Seeking the best path (American College of Cardiology scientific session)
■ Studies indicate that the way heart health markers are lowered may be as important as getting them down.
By Victoria Stagg Elliott — Posted May 19, 2008
The way blood pressure, lipids or blood sugar levels are reduced may be as important to heart health as getting those numbers to go low, according to studies presented at the American College of Cardiology's scientific session.
For instance, one paper indicated that taking ezetimibe with a statin lowered both LDL cholesterol and C-reactive protein levels more than taking a statin alone, but the combination did not have any added benefit on intima-media thickness. This finding suggests that, although the combination makes an impact on the numbers many physicians regard as important, it may not make a difference to overall cardiovascular health, according to data from the ENHANCE -- Effect of Combination Ezetimibe and High-dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia -- trial.
"There's some evidence that statin therapy has benefits over and above LDL lowering. Could it be that [ezetimibe] lacks some of the other effects that are supposed to be conferred by the statins?" said Dr. John Kastelein, lead author and professor of medicine and chair of vascular medicine at the Academic Medical Center in Amsterdam, the Netherlands.
In the wake of these data, which were released Jan. 14 in limited form by the drug's manufacturers, ACC officials and other experts are calling for physicians to rely more on the cholesterol-lowering drugs with the most outcome data supporting their use.
Ezetimibe "lowered LDL but it did not reduce the progression of atherosclerosis," said Harlan M. Krumholz, MD, a member of the ACC's panel organized to discuss the ENHANCE results. He also is a professor of medicine and epidemiology and public health at Yale University in Connecticut.
"This medication has been rapidly adopted into practices. ... We need to turn back to the statins," he said.
But many physicians said they would continue to prescribe ezetimibe. This study supported its safety, and patients often are either unable to reach their LDL goals on statins alone or cannot stand the amounts required to get there. Other medications that can make an impact on these numbers have their own side-effect issues or limited data supporting their use.
"We are being reminded that we have to optimize statin treatment in our patients because the alternatives are not ready yet," said Dr. Frank Ruschitzka, director of preventive cardiology at the University of Zurich, Switzerland. "But it's not that easy to get to the low levels. With a statin alone, we don't get to goal all the time, and not all of my patients tolerate high doses."
Also, intima-media thickness is a surrogate marker for heart health. Some experts are waiting for outcome data expected in 2012 before making major changes. "We have been too often misled by surrogates," said Dr. Ruschitzka. "I want to see the outcome trials."
Hypertension: Also a two-drug debate
With regard to hypertension, the ACCOMPLISH -- Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension -- trial compared a single pill combining an ACE inhibitor and a calcium channel blocker with one made up of an ACE and a thiazide diuretic. Both reduced blood pressure, but the ACE/CCB combination also decreased the risk of any cardiovascular event or death by 20%. The authors state that two medications may be a better first choice than only one, and the two drugs chosen should be an ACE and a CCB.
"These data suggest an ACE and a CCB might have synergistic effects on vascular health," said Kenneth Jamerson, MD, lead author and professor of internal medicine at the University of Michigan Medical School.
Experts agreed with starting with two drugs and expect guidelines to be revised within the next year, but many disagreed that a diuretic should be taken off the front line.
"It's a very good study. It may change a lot, but I'm not sure it's definitive enough to get rid of diuretics," said Marvin Moser, MD, a Yale University clinical professor of medicine.
Another paper also suggested that some ways to lower blood glucose may be better than others. Drugs that cause the body to use insulin more efficiently or increase the amount of insulin the body secretes both reduce hyperglycemia in those with type 2 diabetes, but one strategy more effectively reduced heart disease risk.
Pioglitazone increased HDL cholesterol, decreased fasting triglycerides and slowed the progression of coronary atherosclerosis better than glimepiride, according to the results of PERISCOPE, or Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation. Those who took glimepiride had more problems with hypoglycemia and angina. Patients on pioglitazone experienced more edema and a greater number of fractures.
"Few studies have compared outcomes for diabetes medications beyond glucose lowering, but we must close this knowledge gap," said Steven E. Nissen, MD, lead author and chair of cardiovascular medicine at the Cleveland Clinic. "We cannot just focus on getting blood sugar down and say that's the goal of therapy. The goal is to prevent the complications, and the first and foremost complication is heart disease. It does make a difference how we lower blood sugar."
This study is also the latest one to shed light on the safety profile of pioglitazone, which -- along with rosiglitazone -- has been the subject of questions over its safety during the past year. The Food and Drug Administration added black-box warnings about the possible increased risk of heart failure associated with both drugs.
Data suggesting that rosiglitazone also may be associated with an increased risk of heart attack are under review.