Nissen Urges Prompt Revision Of Cardiovascular Guidelines Reply

Sparked by a new study that once again finds serious flaws in the cardiovascular risk calculator at the heart of the American College of Cardiology/American Heart Association cardiovascular guidelines, Steve Nissen states that “the ACC and AHA should promptly revise the guidelines to address the criticisms offered by independent authorities.” The CV risk calculator is a key component of the guidelines, since people are generally considered candidates for statins if they have a 10-year estimated risk of CV disease of 7.5% or higher according to the equations used by the calculator.

In a study published in JAMA Internal MedicineNancy Cook and Paul Ridker, analyzing data from the Women’s Health Study, offer fresh evidence that the cardiovascular risk calculator used in the ACC/AHA cholesterol guideline is flawed. They found that the predicted rate of cardiovascular disease using the guideline calculator was significantly higher than the actual observed rate in the trial. They considered and ruled out several “alternative explanations” for the discrepancy, including underascertainment of events and the increased use of statins and revascularization procedures in their population.

Click here to read the full post on Forbes.


Cholesterol Drugs Haunted By Ghosts Of Past, Present, And Future Reply

Cholesterol drugs, both new and old, are in the news again. There’s a lot going on now but the picture won’t really become clear until next month, when the results of a decade-old trial will finally be revealed. Briefly, here’s what’s happening:

  • Two new trials presented fresh evidence that PCSK9s, the much discussed new class of cholesterol drugs, have powerful LDL-lowering properties.
  • A new drug from Esperion, the phoenix of biotech companies, also showed promising results. The drug, ETC-1002, is a few years behind the PCSK9s in development but has some important theoretical advantages that may prove very important down the road.
  • At the annual meeting of the American Heart Association in November the results of the IMPROVE-IT trial will be presented. The results of this trial, as I have argued in the past, may have a broad if not decisive impact on the future of the PCSK9s and ETC-1002.


Click here to read the full post on Forbes.


Cheaper Generic Statins Beat Brand-Name Statins in Adherence and Outcomes Reply

A large observational study finds that people who received a prescription for a generic statin were more likely to take their pills than people who received a prescription for a brand-name statin. This increased adherence appeared to lead to a small but significant improvement in outcomes.

Click here to read the full post on Forbes.


FDA Advisory Panel Offers Cautious Support For Polypill Reply

The controversial polypill took one step closer to reaching the US market after receiving a mostly positive reception from the FDA’s Cardiovascular and Renal Drugs Advisory Committee on Wednesday. The idea for the polypill– which in this case would be composed of aspirin, a statin, and one or more blood pressure drugs– has been kicking around for more than a decade and has attracted considerable doses of support as well as skepticism.

An all-star group of cardiology leaders– including Sir Nicholas Wald, Salim Yusuf, Suzanne Oparil, Sidney Smith, and Clyde Yancy– helped provide the spoonful of sugar that helped the committee swallow the polypill. The FDA also eased the way by limiting the discussion to the use of the polypill for secondary prevention in people who have already had a MI or a stroke.

Click here to read the full post on Forbes.


Statins And Diabetes: A Clearer Picture Emerges 1

In recent years, the medical community has become increasingly aware that taking statins can result in slightly higher glucose levels, and this can lead to a diagnosis of diabetes in a small but statistically significant number of people. But it has been unclear whether the diagnosis of diabetes in people taking statins also places them at increased risk for the microvascular complications linked to diabetes. Now, an observational study published in the Lancet Diabetes & Endocrinology finds that among people newly diagnosed with diabetes, statin users are less likely than nonusers to develop most of these complications. (The beneficial effects of statins in reducing macrovascular complications — cardiovascular disease — in diabetics and others is well established in people at high risk for these events.) 

Danish researchers examined the rate of microvascular outcomes in more than 15,000 statin users who developed diabetes and 47,000 nonusers of statins who developed diabetes.

Click here to read the full post on Forbes.


Why Guidelines Should Be Waged Like War 1

Here’s a modest proposal: we need fewer and shorter guidelines. In fact, I’d like to propose that guidelines, like war, should be waged only when there is absolute consensus and overwhelming evidence.

Anyone interested in the subject is aware that guidelines are in a complete mess.

Click here to read the full post on Forbes.

United Nations Security Council Resolution 707

United Nations Security Council Resolution 707 (Photo credit: Wikipedia)


No Retraction For You! Review Panel Exonerates Medical Journal In Statin Kerfuffle Reply

An independent review panel has rejected a demand by a prominent researcher that TheBMJ retract two controversial articles. The report largely exonerates the journal’s editors from any wrongdoing.

As previously reported, Rory Collins, a prominent researcher and head of the Cholesterol Treatment Trialists’ (CTT) Collaboration, had demanded that TheBMJ retract two articles that were highly critical of statins. Although TheBMJ issued a correction for both papers for inaccurately citing an earlier publication and therefore overstating the incidence of adverse effects of statins, this response did not satisfy Collins. He repeatedly demanded that the journal issue a full retraction of the articles, prompting TheBMJ’s editor-in-chief, Fiona Godlee, to convene an outside panel of experts to review the problem.

The report of the independent statins review panel exonerates TheBMJ from wrongdoing and said the controversial articles should not be retracted:

Click here to read the full post on Forbes.


Guideline Critics Shift Attacks From Beta Blockers To Statins Reply

With the release today of updated European and US guidelines the ongoing controversy regarding beta-blockers appears to be resolved. But that doesn’t necessarily mean there will be an outbreak of guideline peace and harmony. The critics who helped ignite the controversy over beta blockers now say new statin recommendations contained in the guidelines are based on deeply flawed evidence.

Both the new European and US guidelines say that preoperative initiation of statin therapy may be considered in patients undergoing vascular surgery and that people already taking statins should continue taking them. Now some of the same critics who attacked the reliability of the beta blocker guideline say that this recommendation is not supported by the evidence.

Click here to read the full post on Forbes.




BMJ Names Panel Members To Review Disputed Statin Articles Reply

The BMJ has released the names of an outside expert panel who will decide the fate of two articles that are the subject of a heated dispute.

As previously reported, last week the BMJ published a correction to two papers published last year, explaining that both papers had  inaccurately overstated the incidence of the adverse effects of statins. However, a fierce critic of the papers, the head of the Cholesterol Treatment Trialists’ (CTT) Collaboration, Rory Collins, still insisted upon a full retraction. In an editorial published in BMJ, the journal’s editor-in-chief, Fiona Godlee, wrote that she was  uncertain “whether the error is sufficient for retraction, given that the incorrect statements were in each case secondary to the article’s primary focus.” As a result the BMJ has convened an outside panel of experts “with no dog in this fight.”

Iona Heath, former chair of the Royal College of General Practitioners and of The BMJ’s ethics committee, will be the chair of the panel. There are six additional members…

Click here to read the full post on Forbes.


Disappointing Results For Statins In Two NIH Trials Reply

Two NHLBI studies have failed to find any benefit for statin therapy in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). Previous observational studies had raised the possibility that statins, perhaps due to their anti-inflammatory effects, might improve outcomes in people with these serious diseases. But both trials were stopped early by their data and safety monitoring boards for futility. The results of the trials were presented at the annual meeting of the American Thoracic Society and published simultaneously in the New England Journal of Medicine.

Click here to read the entire post on Forbes.


BMJ Articles Critical Of Statins Provoke Kerfuffle Reply

The authors of two BMJ articles have withdrawn statements about the adverse effects of statins. The two papers inaccurately cite an earlier publication and therefore overstate the incidence of adverse effects of statins. As a result, the two papers have drawn much criticism and set off a kerfuffle involving the editor of BMJ and a prominent British trialist who is demanding a full retraction of the articles. But the controversy probably won’t be resolved any time soon, since an independent panel, which will be asked to decide the issue, is still in the process of being assembled.

Click here to read the entire post on Forbes.


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.


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 ( 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


  • 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…