{"id":40772,"date":"2013-12-23T09:00:13","date_gmt":"2013-12-23T14:00:13","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=voices&p=40772"},"modified":"2013-12-23T10:25:43","modified_gmt":"2013-12-23T15:25:43","slug":"statins-targeting-risk-but-risking-diabetes","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2013\/12\/23\/statins-targeting-risk-but-risking-diabetes\/","title":{"rendered":"Statins: Targeting Risk, but Risking Diabetes?"},"content":{"rendered":"

One of Richard Lehman\u2019s recent blog posts<\/a> lauding a <\/a><\/em>BMJ<\/a> editorial<\/a> about targeting cardiovascular risk rather than cholesterol concentration from CardioExchange\u2019s Editor, Harlan Krumholz, struck a chord with member Emma Morton-Eggleston. Emma, who is an endocrinologist at the Brigham and Women\u2019s Hospital in Boston, wrote to Richard with her perspective, who responded, and they\u2019ve agreed to share their debate with CardioExchange:<\/em><\/p>\n

Dear Richard,<\/p>\n

Hope all is well \u2014 and as always thanks for your weekly reviews. They are guaranteed to provoke a smile at your incisive (and instructive) skepticism. But I have to disagree with you on Dr. Krumholz\u2019s editorial \u2014 which surprised me, as did your response to it, precisely because it was so optimistic.<\/p>\n

While I completely agree with his primary points regarding the jettisoning of targets and the importance of grounding the translation of guidelines in shared decision-making with patients, the suggestion that we can let time and further studies fix the potential over-medicalization of millions of people (and if the global medical community follows suit, hundreds of millions) from a likely flawed risk calculator is puzzling to me. To my mind, the potential medicalization of low-risk populations for primary prevention is a fundamental problem that can’t be left to a promissory note on future work that accurately defines risk. Even if such work comes to pass, as noted in the JAMA<\/em> Viewpoint<\/a> you also referenced by John Ioannidis, risk prediction is an inherently tricky business even in the most thoughtful and rigorous of hands.<\/p>\n

The diabetes experience made clear that once a guideline is in place, distracted following is the norm given the time pressures of modern medicine and the natural tendency towards inertia in critical thought that you have described so well. Why now is it statins and heart disease, not diabetes and anti-glycemic medications, do we do an about-face on decrying over-medicalization? And abandon prior attention to absolute risk of disease, and of benefit and harm of intervention, in the process?<\/p>\n

You have howled (as have I across the Atlantic in agreement) about the potential creation of vast global pharma markets for quasi \u201cdiseases\u201d including pre-diabetes. Why no howling now? The availability of generic statins may mean little profit is made for the time being, but it seems highly unlikely that opening the door to medical treatment for the prevention of arteriosclerotic cardiovascular disease (CVD) in low-risk populations will not herald targeting of these populations for new antilipidemic agents in the future.<\/p>\n

The potential harms attributed to statins are no small thing and can impact quality of life in very real ways \u2014 I am not sure how this squares with patient-centered care in low-risk patients. Last \u2014 and you knew this one was coming as I am an eternal hammer when diabetes is the nail \u2014 the dismissal of potential diabetes risk with statin use in patients at low risk for CVD because of the absence of long-term data is baffling. It is an increased risk that two large studies \u2014 an RCT<\/a> and a retrospective cohort analysis<\/a> \u2014 have suggested may approximate 50% in women. The CV benefit of statins in high-risk groups is about as close as we can get to true evidence-based medicine, and benefit appears to far outweigh risk of diabetes in these patients. But it is not at all clear that small decrements in absolute risk of CVD outweigh harms in low-risk patients.<\/p>\n

Muscle aches (at times profound), myopathy, and diabetes aside, overmedicalization is never a good thing. Okay, I’ll say rarely since nothing is never except immortality and nothing is always other than death, splendid gardens, friendship\/family for the lucky, and good cheese with a ripe pear.<\/p>\n

Looking forward to your thoughts,
\nEmma<\/p>\n

 <\/p>\n

Dear Emma,<\/p>\n

Thank you so much for writing. I’m really glad you’ve raised these issues because they puzzle me. I am trying to draw up a simple option grid to help people discuss this with their doctors, since most people still need to see a doctor to get hold of a statin. This discussion might then proceed to a personal cardiovascular risk assessment using one of the current instruments \u2014 not the flawed one you mention, but either Victor Montori’s<\/a> or James McCormack’s<\/a> \u2014 to give people a ball-park idea of where they lie in the risk spectrum and what the absolute benefit might be from taking a statin.<\/p>\n

I would leave guidelines aside here \u2014 this is not about health professionals but about a personal decision by a healthy person about how they want to play the odds of dying in a particular way. We can point people to fairly accurate information about that in relation to this class of drugs, though we could argue endlessly about the detail.<\/p>\n

This doesn’t need to be done by a doctor \u2014 in fact it is probably best done by a web-based program, with the doctor merely signing the prescription according to what the person chooses. I don’t even see this as a domain of “shared decision making” because doctors really have no business telling asymptomatic people what to do. We can give our personal advice, but in the end it is the individual’s choice, based on full and accurate information \u2014 i.e., the kind that doctors rarely have the time and knowledge to provide. And as these are lifelong choices, they should be made at leisure and revoked at will \u2014 by the individual. In this way “overmedicalization” is not an issue \u2014 we simply accept the free choices of autonomous individuals. Some people may want an absolute risk reduction of 0.01% \u2014 that’s their affair. Others may have an irrational fear of all tablets and simply not take them whatever their risk \u2014 and there is nothing we can do to change that. Given such a free choice, “compliance” or “adherence” become meaningless terms.<\/p>\n

That’s the way I see this issue. If a statin makes your muscles ache, you simply stop taking it. A recent study showed that most patients can be successfully started back on a different statin, though that is not my experience. I think \u2014 though I do not know for certain \u2014 that this applies to every adverse effect attributed to statins, including the rise in blood sugar which takes some people over the arbitrary threshold into “type 2 diabetes.” I would like to know more about the reversibility of this: I hope it is similar to the “diabetes” caused by thiazides, which stops when you stop the thiazide and has no prognostic importance anyway, since it is just a short-term biochemical effect of the agent and does not indicate beta-cell damage. If you are interested in the herd, rather than the individual, then the benefit of the statin in this borderline group outweighs any conceivable harm from a small rise in fasting blood sugar. But again, it’s up to the individual whether to carry on taking the stuff or not. You are not going to feel any different whether your fasting sugar is 6.5 or 7 and the odds are that you will live longer taking the statin, though not by much.<\/p>\n

Does this make sense? I am sorry to find that my views on this differ from those of many friends who seem to think there is a pharma-led conspiracy to overmedicate the world. There is no money in this for anyone, and I just hope the whole saga will be one more nail in the coffin of target-driven “care”, where the quality of practice is measured by how many people you persuade to take a particular action. We are not here to increase the life expectancy of the adult general population by imposing interventions, but to help people live and die in the way that they choose, according to the skills we may possess. At least, that is my philosophy, and I still owe Harlan a book about it, which I hope to call “Sharing Medicine.”<\/p>\n

I’d really value your thoughts about my option grid if you have time. And I hope you are enjoying\/surviving the snow and obtaining a good supply of ripe pears and cheese.<\/p>\n

All the very best,
\nRichard<\/p>\n

 <\/p>\n

Dear Richard,<\/p>\n

Beautifully said! The framework for shared decision making you lay out is what we should all be working to ensure \u2014 and your reminder that the choice is entirely the patient\u2019s to make is critical in informing how one views making clinical recommendations. I find it very helpful. But I still worry that the act of making the recommendation to start a statin is a form of medicalization. Even within the fluid bounds of shared decision-making, to start that conversation you have to invoke the specter of risk and lay a diagnosis of sorts on the patient. You are changing how they (and their insurance company) view themselves. Perhaps this perspective just shows my own medical paternalism (maternalism?). It is hard to shake.<\/p>\n

Regarding glycemic thresholds, your point that the diagnosis of diabetes is but a number on a glucose continuum is well taken and, as you suggest, in the case of statins there may be little correlation between meaningful clinical outcomes and observed glycemic rise. But the metabolic and pancreatic reality underlying glycemic thresholds is often more complicated, and variable, than that and we simply don\u2019t yet understand whether the \u201cdiabetes\u201d of statin use is metabolically the same as the inflamed environment\/beta-cell dance that is \u201cdiabetes\u201d as we know it. Nor do we know whether statin-potentiated diabetes progresses or carries the same (or lower), risk of complications and all-cause mortality in low-risk patients. We do know that the large majority of observational studies demonstrate a strong relationship between glycemia and all-cause mortality \u2013 and at A1Cs well less than 7%. And we increasingly acknowledge that we can\u2019t effectively decrease that risk with treatment in many people.<\/p>\n

As far as I know (but please correct me if I\u2019m wrong) there is little good evidence that statin therapy decreases all-cause mortality in low-risk patients. So are we saying that in groups at low risk for\u00a0 arteriosclerotic CVD we will recommend a drug for primary prevention that for most may modestly, but for some (women) may substantially, increase their risk of a disease that is itself a strong risk factor for mortality from any cause \u2014 not to mention a whole host of lesser, but no less relevant to patients, harms over time? And one that we can\u2019t treat well once it develops? I\u2019m open to the possibility, but will wait on the means to accurately identify risk \u2014 and the data demonstrating clear benefit that outweighs harms, before I do recommend it.<\/p>\n

Best,
\nEmma<\/p>\n","protected":false},"excerpt":{"rendered":"

Emma Morton-Eggleston and Richard Lehman share their correspondence with us, in which they debate whether it’s worth using statins to target CV risk if they might increase other risks, such as diabetes.<\/p>\n","protected":false},"author":883,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[495,1,7],"tags":[200,2108,977,584],"class_list":["post-40772","post","type-post","status-publish","format-standard","hentry","category-anticoagulation-2","category-general","category-prevention","tag-diabetes","tag-diabetes-risk","tag-prevention-2","tag-statins"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/40772","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/users\/883"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=40772"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/40772\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=40772"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=40772"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=40772"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}