Download PDF
Homeopathy 2010; 99(04): 255-262
DOI: 10.1016/j.homp.2010.01.001
Original Paper
Copyright © The Faculty of Homeopathy 2010

Statins withdrawal, vascular complications, rebound effect and similitude

Marcus Zulian Teixeira
Subject Editor:
Further Information

Publication History

Received04 July 2009
revised12 January 2010

accepted31 January 2010

Publication Date:
17 December 2017 (online)

    Permissions and Reprints

Hahnemann considered the secondary action of medicines to be a law of nature and reviewed the conditions under which it occurs. It is closely related to the rebound effects observed with many modern drugs. I review the evidence of the rebound effect of statins that support the similitude principle. In view of their indications in primary and secondary prevention of cardiovascular diseases, statins are widely prescribed. Besides reducing cholesterol biosynthesis, they provide vasculoprotective effects (pleiotropic effects), including improvement of endothelial function, increased nitric oxide bioavailability, antioxidant properties, inhibition of inflammatory and thrombogenic responses, stabilisation of atherosclerotic plaques, and others. Recent studies suggest that suspension of statin treatment leads to a rebound imparing of vascular function, and increasing morbidity and mortality in patients with vascular diseases. Similarly to other classes of modern palliative drugs, this rebound effect is the same as a secondary action or vital reaction described by Samuel Hahnemann, and used in homeopathy in a therapeutic sense.

Keywords

Similitude - Secondary effect - Rebound effect - Paradoxical reaction - Substance withdrawal syndrome - Statin - Vascular diseases - Homeopathy
 

  • References

  • 1 Hahnemann S. Organon of medicine. [Boericke W, Trans.] 6th edn. New Delhi: B Jain Publishers; 1991.
    Google Scholar
  • 2 Teixeira M.Z. Semelhante cura semelhante: o princípio de cura homeopático fundamentado pela racionalidade médica e científica. Similar cures similar: the homeopathic cure principle based by the medical and scientific rationality. São Paulo: Editorial Petrus; 1998.
    Google Scholar
  • 3 Teixeira M.Z. Similitude in modern pharmacology. Homeopathy 1999; 88 (03) 112-120.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Teixeira M.Z. Homeopathic use of modern medicines: utilisation of the curative rebound effect. Med Hypotheses 2003; 60 (02) 276-283.
    CrossrefPubMedGoogle Scholar
  • 5 Teixeira M.Z. ‘Paradoxical strategy for treating chronic diseases’: a therapeutic model used in homeopathy for more than two centuries. Homeopathy 2005; 94 (04) 265-266.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Teixeira M.Z. Evidence of the principle of similitude in modern fatal iatrogenic events. Homeopathy 2006; 95 (04) 229-236.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Teixeira M.Z. NSAIDs, myocardial infarction, rebound effect and similitude. Homeopathy 2007; 96 (01) 67-68.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Teixeira M.Z. Bronchodilators, fatal asthma, rebound effect and similitude. Homeopathy 2007; 96 (02) 135-137.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Teixeira M.Z. Antidepressants, suicidality and rebound effect: evidence of similitude?. Homeopathy 2009; 98 (01) 114-121.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Zhou Q., Liao J.K. Statins and cardiovascular diseases: from cholesterol lowering to pleiotropy. Curr Pharm Des 2009; 15 (05) 467-478.
    CrossrefPubMedGoogle Scholar
  • 11 Ludman A., Venugopal V., Yellon D.M., Hausenloy D.J. Statins and cardioprotection – more than just lipid lowering?. Pharmacol Ther 2009; 122 (01) 30-43.
    CrossrefPubMedGoogle Scholar
  • 12 Bełtowski J., Wójcicka G., Jamroz-Wiśniewska A. Adverse effects of statins – mechanisms and consequences. Curr Drug Safety 2009 sep 1; [Epub ahead of print].
    PubMedGoogle Scholar
  • 13 Endres M., Laufs U. Discontinuation of statin treatment in stroke patients. Stroke 2006; 37 (10) 2640-2643.
    CrossrefPubMedGoogle Scholar
  • 14 Biccard B.M. A peri-operative statin update for non-cardiac surgery. Part I: the effects of statin therapy on atherosclerotic disease and lessons learnt from statin therapy in medical (non-surgical) patients. Anaesthesia 2008; 63 (01) 52-64.
    PubMedGoogle Scholar
  • 15 Williams T.M., Harken A.H. Statins for surgical patients. Ann Surg 2008; 247 (01) 30-37.
    CrossrefPubMedGoogle Scholar
  • 16 Fuentes B., Martínez-Sánchez P., Díez-Tejedor E. Lipid-lowering drugs in ischemic stroke prevention and their influence on acute stroke outcome. Cerebrovasc Dis 2009; 27 (Suppl. 01) 126-133.
    CrossrefPubMedGoogle Scholar
  • 17 Stone B.G., Evans C.D., Prigge W.F., Duane W.C., Gebhard R.L. Lovastatin treatment inhibits sterol synthesis and induces HMG-CoA reductase activity in mononuclear leukocytes of normal subjects. J Lipid Res 1989; 30 (12) 1943-1952.
    PubMedGoogle Scholar
  • 18 Pappu A.S., Bacon S.P., Illingworth D.R. Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia. J Lab Clin Med 2003; 141 (04) 250-256.
    CrossrefPubMedGoogle Scholar
  • 19 Chu C.S., Lee K.T., Lee M.Y. et al. Effects of atorvastatin and atorvastatin withdrawal on soluble CD40L and adipocytokines in patients with hypercholesterolaemia. Acta Cardiol 2006; 61 (03) 263-269.
    CrossrefPubMedGoogle Scholar
  • 20 Chen H., Ren J.Y., Xing Y. et al. Short-term withdrawal of simvastatin induces endothelial dysfunction in patients with coronary artery disease: a dose-response effect dependent on endothelial nitric oxide synthase. Int J Cardiol 2009; 131 (03) 313-320.
    CrossrefPubMedGoogle Scholar
  • 21 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 (25) 3104-3110.
    CrossrefPubMedGoogle Scholar
  • 22 Gertz K., Laufs U., Lindauer U. et al. Withdrawal of statin treatment abrogates stroke protection in mice. Stroke 2003; 34 (02) 551-557.
    CrossrefPubMedGoogle Scholar
  • 23 Rosengarten B., Auch D., Kaps M. Effects of initiation and acute withdrawal of statins on the neurovascular coupling mechanism in healthy, normocholesterolemic humans. Stroke 2007; 38 (12) 3193-3197.
    CrossrefPubMedGoogle Scholar
  • 24 Lee K.T., Lai W.T., Chu C.S. et al. Effect of withdrawal of statin on C-reactive protein. Cardiology 2004; 102 (03) 166-170.
    CrossrefPubMedGoogle Scholar
  • 25 Li J.J., Li Y.S., Chu J.M. et al. Changes of plasma inflammatory markers after withdrawal of statin therapy in patients with hyperlipidemia. Clin Chim Acta 2006; 366 (01/02) 269-273.
    CrossrefPubMedGoogle Scholar
  • 26 Thomas M.K., Narang D., Lakshmy R., Gupta R., Naik N., Maulik S.K. Correlation between inflammation and oxidative stress in normocholesterolemic coronary artery disease patients ‘on’ and ‘off’ atorvastatin for short time intervals. Cardiovasc Drugs Ther 2006; 20 (01) 37-44.
    CrossrefPubMedGoogle Scholar
  • 27 Sposito A.C., Carvalho L.S., Cintra R.M. et al. Rebound inflammatory response during the acute phase of myocardial infarction after simvastatin withdrawal. Atherosclerosis 2009; 207 (01) 191-194.
    CrossrefPubMedGoogle Scholar
  • 28 Puccetti L., Pasqui A.L., Pastorelli M. et al. Platelet hyperactivity after statin treatment discontinuation. Thromb Haemost 2003; 90 (03) 476-482.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Heeschen C., Hamm C.W., Laufs U., Snapinn S., Böhm M., White H.D. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation 2002; 105 (12) 1446-1452.
    CrossrefPubMedGoogle Scholar
  • 30 Heeschen C., Hamm C.W., Laufs U., Snapinn S., Böhm M., White H.D. Withdrawal of statins in patients with acute coronary syndromes. Circulation 2003; 107 (03) e27.
    CrossrefPubMedGoogle Scholar
  • 31 Spencer F.A., Fonarow G.C., Frederick P.D. 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 (19) 2162-2168.
    CrossrefPubMedGoogle Scholar
  • 32 Fonarow G.C., Wright R.S., Spencer F.A. et al. Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality. Am J Cardiol 2005; 96 (05) 611-616.
    CrossrefPubMedGoogle Scholar
  • 33 Schouten O., Hoeks S.E., Welten G.M. et al. Effect of statin withdrawal on frequency of cardiac events after vascular surgery. Am J Cardiol 2007; 100 (02) 316-320.
    CrossrefPubMedGoogle Scholar
  • 34 Cubeddu L.X., Seamon M.J. Statin withdrawal: clinical implications and molecular mechanisms. Pharmacotherapy 2006; 26 (09) 1288-1296.
    CrossrefPubMedGoogle Scholar
  • 35 Risselada R., Straatman H., van Kooten F. et al. Withdrawal of statins and risk of subarachnoid hemorrhage. Stroke 2009 Jun 11; [Epub ahead of print].
    PubMedGoogle Scholar
  • 36 Lesaffre E., Kocmanová D., Lemos P.A., Disco C.M., Serruys P.W. A retrospective analysis of the effect of noncompliance on time to first major adverse cardiac event in LIPS. Clin Ther 2003; 25 (09) 2431-2447.
    CrossrefPubMedGoogle Scholar
  • 37 Colivicchi F., Bassi A., Santini M., Caltagirone C. Discontinuation of statin therapy and clinical outcome after ischemic stroke. Stroke 2007; 38 (10) 2652-2657.
    CrossrefPubMedGoogle Scholar
  • 38 Blanco M., Nombela F., Castellanos M. et al. Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology 2007; 69 (09) 904-910.
    CrossrefPubMedGoogle Scholar
  • 39 Simons J. The $10 billion pill holds the fries, please. Lipitor, the cholesterol-lowering drug, has become the bestselling pharmaceutical in history. Here’s how Pfizer did it. Fortune Mag 2003, Jan 20. Available from: http://money.cnn.com/magazines/fortune/fortune_archive/2003/01/20/335643/index.htm.
    PubMed
  • 40 Beck M. Can a drug that helps hearts be harmful to the brain? Wall St J 2008, Feb 13 Health. Available from: http://online.wsj.com/article/SB120277403869360595.html.html?mod=home_health_right.
    PubMed
  • 41 Perreault S., Blais L., Lamarre D. et al. Persistence and determinants of statin therapy among middle-aged patients for primary and secondary prevention. Br J Clin Pharmacol 2005; 59 (05) 564-573.
    CrossrefPubMedGoogle Scholar
  • 42 Deambrosis P., Saramin C., Terrazzani G. et al. Evaluation of the prescription and utilization patterns of statins in an Italian local health unit during the period 1994–2003. Eur J Clin Pharmacol 2007; 63 (02) 197-203.
    CrossrefPubMedGoogle Scholar
  • 43 Ridker P.M., Danielson E., Fonseca F.A. et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359 (21) 2195-2207.
    CrossrefPubMedGoogle Scholar
  • 44 Ridker P.M., Danielson E., Fonseca F.A. et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 2009; 373 (9670): 1175-1182.
    CrossrefPubMedGoogle Scholar
  • 45 Daskalopoulou S.S. When statin therapy stops: implications for the patient. Curr Opin Cardiol 2009; 24 (05) 454-460.
    CrossrefPubMedGoogle Scholar