Thursday, August 14, 2014

More SALT Controversy - Nestle

It’s salt war time again: new research, arguments over public health recommendations, and issues of conflicts of interest

Here are the burning questions about sodium (which is 40% of salt) intake:
(a) Does too much dietary sodium cause high blood pressure?   Answer: an unambiguous yes (although not necessarily in everyone).
(b) Are public health recommendations to reduce salt intake warranted?  I think so, but others disagree.
(c) If so, to what level?  Although virtually all committees reviewing the evidence on salt and hypertension view public health recommendations as warranted, and advise an upper limit of about 2 grams of sodium (5 grams of salt, a bit more than a teaspoon (see table from the Wall Street Journal), these too are under debate.

These recommendations are strongly opposed by The Salt Institute, the trade association for the salt industry, its industry supporters, and some groups of investigators.
Now the New England Journal of Medicine weighs in with three new studies, an editorial, and a cartoon video.  The papers:
Start with the video,  narrated by the editor, Dr. Jeffrey Drazen (click on video link on the right side).  It gives an excellent summary of the three papers.  Despite their methodological differences, all confirm (a).  They disagree on (c) and, therefore, (b).

Are public health recommendations warranted?
But note Dr. Drazen’s suggestion: “throw away the salt shaker.”
He is in favor of reducing salt intake.  But the salt shaker is not where most dietary salt comes from.  At least 75% of salt in American diets comes from restaurant and processed foods.   As Dr. Yoni Freedhoff explains:
If you’d like to reduce the sodium in your diet, rather than keep a running tally of how much you’re actually consuming, why not try instead to determine what percentage of your diet comes from restaurants and boxes? Sure, there’s data to suggest you might simply find other ways to add salt to your diet. But visit restaurants and consume processed foods less frequently, and I’d be willing to wager that you’ll be far more likely to see health benefits than were you to simply fill your grocery cart with low-sodium versions of highly processed foods.
Individuals cannot cut down on salt on their own.  That’s one reason why public health policies are needed—to get restaurants and processed food manufacturers to reduce salt content.
Two of the papers say that the only people who need to cut down on salt are those with hypertension and older people (one of the studies says that means people over age 55).
You can’t expect 70 or 80 million people to reduce salt intake on their own.  Hence: public health recommendations.

Conflict of interest alert
Some of the investigators report receiving grants or fees from companies that make anti-hypertensive drugs but the editorial accompanying the papers is of special concern.   Written by Dr. Suzanne Oparil, it says about one of the studies:
These provocative findings beg for a randomized, controlled outcome trial to compare reduced sodium intake with usual diet. In the absence of such a trial, the results argue against reduction of dietary sodium as an isolated public health recommendation.
These conclusions sent me right to her conflict-of-interest disclosure statement.  Although Dr. Oparil reports receiving grants or fees from companies making anti-hypertensive drugs—-and, even more remarkable, from The Salt Institute—she states that she has no conflicts of interest.
I think she does.

Her editorial is especially unfortunate because it influences the way reporters write about the studies.
The Associated Press account, for example, begins:
A large international study questions the conventional wisdom that most people should cut back on salt, suggesting that the amount most folks consume is OK for heart health — and too little may be as bad as too much. The findings came under immediate attack by other scientists.
As well they should.  Blood pressure rises with age and huge swaths of the population would be healthier eating less salt.   The AP reporter quoted me saying so:
“People don’t eat salt, they eat food,” she said. “Lots of people have high blood pressure and lots of people are getting older,” making salt a growing concern, she said. “That’s the context in which this is taking place.”
The three studies are complicated to interpret because of differences in methods and discrepancies in outcomes.  They agree that if you already have hypertension or are “elderly,” or eat a lot of salt, you should cut down.

This seems like a good idea for just about anyone.   People don’t eat salt; they eat foods containing salt, and foods high in salt tend to be high in other things best consumed in small amounts.
The studies also talk about the protective effects of potassium, best obtained from vegetables.
Eat a lot of vegetables and not too much junk food, and you don’t have to worry about any of this.
Read the complete article here.

Wednesday, August 6, 2014

The Lancet published a meta-analysis of 27 statin trials

Data, Drugs, and Deception: a True Story

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 the Archives of Internal Medicine, and with analyses from two equally respected publications, the Therapeutics 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.

But LDL drop cannot be predicted. Some won’t drop at all, some will drop just a bit, and some may drop more. Therefore the numbers here tell an interesting story about certain patients who took statins, but they have no relevance to patients and doctors considering statins. And yet, the latter group is the target of the study's concusions.

True story: in prior meta-analyses that found no mortality benefit the investigators simply looked at studies of patients without heart disease and compared mortality between the statin groups and the placebo groups. No machinations, no acrobatics, no per-unit-cholesterol. They took a Joe Friday approach (just the facts, ma’am), and found no mortality benefit.

Perhaps never has a statistical deception been so cleverly buried, in plain sight. The study answers this question: how much did the people who responded well to the drug benefit? This is, by definition, a circular and retrospective question: revisiting old data and re-tailoring the question to arrive at a conclusion. And to be fair they may have answered an interesting, and in some ways contributory, question. However the authors’ conclusions imply that they answered a different, much bigger question. And that is not a true story.

Guideline writers, doctors, patients, journalists, and policy makers will all have to pay close attention to avoid the trappings of deceptive data, dressed up as a true story.

*The Cochrane Collaboration analysis reports an overall mortality benefit with statins (RR=0.86), however their summary suggests that statins should be used for primary prevention “with caution.” In particular on p.12, after a discussion of the biases in many of the trials that led to their numerical finding, they clearly state that using statins for patients with anything less than a 2% per year risk of coronary events “is not supported by existing evidence.” This cutoff encompasses virtually all people that would be considered candidates for primary prevention.

Read the complete article here.

Sunday, August 3, 2014

Thousands of Women in Lipitor diabetes Lawsuit - Liebhard

Thousands of Women in Lipitor Lawsuit Claims to Join South Carolina Litigation, Status Report Shows

Published on June 16, 2014 by Sandy Liebhard 
More than a hundred cases filed by some 3,000 female Lipitor lawsuit plaintiffs will soon join the federal diabetes drug litigation in the U.S. District Court, District of South Carolina, according to court documents.

A status report recently submitted by parties involved in the federal litigation indicates that 134 cases alleging new-onset Type 2 diabetes will be transferred to the multidistrict litigation in the coming weeks, on behalf of 3,000 plaintiffs.

According to Lipitor lawsuits included in the soon-to-be transferred claims, use of the cholesterol medication, may increase a woman’s likelihood of developing Type 2 diabetes, which its manufacturer allegedly knew about but concealed from the public. Lipitor diabetes lawsuits included in the federal proceeding, which was created by the U.S. Judicial Panel on Multidistrict Litigation (JPML) less than six months ago, include similar actions against Pfizer Inc. that accuse the company of marketing a product that was designed defectively.

A Case List updated June 16th by the JPML also shows a continued increase in the number of Lipitor lawsuits filed in South Carolina federal court. An update posted that day reflects 846 cases now pending in the federal litigation, which held its most recent status conference on June 13th. A month earlier, a total of 703 claims had been filed in South Carolina.

More than 840 Claims Now Filed in Lipitor Diabetes Litigation

Lipitor is a medication approved by the U.S. Food and Drug Administration (FDA) to help lower cholesterol levels in individuals who may be at an increased risk for strokes and heart attacks.
Since entering the market in 1996, the FDA issued a mandate in February 2012 that required Pfizer to adjust Lipitor’s labeling to include its possible association with Type 2 diabetes.  This action was prompted by research published a month earlier in JAMA: Internal Medicine that found post-menopausal women at an increased risk for developing the disease. In May 2013, results of a study published in the British Medical Journal showed a 22 percent increased risk for Type 2 diabetes in patients taking atorvastatin, the generic version of Lipitor.
Read the complete article here.


Pfizer confronts surge of lawsuits over Lipitor

Fri Aug 8, 2014 1:22am EDT

Saturday, August 2, 2014

British Medical Journal acted correctly in controversy over statins

British Medical Journal acted correctly in controversy over statins

Articles containing mistaken fears over side effects of heart drugs did not need to be retracted, says independent panel
Statin pills
An independent expert panel has found that the British Medical Journal did not need to retract two articles with erroneous fears about the side-effects of statins. Photograph: Alamy
The British Medical Journal, which withdrew erroneous statements about the side-effects of statins, did not need to retract the two articles that contained them, an independent expert panel commissioned by the journal has ruled.

The panel, headed by Dr Iona Heath, former chair of the BMJ's ethics committee and of the Royal College of GPs, was asked by the editor to investigate following complaints from Professor Sir Rory Collins, co-director of Oxford University's Clinical Trial Service Unit which collates data on statins trials.

Collins called for the two articles to be retracted in their entirety, saying that they would otherwise be reprinted and mislead the public into believing statins were not as safe as the evidence shows.
After a two-month review, the panel has advised the BMJ that its handling of the two articles was appropriate and that its processes were timely and reasonable, said the journal. The panel made suggestions where improvements could be made to some of the BMJ's editorial processes and the journal will act on these recommendations, it said.

One of the articles was written by Professor John Abramson, a clinical instructor at Harvard medical school, and colleagues. The other was an opinion piece by London cardiologist, Aseem Malhotra. Both questioned the value of extending the use of statins to healthy people at low risk of heart disease and included the same incorrect statistic from a published study.

Collins and other eminent scientists say the evidence for the safety of statins, even at people with a low risk of heart attack or stroke, is very clear from the many clinical trials that have been done. They are concerned that a mistaken fear of side-effects will put people off taking drugs that could prevent heart attacks or strokes.

The BMJ has reflected the concern of many patients and GPs about the "medicalisation" of the population following a recommendation from Nice, the National Institute for Health and Care Excellence, that would lead to millions more apparently healthy people in mid-life being offered the drugs by their GP. The journal has called for all the trial data to be made public.

Collins warned that without retraction "patients and their doctors will continue to be misinformed. It seems likely, therefore, that many patients – including those at high risk of heart attacks and strokes – may well stop taking their statin therapy or will not start it, which would lead to unnecessary heart attacks and strokes".

The trials showed that around five people in every 1,000 suffered adverse events because of statins – mostly a slightly earlier diagnosis of diabetes and more rarely muscle problems. Among low risk patents, 30 to 50 per 1000 on statins would avoid heart attacks and strokes, he said.

"This has been a challenging time for the BMJ but I am very pleased the panel has taken the view that we acted appropriately," said BMJ editor in chief, Dr Fiona Godlee.

"I echo the panel's call for the individual patient data from the statins trials be made available for independent scrutiny. Patients and their doctors need access to all relevant information to make informed decisions about their health. Extending statins to healthy people is a topical issue of wide public interest and we will continue to cover the debate from all sides."
Read the complete article here.