12.8 Million More Adults Now Eligible For Statin Therapy Reply

Millions more people are now eligible for statin therapy under the new cholesterol guideline, according to a new estimate published in the New England Journal of Medicine.

There have been many attempts to quantify just how many more people are now eligible for statin therapy under the new guideline. Now in the new paper in NEJM, Michael Pencina and colleagues estimate that the new guideline results in a net increase of 12.8 million people who are now eligible for statins.

Click here to read the full post on Forbes.

 

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Reassuring News About Statins From Two Very Different Studies Reply

Although clinical trials have consistently demonstrated the benefits of statins, the perception that the drugs can cause serious side effects has prompted some patients to discontinue or not take the drugs. Now two new very different studies, one a large meta-analysis and one a tiny study with only a handful of patients, provide some convincing reassurance that most of the side effects that have been tied to statins do not appear to be actually caused by the drugs.

Click here to read the full post on Forbes.

 

Pfizer Starts Testing For Over-The-Counter Lipitor Reply

Looking backward to improve its future, Pfizer will once again try to gain FDA approval to market its blockbuster drug, atorvastatin (Lipitor), over-the-counter (OTC). Peter Loftus reports in the Wall Street Journal that the company has started a clinical study to support the application for low-dose atorvastatin (10 mg).

Click here to read the full post on Forbes.

 

Dispatch From The Wild Frontier Of The Statin Wars Reply

The long simmering controversy over the relative benefits and harms of statins has heated to a high boil with the release of the new AHA/ACC US guidelines. But nowhere is the battle more intense right now than in Australia where, according to the National Heart Foundation, a TV show may be the cause of 2,000 heart attacks and strokes over the next five years.

The show was a 2-part documentary  (click here for part 1 and part 2) broadcast in October on the Australian ABC network about dietary fat and cholesterol.

The program, wrote Amy Corderoy, the health editor of the Sydney Morning Herald, “claimed the causal link between saturated fat, cholesterol and heart disease was ‘the biggest myth in medical history’… [and described statins] as toxic and potentially deadly.”

Catalyst delved into a raging debate: has dietary guidance telling us to avoid fats pushed us towards more harmful sugar and carbohydrates instead?

But the program also went a step further, arguing cholesterol was just an innocent bystander in the body’s attempts to deal with the sugar-damage. It was not a big leap to claim statins were dangerous, and the research supporting them fraudulent.

Click here to read the full post on Forbes.

 

Heart of the Matter screen shot

 

 

A Clear-Eyed View Of Statins And Cataracts 1

Past observational studies have turned up conflicting findings about the effects, if any, of statins on developing cataracts. Now a large new observational study finds a small but significant increase in cataracts in statin users, but experts warn that without further support the new finding should probably not influence clinical practice.

In a paper published in JAMA Ophthalmology, Jessica Leuschen and colleagues analyzed data from a military health care system. In their primary analysis they performed a propensity analysis comparing 6,972 propensity-matched pairs of statin users and nonusers. The authors reported a significant…

Click here to read the full story on Forbes.

Cataract in Human Eye
Cataract in Human Eye (Photo credit: Wikipedia)

 

FDA Approves Combination Of Ezetimibe And Atorvastatin Reply

The FDA has approved a new combination drug from Merck for lowering cholesterol. The drug, which will carry the brand name of Liptruzet, is a combination of two previously approved cholesterol-lowering drugs, ezetimibe and atorvastatin.

Merck said the new drug (pronounced “LIP-true-zett”) would be commercially available starting next week. Liptruzet will be available as a once-daily tablet combining 10 mg of ezetimibe with either 10, 20, 40, or 80 mg of atorvastatin. In clinical trials Liptruzet lowered LDL cholesterol from 53% to 61%, depending on dosage.

Click here to read the full post on Forbes.

 

Lifelong Statin Sentence Now Includes Furloughs 1

Although the benefits of statins are among the best documented in all of medicine, continuous lifelong statin therapy is not always easy to achieve in clinical practice. Now a new retrospective study suggests that although clinical events causing temporary cessation of statin therapy occur often, most of these patients are later able to resume statin therapy.

In a paper published in Annals of Internal Medicine, researchers analyzed data from 107,835 patients with a statin prescription treated by physicians associated with Massachusetts General Hospital and Brigham and Women’s Hospital. 18,778 of these patients had documented events that were statin related, resulting in 11,124 patients who stopped taking statins. Within a year more than half of these (6,579) were rechallenged with a statin, and most of these (92.2%) were taking a statin a year after the initial statin-related event.

Click here to read the full story on Forbes.

 

 

Following Earlier Recall, Ranbaxy Halts Manufacturing Atorvastatin Reply

Ranbaxy, the often-troubled manufacturer of generic drugs, will temporarily stop manufacturing generic atorvastatin. On November 9, 2012 the company announced a voluntary recall of some lots of atorvastatin because of possible contamination with glass particles. An FDA statement today said that Ranbaxy will discontinue making the drug “until it has thoroughly investigated the cause of the glass particulates and remedied the problem.”

To date, no reports of harm from the contamination have been received by the FDA. Both FDA and Ranbaxy believe there is only a low likelihood that there will be adverse events related to the problem.

The FDA said it does not anticipate a shortage of atorvastatin because of the recall, but that it “is working with other manufacturers of atorvastatin to ensure adequate market supply.”
Click to read the FDA statement…

Statins and Exercise, Independently Beneficial, Even Better In Combination 2

It’s no secret that statins and exercise are good for people with cholesterol problems. Now a new study published in the Lancet offers fresh evidence that the two appear to be independently beneficial, and that adding the two together may result in greater benefits than either alone.

US researchers analyzed data from 10,043 people with dyslipidemia treated at 2 Veterans Affairs Medical Centers. Participants were followed for a median of 10 years, during which time nearly a quarter of them died. After adjusting for baseline characteristics and other risk factors, mortality was separately and independently reduced by statins and by fitness level, with the greatest benefit found in the group of patients who were taking statins and were highly fit (>9 MET). The researchers further reported that only a moderate and achievable amount of exercise produced an effect similar to that of statins in people not taking statins. “Improved fitness,” they wrote, “is an attractive adjunct treatment to statins or an alternative when statins cannot be taken.”

“The fitness necessary to attain protection that is much the same or greater than that achieved by statin treatment in unfit individuals is moderate and feasible for many middle-aged and older adults through moderate intensity physical activity such as walking, gardening, and gym classes,” said lead researcher Peter Kokkinos, in a Lancet press release.

In an accompanying editorial, Pedro Hallal and I-Min Lee write that “the undervaluation of physical activity in clinical practice” is “unacceptable.” “Prescription of physical activity should be placed on a par with drug prescription.”

Photo by T-Rex Runner (click on the the picture for more background)

Click here to read the Lancet press release…

Statins Use Linked To Reduction In Cancer Mortality 1

A large new population study rasies the possibility that statin use may lead to a decline in cancer mortality. Researchers in Denmark utilized health data from the entire population of the country and analyzed the information from nearly 300,000 patients who were diagnosed with cancer between 1995 and 2007. The authors note that the relationship is biologically plausible, since cholesterol synthesis is required for cell proliferation and other critical cellular functions.

In their paper published in the New England Journal of Medicine, the researchers compared 18,721 cancer patients who were statin users prior to their diagnosis with 277,204 had never used statins: Here is the adjusted hazard ratios for statin users:

  • All cause mortality: 0.85 (0.83-0.87)
  • Death from cancer: 0.85 (0.82-0.87)

There was no dose response relationship observed in the study. A similar and consistent pattern was observed for different types of cancer, though these differences not always achieve statistical significance.

In an accompanying editorial, Neil Caporaso notes that despite the considerable strengths of the study, which used data from the entire country of Denmark, the researchers were nevertheless unable to account for residual confouding differences between statin users and nonusers. The “consistent and substantial declines in mortality across diverse diverse cancers”  need to be interpreted with caution, he wrote. Caporaso suggests a variety of different research directions for further study of the important question of the relationship between statins and cancer.

 

Reports From JUPITER And Taiwan: Benefits Of Statins Outweigh Risk Of Diabetes 1

Two new papers provide further evidence that statin usage is associated with an increased risk of diabetes, but both studies also find that the benefits of statins still outweigh the risks.

In the first report, published in the Lancet, Paul Ridker and colleagues analyze data from the JUPITER trial, which compared rosuvastatin to placebo in a primary prevention population.

Among the 17,603 patients randomized in the trial, 11,508 had at least one major risk factor for developing diabetes. In this group, the primary endpoint (MI, stroke, hospitalization for unstable angina, revascularization, or CV death) was reduced by 39% in the statin group (hazard ratio 0·61, CI 0.47–0.79, p=0·0001). The authors calculated that in the statin group 134 vascular events or deaths were avoided  for every 54 new cases of diabetes. For the 6,095 patients without a major risk factor for diabetes, the primary endpoint was reduced by 52%  (HR 0·48, CI 0.33–0.68, p=0·0001). No increase in diabetes was observed. In this group, 86 vascular events or deaths were avoided.

During the JUPITER trial 486 subjects developed diabetes  (270 in the rosuvastatin group and 216 in the placebo group). The risk reduction in this group was consistent with the overall reduction observed in the trial.

“Our results show that in participants with and without diabetes risk, the absolute benefits of statin therapy are greater than the hazards of developing diabetes,” said Paul Ridker, in a press release issued by the Lancet. “We believe that most physicians and patients would regard heart attack, stroke and death to be more severe outcomes than the onset of diabetes, and so we hope that these results ease concern about the risks associated with statin therapy when these drugs are appropriately prescribed – in conjunction with improved diet, exercise and smoking cessation – to reduce patients’ risk of cardiovascular disease.”

The findings from JUPITER were echoed in a large observational study from Taiwan published in the Journal of the American College of Cardiology that compared 8,412 people receiving statins with 33,648 matched controls. The Taiwan investigators found that although, over a median of 7.2 years, the rate of diabetes was significantly higher among statin users  (2.4% vs. 2.1%, p < 0.001), statins were associated with a significant reduction in cardiovascular events (HR 0.91, CI 0.84 to 0.99, p = 0.031).
Click here to read the Lancet press release…

Authors Retract Article About Websites That Sell Statins Without Prescriptions Reply

An article in Pharmacoepidemiology and Drug Safety about websites that advertise statins to consumers has been retracted by the authors after one company mentioned in the article disputed the authors’ assertion that the company sold statins to patients who did not have a prescription. The news was reported on Retraction Watch.

Here’s the notice:

The following article from Pharmacoepidemiology and Drug Safety, “Direct to consumer Internet advertising of statins: an assessment of safety”, by Bethan Williams and David Brown, published online on 2nd February 2012 on Wiley Online Library (wileyonlinelibrary.com) and in Volume 21, Issue 4, pages 352–365, April 2012, has been retracted by agreement between the authors, the journal Editor-in-Chief, and John Wiley & Sons Ltd. The retraction has been agreed due to the inability to verify the accuracy of the data in Appendix 1.

According to Retraction Watch, Appendix 1 contained a list of 184 websites that appeared to have sold statins without a prescription.The journal’s editor told Retraction Watch:

A lawyer for a company specified in the appendix threatened a suit, claiming they never dispensed meds without a prescription.  We told the author we would back them, but we needed to see proof the website ever said that.  The authors had no evidence to back up their statement.

The corresponding author, of the paper, David Brown, of the University of Portsmouth in the United Kingdom, told Retraction Watch:

We conducted our study in good faith; however, on publication, it was brought to our attention by one of the editors that the producers of one of the websites listed in the Appendix to the paper had indicated that the site was listed in error as offering statins for sale without a prescription.

We did not keep the original screen-dumps of websites at the time of our study (19th November – 23rd December 2010) and as we could not verify the inclusion of the website, we immediately agreed to retract the paper in accordance with the editor’s wishes.

I must stress that this was an honest error on our part; there never was any intention to mislead the journal or its readership. This stance was accepted by the journal editor.

Are Statins Equally Effective In Women And In Men? 1

Jose Gutierrez and colleagues performed a sex-based meta-analysis, seeking to determine if statins yield a similar protective effect on both men and women in preventing recurrent cardiovascular events. In a paper published in the Archives of Internal Medicine, they report the results of their meta-analysis of 11 secondary prevention, double-blinded, placebo-controlled trials, which included 43, 193 patients (11,229 women and 31,962 men).

Overall, statin therapy was associated with a significant reduction in overall CV outcomes for both men and women. For all-cause mortality and stroke, however, the benefit in women did not achieve statistical significance.

All CV outcomes:

  • women: RR 0.81, CI 0.74-0.89
  • men: RR 0.82, CI 0.78- 0.85]

All-cause mortality:

  • women: RR 0.92, CI 0.76-1.13
  • men: RR 0.79, CI 0.72-.87

Stroke:

  • women: RR 0.92, CI 0.76-1.10
  • men: RR 0.81, CI 0.72-0.92

The smaller sample size of women is one possible explanation for the lack of a significant difference in mortality and stroke, according to the authors. Other factors — including the worse cardiovascular profile of women and lower use of antiplatelet agents in women — might also play a role, they speculate.

In an invited commentary, Fiona Taylor and Shah Ebrahim write that it is “misleading” to focus on the lack of statistical significance in women. “The real issue is not significance but whether the effect size in women is materially different from the effect size in men,” they write, and note that “the effect on stroke and all-cause mortality in women is consistent with the effect in men.” They conclude that “statins work just as well in women as in men.”

In an editor’s note, Rita Redberg states that we should not “assume women are the same as men.” She writes that “unless we increase inclusion of women in clinical trials and report sex-specific data, there will never be sufficient data to achieve optimal care of all of our patients.”

Click here to read the Archives press release…

Fascinating Debate Over Statins For Primary Prevention 2

The recent guest post by David Newman has prompted several thought-provoking comments. Since most readers will likely miss the comments, I’ve moved these comments to a separate post.

Statin Island May 27, 2012, 3:35 PM:

Thank you. Clearly, this important commentary raises questions about the integrity of Lancet as well as the authors of the study.

But what is most discouraging, and dangerous, is that this kind of deception occurs so frequently. Meanwhile, major news outlets, television channels, etc. have reported the results as the authors intended. And so the gravy train has left the station.

Lancet should publish a clarifying editorial and send it everywhere they can. They are an accessory to any harm that has resulted, to patients and to the credibility of medical science.

Michael V Holmes (@mvholmes) (May 28, 2012, 10:10 AM:

I disagree with this critique. The authors weighed each RCT by the LDL-C lowering to be able to provide a standardized comparison across the studies (it’s in the Methods of the paper). By doing so, they didn’t break the randomization, and shouldn’t have introduced confounding, as suggested by this commentary piece. And being able to say “for each 1 mmol/L LDL-C reduced, the RR of CHD is 0.79, 95% CI 0.77, 0.81″ is very helpful metric.

Larry Husten (May 28, 2012, 12:31 PM:

I don’t claim to be an expert in meta-analysis but I’m not sure that Holmes is responding to the fundamental flaw in logic in the Lancet paper raised by Newman. The Lancet paper– correctly, as Newman acknowledges– identifies a benefit for statins in people who respond to statins, but it says nothing about the broader primary prevention population, some of whom will not respond to statins. The conclusion reached by the CTT authors, that statins should be more widely used in this primary population, is therefore unwarranted.

I am hopeful that Dr. Newman will respond in more detail and discuss the technical issues raised by Holmes.

MDinSTL (May 30, 2012, 11:32 AM):

Within any randomized group, some will do better than others. When targeting a lower LDL, those who achieve and maintain the target do better than those who do not. This phenomenon has been called dose targeting bias.

What is key to understand though is that an intervention may have NO benefit, yet this relationship of better LDL lowering to better outcomes can still be observed.

Therefore if the trials show no net benefit between statin vs placebo, it is not necessarily true that the subgroup analysis the Lancet group employs means some people benefited.

This is easiest to see by considering this point: If the statin-treated non-CAD patients had no overall reduction in mortality, and the subgroup with a large LDL drop did have lower mortality, then those without a large LDL drop must have been harmed by statins to account for the lack of overall effect compared to the placebo-treated patients.

If investigators really believe some benefit from statins accrues to those without apparent CAD provided LDL falls at least 40 pts, then the answer is to perform a trial where entry criteria include an ability to show a 40 pt drop in LDL, then randomize pts to statin vs no statin. That ain’t gonna happen because 1. few seriously believe that, and 2. this message is really a marketing message intended to promote use of statins in the general population.

DH Newman(May 28, 2012, 5:08 PM: 
Click to continue reading…

Guest Post: Data, Drugs, And Deception– A True Story 13

Editor’s Note: The following guest post by Dr. David Newman is reprinted with permission from his website and blog, Smartem.Org. Dr. Newman is an Emergency Physician and Director of Clinical Research at Mt. Sinai School of Medicine in the Department of Emergency Medicine.  He is the author of the critically-acclaimed Hippocrates’ Shadow: Secrets From the House of Medicine. CardioBrief readers might also enjoy watching his TED talk, Truth That Lasts.

Data, Drugs, And Deception– A True Story

by Dr. David Newman

Last week The Lancet published a meta-analysis of 27 statin trials, an attempt to determine whether patients with no history of heart problems benefit from the drugs — true story. The topic is controversial, and no less than six conflicting meta-analyses have been performed — also a true story. But last week’s study claims to show, once and for all, that for these very low risk patients, statins save lives — true story.

Actual true story: the conclusions of this study are neither novel nor valid.

The Lancet meta-analysis, authored by the Cholesterol Treatment Trialists group, examines individual patient data from 27 statin studies. Their findings disagree with an analysis published in 2010 in theArchives of Internal Medicine, and with analyses from two equally respected publications, theTherapeutics Letter and the Cochrane Collaboration.* Despite this history of dueling data the authors of last week’s meta-analysis, in a remarkable break from scientific decorum, conclude their report with a directive for the writers of statin guidelines: the drugs should be broadly recommended based on the new analysis.

As an editorialist points out, if implemented, the CTT group recommendations in the United States would lead to 64 million people, more than half of the population over the age of 35, being started on statin therapy — true story.

Where is the magic, you ask, in this latest effort? What is different? In some ways, nothing. Indeed just a year and a half earlier The Lancet published a meta-analysis of 26 of the same 27 studies, with the same results, by the same authors (true story, and an odd choice on the part of the journal). So the findings aren’t new. They are, however, at odds with other meta-analyses. Why? It is the way they calculated their numbers. This meta-analysis, like the earlier one from the same group, reports outcomes per-cholesterol-reduction. The unit they use is a “1 mmol/L reduction in low density lipoprotein (LDL)”, in common U.S. terms, a roughly 40-point drop in LDL.

That’s the magic: each of the benefits reported in the paper refers to patients with a 40-point cholesterol drop. Voilá. One can immediately see why these numbers would look different than numbers from reviews that asked a more basic question: did people who took statins die less often than people taking a placebo? (The only important question.) Instead, they shifted the data so that their numbers corresponded precisely to patients whose cholesterol responded perfectly.

Patients whose cholesterol drops 40 points are different than others, and not just because their body had an ideal response to the drug. They may also be taking the drug more regularly, and more motivated. Or they may be exercising more, or eating right, and more health conscious than other patients. So it should be no surprise that this analysis comes up with different numbers than a simple comparison of statins versus placebo pills. Ultimately, then, this new information tells us little or nothing about the benefits someone might expect if they take a statin. Instead it tells us the average benefits among those who had a 40-point drop in LDL.
Click to continue reading…

You Know Nothing, Dr. Snow: Why Medicine Can’t Be More Like Facebook 3

Medicine can never be like Facebook, despite what Matt Herper argues over at Forbes. Perhaps he was just trolling for hits on a day when everyone is thinking about the Facebook IPO, but Herper proposed, with apparently seriousness, that medicine needs to model itself on the tech world in order to match the kind of progress– and profits– of a Facebook. But the medical news this week provided ample evidence why this will never happen. Biology is much more complex and resistant than the digital world.

For a medical journalist like myself this was a frustrating week. There were a whole bunch of large, major studies on important subjects published in top journals. But the take-away message from these studies, both individually and combined, is that achieving any kind of real progress in medicine is incredibly hard.

Let’s take a quick look at these studies:

1. Coffee in the New England Journal of Medicine: Despite some of the breathless news reports, some of which erroneously claimed that the study proved that drinking coffee can extend your life, this large study added little or nothing new to our knowledge about coffee. Even the editor of the journal, Jeff Drazen, acknowledged the limitations of this sort of study. The simple truth is this: although coffee is ubiquitous and has been the subject of hundreds of different studies of all different types and designs, we will almost certainly never learn to any degree of certainty whether coffee is good or bad for us. An enormous, decades-long randomized controlled clinical trial, which is the only possible way to ascertain the truth about coffee with any degree of certainty, would be nearly impossible to perform, for multiple reasons.

I don’t want to overstate my pessimism here. I think there is a much more limited lesson that can be derived from this NEJM study and the rest of the coffee literature. From the totality of the evidence it seems highly unlikely that coffee has any large effect, either positive or negative, on important outcomes like mortality or cancer. But we’ll never know for sure about small effects, and we will certainly never know if there are small populations or individuals who are particularly likely to derive benefit or harm from coffee.

2. HDL Cholesterol in the Lancet. In some respects the HDL cholesterol story is exactly the opposite of the coffee story. Unlike coffee, the epidemiology of HDL is clear-cut, and therefore the reverse association of HDL with cardiovascular disease is among the best established facts in all of medicine. But association is not causation, and despite more than a generation of intense research we still don’t know how– or even if– HDL works. In fact, as its name implies, high density lipoprotein is not so much a biological entity as an artificial construct of something that we can measure easily.
Click to continue reading…

Large Metaanalysis Finds Statins Effective in Low Risk Patients Reply

A very large metaanalysis provides strong evidence that the relative reduction in risk of statins is at least as great in low-risk patients as in high-risk patients. The finding, write the authors, provides evidence that expansion of guidelines to lower risk populations should be considered.

In their paper in the Lancet, the  the Cholesterol Treatment Trialists’ (CTT) Collaborators analyzed data from 134,537 patients in trials comparing statins to control therapy and 39,612 patients in trials comparing low and high dose statins. They examined the impact of statin therapy according to the baseline 5-year risk of a major vascular event on control therapy.  Statin therapy caused a consistent reduction in the relative risk of major vascular events and all-cause mortality independent of other factors, including age, sex, baseline LDL cholesterol, or established CV disease.

Here is the rate ratio for major vascular events across five levels of risk at baseline (note that 1 mmol of LDL cholesterol is equivalent to about 39 mg/dl of LDL):

        5 Year Risk         Rate ratio per 1.0 mmol/L of LDL reduction

  • <5%                          0·62 [99% CI 0·47–0·81]
  • ≥5% to <10%          0·69 [99% CI 0·60–0·79]
  • ≥10% to <20%       0·79 [99% CI 0·74–0·85]
  • ≥20% to <30%       0·81 [99% CI 0·77–0·86]
  •  ≥30%                       0·79 [99% CI 0·74–0·84]

The metaanalysis found no evidence for harm associated with statin therapy, including cancer or other non-vascular mortality.

The authors noted that people in the lowest two categories of risk in the study, who are expected to have a 5 year event rate lower than 10%, are not recommended for statin therapy in current guidelines. As generic statins are highly cost-effective, the result “suggests that these guidelines might need to be reconsidered.”

In an accompanying comment, Shah Ebrahim and Juan Casas ask whether everyone over the age of 50 should take statins. They calculate that, in the UK, adoption of a threshold of 10% would result in 83% of men over 50 years of age and 56% of women over the age of 60 as needing statins.
Click here to read the Lancet press release…

Preoperative Statins Found to Reduce AF and Length of Stay But Not Mortality Reply

In a systematic review published in the Cochrane Library investigators at the University of Cologne in Germany analyzed data from 11 trials that tested the effects of preoperative statins in 984 patients undergoing heart surgery. Preoperative administration of statins reduced the risk of developing atrial fibrillation (AF) and shortened the length of stay on the ICU and in the hospital, but did not have a statistically significant effect on mortality or MI:

  • Post-operative AF: OR: 0.40, CI: 0.29 to 0.55, p<0.01
  • Short-term mortality: OR: 0.98, CI: 0.14 to 7.10, p=0.98
  • ICU length of stay: WMD (weighted mean difference): -3.39 hours, CI -5.77 to -1.01
  • Hospital length of stay: WMD: -0.48 days, CI: -0.85 to -0.11
  • MI: OR: 0.52, CI: 0.2. to 1.30

The authors noted that the studies mostly contained patients undergoing myocardial revascularization, so the findings may not apply to other cardiac procedures.

“To get a clearer picture of the potential benefits of taking statins before a heart operation, we need to have more clinical trials and find out whether clinical outcomes can be further improved if patients use special statin dosing regimens shortly before a heart procedure,” said  lead researcher Oliver Liakopoulos, in a Cochrane Library press release.
Click here to read the press release from the Cochrane Library…

Guest Post: Another Round in the Debate on Diabetes and Statins 4

Another Round in the Debate on Diabetes and Statins

by Roger Blumenthal

Let me start by saying that I am proud to have Eric Topol as a friend and a trusted advisor over the past 20 years. His work has been an inspiration to cardiovascular health professionals for several decades. His new book, The Creative Destruction of Medicine: How the Digital Revolution Will Create Better Health Care, should be required reading by all physicians and in all medical schools. It is simply that good.

Eric is a strong believer that we need to have more personalized medicine. I agree. I predict that he and his research group will lead the way to help us understand why certain people benefit more from certain medications and others may not. So far, the only ways we have to decide which asymptomatic persons would benefit from statin therapy are the traditional risk factors which make up the Framingham risk score, hsCRP, and coronary calcium measurements. Both of the latter two tests have been given a class IIa indication from the AHA for use in intermediate risk adults (Framingham score of 10-20% risk of an MI over the next decade.)

Eric is concerned about the apparent increased risk of diabetes with statin use. A 2010 meta-analysis in the Lancet found about a 10% increased risk in statin users. Eric rightly points out that the relative risk was higher with the more potent rosuvastatin in JUPITER. Yet, that is where we saw a  significant decrease in total mortality and the largest relative risk reduction in CVD events.
Click to continue reading…

Eric Topol, Megamind 2

Ralph Waldo Emerson famously wrote that “a foolish consistency is the hobgoblin of little minds.” If this is true then Eric Topol, who earlier today wrote a New York Times editorial highly critical of statins, is Megamind.

Here’s what he wrote in a 2004 editorial in the New England Journal of Medicine:

Even today, only a fraction of the patients who should be treated with a statin are actually receiving such therapy. It is estimated on the basis of the criteria in current national guidelines that 36 million people in the United States should be taking a statin, but only 11 million are currently being treated. Worldwide, the discrepancy is even more staggering; more than 200 million people meet the criteria for treatment, but fewer than 25 million take statins.

There will soon be a sea change in the prevention and management of atherosclerotic vascular disease. The proportional reduction in major clinical outcomes that results from aggressive statin therapy is of the same order of magnitude as that seen when statins were compared with placebo in controlled trials. Intensive therapy with statins, monitored by means of measurements of LDL cholesterol or biologic markers of inflammation, is likely to result in even greater steps toward actualizing the full benefit of this remarkable class of medicines.

To be fair, I think Topol deserves credit for being willing to change his mind. It’s a rare trait. But I’m not sure that every single current controversy in medicine should be seen in the light of a crusade in favor of genomics, so when a cardiologist with a long memory sent me this editorial I couldn’t resist posting this blast from the past.

Update: In all fairness, here is Dr. Topol’s response to the above post:

The op-ed on the risk of diabetes from statins had nothing to do with changing my mind. It has everything to do with new data that were not available in 2004. As I pointed out in the Times op-ed, the diabetes issue only surfaced in recent trials with higher doses (40 mg of Simvastatin) and atorvastatin (Lipitor) and rosuvastatin (Crestor). Prior to these trials, there was no signal about the risk of diabetes. The trial my NEJM editorial was written on in 2004–PROVE IT–showed no difference in diabetes for intensive vs moderate statins (5.9% in both groups). All of the subsequent intensive statin randomized trials–TNT, IDEAL, SEARCH showed an important excess. Even folding PROVE-IT to the mix, collectively the excess of an absolute 0.8% equates to developing diabetes in 1 of every 125 patients treated with intensive statins compared with moderate dose statins.

JUPITER, one of the largest trial of statins, with 17,802 patients, was not published until 2008, nor did we have diabetes data available from many of the other placebo-controlled trials until after 2004.The initial HPS trial primary report published in 2002 did not even mention the diabetes risk, which only came out much later!

Furthermore, this is not a crusade about genomics, which is a baseless point. This op-ed was aimed at consumers, who have every right to know the real data, the real risks and benefit of primary prevention with potent statins. The fact that we are in 2012, and have recognized the problem of statins engendering diabetes for the past 4-5 years, have no clue for why it occurs, and that nothing has been done about it in the medical community or by the life science industry, is truly remarkable.
Finally the author of this blog and I have a history of working together for many years on theheart.org — as a journalist he should recuse himself of writing on this subject with clearcut evidence of bias.

 

 

Statins and Diabetes: Real Concern or Much Ado About Nothing? 6

Updated at 7 PM with a detailed comment at the bottom from C. Michael Minder of Johns Hopkins–

In New York Times Op-Ed piece on Monday, Eric Topol comments on last week’s announcement by the FDA that it was changing the label for statins. Topol focuses on the new warning that statins raise the risk of diabetes. He opens with a provocative statement:

We’re overdosing on cholesterol-lowering statins, and the consequence could be a sharp increase in the incidence of Type 2 diabetes.

Topol does the math and calculates that 20 million Americans taking statins equates to 100,000 new statin-induced diabetics:

Not a good thing for the public health and certainly not good for the individual affected with a new serious chronic illness… If there were a major suppression of heart attacks or strokes or deaths, that might be justified. But in patients who have never had heart disease and are taking statins to lower their risk (so-called primary prevention), the reduction of heart attacks and other major events is only 2 per 100. And we don’t know who the 2 per 100 patients are who benefit or the one per 200 who will get diabetes! Moreover, the margin of benefit to risk is quite narrow.

Topol then concludes that statins are beneficial for secondary prevention in people with a history of heart disease or stroke but for “the vast majority of people who take statins — those who have never had any heart disease — there should be a careful review of whether the statin is necessary, in light of the risk of diabetes and the relatively small benefit that can be derived.”
Click to continue reading…

FDA Revises the Safety Labeling of Statins 2

The FDA today announced important new changes to the safety language on the labels of statins:

Routine periodic monitoring of liver enzymes is no longer recommended. Serious liver injury associated with statins is “rare and unpredictable in individual patients” and “routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing this rare side effect,” according to the FDA.  The FDA now says that liver enzyme tests only need to be performed before starting statin therapy and “as clinically indicated thereafter.”

Memory loss and confusion will now be included in the label. But, the FDA notes, reports about the cognitive effects of statins have usually “not been serious and the patients’ symptoms were reversed by stopping the statin.” In a story published on Forbes, Matt Herper writes that the “new labeling will lead patients and doctors to take memory issues on the drugs more seriously, and it will also lead patients to link normal lapses of memory to their drugs.”

The increased risk of hyperglycemia and type 2 diabetes will be mentioned in the label. The label will now reflect data showing the small increased risk for type 2 diabetes in people taking statins.

The FDA is also making specific recommendations about lovastatin, noting that when used with some other drugs lovastatin can increase the risk of muscle injury.
Click here to read the press release from the FDA…