ACC: Preloading Statin Before Cardiac Intervention Reduces Complications

NEW ORLEANS, March 26 -- A burst of high-dose statins just before angioplasty and stenting for stable acute coronary syndrome appears to reduce cardiac complications, according to an Italian trial.

Atorvastatin (Lipitor) given 12 hours before non-emergent percutaneous coronary intervention yielded a significant 12% absolute reduction in major adverse cardiac events over placebo, said Germano Di Sciascio, M.D., of the University of Rome, and colleagues.

The 88% risk reduction for patients in the ARMYDA-ACS (Atorvastatin for Reduction of Myocardial Damage During Angioplasty-Acute Coronary Syndromes) trial mirrored an 81% risk reduction reported for stable angina patients with one week of pretreatment in the previous ARMYDA study.

The findings, presented at the American College of Cardiology meeting here, were also published in the March 27 Journal of the American College of Cardiology.

Although statins have not been part of the interventional cardiologist's armamentarium, the study suggests that they should be, Dr. Di Sciascio said.

"These findings may support routine use of high-dose statins before intervention in patients with acute coronary syndrome," he and colleagues wrote in the JACC paper.

However, "I'm a little nervous about over-interpreting these numbers," said Paul M. Ridker, M.D., of Brigham and Women's Hospital and Harvard Medical School, who commented on the study as one of the panelists in the session.

"I wouldn't want people to delay care," he cautioned.

The double-blind trial included 171 patients with non-ST segment elevation myocardial infarction or unstable angina sent to early angiography at three Italian institutions. They were randomized to pretreatment 12 hours before percutaneous coronary intervention, with placebo or 80 mg atorvastatin and 40 mg immediately prior to the procedure.

All patients received a 600-mg clopidogrel (Plavix) loading dose. After percutaneous coronary intervention, all patients received standard aspirin and warfarin (Coumadin) regimens plus long-term atorvastatin (40 mg daily).

Those with high-risk features warranting emergency coronary angiography or prior or current statin use were excluded. The groups had similar baseline and treatment characteristics.

The 30-day findings were:

• A significant advantage in the primary combined endpoint of death, myocardial infarction and unplanned target vessel revascularization (5% versus 17%, P=0.01).
• A significant reduction in myocardial infarction occurrence (5% versus 15%, P=0.04), which appeared to drive the primary endpoint findings.
• No deaths in either treatment arm.
• An 88% risk reduction in 30-day major adverse cardiac events at multivariable analysis with atorvastatin over placebo (odds ratio 0.12, 95% confidence interval 0.05 to 0.50, P=0.004).
• Less frequent elevation of cardiac markers with atorvastatin (creatine kinase-MB 7% versus 27%, P=0.001 and troponin-I 41% versus 58%, P=0.039).
• Significantly lower increase in C-reactive protein levels from baseline in the atorvastatin arm (63114% versus 147274%, P=0.01).

"This is a much greater effect than that observed in other large studies using a high dose of statins in acute coronary syndromes, albeit without early invasive strategy," the researchers wrote.

For example, early post-procedure statin therapy yielded a 16% risk reduction in cardiac events in the MIRACL (Myocardial Ischemia Reducation with Aggressive Cholesterol Lowering) trial, 25% risk reduction in the A to Z (Aggrastat to Zocor) trial, and 28% risk reduction in the PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy) trial.

However, Dr. Di Sciascio cautioned that the results cannot be extrapolated directly to patients with ST-segment elevation myocardial infarction (STEMI), to those with medically or surgically treated unstable acute coronary syndrome, or to patients undergoing emergency revascularization.

Dr. Ridker also emphasized that physicians should not consider delaying percutaneous coronary intervention in favor of statin loading and cautioned that the study was underpowered.

"It's a very confused message," he said.

He and colleagues noted that it is unclear whether a single loading dose of atorvastatin may help patients undergoing emergency procedures as well as whether patients on chronic statin treatment would have a similar benefit.

"If confirmed by larger additional randomized studies, these findings may support the indication of 'upstream' administration of high-dose statins in patients with acute coronary syndromes treated with an early invasive strategy," they concluded.

Further studies are needed "to see if it translates into events," commented C. Noel Bairey Mertz, of Cedars-Sinai Medical Center in Los Angeles, who chaired of the session in which the study was presented.

Nonetheless, statin preloading is "a very fascinating concept," said Christie M. Ballantyne, M.D., of Baylor in Houston, who also moderated the session.