Response to Letter by Hadjiev et al

Abstract

HomeStrokeVol. 42, No. 2Response to Letter by Hadjiev et al Free AccessReplyPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReplyPDF/EPUBResponse to Letter by Hadjiev et al J. David Spence, BA, MBA, MD and Daniel G. Hackam, BSc, MD, PhD J. David SpenceJ. David Spence Stroke Prevention & Atherosclerosis Research Centre Robarts Research Institute University of Western Ontario London, Ontario, Canada (Spence,Hackam) Search for more papers by this author and Daniel G. HackamDaniel G. Hackam Stroke Prevention & Atherosclerosis Research Centre Robarts Research Institute University of Western Ontario London, Ontario, Canada (Spence,Hackam) Search for more papers by this author Originally published30 Dec 2010https://doi.org/10.1161/STROKEAHA.110.595132Stroke. 2011;42:e22Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2010: Previous Version 1 We thank Hadjiev and colleagues for their interest in our article.They seem to suggest that adverse effects are more common with rosuvastatin than with other statins. We think the adverse effects they mention are class effects and that differences among statins are related to potency of statins. Indeed, this was the conclusion of a recent meta-analysis of head-to-head trials of atorvastatin and rosuvastatin.1 We do not have complete data on adverse effects of statins in our study population but estimate that approximately 10% of our patients have myalgias or myopathy with statins. This adverse effect is probably due to depletion of intramuscular ubiquinone (coenzyme Q10) by statins in people predisposed to myopathy because of an inherited disorder of mitochondrial function2,3; myalgias may improve with coenzyme Q10 supplementation.3,4 Similarly, the increase in incident diabetes with statins was shown in the meta-analysis to which they refer5 to apply to all statins with little heterogeneity among statins. The apparent excess with rosuvastatin to which Hadjiev et al refers may have been due to the larger sample size of the Jupiter study, which at 17 802 was the biggest of the studies included in that meta-analysis, but the relative potency of statins may also be the key issue here. Thus, the use of statins involves a tradeoff between benefits and adverse effects.With regard to the question of intracerebral hemorrhage from statins, it should be said that this is probably a myth. In a meta-analysis of 90 056 patients on statins,6 there was no increased risk of intracerebral hemorrhage with statins. The excess risk reported in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial7 to which they refer was probably not causally related to statin use, because there was no association of intracerebral hemorrhage with lower low-density lipoprotein. Because the control group was a placebo, the low-density lipoprotein should have been lower on 80 mg atorvastatin had the patients been taking it. This means that patients who had intracerebral hemorrhage were noncompliant with their statin therapy; the most likely explanation for the intracerebral hemorrhages was that they were also noncompliant with their antihypertensive therapy.With regard to calcium channel antagonists, there was no significant difference between the two eras in the proportion of patients taking these drugs at baseline (8.2% before versus 8.8% since 2003; P=0.31). We suspect that addition of ezetimibe, particularly in patients with plaque progression who were intolerant of high-dose statin, may account for some of our findings (unpublished data; ezetimibe became available in Canada in June 2003).The reasons for plaque progression despite good control of traditional risk factors probably include as yet unknown factors that are mainly genetic. Plaque measurement can be used to quantify the extent to which patients have plaque that is not explained by traditional risk factors. That approach can markedly increase statistical power for genomewide association studies8 and lead to new therapeutic targets and new therapies for atherosclerosis. However, until then, all that is available is more intensive application of therapies now in existence: if all one has is a hammer, everything is a nail (in this case, low-density lipoprotein).Patients with plaque progression despite already low levels of low-density lipoprotein and control of traditional risk factors such as smoking and blood pressure can only be identified by measuring the burden of atherosclerosis. Treating atherosclerosis without measuring plaque burden would be like treating hypertension without measuring blood pressure.J. David Spence, BA, MBA, MDDaniel G. Hackam, BSc, MD, PhD Stroke Prevention & Atherosclerosis Research Centre Robarts Research Institute University of Western Ontario London, Ontario, CanadaDisclosuresNone.FootnotesStroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. Letters must reference a Stroke published-ahead-of-print article or an article printed within the past 3 weeks. The maximum length is 750 words including no more than 5 references and 3 authors. Please submit letters typed double-spaced. Letters may be shortened or edited. Include a completed copyright transfer agreement form (available online at http://stroke.ahajournals.org and http://submit-stroke.ahajournals.org).