New Drugs a Boon for Cardiac Patients
Artificial hearts and new surgical techniques may be the glamorous arm of cardiac care, but medications are the backbone. A broad spectrum of drugs developed over the past two decades has dramatically improved heart care, keeping large numbers of patients alive much longer than previously possible.
Though many niches remain unfilled, research presented at last week’s Anaheim meeting of the American Heart Assn. suggests that progress is being made. In some cases, old drugs are finding new applications. In others, new classes of drugs are being developed.
And researchers are rethinking how they use existing drugs. One good example is ACE inhibitors--blood pressure drugs long thought not to be effective in African Americans. New results presented in Anaheim show that they are actually the most effective way to control blood pressure and prevent kidney damage in black people. Calcium-channel blockers, in contrast, were found to actually be dangerous to African Americans.
Hypertension is a particular problem in blacks, who suffer unusually high rates of kidney damage as a result. Although blacks make up only 12% of the U.S. population, they account for more than 30% of all cases of advanced kidney disease requiring dialysis.
In the recent study of the condition, sponsored by the National Institutes of Health, Dr. Janice Douglas of Case Western Reserve University and her colleagues enrolled 1,094 hypertensive blacks with mild to moderate kidney damage. Patients were randomly assigned to receive either an ACE (angiotensin-converting enzyme) inhibitor, a calcium-channel blocker or a beta-blocker. Beta-blockers control hypertension by reducing heart rate. Calcium-channel blockers relax blood vessels. ACE-inhibitors affect retention of water and salt and relax blood vessels. Patients were also given diuretics and other drugs as needed.
The calcium-channel blocker arm of the trial was halted prematurely because patients taking the drug were more likely to develop kidney disease, Douglas said. Overall, patients taking the ACE inhibitor (Altace) were 41% less likely to develop end-stage kidney disease or to die than patients taking the calcium-channel blocker (Norvasc). The rate of decline in kidney function was 25% lower in patients taking the ACE inhibitor than in those taking the beta-blocker (Toprol).
There was some good news for angina sufferers as well, with one drug found to improve life expectancy and another showing promise for pain relief.
In the first study, a drug used to treat angina in Europe but not in the United States significantly reduced deaths and nonfatal heart attacks from the condition. Angina, a crippling pain in the chest and arm caused by clogged blood vessels, affects more than 6 million Americans, sharply limiting daily activities.
Three existing classes of drugs--nitroglycerin, calcium-channel blockers and beta-blockers--are used to treat the condition but have limited efficacy and cause several side effects, including impotence.
Dr. Henry Dargie of the University of Glasgow and his colleagues studied 5,126 angina patients in what he called the first study ever to demonstrate such a reduction in heart attacks and strokes in patients with stable angina. Half of the patients received the new drug, nicorandil, in addition to their regular therapy, and half received a placebo with their therapy.
Dargie said patients receiving nicorandil had a 17% reduction in risk of heart disease-related death, nonfatal heart attack, or hospitalization for chest pain over the period of the trial compared with patients taking a placebo. Dargie said the drug apparently trains the heart muscle to better tolerate new incidents of angina by affecting potassium channels, molecular gateways that control the flow of potassium into and out of heart cells.
In the other angina study, a new drug with an unusual mechanism of action was shown to provide modest decreases in pain and increases in endurance in angina patients. The drug, called ranolazine, should provide a useful supplement to existing therapies, said Dr. Bernard R. Chaitman of St. Louis University, who chaired the study.
Ranolazine is the first of a new class of drugs called partial fatty acid oxidation, or pFOX, inhibitors. Normally, the heart prefers to burn fatty acids as fuel, a process that requires substantial amounts of oxygen. PFOX inhibitors reduce heart tissue’s ability to oxidize fats, thereby increasing their consumption of sugars, which require less oxygen. That can reduce pain when the heart is not receiving enough oxygen-rich blood, as is the case with blocked arteries.
Chaitman and his colleagues studied 823 angina patients who were randomly assigned to receive either ranolazine or a placebo in addition to their regular medications.
Those receiving the drug had an average of 25% fewer angina episodes per week. Their endurance on a treadmill also increased. At the beginning of the study, they were able to walk an average of about 7 minutes. Those getting a placebo increased their treadmill time by 92 seconds; those receiving ranolazine increased it by 116 seconds.
That may not sound like much, but Chaitman said it could mean being able to carry groceries upstairs without stopping for a rest along the way.
An old drug that might find application in patients with congestive heart failure is allopurinol, which is now used to treat gout. Allopurinol blocks the production of xanthine oxidase, an enzyme that is known to exist in unusually high levels in damaged heart tissue and is thought to contribute to its destruction.
Dr. Joshua M. Hare and his colleagues at Johns Hopkins University injected allopurinol directly into the hearts of seven men and two women with dilated cardiomyopathy, in which the lower left chamber of the heart becomes enlarged and weakened, lowering its ability to pump blood.
Hare said the drug increased overall heart efficiency. The patients’ hearts had a 20% reduction in energy consumption with no reduction in the strength of contractions. The researchers plan to start a clinical trial next year.
But among the promising reports on drugs new and old was one in which a new drug failed to meet expectations. The drug is Azimilide, which is being developed by Procter & Gamble to correct a heart rhythm problem called atrial fibrillation. Another trial showed that the drug failed to increase survival of patients with a more serious type of rhythm disturbance.
The new study involved 3,717 heart attack survivors thought to be at risk of sudden death from ventricular fibrillation--in which the heart’s two lower chambers twitch so quickly that no blood is pumped from the heart.
Patients enrolled in the trial were all deemed at risk because of reduced heart-pumping ability or because their heart rates were overly uniform throughout the day, a suspected cause of sudden death. The patients received either Azimilide or a placebo in addition to conventional treatment and were monitored for a year.
