally, we must deal with all vascular risk factors
(e.g. hypertension, smoking, DM, obesity) and not
just lipids [31, 32]. We should also keep in mind the
increased CVD risk of certain populations (e.g. South
Asians) and the possibility of different therapeutic
targets in those patients [33, 34].
1. Mark L, Paragh G, Karadi I, et al. Changes in attaining lipid
goals by general practitioners and specialists in patients
at high cardiovascular risk in Hungary between 2004-
2008. Arch Med Sci 2010; 6: 695-700.
2. Athyros VG, Karagiannis A, Hatzitolios AI, et al.
Standardized arrangement for a guideline-driven
treatment of the metabolic syndrome: the SAGE-METS
study. Curr Med Res Opin 2009; 25: 971-80.
3. Athyros VG, Hatzitolios AI, Karagiannis A, et al. Initiative
for a new diabetes therapeutic approach in a Mediter -
ranean country: the INDEED study. Curr Med Res Opin
2009; 25: 1931-40.
4. Karagiannis A, Hatzitolios AI, Athyros VG, et al.
Implementation of guidelines for the management of
arterial hypertension. The impulsion study. Open
Cardiovasc Med J 2009; 3: 26-34.
5. Hatzitolios AI, Athyros VG, Karagiannis A, et al.
Implementation of strategy for the management of overt
dyslipidemia: the IMPROVE-dyslipidemia study. Int
J Cardiol 2009; 134: 322-9.
6. Fras Z, Mikhailidis DP . Statin plus ezetimibe treatment in
clinical practice: the SI-SPECT (Slovenia (SI) Statin Plus
Ezetimibe in Cholesterol Treatment) monitoring of clinical
practice study. Curr Med Res Opin 2008; 24: 2467-76.
7. Migdalis I, Efthimiadis A, Pappas S, et al. Clinical
experience with ezetimibe/simvastatin in a Mediter -
ranean population. Curr Med Res Opin 2009; 25: 2571-6.
8. Mikhailidis DP, Sibbring GC, Ballantyne CM, et al. Meta-
analysis of the cholesterol-lowering effect of ezetimibe
added to ongoing statin therapy. Curr Med Res Opin 2007;
9. Angelopoulos J, Krassakopoulos N, Nathanson R, Boukas
S, Sampalis JS. Co-administration of ezetimibe and
a statin in management of dyslipidemias: a meta-analysis
of clinical trials. Arch Med Sci 2009; 5: 347-63.
10. Kiortsis DN, Filippatos TD, Mikhailidis DP, et al. Statin-
associated adverse effects beyond muscle and liver
toxicity. Atherosclerosis 2007; 195: 7-16.
11. Athyros VG, Mikhailidis DP, Kakafika AI, et al. Identifying
and attaining LDL-C goals: mission accomplished? Next
target: new therapeutic options to raise HDL-C levels. Curr
Drug Targets 2007; 8: 483-8.
12. Wainwright G, Mascitelli L, Goldstein MR. Cholesterol-
lowering therapy and cell membranes. Stable plaque at
Arch Med Sci 5, October / 2010 641 Download full-text
Are we getting to lipid targets in real life?
the expense of unstable membranes? Arch Med Sci 2009;
13. Tziomalos K, Athyors VG, Karagiannis A, et al. Triglycerides
and vascular risk: insights from epidemiological data and
interventional studies. Curr Drug Targets 2009; 10: 320-7.
14. Brunzell JD, Davidson M, Furberg C, et al. Lipoprotein
management in patients with cardiometabolic risk.
Consensus statement from the American Diabetes
Association and the American College of Cardiology
Foundation. Diabetes Care 2008; 31: 811-22.
15. Brewer HB Jr. New features of the National Cholesterol
Education Program Adult Treatment Panel III lipid-lowering
guidelines. Clin Cardiol 2003; 26 (Suppl. 3): III19-24.
16. McQueen MJ, Hawken S, Wang X, et al; INTERHEART study
investigators. Lipids, lipoproteins anf apolipoproteins as
risk markers of myocardial infarction in 52 countries (the
INTERHEART study): a case-control study. Lancet 2008;
17. The Emerging Risk Factors Collaboration. Major lipids,
apolipoproteins and risk of vascular disease. JAMA 2009;
18. Sniderman A, Solhpour A. Targeting targets for LDL-lowering
therapy: lessons from the Collaborative Atorvastatin
Diabetes Study (CARDS). Clin Chem 2009; 55: 391-3.
19. Briel M, Ferreira-Gonzalez I, You JJ, et al. Association
between changes in high density lipoprotein cholesterol
and cardiovascular disease morbidity and mortality:
systematic review and meta-regression analysis. BMJ
2009; 338: b92.doi: 10.1136/bmj.b92
20. Ridker PM, Genest J, Boekholdt SM, et al; JUPITER Trial
Study Group. HDL cholesterol and residual risk of first
cardiovascular events after treatment with potent statin
therapy: an analysis from the Jupiter trial. Lancet 2010;
21. Triglyceride Coronary Disease Genetics Consortium and
Emerging Risk Factors Collaboration. Triglyceride-mediated
pathways and coronary disease: collaborative analysis of
101 studies. Lancet 2010; 375: 1634-9.
22. Sarwar N, Danesh J, Eiriksdottir G, et al. Triglycerides and
the risk of coronary heart disease: 10,158 incident cases
among 262,525 participants in 29 Western prospective
studies. Circulation 2007; 115: 450-8.
23. Harchaoui KE, Visser ME, Kastelein JJ, et al. Triglycerides
and cardiovascular risk. Curr Cardiol Rev 2009; 5: 216-22.
24. Kolovou G, Anagnostopoulou K, Mikhailidis DP. One
century of triglycerides, but there is still lots to learn! Curr
Drug Targets 2009; 10: 299-301.
25. Banach M, Mikhailidis DP, Kjeldsen SE, Rysz J. Time for new
indications for statins? Med Sci Monit 2009; 15: MS1-5.
26. MHRA 2004. Reclassification summary for simvastatin
POM to P . Medicines and Healthcare Products Regulatory
Agency at http:// medicines.mhra_gov.uk.
27. Royal Pharmaceutical Society of Great Britain, 2004.
Practice guidance on sale of over-the-counter simvastatin
[online]. Available: http:// www.rpsgb.org.uk/pdfs/
28. Tinetti ME. Over-the-Counter Sales of Statins and Other
Drugs for Asymptomatic Conditions. New Engl J Med
2008; 358: 2728-32.
29. Brass EP, Vassil T, Replogle A, et al. Can consumers self-
select for appropriate use of an over-the-counter statin?
The Self Evaluation of Lovastatin to Enhance Cholesterol
Treatment Study. Am J Cardiol 2008; 101: 1448-50.
30. Gemmel I, Verma A, Harrison RA. Should we encourage
over-the-counter statins? A population perspective for
coronary heart disease prevention. Am J Cardiovasc Drugs
2007; 7: 299-302.
31. Landini L, Leone A, Mikhailidis DP . Modifying cardiovascular
risk factors: newer insights and preventive measures. Curr
Pharm Des 2009; 15: 1034-7.
32. Desai RV, Banach M, Ahmed MI, et al. Impact of baseline
systolic blood pressure on long-term outcomes in patients
with advanced chronic systolic heart failure (insights from
the BEST trial). Am J Cardiol 2010; 106: 221-7.
33. Dreiher J, Cohen A, Weitzman S, Sharf A, Shvartzman P.
Lipid levels among African and Middle-Eastern Bedouin
populations. Med Sci Monit 2008; 14: CR339-344.
34. Tziomalos K, Weerasinghe CN, Mikhailidis DP, Seifalian
AM. Vascular risk factors in South Asians. Int J Cardiol
2008; 128: 5-16.