Canadian Journal of Cardiology 31 (2015) 691.e11 www.onlinecjc.ca
Letters to the Editor Statins and Cataracts: Reverse Causality? To the Editor: The report of Wise et al.,1 on increased risk of cataracts among patients who receive statins, is burdened by the risk of reverse causality inherent in such observational studies. Perhaps the best known example of this problem is the report from a US Health Cooperative, (see Supplemental Reference S1) that patients taking calcium channel antagonists had a greater risk of myocardial infarction, leading to an enormous tempest in a teapot. This fiasco was finally understood when it became apparent that the patients were receiving calcium channel antagonists for angina. In their analyses, participants with cataracts were significantly more likely to have all the risk factors for cataracts listed in Table 2 of the report by Wise et al.,1 including diabetes, cardiovascular disease, and chronic obstructive pulmonary disease, in the year preceding the index event. Although adjustment for these risk factors was attempted, it could not take into account that cataracts take years to develop, and it is likely that participants with cataracts were exposed to the risks long before they started statin therapy. The higher level of risk reported might well be because of a greater exposure of these patients to the risk factors for cataracts, leading to prescription of statins (ie, reverse causality). Oxidative stress causes a predisposition for cataracts, (Supplemental References S2 and S3) which are associated with diabetes, galactosemia, smoking, and cardiovascular disease. If statins increased the risk of cataracts significantly within a year or a few years of starting statin therapy, as these analyses are forced to assume, then a greater risk of cataracts should have been observed in randomized trials. In the Heart Protection Study2 (> 20,000 patients followed for an average of 5 years), the number of patients with cataracts was 393 (3.8%) in those who received simvastatin vs 404 (3.9%) in those who received placebo (personal communication December 15, 2014; Prof Rory Collins and Prof Jane Armitage). There was also no increase of cataracts over 5 years among patients randomized to simvastatin vs placebo in the Scandinavian Simvastatin Survival Study.3 In the Excel lens study4 (8245
patients followed for 48 months) there was no difference between placebo and lovastatin in development of cataracts or visual acuity. A meta-analysis of studies of cataracts in patients who received statins (Supplemental Reference S4), mentioned in the Editorial (Supplemental Reference S5) accompanying the article by Wise et al.,1 showed a significant (19%) reduction of cataracts in patients who received statins, with a greater (34%) reduction of the more difficult end point of cataract extractions, and occurrence of cataracts decreased further with more prolonged use of statins (by 46% over 14 years). Statins probably do not increase the risk of cataracts. J. David Spence, BA, MBA, MD, FRCPC, FAHA, FCAHS [email protected]
Disclosures The author has no conflicts of interest to disclose. References 1. Wise SJ, Nathoo NA, Etminan M, Mikelberg FS, Mancini GB. Statin use and risk for cataract: a nested case-control study of 2 populations in Canada and the United States. Can J Cardiol 2014;30:1613-9. 2. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22. 3. Pedersen TR, Berg K, Cook TJ, et al. Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study. Arch Intern Med 1996;156:2085-92. 4. Laties AM, Shear CL, Lippa EA, et al. Expanded clinical evaluation of lovastatin (EXCEL) study results. II. Assessment of the human lens after 48 weeks of treatment with lovastatin. Am J Cardiol 1991;67:447-53.
Supplementary Material To access the supplementary material accompanying this article, visit the online version of the Canadian Journal of Cardiology at www.onlinecjc.ca and at http://dx.doi.org/10. 1016/j.cjca.2014.12.018.
http://dx.doi.org/10.1016/j.cjca.2014.12.018 0828-282X/Ó 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Letters to the Editor Statins and Cataracts: Reverse Causality? To the Editor: The report of Wise et al.,1 on increased risk of cataracts among patients who receive statins, is burdened by the risk of reverse causality inherent in such observational studies. Perhaps the best known example of this problem is the report from a US Health Cooperative, (see Supplemental Reference S1) that patients taking calcium channel antagonists had a greater risk of myocardial infarction, leading to an enormous tempest in a teapot. This fiasco was finally understood when it became apparent that the patients were receiving calcium channel antagonists for angina. In their analyses, participants with cataracts were significantly more likely to have all the risk factors for cataracts listed in Table 2 of the report by Wise et al.,1 including diabetes, cardiovascular disease, and chronic obstructive pulmonary disease, in the year preceding the index event. Although adjustment for these risk factors was attempted, it could not take into account that cataracts take years to develop, and it is likely that participants with cataracts were exposed to the risks long before they started statin therapy. The higher level of risk reported might well be because of a greater exposure of these patients to the risk factors for cataracts, leading to prescription of statins (ie, reverse causality). Oxidative stress causes a predisposition for cataracts, (Supplemental References S2 and S3) which are associated with diabetes, galactosemia, smoking, and cardiovascular disease. If statins increased the risk of cataracts significantly within a year or a few years of starting statin therapy, as these analyses are forced to assume, then a greater risk of cataracts should have been observed in randomized trials. In the Heart Protection Study2 (> 20,000 patients followed for an average of 5 years), the number of patients with cataracts was 393 (3.8%) in those who received simvastatin vs 404 (3.9%) in those who received placebo (personal communication December 15, 2014; Prof Rory Collins and Prof Jane Armitage). There was also no increase of cataracts over 5 years among patients randomized to simvastatin vs placebo in the Scandinavian Simvastatin Survival Study.3 In the Excel lens study4 (8245
patients followed for 48 months) there was no difference between placebo and lovastatin in development of cataracts or visual acuity. A meta-analysis of studies of cataracts in patients who received statins (Supplemental Reference S4), mentioned in the Editorial (Supplemental Reference S5) accompanying the article by Wise et al.,1 showed a significant (19%) reduction of cataracts in patients who received statins, with a greater (34%) reduction of the more difficult end point of cataract extractions, and occurrence of cataracts decreased further with more prolonged use of statins (by 46% over 14 years). Statins probably do not increase the risk of cataracts. J. David Spence, BA, MBA, MD, FRCPC, FAHA, FCAHS [email protected]
Disclosures The author has no conflicts of interest to disclose. References 1. Wise SJ, Nathoo NA, Etminan M, Mikelberg FS, Mancini GB. Statin use and risk for cataract: a nested case-control study of 2 populations in Canada and the United States. Can J Cardiol 2014;30:1613-9. 2. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22. 3. Pedersen TR, Berg K, Cook TJ, et al. Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study. Arch Intern Med 1996;156:2085-92. 4. Laties AM, Shear CL, Lippa EA, et al. Expanded clinical evaluation of lovastatin (EXCEL) study results. II. Assessment of the human lens after 48 weeks of treatment with lovastatin. Am J Cardiol 1991;67:447-53.
Supplementary Material To access the supplementary material accompanying this article, visit the online version of the Canadian Journal of Cardiology at www.onlinecjc.ca and at http://dx.doi.org/10. 1016/j.cjca.2014.12.018.
http://dx.doi.org/10.1016/j.cjca.2014.12.018 0828-282X/Ó 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
