Changes of the Lipoprotein Profiles with Time after Discontinuation of Statin Therapy

Min-Kyung Kim; Hack-Lyoung Kim; Hee-Suk Min; Min-Seok Kim; Yeonyee Elizabeth Yoon; Kyoung-Woo Park; Sang-Hyun Kim; Joo-Hee Zo; Myung-A Kim; Hyun-Jong Moon; Hyo-Soo Kim; Dae-Won Sohn; Byung-Hee Oh; Young-Bae Park; Yun-Sik Choi

doi:10.4070/kcj.2008.38.1.36

Journal List > Korean Circ J > v.38(1) > 1016355

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Kim, Kim, Min, Kim, Yoon, Park, Kim, Zo, Kim, Moon, Kim, Sohn, Oh, Park, and Choi: Changes of the Lipoprotein Profiles with Time after Discontinuation of Statin Therapy

Original Article

Korean Circulation J 2008;38(1):36-42.

Published online: 20 January 2008

DOI: https://doi.org/10.4070/kcj.2008.38.1.36

Changes of the Lipoprotein Profiles with Time after Discontinuation of Statin Therapy

Min-Kyung Kim, MD^1,⁴, Hack-Lyoung Kim, MD^1,⁴, Hee-Suk Min, MD^1,⁴, Min-Seok Kim, MD^1,⁴, Yeonyee Elizabeth Yoon, MD^1,⁴, Kyoung-Woo Park, MD^1,⁴, Sang-Hyun Kim, MD^2,^4,, Joo-Hee Zo, MD^2,⁴, Myung-A Kim, MD^2,⁴, Hyun-Jong Moon, MD³, Hyo-Soo Kim, MD^1,⁴, Dae-Won Sohn, MD^1,⁴, Byung-Hee Oh, MD^1,⁴, Young-Bae Park, MD^1,⁴, Yun-Sik Choi, MD^1,⁴

¹Cardiovascular Center, Seoul National University Hospital, Seoul, Korea

²Department of Internal Medicine, Seoul Metropolitan Boramae Hospital, Seoul, Korea

³Department of Thoracic and Cardiovascular Surgery, Seoul Metropolitan Boramae Hospital, Seoul, Korea

⁴Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Correspondence: Sang-Hyun Kim, MD, Department of Internal Medicine, Seoul Metropolitan Boramae Hospital, 425 Sindaebang 2-dong, Dong-jak-gu, Seoul 156-707, Korea Tel: 82-2-840-2643, Fax: 82-2-831-2826 E-mail: shkimmd@snu.ac.kr

Received 20 September 2007 Revised 31 October 2007 Accepted 1 November 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background and Objectives

Some patients stop statin therapy in spite of their doctors' advice. This study was designed to assess the pattern of lipoprotein profile changes and clinical characteristics of the patients who discontinued statin therapy.

Subjects and Methods

69 patients (male 42.0%) were enrolled. The clinical characteristics and laboratory data on the lipoprotein levels were obtained from the medical records.

Results

The coexistence of diabetes mellitus (DM) was seen in 28% of the patients, hypertension was noted in 72% and coronary artery disease (CAD) was noted in 42%. The average lipoprotein levels during statin therapy were total cholesterol (TC)= 163.8 mg/dL, triglycerides (TG)=174.3 mg/dL, high-density lipoprotein cholesterol (HDL-C)=34.8 mg/dL and low-density lipoprotein cholesterol (LDL-C)=94.2 mg/dL. LDL-C level increased by 44.9% at 2–3 months after ceasing statin therapy and by 54.6% at 4–6 months after ceasing statin therapy (p<0.01). The changes of the lipoprotein levels from baseline to 2–3 months and 4–6 months after discontinuation were +22.6% and +30.0% for the TC level, +20.8% and +24.0% for the TG level, and 0.06% and −0.65% for the HDL-C level respectively (p<0.01 for TC and TG, p=not significant (NS) for HDL-C). The achievement rate of target LDL-C level as suggested by the Adult Treatment Panel III (ATP III) of National Cholesterol Education Program (NCEP) was decreased 62.7% at 2–3 months and then it was decreased to 61.8% at 4–6 months after statin discontinuation. DM and CAD were more frequent in the patients who did not achieve the target LDL-C level even with life style modification.

Conclusion

After statin discontinuation, TC and LDL-C were increased within 3 months. DM and CAD were highly prevalent in patients who didn't achieve their treatment goal.

Keywords: Statin, Lipoprotein, Cholesterol

References

1. Shepherd J, Cobe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995; 333:1301–7.

2. Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lo-weringArm (ASCOT-LLA): a multicentre randomised controll-edtrial. Lancet. 2003; 361:1149–58.

3. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. JAMA. 1998; 279:1615–22.

4. The LIPID Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998; 339:1349–57.

5. Jun JE. Cholesterol lowering therapy in coronary artery disease. Korean Circ J. 2001; 31:849–56.

6. Chun KJ, Chung NS, Ha JW, et al. Efficacy and safety of atorvastatin in patients with elevated LDL-cholesterolemia. Korean Circ J. 1999; 29:1309–16.

7. Bae JH, Choe KH, Jun JE, et al. Multicenter clinical trial of atorvastatin in patients with hypercholesterolemia. Korean Circ J. 2001; 31:434–41.

8. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004; 110:227–39.

9. Committee of Treatment Guideline for Hypercholesterolemia. Treatment guideline for hypercholesterolemia. 2nd ed. Korean Society of Lipidology and Atherosclerosis;2003.

10. Kim SH, Park JS, Zo JH, Kim MA, Kim HS. Treatment gap in the management of hypercholesterolemia in Korea: return on expenditure achieved for lipid therap Y (REALITY). Korean Circ J. 2006; 36:593–9.

11. Andrade SE, Walker AM, Gottlieb LK, et al. Discontinuation of antihyperlipidemic drugs: do rates reported in clinical trials reflect rates in primaty care setting? N Engl J Med. 1995; 332:1125–31.

12. Bradford RH, Shear CL, Chremos AN, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study result: I. efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Arch Intern Med. 1991; 151:43–9.

13. Ellis JJ, Erickson SR, Stevenson JG, Bernstein SJ, Stiles RA, Fendrick AM. Suboptimal statin adherence and discontinuation in primary and secondary prevention populations: should we target patients with the most to gain? J Gen Intern Med. 2004; 19:638–45.

14. Senior K. Stopping statin therapy puts heart patients at risk. Lancet. 2002; 359:857.

15. Heeschen C, Hamm CW, Laufs U, Snapinn S, Bohm M, White HD. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation. 2002; 105:1446–52.

16. Li JJ, Li YS, Chu JM, et al. Changes of plasma inflammatory markers after withdrawal of statin therapy in patients with hyperlipidemia. Clin Chim Acta. 2006; 366:269–73.

17. Thomas M, Mann J. Increased thrombotic vascular events after change of. Lancet. 1998; 352:1830–1.

18. Heeschen C, Hamm CW, Laufs U, Snapinn S, Bohm M, White HD. Withdrawal of statins in patients with acute coronary syn-droms. Circulation. 2003; 107:e27.

19. Spencer FA, Fonarow GC, Frederick PD, et al. Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction: national registry of myocardial infarction. Arch Intern Med. 2004; 164:2162–8.

20. Spencer FA, Allegrone J, Goldberg RJ, et al. Association of statin therapy with outcomes of acute coronary syndromes: the RACE study. Ann Intern Med. 2004; 140:857–66.

21. Endres M, Laufs U. Discontinuation of statin treatment in stroke patients. Stroke. 2006; 37:2640–3.

22. Colivicchi F, Bassi A, Santini M, Caltagirone C. Discontinuation of statin therapy and clinical outcome after ischemic stroke. Stroke. 2007; 38:2652–7.

23. Tristano AG, Castejon AM, Castro A, Cubeddu LX. Effect of statin treatment and withdrawal on angiotensin II-induced phosphorylation of p38 MAPK and ERK1/2 in cultured vascular smooth muscle cells. Biochem Biophys Res Commun. 2007; 353:11–7.

24. Lee KT, Lai WT, Chu CS, et al. Effect of withdrawal of statin on C-reactive protein. Cardiology. 2004; 102:166–70.

25. Laufs U, Endres M, Custodis F, et al. Suppression of endothelial nitric oxide production after withdrawal of statin treatment is mediated by negative feedback regulation of rho GTPase gene transcription. Circulation. 2000; 102:3104–10.

26. Vecchione C, Brandes RP. Withdrawal of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors elicits oxidative stress and induces endothelial dysfunction in mice. Circ Res. 2002; 91:173–9.

27. Brandes RP, Beer S, Ha T, Busse R. Withdrawal of cerivastatin induces monocyte chemoattractant protein 1 and tissue factor expression in cultured vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2003; 23:1794–800.

28. McGowan MD. There is no evidence for an increase in acute coronary syndromes after short-term abrupt discontinuation of statins in stable cardiac patients. Circulation. 2004; 110:2333–5.

29. Laufs U, Wassmann S, Hilgers S, Ribaudo N, Bohm M, Nick-ening G. Rapid effects on vascular function after initiation and withdrawal of atorvastatin in healthy, normocholes-terolemic men. Am J Cardiol. 2001; 88:1306–7.

Fig. 1.

The changes of serum lipoprotein levels after statin discontinuation. ∗p<0.001. TC: total cholesterol, TG: triglycerides, HDL-C: high-density lipoprotein cholesterol, LDL-C: low-density lipoprotein cholesterol.

Fig. 2.

The percentages of patients whose HDL-C levels were lower than 40 mg/dL (p=NS). HDL-C: high-density lipoprotein cholesterol.

Fig. 3.

The achievement rate of target LDL-C level by NCEP-ATP III guideline. ∗p<0.001 when compared with goal-achievement rate during statin therapy. LDL-C: low-density lipoprotein cholesterol. NCEP-ATP III: National Cholesterol Education Program Adult Treatment Panel III.

Table 1.

Baseline clinical characteristics of the patients

Patients (n=69)
Male, n (%)	27 (42)
Age (years), mean±SD	63.6±9.1
BMI (kg/m²), mean±SD	25.5±3.4
Hypertension, n (%)	46 (72)
Diabetes mellitus, n (%)	19 (28)
Coronary artery disease, n (%)	27 (42)

BMI: body mass index, SD: standard deviation

Table 2.

The changes of lipoprotein profiles after statin discontinuation

Lipoprotein levels (mg/dL), mean±SD
	Baseline	2 to 3 months after discontinuation	p	4 to 6 months after discontinuation	p
TC	163.8±39.3	199.4±40.7	<0.001	205.3±36.7	<0.001
TG	174.3±118.2	196.5±108.0	<0.971	182.0±99.1	<0.444
HDL-C	34.8±7.6	35.2±8.9	<0.981	34.9±8.6	<0.451
LDL-C	94.2±33.5	124.8±38.8	<0.001	134.0±36.0	<0.001

TC: total cholesterol, TG: triglycerides, HDL-C: high-density lipoprotein cholesterol, LDL-C: low-density lipoprotein cholesterol, SD: standard deviation

Table 3.

Clinical characteristics comparing goal achievement group and the others, whose LDL-C level were not achieved treatment goal

	2–3 mo. after discontinuation			4–6 mo. after discontinuation
	Goal achievement group	The others	p	Goal achievement group	The others	p
Age (years)	62.0±9.4	67.7±7.9	0.30	62.4±10.6	63.5±8.0	0.69
Male (%)	66	41	0.10	62	53	0.53
DM (%)	18	53	0.01	13	37	0.04
HTN (%)	79	65	0.32	68	68	0.96
CAD (%)	21	76	0.01	19	84	<0.01

LDL-C: low-density lipoprotein cholesterol, SD: standard deviation, DM: diabetes mellitus, HTN: hypertension, CAD: coronary artery disease, mo.: months

TOOLS

Similar articles