heartnews2007

Heart News 2007

The heart-related news has lately been a roller coaster of good, bad, and maybe not so bad. One popular prescription cholesterol-lowering statin drug might soon be sold over the counter. Defibrillators of the kind implanted years ago in Vice President Dick Cheney were in the news last month when studies showed they are more likely to be given to white men. But this needn’t be seen as yet-another example of women and minorities deprived of appropriate heart care. A new study showed that men with implanted defibrillators had a higher death rate than women with exactly the same heart condition who were not given implanted defibrillators.

And remember those drug-coated stents that scared heart patients over a year ago when it was announced that they increased the risk of potentially fatal blood clots long after they were inserted to prop open a constricted artery? Well, drug-coated stents made headlines again last month suggesting that they may not be so dangerous after all.

What do we make of all this?

For starters, an over-the-counter cholesterol-lowering drug might be a good idea for certain people. Not simply as a money-saver, but as a means of getting good-quality written drug information to the user. With a few exceptions, prescription drugs do not automatically come with FDA-approved printed information, though it comes tucked into the packaging of virtually all drugs sold over the counter.

We might be grasping at straws here, but mandated consumer drug information produced with FDA oversight is far better than the current situation. Then warnings like this about Lipitor—“tell your doctor if you have more than two drinks a day”—might actually reach the people who take the drug.

The prescription drug under consideration for over-the-counter status is Mevacor. That it is a statin drug and therefore a member of the top-selling drug class worldwide—$35 billion in annual sales—makes the switch all the more interesting. (Other statins are Lipitor, Crestor, Lescol, Pravachol, and Zocor.) Merck, the company that makes Mevacor, has recently applied to the FDA for permission to sell the drug over the counter. And an advisory committee of experts will decide the issue this month. (In 2005, an FDA Advisory Committee rejected a similar application for Mevacor.)

Two statin drugs Pravachol and Zocor are already available generically, which means that their patents have run out and now any company can produce these drugs under their generic names at a far lower cost than any brand-name statin. For example, Zocor, prescribed generically as simvastatin, costs from 75 cents to $1 a day at most retail drug stores and 10 cents a day, if purchased at a discount pharmacy like Costco’s. Lipitor, on the other hand, can cost $2.50 to $4 a day. From the FDA point of view, generic versions are equivalent to branded drugs because they must go through a process of proving that to the agency.

Many drug plans are encouraging members who take an expensive statin to switch to one of the generic versions with financial incentives like lower co-payments. And if Mevacor gets FDA approval for over-the-counter sale, statin users will have yet another low-cost alternative with the added feature of eliminating some doctor visit charges.

All this is cutting into the huge profits long enjoyed by Pfizer, the company that makes Lipitor, which is the most prescribed drug in the world. Naturally, the company wants to make as much money as possible before Lipitor loses its patent in March 2010. Consequently, Pfizer has escalated its long-running ad campaign featuring Dr. Robert Jarvik, inventor of the Jarvik artificial heart, who has been hugely successful in convincing many doctors and consumers that Lipitor is superior to other statins.

Currently, some of the Jarvik/Lipitor ads, say, “There’s a common misconception that all cholesterol-lowering medications are the same.” And more specifically, “In clinical studies LIPITOR lowered bad cholesterol significantly more than generic Zocor and Pravachol.”

Both points refer to a 2004 clinical trial that found people with heart disease showed a reduced degree of atherosclerosis progression if they were on high-dose Lipitor (80 mg) for 18 months, compared with those on a moderate dose of Pravachol (40 mg). There was also a greater reduction in LDL, or “bad” cholesterol, shown in the heart patients who took the high-dose Lipitor.

Three things to keep in mind about this trial, known by its acronym REVERSAL: Its participants all had heart disease (the overwhelming majority of U.S. statin-takers do not); REVERSAL was not designed to see whether Lipitor or Pravachol prevented heart attacks or strokes. And lastly, it compared a high-dose of Lipitor with a moderate-dose of Pravachol, leaving open the possibility that Pravachol at 80 mg might be just as good. Still, REVERSAL provides the basis for the Pfizer claim that Lipitor is not only better than other statins but it should also be prescribed in high doses for people with heart disease.

As for the most crucial goals of statin therapy: all statins, with the exception of Crestor, have been shown in clinical trials that predate REVERSAL to reduce the risk of heart attack and stroke in people who already have heart disease.

Healthy But High Risk

As for people without heart disease, the proven benefit of statins is largely confined to high-risk men between 30 and 69 years. The magnitude of this benefit, however, is not impressive—1.5% fewer of those taking a statin will suffer a non-fatal heart attack. But one analysis of all statin primary prevention trials showed that this 1.5% benefit was canceled out by an equivalent risk of experiencing a serious reaction to the statin.

The promotional activities of statin manufacturers have successfully focused most doctors and the general public on the excellent cholesterol-lowering effects of these drugs. But no head-to-head comparison study of all six statins has answered the most important-to-consumers questions: Which drug is best at preventing a heart attack or stroke? How large is the benefit?

There is a Jarvik/Lipitor print ad that answers the how-large-is-the-benefit question for high-risk people without heart disease. “In patients with multiple risk factors for heart disease, Lipitor reduces risk of heart attack by 36%* if you have risk factors such as family history, high blood pressure, age, low HDL (‘good’ cholesterol) or smoking.” In smaller print, the same ad has this explanation of “reduces risk” under the asterisk: “That means in a large clinical study, 3% of patients taking a sugar pill or placebo had a heart attack compared to 2% of patients taking Lipitor.” This ad is a rarity because it explains the 36% reduced risk. Take Lipitor for years and your risk of having a heart attack drops from 3% to 2%.

Lately, Pfizer has been trying to stem the exodus to generic statins by touting a new study that purportedly shows more heart attacks or strokes in people who switched from Lipitor to simvastatin, compared with those who stayed on Lipitor. There’s little reason to take this study too seriously.

First of all, Pfizer funded the study, and drug company-funded studies are notorious for coming up with conclusions that favor their products. Second, it was presented on a poster at a recent European cardiology conference, and has yet to be published or fully peer reviewed. (The New York Times, however, recently reported that this study has been accepted by the British Journal of Cardiology and will soon be published.) Lastly, the study is based on an analysis of medical records of British heart patients who did or did not switch from Lipitor to the generic version of Zocor (simvastatin). The study’s design is not regarded as high quality; in fact the authors describe its limitations this way: “This is an observational database study, and as such has recognizable limitations; therefore the findings should be regarded as hypothesis-generating.”

NB: There’s a consensus among cardiologists that statins are generally safe and are extensively studied. Perhaps they are, but three of the five major primary prevention randomized trials have not released all of their statistics on serious adverse reactions, according to James Wright, MD, and John Abramson, MD, who co-authored a commentary early this year in The Lancet, entitled “Are Lipid-Lowering Guidelines Evidence-Based?” The full story about the safety of statin drugs is unknown.

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NEWS ABOUT DEFIBRILLATORS

An unexpected finding showed up when a team of Duke University researchers tracked elderly people with heart failure who did and did not have defibrillators implanted to prevent sudden death. Those who had a defibrillator implanted lived no longer than those who did not. That was the contrary-to-expectations finding 180 days after implantation.

But when these heart patients were followed longer, the results were worse for the men. Their mortality rate in the year after implantation was higher than that of women without defibrillators, though all had similar heart problems. To take into account the fact that women live longer than men, Leslie H. Curtis, PhD, and colleagues at Duke University School of Medicine, confined their study to men and women under the age of 75 years.

Their new findings come at a time when implantable defibrillators are, once again, in the news for having serious defects that have caused a few deaths. These devices monitor the patient’s heart rhythm and deliver an electric shock once dangerously erratic rhythms are detected.

The Duke researchers analyzed a national 5% sample of the Medicare claims filed for more than 35,000 people from 1991 through 2005. All had been diagnosed with heart attack and either heart failure or cardiomyopathy. Men were three times more likely than women to have the device implanted. Of those with heart disease but no prior cardiac arrest or tachycardia (rapid heartbeat), defibrillators were implanted in 32 per 1,000 men and about 9 per 1,000 women.

The gap between man and women didn’t close for the most seriously ill patients—those with prior cardiac arrest or tachycardia. For this group, the implanted defibrillator rate was 102 per 1,000 men and 38 per 1,000 women.

A related study, published in the same October 3 issue of the Journal of the American Medical Association, found that black men and women were also less likely to have a defibrillator implanted than white men.

“The bad news may not be for women and minorities, but for white men who are undergoing a procedure that for primary prevention does not extend their lives,” wrote Rita F. Redberg, MD, in an editorial that accompanied the two studies.

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NEWS ABOUT DRUG-COATED STENTS

The bad news about this topic originally came from the World Congress of Cardiology in September 2006. Presented at this international conference were clinical trials that found a slightly increased risk of death and a higher rate of potentially fatal blood clots in people who had drug-coated stents implanted during a coronary-artery-opening procedure called angioplasty. The trials compared them with other heart patients whose constricted coronary arteries were propped open with stents not coated with a drug.

The higher risks among those given drug-coated stents did not show up until four years of follow-up. These complications were confirmed in two separate analyses of the combined results of company-sponsored trials by Boston Scientific, maker of the Taxus stent, or Johnson & Johnson, maker of the Cypher stent. The medicine coating these stents is intended to keep the constricted arteries from closing up again.

Last month the national media reported good news about drug-coated stents from the annual meeting of the American Heart Association in Orlando, Florida. Two-year follow-up results from a new, yet-to-be-published clinical trial showed that drug-coated stents are no more risky than bare-metal stents. Some media reports left the impression that the issue of stent safety had been resolved with this trial. “Heart Stent Gets a Reprieve From Doctors” was the over-the-top New York Times headline.

Keep in mind that the new trial announced at the heart meeting lasted only two years and the blood clots in the above-mentioned company-sponsored trials did not show up until four years. More details will be available when the new trial is published in Circulation, the journal of the American Heart Association, according to a “Late-Breaking News Release” from the heart meeting.

The meeting organizers managed to focus the media on stents rather than the more critical issue—overuse of artery-opening procedures. Many of the one million or so Americans who undergo angioplasty each year (with or without stents) can be treated just as successfully with drug therapy. It is generally the same multiple drug therapy advised for everyone who undergoes angioplasty. This was proven in a government-sponsored study called the Occluded Artery Trial, or OAT, published last year in The New England Journal of Medicine. A follow-up analysis of the OAT results was presented at the American Heart Association meeting. Yet no mainstream media reported the new OAT analysis, according to Health News Review, a medical media watchdog group led by journalist Gary Schwitzer.

All 2,166 OAT participants had a totally blocked major coronary artery and were 3 to 38 days away from suffering a heart attack. All were randomly assigned to receive an artery-opening procedure plus drug therapy or drug therapy alone. The multiple-drug therapy included daily aspirin, beta-blockers, ACE inhibitors and cholesterol-lowering drugs.

After four years, the OAT participants in the angioplasty/drugs group had the same rate of survival, second heart attack, and heart failure as the group given drug therapy alone. When the 469 American OAT participants were singled out (this was an international trial), the angioplasty-treated heart patients generated costs that were $10,000 higher than the drug-treated people. After three years, the cost difference had dropped to $7,000.

In an editorial that accompanied the OAT findings last year in The New England Journal of Medicine, L. David Hillis, MD, and Richard A. Lange, MD, wrote, “The open-artery hypothesis, although not previously validated in a prospective, randomized study, has nonetheless been embraced by many practicing physicians.” Translation: Heart surgeons have been opening constricted coronary arteries for years on the unproven premise that this will save lives and reduce the risk of a future heart attack. The OAT results failed to validate that hypothesis.

Opening a blocked artery during or right after a heart attack has been proven beneficial, but the OAT results showed no benefit to the common practice of performing angioplasty well after the patient had been stabilized—3 to 38 days after suffering a heart attack.