ACC 2009: Studies Support Statin Preloading, Even a Statin Reload, Prior to PCI

from <a href="http://theheart.org/" target="_blank">Heart<i>wire</i></a> &#151; a professional news service of WebMD

April 01, 2009

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April 1, 2009 (Orlando, Florida) — Two new Italian studies presented Monday during the i2 Summit at the American College of Cardiology 2009 Scientific Sessions point to the benefit of pretreating patients undergoing PCI with statin therapy. One study even suggests that patients already receiving the lipid-lowering medications receive cardioprotective benefit with an additional statin boost prior to the procedure.

"The statin-naive patient population is disappearing," said lead investigator Dr Germano Di Sciascio (Campus Bio-Medico University, Rome, Italy) during a press conference announcing the results of the Atorvastatin for Reduction of Myocardial Damage During Angioplasty-Acute Coronary Syndromes (ARMYDA) RECAPTURE study. "They are an endangered species. The large majority of patients who come to the lab are on statins. In our group, about 70% of patients coming to the lab are on statins. We wanted to test the hypothesis that an acute reload of atorvastatin in those patients on chronic therapy would have the same cardioprotective effect during PCI."

In ARYMDA-RECAPTURE, investigators showed that atorvastatin 80 mg given to statin-treated patients 12 hours prior to PCI, followed by 40 mg just before the procedure, reduced the risk of major adverse coronary events, specifically the risk of MI at 30 days.

Similarly, in the Novel Approaches for Preventing or Limiting Events (NAPLES) II study, investigators, led by Dr Carlo Briguori (Clinica Mediterranea, Naples, Italy), showed that atorvastatin 80 mg loaded 24 hours prior to PCI in statin-naive patients reduced the incidence of periprocedural MI.

Results in Line With Previous ARMYDA Studies

Presenting the results during a morning press conference, Di Sciascio pointed out that the ARMYDA investigators have conducted two prior studies, both reported by heartwire , showing the benefit of statin therapy in patients undergoing PCI.

In ARMYDA-ACS, statin-naive patients with non-ST-segment-elevation acute coronary syndrome were randomized to pretreatment with atorvastatin, and this treatment reduced the risk of adverse events, primarily postprocedural MI at 30 days. An earlier study showed that pretreatment could reduce the risk of myocardial damage after PCI in unstable patients.

In ARMYDA-RECAPTURE, investigators randomized 352 patients with stable angina and non-ST-segment-elevation acute coronary syndrome to the atorvastatin "reload" arm or to placebo. All patients were pretreated with statin therapy, but the reload patients received 80 mg of atorvastatin 12 hours prior to PCI, followed by an additional 40 mg before the procedure. All patients were treated with atorvastatin 40 mg after PCI.

At 30 days, the rate of major adverse cardiac events, a composite of cardiac death, MI, and target vessel revascularization, was significantly lower among patients reloaded with atorvastatin prior to PCI. This benefit was primarily driven by a significant reduction in the incidence of periprocedural MI (3.4% vs 8.6%).

ARMYDA-RECAPTURE: Primary End Point and Secondary End Points at 30 Days

End point Atorvastatin (n=177) Placebo (n=175) p
Major adverse cardiac events 3.4 9.1 0.045
Creatinine kinase-MB (% of patients with elevations 3xULN) 13 23 0.023
Troponin I (% of patients with elevations 3xULN 36 47 0.032
ULN=upper limit of normal

Discussing the results with the media, Di Sciascio said that patients with acute coronary syndrome on admission, and not patients with stable angina, were the primary benefactors of statin therapy. There was only a trend toward reduced major adverse events among those with stable angina, whereas the incidence of adverse events declined to 2.4% among those with acute coronary syndrome, which translated into a relative risk reduction of 87% compared with placebo.

As far as mechanisms are concerned, we can discuss these until we are blue in the face.

"As far as mechanisms are concerned, we can discuss these until we are blue in the face," said Di Sciascio, adding that he believes the mechanism to be independent of LDL lowering. Regardless of how the drugs work, Di Sciascio said, the data, if confirmed in other, larger studies, has the potential to change clinical practice. Specifically, statins might even be administered on first medical contact, not unlike aspirin or clopidogrel.

"I believe in moving very upstream with statin therapy," he said.

Commenting on the results of the study during the late-breaking clinical-trials session, Dr Robert Harrington (Duke Clinical Research Institute, Durham, NC) said the trial is small but important, as it addresses the clinical problem that when clinicians intervene in the coronary artery, they unleash an inflammatory cascade that has the potential to turn into downstream events. However, confirmation of the benefits in larger trials is needed before clinicians start initiating the statin boost prior to PCI. Harrington noted, however, there is a relationship between long-term mortality and myocardial necrosis.

NAPLES II

In NAPLES II, researchers studied whether a high loading dose of atorvastatin given in the 24 hours before an intervention would provide protection against periprocedural MI. In total, 668 statin-naive patients scheduled for elective PCI were randomized to atorvastatin 80 mg or placebo. At 30 days, treatment with atorvastatin significantly reduced the risk of periprocedural MI as defined by elevations of creatine kinase myocardial enzyme (CK-MB) and cardiac troponin I.

NAPLES II: Primary End Point 30 Days

End point Atorvastatin (n=338) Placebo (n=330) p
Creatine kinase-MB (% of patients with elevations 3xULN) 9.5 15.8 0.014
Troponin-I (% of patients with elevations 3xULN) 26.6 39.1 <0.001
ULN=upper limit of normal

Discussing the results of NAPLES II during the late-breaking clinical trials session, Dr Christopher Cannon (Brigham and Women's Hospital, Boston, MA) said that one of the surprises of the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) study was the early separation of event curves, as early as 14 days, which suggested that high-dose atorvastatin might be beneficial in ACS patients beyond LDL lowering. Later studies, including the most recent JUPITER analysis, have suggested that pleiotropic effects, specifically anti-inflammatory effects, are responsible for some of the drug's benefit.

"I think we have now seen a shift where this is probably ready for prime time in our practice, such that the early benefit observed in PROVE-IT, linked to the anti-inflammatory effects of statins, now is shifting into the cath lab," said Cannon. "We're now talking about statin pretreatment as something that will possibly influence the outcomes of PCI."

In practice, said Cannon, clinicians should start intensive statin therapy in acute coronary syndrome patients on hospital admission and potentially the night prior to the procedure in elective PCI. During a discussion of the results following the late-breaking clinical-trials session, others were more cautious and focused on the definition of periprocedural MI and whether these enzyme elevations translate into clinical significance, particularly elevations in troponin I, which is considered a sensitive marker.

Briguori and Di Sciascio report no conflicts of interest. Cannon reports research support from Merck, AstraZeneca, Schering-Plough, Accumetrics, GlaxoSmithKline, and Sanofi-Aventis/Bristol-Myers Squibb partnership. Harrington reports consulting fees from WebMD and Schering-Plough, speaker's fees and fellowship support from Johnson & Johnson, Bayer, Daiichi Sankyo, Pfizer, Bristol-Myers Squibb, Baxter, AstraZeneca, Sanofi-Aventis, Lilly, Medtronic, the Medicines Company, GlaxoSmithKline Schering-Plough, Momenta, Medicure, and Portola.

The complete contents of Heartwire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

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