NAPLES II: High loading dose of atorvastatin reduces incidence of periprocedural MI in elective PCI

A loading dose of atorvastatin administered prior to percutaneous coronary intervention was associated with cardioprotective effects and a reduced incidence of periprocedural MI.

Researchers for the NAPLES II trial enrolled 668 statin-naive patients undergoing PCI. They randomly assigned patients to receive either a loading dose of 80 mg atorvastatin (Lipitor, Pfizer) (n=338) or no statin (n=330). Creatinine kinase myocardial isoenzyme (CK-MB) (upper limit of normal 3.5 ng/mL) and cardiac troponin levels (upper limit of normal 0.10 ng/mL) were measured at six hours and 12 hours following PCI. The primary endpoint was the rate of periprocedural MI, with periprocedural MI being defined as CK-MB three times the upper limit of normal.

According to the study results, the incidence of CK-MB elevation three times the upper limit of normal was lower in the atorvastatin group vs. the control group (9.5% vs. 15.8%, OR=0.56; 95% CI, 0.35-0.89). Cardiac troponin levels three times the upper limit of normal were also lower in the atorvastatin group vs. control (26.6% vs. 39.1%, OR=0.56; 95% CI, 0.40-0.78). A post hoc analysis revealed an interaction between treatment strategy and baseline CRP levels (P=.004), and that cardioprotective effects were greater in the subgroup of patients with elevated CRP levels at baseline (P=.016 for elevated CK-MB and P=.002 for elevated cardiac troponin).

“This randomized study supports the cardioprotective effect of a single, high (80 mg) loading dose of atorvastatin administered within 24 hours prior to stent implantation,” the researchers concluded.

Cardiology Today reported the results of the trial when they were presented at the American College of Cardiology's 58th Scientific Sessions earlier this year.

Briguori C. J Am Coll Cardiol. 2009;doi:10.1016/j.jacc.2009.07.005.

The study is really terrific. To my knowledge, the first observation as to a benefit of statins in pretreatment made was actually in a paper by one of my former fellows. I wondered at the time whether statin pretreatment might turn out the way that clopidogrel pretreatment did. Of course, at the time, it seemed a bit outlandish. How could statins, which lower cholesterol and which take several months to do so, have any benefit just given before an angioplasty or stenting procedure? It turned out in that early analysis that it did, but that was a non-randomized analysis and those were observational data. In a follow-up paper, we showed that the benefit might be confined to patients with elevated baseline CRP, suggesting an anti-inflammatory and not lipid-lowering effect.

What this trial and ARMYDA-RECAPTURE have shown in prospective randomized clinical trials is that statin pretreatment really does seem to reduce ischemic events – particularly periprocedural MI. The data are believable and the data from this particular trial are robust. While a purist might say that it is still not enough evidence to routinely recommend statin pretreatment, in my own opinion and in my practice, I do not see the downside. Patients who are undergoing PCI are going to need to be on a statin anyway, barring an allergy or an intolerance, so there really is no harm in starting it beforehand. And now a number of studies – small, randomized clinical trials, and larger, nonrandomized data sets, support the concept that statin pretreatment reduces preprocedural MI. I do not see a downside and I would probably recommend it. Having said that, sure it would be nice to have larger studies examining this to see whether endpoints such as mortality are favorably reduced, but those would be extremely large trials and they probably are not going to happen. In the absence of those trials, this smaller, mechanistic study is quite believable and enough to influence my practice.

– Deepak L. Bhatt, MD

Cardiology Today Editorial Board member