Promising Rx for Heart Disease Didn't Deliver

Darapladib did well in animal studies but not as effective in human study

(RxWiki News) Drug trials exist for a reason — so researchers can check a medication’s effectiveness and side effects to be sure it’s safe for human consumption. Unfortunately, not all medications live up to their initial promise.

The latest medication to disappoint researchers is darapladib.

In a recent large study, patients who took the drug were not much less likely to have heart attacks, did not have notably fewer strokes and were not significantly less likely to die for any reason, compared to those taking placebo (sugar pills).

"Ask your pharmacist about new treatments for heart disease."

This study was led by Harvey D. White, D. Sc. of Auckland City Hospital in New Zealand.

Between December 2008 and April 2010, the researchers enrolled 15,828 patients at 663 centers in 39 countries. All had coronary artery disease and were predicted to be at cardiovascular risk. For example, they were at least 60 years old or they smoked at least five cigarettes a day.

The participants were randomly assigned to darapladib (1600 mg) once a day or a placebo (sugar pill) once day. A total of 7,924 people took the medication, while 7,904 took the placebo. The average follow-up was 3.7 years.

Darapladib was expected to reduce the development of plaque build-up on the arteries by reducing lipoprotein-associated phospholipase A 2. A high level of this enzyme is considered to increase the risk for coronary events.

While the incidence of cardiovascular death, heart attacks, stroke or all-cause death occurred in 9.7 percent (769) of patients taking darapladib, this was true of 10.4 percent (819) of the group taking placebo.

There was a very slight but notably less chance of major coronary events in the patients taking darapladib, which is a signal of possible efficacy, the authors wrote.

More patients taking darapladib (19.8 percent) dropped out of the study due to side effects, compared with 13.5 percent of those taking placebo. Patients typically complained of diarrhea, odor of their feces, urine odor or skin odor while on darapladib.

There was a small incidence (1.5 percent) of kidney failure among the group taking darapladib, compared with 1.1 percent of the placebo group.

The authors of this study suggested that coronary risk may have been minimized by therapy the patients were already taking (such as statins) or had received (such as revascularization, which is re-establishment of blood to the heart) prior to the study.

E. Lee Carter, RPh, a Clinical Pharmacist at the Department of Veterans Affairs in Prestonsburg, Kentucky, told dailyRx News that he is looking forward to hearing news of a second study.

“I would agree that, with regard to the primary endpoint of the trial, which was time to first occurrence of any major adverse cardiovascular event (MACE) comprising cardiovascular death, myocardial infarction (MI) and stroke, the results have to be considered a disappointment,” Carter said.

"Interestingly, the STABILITY trial data suggest that darapladib may have a favorable effect on the reduction of coronary events found in patients with heart disease. We are still awaiting results of a second study, SOLID-TIMI 52, which may help provide some further direction on whether these compounds justify further research and development,” he said.

This study was published March 30 in the New England Journal of Medicine, and updated May 1 in the online edition.

The study was funded by Glaxo-Smith Kline. 

Some of the study's authors reported conflicts of interest, such as receiving grants and personal fees from multiple pharmaceutical companies — including Pfizer, Merck and Bristol-Myers Squibb.

Review Date: 
May 2, 2014