Cardiologists hail stats on standards, stents, and statins

April 15, 2002

Cardiology meeting highlights

 

HEALTH-SYSTEM EDITION
CLINICAL PRACTICE

Cardiologists hail stats on standards, stents, and statins

The rules governing which cardiac patients should get what therapy seem to be changing, based on the results of studies reported at the annual meeting of the American College of Cardiology (ACC), held in Atlanta last month. Another reason for change is the recent revision of some ACC/American Heart Association (AHA) guidelines dealing specifically with the treatment of patients with unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI).

One thing that stood out clearly, too, is that many patients who could benefit are not now getting optimal therapy, according to Duke University researcher Eric Peterson, M.D. He reported that only 25% of patients with acute coronary syndromes are receiv-ing glycoprotein (GP) IIb/IIIa inhibitors, which have been shown to reduce the incidence of heart attacks, strokes, and other problems in many high-risk patients. He based this conclusion on a study by the National Registry of Myocardial Infarction, which found that of the 186,727 patients registered, 60,770 were eligible for this class of drugs, but only a quarter had gotten them.

Also, a so-called Crusade initiative, which involved the study in 80 hospitals of physician practices, showed that only 36% of patients were getting the GP IIb/IIa inhibitors, which are recommended to be given to patients within 24 hours of their arrival in the emergency room.

At the same time, however, the new ACC/AHA guidelines call for the use of the inhibitor abciximab (ReoPro, Lilly) only in patients having invasive procedures, such as balloon angioplasty or stenting. The use of two other GP IIb/IIIa inhibitors, eptifibatide (Integrilin injection, Millennium Pharmaceuticals) and tirofiban (Aggrastat injection, Merck), should be confined to high-risk patients who will be treated with medication only, according to the new guidelines drawn up by an expert panel headed by Eugene Braunwald, M.D., Distinguished Hersey Professor of Medicine at Harvard Medical School. As he put it, "We've learned more in a year about unstable angina and NSTEMI than we did in the preceding 20 years."

The new guidelines also recommend adding clopidogrel (Plavix, Bristol-Myers Squibb) to standard therapy, including aspirin, for the acute and continued treatment of unstable angina and mild heart attacks. The Food & Drug Administration recently approved clopidogrel for this purpose.

Meanwhile, at the ACC convention, one study indicated that there is something better than the ACC/AHA guidelines, which called for the use of unfractionated heparin with eptifibatide. Rather, the study, called INTERACT (Integrilin and Enoxaparin Randomized Assessment of Acute Coronary syndrome Treatment), showed that patients receiving a combination of eptifibatide plus the low molecular weight heparin enoxaparin sodium (Lovenox injection, Aventis) experienced a 44% reduction in the risk of heart attack or death compared with patients receiving eptifibatide plus unfractionated heparin, which was the standard. The newer combination was also associated with a 44% decrease in ischemia and a reduced incidence of major bleeding.

All the studies presented at the ACC meeting also highlighted what has become increasingly evident—that each patient is an individual, and not all will benefit from the same drugs. Indeed some patients, according to reports presented at the meeting, would benefit more from expensive implanted $20,000 devices than they would from drugs. Still, it is pharmacotherapy that is the mainstay of the treatment of cardiovascular disease, and below are some of the highlights from this year's ACC meeting:

• Is blocking two enzymes better than one? OVERTURE (Omapatrilat vs. Enalapril Randomized Trial of Utility in Reducing Events) had a combined endpoint of all-cause mortality or hospitalization for heart failure, and randomized 5,770 patients to either the standard ACE inhibitor enalapril or to omapatrilat (Vanlev, Bristol-Myers Squibb), a novel agent that inhi-bits neutral endopeptidase (NEP)/ angiotensin-converting enzyme (ACE), according to Milton Packer, M.D., of Columbia Presbyterian Medical Center in New York. The dosage of omapatrilat in the trial was 40 mg once daily; for enalapril, it was 10 mg once a day.

Patients in the trial had to have an ejection fraction of less than 30% and to have been hospitalized for heart failure within the previous 12 months. Packer said this group had been exceptionally well treated, since about 50% were receiving a beta-blocker and about 40% were receiving spironolactone when they entered the study.

The results of the study showed that in the primary endpoints patients on omapatrilat did slightly better at the dosages used—there were 6% fewer events or deaths, but this was not statistically significant. Packer told his fellow cardiologists that the patients with the highest blood pressures to start with did better on omapatrilat. Those who took this drug also had 40% less renal insufficiency, so again there is the idea of matching drug to patient. But, he added, "first we have to fully define the benefits, and then people have to decide whether the benefits of the drug are worth the cost of the drug." In the meantime, he added, "we have a million pieces of data, so we're going to be busy for a while."

• More good marks for the statins. Patients who received a statin before elective or urgent coronary angioplasty had a 33% lower death rate at six months compared with those who had not taken this type of cholesterol- lowering drug, according to a report by Albert Chan, M.D., of the Cleveland Clinic Foundation, which analyzed more than 5,000 such cases. In this group, 26.5% had been receiving a statin prior to the procedure. Chan said that "these results support the practice of initiating statin therapy as soon as possible before angioplasty and stenting."

In another statin report, this one involving only the use of fluvastatin (Lescol, Novartis), Patrick Serruys, M.D., of Erasmus University in Rotterdam, the Netherlands, also found a reduction in risk for patients undergoing angioplasty, if they were on this drug. In a group of 1,677 patients, there was a 22% reduction after four years in the risk of heart attacks or the need for a repeat angioplasty or coronary bypass surgery for those patients on fluvastatin.

• Coating stents may keep them open. Restenosis has been a major problem when stents are used to prop up arteries cleared of plaques and clots by angioplasty. So there have been several stabs—some successful and some not—at correcting this problem by coating the stent with a drug, and yet more so-called drug- eluting stents are being studied, to try to prevent those stents from clogging up again.

In some cases, drug-eluting stents are even being placed inside stents already in the artery. John Hirshfeld, M.D., director of the cardiac catheterization laboratory at the University of Pennsylvania Medical Center, called this approach a "stent sandwich."

In the meantime, trials of drugs to keep stents clear include two oncology drugs, paclitaxel (Taxol, Bristol-Myers Squibb) and rapamycin (Rapamune, Wyeth). The latter drug, according to Hirshfeld, is probably closest to market for this purpose, thanks to favorable studies in the Netherlands and Brazil. Jean Fajadet, M.D., of the Thoraxcenter in Rotterdam, reported that 238 patients with rapamycin stents had no clogging after seven months.

Not all drugs work, however. In 600 patients who received heparin-coated stents, for example, there was no improvement in preventing further narrowing over plain stents, according to Michael Haude, M.D., University of Essen in Germany.

• Good news and bad news for diabetics. People with diabetes who have acute coronary syndromes such as unstable angina or minor heart attacks have nearly twice the risk of dying within the month compared with nondiabetics. So reported Marco Roffi, M.D., of the Cleveland Clinic, after completing a pooled analysis of four trials including 24,000 patients, of whom 5,400 had diabetes. The 30-day mortality rate was 5.5% for those with diabetes, compared with 3% for those without.

More than one million people in this country are hospitalized each year with acute coronary syndromes, and an estimated 20%-30% of them have diabetes, although about one-third of the cases in the estimated 16 million Americans were said to be undiagnosed. Especially at risk, Roffi said, are those who take insulin, have reduced kidney function, or are older.

In addition, those who take certain medications used for Type 2 diabetes are at greater risk for heart failure, according to Thomas Delea of Policy Analysis Inc. in Brookline, Mass. These are medications in the glitazone family. He said these data come from analyzing health insurance claims in more than 8,000 people treated with a glitazone, compared with 41,000 who were not. The comparison showed that the risk of developing heart failure was increased by more than half in the former group.

The good news for diabetes patients, however, is that if they receive a half of a standard dose of reteplase (Retavase, Centocor) to dissolve their blood clots, along with a standard dose of abciximab to keep blood clots from forming, they were less likely to have a second heart attack or to require emergency treatment to reopen blocked arteries. That was reported by Hitinder Gurm, M.D., of the Cleveland Clinic. Patients were also less likely to develop malignant arrhythmias with the combination therapy, he said.

The study showed that about 13% of diabetes patients who did not receive the combination treatment required urgent coronary bypass grafting, versus 10.9% of those who received combination therapy.

Jean McCann

Based in Ohio, the author has extensive experience covering national and international medical and pharmaceutical meetings.

 



Jean Mccann. Cardiologists hail stats on standards, stents, and statins.

Drug Topics

2002;8:hse9.