Op-Ed The Healthcare Channel
April 5, 2010
The New York Times recently ran a front-page story raising concern about expanding the indication for statins to people with normal cholesterol levels, per the Crestor JUPITER trial. The article mentioned the new data in Lancet that suggest a diabetes risk from taking statins and compared that risk to the low absolute benefit from the statins. As has become common practice in the mainstream media, Dr. Steve Nissen was interviewed and quoted in the article. Dr. Nissen has been paid by AstraZeneca, maker of Crestor, and many other drug companies, but states that the funds were donated to charity and that there were no tax deduction benefits to him.
In the Times article, Dr. Nissen expressed his unwavering support for prescribing statins to people with normal cholesterol levels. He stated the JUPITER trial results in terms of relative risk rather than the very modest absolute numbers. He was quoted, “I don’t understand the antipathy out there…If somebody comes into my office and meets the criteria, am I going to deny them a drug that reduces their chance of a heart attack or stroke by 40 or 50 percent?”
The Times then correctly pointed out, “But critics said the claim of cutting heart disease risk in half — repeated in news reports nationwide — may have misled some doctors and consumers because the patients were so healthy that they had little risk to begin with. The rate of heart attacks, for example, was 0.37 percent, or 68 patients out of 8,901 who took a sugar pill. Among the Crestor patients it was 0.17 percent, or 31 patients. That 55 percent relative difference between the two groups translates to only 0.2 percentage points in absolute terms — or 2 people out of 1,000. Stated another way, 500 people would need to be treated with Crestor for a year to avoid one usually survivable heart attack. Stroke numbers were similar. “
How could Steve Nissen, an expert on clinical trials and Chief of Cardiology at the Cleveland Clinic, have made the mistake of using the industry-preferred relative risk method of expressing Crestor’s benefit? How could he responsibly have omitted any mention of the health risks and costs associated with the expansion of statins into millions of more Americans? Was Dr. Nissen naïve or was he manipulating the media for a personal agenda?
In the Fall of 2009 at the AHA meeting, the big news was the ARBITER study that tested whether adding Abbott’s Niaspan or Merck’s Zetia to a base of statin therapy would improve atherosclerosis as measured by carotid artery wall thickness. The results were controversial because the study was stopped early, possibly inflating the benefits of Niaspan, and was too small to draw meaningful conclusions. The major press detailed the flaws of the study and an accompanying editorial in the New England Journal of Medicine explained the limitations as well.
Once again, the press interviewed Dr. Nissen about the ARBITER 6-HALTS trial despite his past conflicts with Merck. It is important to recall that Steve Nissen has been a thorn in the side to Merck, maker of the drug Zetia studied in the ARBITER trial. It was Dr. Nissen’s work that led to the demise of Merck’s Vioxx, and Dr. Nissen has been vocally critical of Zetia calling for a “moratorium” on the use of Zetia.
When interviewed about ARBITER, Dr. Nissen made little mention of the flaws rendering the trial meaningless to some experts, but emphasized the positive implications for Niaspan. In Theheart.org, Nissen actually praised the ARBITER study as “(Nissen) called ARBITER 6-HALTS a classic “comparative-effectiveness” study and said there have been calls in the US legislature for such trials for the past few years. “Now, here it is,” Nissen said. “Niacin is a 50-year-old drug, …niacin looks to be a better strategy.” In an interview with CNBC, Dr. Nissen defended the ARBITER study, “..this study was in fact well done…were there flaws?..no study is ever perfect…do we believe the results? Yes. The vast majority of us do believe these results”
It is not clear as to what Dr. Nissen was basing his statements given the ample data to suggest that many in the cardiology community, in fact, did not believe the results. The NEJM editorial by Dr. Blumenthal of Johns Hopkins wrote, “Unfortunately, the premature termination of the ARBITER 6–HALTS trial, the small number of patients studied, and the limited duration of follow-up preclude us from conclusively declaring niacin the adjunctive agent of choice on the basis of the evidence.”
How could Dr. Nissen fail to mention the egregious flaw of the ARBITER trial: that it was halted early for no compelling safety reason? Was Steve Nissen naïve again and incompetent when it comes to these basics of clinical trial design, or was he manipulating the mainstream press and pushing an agenda?
Perhaps Steve Nissen’s most controversial interaction with the media was on February 22 of this year when he gave a New York Times reporter exclusive access to audiotape recordings he secretly made while meeting with GlaxoSmithKline executives. Prior to releasing a damaging report Dr. Nissen had written showing an alleged safety risk with Glaxo’s drug Avandia, Dr. Nissen met with the executives to discuss the matter in 2007.
It is not clear what his objective was in speaking with the company prior to the imminent publication. What did he want from Glaxo? Was there a chance he would withhold the paper or change the conclusions? The Times quoted Nissen asking a Glaxo executive, “Now, what am I going to do? What is my responsibility? I mean, answer the question for me. Do I sit on it? Drug’s being used by how many people?” The NEJM, where the article was later published, has author guidelines prohibiting the discussion of a paper prior to publication. Dr. Nissen did not reply to our questions.
Why did Steve Nissen do such an unusual act of releasing Watergate-like secret tapes to a major paper in an effort to vilify a drug company, and why the timing: years after his NEJM paper? Nissen has clearly stated that he thinks Glaxo should pull Avandia from the market. In a CNBC interview, he said, “I think it’s time (to pull Avandia from the market)”. The problem for Dr. Nissen and his agenda is that the FDA convened an advisory committee and a panel of experts deemed that Avandia was safe enough to continue to be offered to patients currently taking the drug. The safety-oriented FDA officers made their concerns public at that meeting. There were no “silenced critics” within the FDA. Also, peer-reviewed articles have criticized the Nissen 2007 NEJM metanalysis for using poor methodology and being underpowered, making Nissen’s conclusions on safety inappropriate.
But why did Nissen choose late February 2010 to revive this Avandia controversy by giving secret tapes to the New York Times? One can only speculate, but a few days after the Nissen “Avandiagate” salvo in the media, the cardiology societies of The AHA and ACC jointly released the official guidelines on Avandia (rosiglitazone) for doctors and they did not recommend pulling the drug from the market. The guidelines are a lengthy report and were in the works for months with many doctors aware of them. Was Steve Nissen trying to frontrun this report in his effort to make his case that Avandia should be pulled from the market like Vioxx? Dr. Nissen did not reply to our questions.Share and Enjoy: