乌鸦传媒

NEWARK, Del., Aug. 13 -- When angioplasty was combined with optimal medical therapy, stable angina patients had faster and slightly better symptomatic relief, but after 36 months the early advantage with the percutaneous approach had disappeared.

The equivalent benefit seen after 36 months for optimal medical therapy alone, reported in the Aug. 14 issue of the New England Journal of Medicine, was the latest finding to emerge from the 2,287-patient COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial. It was designed to compare the efficacy of the two treatments.

The primary endpoint of the COURAGE trial was a combination of death and/or MI rate, which was 19% in the percutaneous coronary intervention group versus 18.5% in the medical therapy arm, a statistical dead heat that ignited a firestorm of controversy when reported at American College of Cardiology meeting in March 2006.

At that time, stenting proponents argued that the fast symptom relief still made percutaneous coronary intervention an attractive option for patients. (See: ACC: Stenting Found No Better than Optimal Medical Therapy)

And there was a real measurable difference with 53% of stent patients angina-free at three months versus 42% of medical-therapy patients (P
Scores on the Seattle Angina Questionnaire and the RAND 36-item health survey also favored the stent group at three months in the domains of physical limitations (P=0.004), angina stability (P=0.002), angina frequency (PP
In the stent group, patients who had the most severe angina at baseline received the greatest benefit, said William S. Weintraub, M.D., of Christiana Care Health System here.

The incremental benefit for stenting was apparent for six to 24 months, and then the two groups began to converge because "there was significant and rapid improvement in Seattle Angina Questionnaire scores among patients in the medical therapy group," wrote Dr. Weintraub and colleagues.

"On the basis of these data, 17 patients would need to be treated with percutaneous coronary intervention, versus optimal medical therapy, as compared with optimal medical therapy alone, for one to have a significantly greater angina relief, 11 would need to be treated for one to have a significant benefit in physical function, and 12.5 would need to be treated for one to have a significant improvement in quality of life," they wrote.

The take-away message, said Robert O. Bonow, M.D., of Northwestern, is that "we now can offer patients the option of optimal medical therapy with the assurance that over time the outcome will be the same as stenting."

Dr. Bonow, who was not involved in the study, cautioned against over-interpreting the latest COURAGE analysis.

"This in no way diminishes the role of stenting in treating unstable angina or MI," he said.

Steven Nissen, M.D., director of cardiovascular medicine at the Cleveland Clinic, agreed that the findings reinforce "choices for patients."

Like Dr. Bonow, Dr. Nissen was not involved in the trial but he was ACC president when the COURAGE results were reported and as such he was widely quoted at the time.

Almost 17 months after that initial release, Dr. Nissen said he doubted the latest findings would ignite a new controversy between interventional and medical cardiologists, but he restated his position that COURAGE was a landmark trial with findings that are likely to "find their way into our guidelines."

From 1999 through 2004, the trial recruited 2,287 patients who had stable angina at 50 U.S. and Canadian centers and assigned 1,149 patients to percutaneous coronary intervention plus maximum medical therapy and 1,138 to maximum medical therapy alone.

The primary outcome was death from any cause and non-fatal myocardial infarction during a follow-up of 2.5 to seven years.

Inclusion criteria included Canadian Cardiovascular Society Class IV angina, which had been stabilized medically, as well as stenosis of at least 70% in at least one proximal epicardial coronary artery and objective evidence of myocardial ischemia on stress testing.

Optimum medical therapy included daily aspirin (81 mg to 325 mg), or 75 mg of clopidogrel (Plavix) for patients who were aspirin intolerant; long-acting metoprolol, amlopidine, and isosorbide mononitrate alone or in combination along with either lisinopril or losartan.

Patients also received aggressive statin therapy to lower LDLs to a goal of 60 to 85 mg/dL. When the LDL goal was reached, "an attempt was made" to raise HDL to above a threshold of 40 mg/dL and lower triglyceride to a goal of less than 150 mg/dL. That intervention included diet, exercise, extended-release niacin, and fibrates alone or in combination.

Dr. Weintraub said there were a number of limitations to the study -- patients were mainly white men, and the trial had such high standards of optimal medical treatment that they may not be applicable to every day clinical practice.

Moreover, only a small number of patients had drug-eluting stents, which are considered more effective than the bare metal stents that most of the PCI patients received.

Nonetheless, Eric D. Peterson, M.D., M.P.H., of the Duke Clinical Research Institute, and John S. Rumsfeld, M.D., Ph.D., of the University of Colorado, wrote in an NEJM editorial that the trial redefined "the contemporary roles of optimal medical therapy and percutaneous coronary intervention in the management of patients with stable angina."

"Rather than one victor, COURAGE demonstrates that both treatment strategies can have a profoundly positive effect on patients' health status and suggests complementary roles -- optimal medical therapy as first-line therapy, with PCI reserved for patients who do not have a response or who have severe baseline symptoms," concluded Drs. Peterson and Rumsfeld.

From the Milwaukee Journal Sentinel: