February 22, 2010

The Avandia beatup

I would normally cover this on my FOOD & HEALTH SKEPTIC blog but as it seems to be part of a political war against the drug companies designed to shore up support for Obamacare, I am covering it here. It is a huge crock, as I will point out at the foot of the article below. Politicians faulting the super-cautious FDA on drug safety really is a laugh

A Senate report that revives concerns about a GlaxoSmithKline PLC diabetes drug's link to heart attacks is putting pressure on the Food and Drug Administration to make changes to its drug-safety program. People familiar with the situation say agency leaders held calls over the weekend to discuss how to address complaints from Sens. Max Baucus (D., Mont.) and Chuck Grassley (R., Iowa), who released a new report Saturday on the Glaxo drug, called Avandia.

The FDA is trying to assemble a timeline of what the FDA knew of risks associated with Avandia, these people say, and plans to call a meeting of an outside advisory committee in the next few months to look at recent information on the drug, which Glaxo reported as having global sales of o771 million ($1.2 billion) in 2009.

According to a two-year investigation by the Senate Finance Committee, Glaxo knew about data linking Avandia to elevated risk of cardiovascular events for several years, but played down the information and tried to suppress doctors who raised concerns. Starting in 1999, Glaxo executives complained to superiors about researchers who questioned Avandia's safety, the report says.

Glaxo rejected those conclusions. It said in a statement that the increased risk of heart attacks hasn't been proven and noted that the FDA "has ruled that Avandia remain available." The company says it never tried to suppress doctors' views but sought to correct what it considered misinformation.

Internal FDA reviews included in the Senate report show that in 2008, longtime FDA scientists David Graham and Kate Gelperin urged the FDA to get Avandia off the market. They analyzed data on side effects in dozens of Avandia studies, but their recommendations were rejected by FDA chiefs. The senators want to know why.

Avandia is still on the market, but it has a strong warning label about cardiac risks. Its sales dropped after a widely publicized study in May 2007 by the Cleveland Clinic's Steven Nissen that linked Avandia to a 43% greater risk for heart attack.

More HERE

Below is a meta-analysis of the data upon which the FDA based its decision. The meta-analysis appeared in the prestigious "Journal of the American Medical Association"

Long-term Risk of Cardiovascular Events With Rosiglitazone: A Meta-analysis

By Sonal Singh et al.

Context: Recent reports of serious adverse events with rosiglitazone use have raised questions about whether the evidence of harm justifies its use for treatment of type 2 diabetes.

Objective: To systematically review the long-term cardiovascular risks of rosiglitazone, including myocardial infarction, heart failure, and cardiovascular mortality.

Data Sources: We searched MEDLINE, the GlaxoSmithKline clinical trials register, the US Food and Drug Administration Web site, and product information sheets for randomized controlled trials, systematic reviews, and meta-analyses published in English through May 2007.

Study Selection: Studies were selected for inclusion if they were randomized controlled trials of rosiglitazone for prevention or treatment of type 2 diabetes, had at least 12 months of follow-up, and monitored cardiovascular adverse events and provided numerical data on all adverse events. Four studies were included after detailed screening of 140 trials for cardiovascular events.

Data Extraction: Relative risks (RRs) of myocardial infarction, heart failure, and cardiovascular mortality were estimated using a fixed-effects meta-analysis of 4 randomized controlled trials (n = 14 291, including 6421 receiving rosiglitazone and 7870 receiving control therapy, with a duration of follow-up of 1-4 years).

Results: Rosiglitazone significantly increased the risk of myocardial infarction (n = 94/6421 vs 83/7870; RR, 1.42; 95% confidence interval [CI], 1.06-1.91; P = .02) and heart failure (n = 102/6421 vs 62/7870; RR, 2.09; 95% CI, 1.52-2.88; P < .001) without a significant increase in risk of cardiovascular mortality (n = 59/6421 vs 72/7870; RR, 0.90; 95% CI, 0.63-1.26; P = .53). There was no evidence of substantial heterogeneity among the trials for these end points (I2 = 0% for myocardial infarction, 18% for heart failure, and 0% for cardiovascular mortality).

Conclusion: Among patients with impaired glucose tolerance or type 2 diabetes, rosiglitazone use for at least 12 months is associated with a significantly increased risk of myocardial infarction and heart failure, without a significantly increased risk of cardiovascular mortality.

JAMA Vol. 298 No. 10, 1189-1195, September 12, 2007

In other words, a survey of the strongest data available showed that taking Avandia increased your risk of having a heart attack from 1.05% to 1.46%, an increase in risk of less than one half of one percent -- which is vanishingly trivial compared to the risks we take in most things we do. Given the large sample size, however, the result is statistically significant, if not significant in any other sense. If we were to reject such small risks as that we would have NO drugs on the market because all drugs have some adverse side-effects.

But here's the real kicker. Read the last clause in the abstract above. What it means in plain English is this: Although Avandia takers had a minutely greater risk of having heart attacks, the "extra" heart attacks DID NOT KILL THEM. Avandia takers were no more likely to die from a heart attack than anybody else! And THAT is the drug that is so evil that the Senate Democrats are making a huge fuss about it! It's just the usual search for evil in the world about them that IS Leftism.

Update

Grassley is a Republican but he was an easy target to get sucked into this affair as he has in the past made something of a career of exposing researchers who had failed to declare payments received from drug companies. His interest is clearly in the possibility of corruption rather than in the science.



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