Cardio meeting reveals cost-saving strategies

Drug therapies show promise

Physicians attending the American College of Cardiology’s (ACC) 46th annual meeting in Anaheim, CA, came away with some promising news both on patient outcomes and cost-effectiveness issues.

Better drug therapy continues to contribute to improved outcomes for heart and vascular disease, and many presenters at the ACC meeting focused on those that reduce care costs by keeping patients with chronic heart disease out of the hospital.

New clot busters no better than gold standard

Meeting attendees learned that for patients with myocardial infarction (MI), which tissue-type plasminogen activator is administered to open blocked arteries doesn’t seem to affect outcomes. Ease of administration may be an issue, however. The Global Use of Strategies to Open Occluded Coronary Arteries and Intravenous n-PA for Treatment of Infarcting Myocardium Early studies showed that outcomes following administration of r-PA (retaplase) or n-PA (novel plasminogen activator lanoteplase ) are not significantly different from those following t-PA (alteplase) use.

T-PA, marketed as Activase by Genentech of San Francisco, is a natural agent and a commonly used thrombolytic; r-PA and n-PA are bioengineered mutants of t-PA and have longer half-lives and less fibrin affinity. The mutants can be administered as a single bolus whereas t-PA requires an intravenous infusion. R-PA is marketed as Retavase by Boehringer-Mannheim of Gaithersburg, MD, and n-PA is marketed as lanoteplase by Bristol-Myers Squibb of Princeton, NJ.

Aggrastat promising for unstable angina

Enthusiasm for platelet blockers was reignited when two large-scale studies revealed that Merck’s Aggrastat (tirofiban) reduces death, heart attack, and complications in patients with severe chest pain. Unstable angina, a precursor to heart attack, causes 1.2 million hospitalizations a year. If used widely, with or without standard therapy for unstable angina, Aggrastat could prevent 5,000 to 10,000 deaths and 30,000 to 40,000 heart attacks annually. It could also reduce the need for urgent open-heart procedures. Merck, based in Whitehouse Station, NJ, plans to apply to the Food and Drug Administration to market Aggrastat later this year.

The drug functions by blocking 90 angina pathways that provoke the aggregation of platelets. In preventing platelets from clumping, the drug is one of a class called platelet blockers or super aspirin. Other drugs in that class are ReoPro and Integrilin. ReoPro, but not Integrilin, is on the market and has proved effective in reducing complications in patients undergoing angioplasty.

The primary focus of one of the tirofiban trials, the Platelet Receptor Inhibition for Ischemic Syndrome Management study, was on patient outcomes two to seven days following treatment. Aspirin and heparin are typically given to patients admitted with unstable angina. When Aggrastat was administered IV in addition to heparin and aspirin in the studies, heart attacks were reduced by 47%. Fewer than 4% of patients who had Aggrastat added to their regimen had heart attacks within seven days as compared to 7% who were given heparin and aspirin alone.

Previous reports had revealed that beneficial effects waned by 30 days. After 30 days of Aggrastat use in these studies, the overall benefit for death, heart attack, and angina symptoms fell to 23%.

Don’t rush to surgery following MI

The routine aggressive surgeries — bypass or angioplasty — that immediately follow about half of the 1.5 million heart attacks in the United States may cause yet more heart attacks and death. Early, aggressive treatment for non-Q wave MI may be harmful, say investigators in the Veterans Affairs Non-Q-Wave Infarction Strategies in-Hospital (VANQWISH) trial. Conservative treatment with noninvasive testing and watchful waiting produced outcomes better than those of the more aggressive bypass or cardiac catheterization followed by revascularization.

VANQWISH outcomes surprised the investigators. They expected similar, not more harmful, results from aggressive treatment. What they saw was a three-fold higher death rate at the nine-day mark in patients managed aggressively compared to those managed conservatively. The one-month mortality rate was 34% higher among the aggressively managed.

Investigator William E. Boden, MD, of the VA Upstate Healthcare System in Syracuse, NY, says physicians should not do invasive procedures immediately post-MI, but selectively and later, when the patient is stable.

Calcium channel blockers face new scrutiny

Researchers at Anaheim reported an increased risk of repeat MI in patients taking calcium antagonists diltiazem or nifedipine when compared to those on beta-blockers. On the other hand, amlodipine — the successor product to nifedipine — may help curb progression of congestive heart failure (CHF), according to researchers at the University of Pennsylvania. Amlodipine appears to reduce levels of cytokine interleukin-6, excessive amounts of which may contribute to a decline of cardiac function in CHF patients.

Warfarin? Why bother?

A Massachusetts General Hospital study presented at the meeting raises questions about warfarin’s effectiveness. Researchers found that patients with congestive heart failure who were discharged on warfarin were worse off six months later than those not taking the drug. Rehospitalization rates — both for heart problems and other disorders — were higher in the warfarin group, sometimes significantly. Rehospitalizations for CHF averaged 32.5% in the warfarin group versus 23.1% in the non-warfarin group.

"Patients with CHF who are put on warfarin tend to be among the sicker group, so I wouldn’t put much emphasis on the cause-and-effect relationship between the warfarin and rehospitalizations," says Mel Weiss, MD, an interventional cardiologist at the George E. Reed Heart Center in Hawthorne, NY. "It’s unclear how beneficial warfarin is. Some indirect evidence points to its being more beneficial than harmful." Weiss told Cost Management in Cardiac Care about another study, part of which was performed a few years ago at the George Reed Heart Center. "The study," says Weiss, "was primarily on left ventricular dysfunction, but we looked at warfarin outcomes as well. Patients on the drug did better and survived longer than those not on the drug. Further independent study looking at that issue is warranted."

ACE inhibitors in cost-saving spotlight

Angiotensin-converting enzyme (ACE) inhibitors are once again getting attention due to studies presented at the meeting showing that the drugs reduce mortality and morbidity among CHF patients, and in turn, can save money.

Two reports suggest that utilization of ACE inhibitors has increased over the past five years. As a result, though hospitals are treating more CHF patients now than 10 years ago, they’re doing it faster and with better results.

The National Hospital Discharge Survey shows that in 1983, there were 463,000 hospital discharges for CHF. The average length of stay was almost 10 days, and mortality neared 10%. By 1993, the latest year available for study, CHF discharges had nearly doubled, but LOS had dropped to 7.5 days, and mortality was cut to 6.1%.

"The decreased length of stay today can be attributed to an increased use of ACE inhibitors and the fact that we’re diagnosing patients earlier," explains Weiss. "ACE inhibitors tend to be expensive, but if they can decrease length of stay, overall cost is reduced. Echocardiography has improved over the last 10 years and so is being used more."

Getting doctors to properly prescribe the antihypertensives can be problematic, however. Louisiana researchers reported findings that some Medicare patients hospitalized with heart failure still may not be getting ACE inhibitors on discharge.

Physicians’ concerns about possible negative effects may be one reason this class of drugs is not utilized more often. Meeting speakers stressed that physicians should be encouraged to refer patients for the initiation of ACE inhibitors to the hospital whenever they are concerned about initiating treatment in their offices.

Meeting attendees learned about a study that provides a strong rationale for the use of ACE inhibitors in diabetics after a myocardial infarction (MI).

Though outcome data are scarce, researchers reported that the beneficial effects of ACE inhibitors on LV function in diabetics in long-term studies are similar to those seen in nondiabetics and that in the acute phase, these effects may actually be greater in diabetics.

Investigators at Loma Linda (CA) University reported their findings on the cause of the ACE inhibitor cough.

The key lies in the effect of ACE inhibitors on the breakdown of two substances: Substance P, which stimulates secretion in the bronchioles, and Neurokinin A, which causes bronchoconstriction.

In a comparison of three drugs — enalapril, fosinopril, and losartan — the researchers found that any time Neurokinin A levels were elevated, patients coughed while on the drugs. Nearly all patients studied showed increased levels of Substance P while taking ACE inhibitors, but only those with accompanying increased levels of Neurokinin A coughed. Enalapril was associated with the worst cough, while losartan was the least likely to cause the side effect.

Two beta blockers and a diuretic cut costs

The inexpensive beta-blocker metoprolol (Lopressor) can slash future costs of cardiac care by 200%, say Anaheim presenters. Swedish researchers reported their estimates of significant differences in future health care costs between a metoprolol-treated group of patients with idiopathic dilated cardiomyopathy and a similar group taking placebo.

A University of California Medical School study suggested that preoperative use of another beta-blocker, betaxolol, can dramatically cut the number of cardiac events — and their costs — in patients undergoing surgery for coronary atherosclerotic disease. Twenty-four patients stabilized on a daily dosage of 10 to 20 mg of betaxolol for two weeks prior to peripheral vascular surgery suffered no perioperative cardiac events. Three of the 10 patients not taking the betaxolol did.

The inexpensive diuretic hydrochlorothiazide (HCTZ) does more than lower blood pressure, according to Georgetown University Hospital researchers. HCTZ was the only drug in a six-product comparison that both decreased blood pressure and caused a sustained decrease in the size of the left atrium. The other drugs studied included prazosin, atenolol, diltiazem, clonidine and captopril. Increased cardiac mass can indicate a poor outcome for hypertensive patients.