It wasn't long ago that coronary disease was the scourge of middle-aged men, and sudden coronary death a dominant widow maker. As a young physician, I saw early coronary care units that looked more like MASH units: Half of those with heart attacks died before they got to the hospital, and a quarter of the ones who crashed through its doors never made it out alive. Many a man or woman lucky enough to survive went home a cardiac cripple, burdened by chest pain, heart failure, and a fear of dying from the next attack. It is one of the greatest feats in medical history that the disease called coronary atherosclerosis, which erodes and clogs up our heart's normally pristine arteries, has been transformed into an everyday, manageable problem for most patients. Yes, a good part of the credit goes to our ability to limit damage during early heart attacks and to restore the heart's blood supply with surgery or stents. But equally powerful is the acceptance of the once revolutionary concept of prevention. You can't change your age or your genes, but you can mitigate and even prevent the clogging of your coronary arteries by controlling what's controllable—lifestyle, particularly smoking, blood pressure, and cholesterol.
No one argues over blood pressure and lifestyle changes. But the lowering of bad cholesterol with medicine has taken a public drubbing of late, in part fueled by surprising findings released last month about the drug Vytorin. Vytorin, which combines the new cholesterol-buster Zetia with the statin Zocor, was expected to lower LDL cholesterol even more than treatment with statin therapy alone. And it did, by an extra 17 percentage points. The surprise was that the extra drop didn't seem to make the carotid arteries in the neck, an indirect measure of what may be happening to the coronaries in the heart, look any better or worse in terms of wall thickness, a surrogate for plaque. Zetia was expected to make them thinner.
There could be many explanations, so the drubbing may be premature. Do the minuscule physical changes in the carotid arteries adequately reflect what's happening in the heart? Was the high-dose statin treatment used by most before the study began so effective that it overshadowed the benefit of the added drop in LDL? Or does the explanation lie more in the way the new drug lowers cholesterol? As Roger Blumenthal, director of the Johns Hopkins preventive cardiology center, says, lowering the total number of LDL particles is the best strategy to minimize the risk of heart attacks, but we don't yet know if adding Zetia to a statin does that better than a statin alone. "My strong feeling is that the combination will be better," he says. "But I also predicted that the Patriots would win the Super Bowl."
Prudence. Blumenthal cautions against overinterpreting this study. Both drugs, equally well tolerated, stabilized the plaque and led to almost no disease progression. Prudence would await the release of the full study next month and, in the next few years, results from major Vytorin trials involving over 10,000 people that look at cardiovascular health outcomes directly. He fears people will prematurely abandon a drug that can be particularly beneficial in those who tolerate only lower doses of statins.
On the other hand, Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, sees this study as concerning. He wants the public to be shaken up by the results, since the onslaught of advertising prompted too many patients and their doctors to go for Vytorin instead of more intensive statin therapy—which should be "the first, second, and third choice" as much because of its positive effect on inflammation and levels of HDL, or "good" cholesterol, as because it lowers LDL. He bets the larger Vytorin trials will show that adding Zetia to Zocor will be no better than Zocor alone. But on three things there's no controversy: LDL cholesterol is a key risk factor for coronary disease. Patients should have their bad cholesterol lowered based on their personal risk, and that often requires drugs. And the jury is still out on Vytorin and Zetia.
Zetia and drugs like it may or may not turn out to be key additions to our cholesterol-lowering arsenal. But the arsenal needs to expand, since not all patients respond to available drugs as they struggle to bring their high cholesterol down. I only hope that the public skirmishes in the search for better ways to do this will enhance, and not diminish, patients' confidence in the importance of cholesterol to all who treasure their beautiful beating hearts.