BMJ editor casts doubt on veracity of statin trials funded by the statin makers - Godlee

Statins for all over 50? No

Fiona Godlee, editor, BMJ

BMJ 2013; 347 doi: http://dx.doi.org/10.1136/bmj.f6412 (Published 23 October 2013)                                         Cite this as: BMJ 2013;347:f6412    

 

Should you prescribe statins to everyone over the age of 50, even those at low cardiovascular risk? A new Cochrane review seems to suggest that you should. An article in this week BMJ cries caution (doi:10.1136/bmj.f6123).

Current guidance from the UK’s National Institute for Health and Care Excellence (NICE) and the American Heart Association recommends statins only when the 10 year risk of cardiovascular disease is 20% or greater. But since these guidelines were written, a large meta-analysis of individual patient data reached a different conclusion. Published in the Lancet in 2012, the Cholesterol Treatment Trialists (CTT) Collaboration meta-analysis found that statins significantly reduced major cardiovascular events and all cause mortality in people at low risk, a benefit which, the paper said, “greatly exceeds any known hazards of statin therapy.”

As John Abramson and colleagues explain, it’s this meta-analysis that led the Cochrane reviewers to embrace the idea that statins should be used far more widely, even perhaps to everyone over 50, as a Lancet editorial suggested at the time.

But Abramson and colleagues’ detailed critique of the CTT meta-analysis should give us pause. Their own analysis of the data finds no evidence of a reduction in all cause mortality or in the total number of serious events. They also highlight the failure of the trials included in the CTT analysis to adequately report important harms of statin treatment, including myopathy and diabetes. They conclude that broadening the use of statins to low risk individuals “will unnecessarily increase the incidence of adverse events without providing overall health benefits.”

There is a concern underlying their critique that will be familiar to BMJ readers. It is that all of the trials included in the CTT meta-analysis were funded by the manufacturer of the statin being studied. They list the various ways in which these trials might have exaggerated the benefits of statins and minimised the harms, and they summarise what low risk patients need to know. Top of the list is the benefit of lifestyle change, something that the dominance of industry sponsored clinical trials too often obscures.

None of this does much to bolster confidence in the published literature. Nor am I reassured by discussions at two recent meetings co-hosted by the European Federation of Pharmaceutical Industry Associations (EFPIA). Drug company AbbVie is suing the European Medicines Agency to stop summary reports of its clinical trials becoming publicly available (doi:10.1136/bmj.f1636). AbbVie’s lawyer made clear that the company considers even the data on adverse events to be commercially confidential. Despite industry’s claims to be in favour of greater transparency, EFPIA and its American counterpart PhRMA are supporting Abbvie. The BMJ and BMA have joined forces to intervene on behalf of the EMA (doi:10.1136/bmj.f4728).

As for a way forward, I can’t improve on the list of solutions proposed by Richard Lehman when emailing out his journal review blog this week (http://bit.ly/HcKvjy): “All phase 3 trials to be designed and conducted independently of manufacturers, using the best available comparator. Research priorities to be determined by patients (James Lind Alliance). Value-based pricing. All data available from all trials, with meta-data: IPD [individual patient data] level for qualified independent centres. Big increase in comparative effectiveness research, much more research into non-pharmacological treatments.”

Notes

Cite this as: BMJ 2013;347:f6412

Footnotes

• Follow BMJ Editor Fiona Godlee on Twitter @fgodlee and the BMJ @bmj_latest

==================================================================================

Emphasis added.

Read the complete article here.

Scant Evidence That Salt Raises BP - Kaiser

Scant Evidence That Salt Raises BP, Review Finds

By Chris Kaiser, Cardiology Editor, MedPage Today  Published: December 04, 2012

 

The evidence for health benefits associated with salt reduction is controversial and the "concealment of scientific uncertainty" is a mistake, researchers suggested.

Controversy about what effect too much sodium intake has on the body goes back to the early part of the 20th century, according to Ronald Bayer, PhD, and colleagues from Columbia University Mailman School of Public Health in New York City.

But in the last few years, the discourse has reached a fever pitch, they wrote online in Health Affairs.

In 2011, for example, the Journal of the American Medical Association published a study by Stolarz-Skrzypek et al. that found only a weak correlation between salt and blood pressure. An editorial in the Lancet lambasted the JAMA study as "disappointingly weak" and "likely to confuse public perceptions of the importance of salt as a risk factor for high blood pressure, heart disease, and stroke."

Also in 2011, the Cochrane Review published two studies finding little or no relationship with all-cause mortality and salt reduction. The Lancet criticized both the Cochrane Library and the authors, saying, "They have seriously misled the press and thereby the public."

One of those reviews had concluded that "after more than 150 randomized controlled trials and 13 population studies without an obvious signal in favor of sodium reduction, another position could be to accept that such a signal may not exist."

Bayer and colleagues cited several studies that could not find a link between salt intake and elevated blood pressure, including a 1967 study of the Framingham cohort, and Japanese and Scottish reports in the 1980s totalling 15,000 people that concluded the association between sodium and blood pressure is "extremely weak."

The researchers noted that most of the evidence pointed to the weakest of correlations between salt and blood pressure. Yet, the cause to reduce salt was taken up by government agencies with special speed.

They cited a 2010 Institute of Medicine report called "Strategies to Reduce Sodium Intake in the United States." In the report, the IOM claimed that the "harmful relationship of salt with hypertension has been known for 40 years," which Bayer and colleagues argue is debatable -- based on the evidence.

"The [IOM] report was welcomed by the incoming president of the the American Society of Hypertension," the investigators wrote, "who warned that the 'outcomes mafia' might challenge the justification for a regulatory approach."

In 2011, the FDA also called for data and recommendations "that would help it shape regulatory policy on salt in food."

"All the while, skeptics still were asking for the evidence," Bayer and colleagues wrote.
More than 20 years prior to the IOM report, C. Everett Koop, MD, the U.S. Surgeon General, issued a report noting that government agencies were "very quick to embrace the importance of salt reduction in the 1970s and 1980s, which stood in stark contrast for the snail's pace of recommendations related to reducing blood cholesterol levels."

The authors cited many more studies finding little association between salt and blood pressure that did not eliminate the stigma attached to the mineral.

Advocates for salt reduction questioned the science behind studies that didn't conform to their opinion, and proponents partially blamed the food industry because it was in their best interest to muddy the waters and keep the debate going.

One of the interesting things about this debate, Bayer and colleagues pointed out, was that you could find respected academics on both sides.

"At the most fundamental level, we believe that it is essential to recognize the role that judgment and values must play in evidence-informed policy making," the authors concluded.

"Science must remain open, skeptical, and concerned about unmeasured confounding and selection bias in studies that accompany even the best efforts to articulate the evidence for new interventions," they added.

The investigators said that one of the reviewers of this paper had asked, "In the end, does the harm of exaggerating certainty do more harm than good? After all, it would be very hard to make any policy from a position of informed, complicated, contextualized ambivalence."

They concluded that the "concealment of scientific uncertainty is a mistake that serves neither the ends of science nor good policy. Simplistic pictures of translation from evidence to action distort our ability to understand how policy is, in fact, made and how it should be made."
==================================================================
Read the complete article here.

Another article here.

More data in the Salt Wars - Aug 14, 2014; http://www.medpagetoday.com/Cardiology/Hypertension/47203

An article by Marion Nestle - http://www.foodpolitics.com/2014/08/its-salt-arguments-again-new-research-arguments-over-public-health-recommendations-and-issues-of-conflicts-of-interest/