Drugs Are For Sick People

March 16, 2010 – 8:50 am
Matthew HerperBio |
Matthew Herper is a senior editor at Forbes

ATLANTA – The big takeaway from this year’s annual confab of the American College of Cardiology is that there are limits to what medicines can do in people who are relatively healthy.

The National Institutes of Health’s $300 million Accord trial in diabetics tested aggressively lowering blood sugar, high blood pressure, and triglycerides compared to just doing what doctors do now, and in every case found the aggressive approach was worse.

The blood sugar part of the study had to be stopped two years ago because patients in the aggressive arm of the study were dying sooner. Using lots of blood pressure drugs may have reduced strokes, but did not affect deaths or other heart problems. The verdict is that pushing blood pressure all the way back down to a perfect 120/80 millimeters of mercury might not be as good as pushing it down to 130 mm Hg.

And adding Abbott Laboratories’ TriCor to a cholesterol-lowering statin drug didn’t have a single statistically significant benefit. Steven Nissen of the Cleveland Clinic and Douglas Weaver of Henry Ford Hospital in Detroit both think doctors should stop using TriCor now that there is no evidence; Sidney Smith of the University of North Carolina, Chapel Hill, argues that use that matches current guidelines is still OK.

Then there was a trial testing the Novartis drugs Starlix and Diovan in people whose high blood sugar levels made them look like sitting ducks for full-blown diabetes. Starlix is a mega-flop Novartis introduced to lower blood sugar a decade ago. Sales are so low analysts don’t track the drug. Diovan is a blockbuster hypertension pill. Starlix actually increased the number of patients who developed diabetes. Diovan prevented diabetes, but failed to have the expected benefits on heart attacks and strokes.

The whole idea of preventing diabetes is “a sleight of hand by pharmaceutical sponsors,” argues James Stein, a cardiologist at the University of Wisconsin-Madison. There’s no difference between a diabetic on a diabetes drug and a pre-diabetic on a diabetes drug, he argues, unless you can show long-term benefits that outweigh the very serious short-term side effects that all of these medicines have.

Cardiology is the blockbuster market that made the drug industry. The two top-selling drugs in the world – the cholesterol-lowerer Lipitor and the blood thinner Plavix – are heart drugs. For two decades, researchers have been finding that their drugs work in ever larger, and relatively healthier, people. This culminated with a trial of AstraZeneca’s Crestor that found that in people who had normal cholesterol levels but other risk factors, a cholesterol-lowering statin drug could save lives.

But statin drugs like Crestor and Lipitor started out in tests for very sick people. When Merck’s Zocor was first shown to save lives, it was in people with high cholesterol who were really at high risk. It’s really only pure luck that the statins turned out to be the rare drug that lowers just about anybody’s heart attack risk by 30%. Blood pressure can get too low. If TriCor lowers heart risk (and nobody has proven it does), it only does so in people who have both high triglycerides and low cholesterol. Blood thinners like Plavix? Take too little, you have a heart attack; too much, you bleed.

“I just think we’re making mistakes when we say treat until proven otherwise,” says Yale University’s Harlan Krumholz. Just because low blood pressure is good doesn’t mean lowering blood pressure is good – it’s good up to a point. He argues that doctors are “programmed to think deterministically” but don’t think enough about the way the small side effects of many drugs can add up to mute their benefits.

All this creates a giant problem for drug companies. They’ve become accustomed to the sales of statins as they are now, after their benefit was widely proven, not to the niche drugs they started out with. But new drugs to find added benefit are requiring gigantic and expensive clinical trials of tens of thousands of cardiovascular patients. All the but the biggest pharmaceutical firms can’t afford this. Even giants like Pfizer and AstraZeneca have backed off of cardiology drug discovery. Pharma’s response has been to find small groups of very sick people for whom they can charge a lot of money. Successful new medicines increasingly tend to launch with an annual price of $100,000 per patient per year.

The next crop of cardiology drugs – including blood thinners to prevent stroke, drugs to remove artery plaque, and medicines that reduce artery inflammation – are being tested in these gigantic studies without more than a hunch that they’ll work. If they fail, new heart treatments may have to wait until they can be genetically targeted to small populations that can really benefit. And one of the drug industry’s biggest cash cows will be put out to pasture.

Sourced and published by Henry Sapiecha 23rd March 2010

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