Meta-analysis: Benefits of High-Dose Statins Confirmed Prior to PCI

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Pretreatment with high-dose statins within a half day of planned percutaneous coronary intervention (PCI) can reduce the likelihood of periprocedural myocardial infarction (MI) and adverse outcomes at 30 days, according to results from a patient-level meta-analysis published online April 4, 2011, ahead of print in Circulation.

Researchers led by Giuseppe Patti, MD, and Germano Di Sciascio, MD, both of the University of Rome (Rome, Italy), performed a meta-analysis using individual patient data from 13 randomized trials including 3,341 subjects who received either high-dose statin therapy (n = 1,692) or no/low-dose statins (n = 1,649) a median of 0.5 days before PCI. The most common regimen in the pretreatment group was atorvastatin, 80 mg, or rosuvastatin, 40 mg. All patients received statin therapy following intervention irrespective of the initial treatment randomization.

The co-primary endpoint of periprocedural MI (defined as CK-MB increase ≥ 3 times the upper limit of normal [ULN]) was reduced by 44% in patients taking high-dose statins for a number-needed-to-treat of 20 to avoid 1 event. Periprocedural MI was decreased with high-dose statin pretreatment regardless of the biochemical definition used (table 1).

 

Table 1. Periprocedural MI by Different Definitions

 

High-Dose Statins
(n = 1,692)

No/Low-Dose Statins
(n = 1,649)

P Value

CK-MB ≥ 3 x ULNa

7.0%

11.9%

< 0.00001

Troponin > 1 x ULN

35.8%

47.9%

< 0.00001

CK-MB > 1 x ULN

25.4%

35.9%

0.00001

a Co-primary endpoint.

 

The other co-primary endpoint of MACE (death, MI, or TVR) at 30 days also showed a 44% risk reduction with high-dose statins and a number-needed-to-treat of 19. Most of the individual component endpoints also were lower with high-dose pretreatment, but the differences were not statistically significant due to small numbers (table 2).

Table 2. Outcomes at 30 Days

 

High-Dose Statins
(n = 1,692)

No/Low-Dose Statins
(n = 1,649)

P Value

MACEa

7.4%

12.6%

< 0.00001

Death

0.24%

0.56%

0.20

MI

0.24%

0.16%

0.66

TVR

0.32%

0.80%

0.10

Stent Thrombosis

0.47%

0.40%

0.77

a Co-primary endpoint.

 

There were no significant side effects associated with high-dose statin treatment in any study. In 9 of the studies, researchers measured CRP levels. In subjects with normal CRP levels at baseline, high-dose statin pretreatment reduced the relative risk of periprocedural MI by 31% (7.8% vs. 10.9%; P = 0.021), but the risk reduction was even greater (68%) in patients with high baseline CRP levels (4.3% vs. 12.3%; P < 0.001). In addition, high-dose statins were associated with a lower-post PCI increase in median CRP levels compared with no/low-dose statins (1.2 mg/L vs. 2.2 mg/L; P = 0.00001).

The benefit of high-dose statins was maintained regardless of presentation (ACS, stable angina) and across multiple subgroups defined by age, sex, diabetes, single vs. multivessel PCI, and glycoprotein IIb/IIIa inhibitor use.

“The consistency across trials and the strength of the effect observed in the present meta-analysis suggest that a strategy of high-dose statin pretreatment should be used routinely in patients undergoing PCI, irrespective of clinical presentation and chronic statin therapy,” the researchers conclude. “Guideline committees should consider updates to incorporate this novel strategy for peri-PCI prevention of ischemic events.”

Multiple Mechanisms Suspected

The finding of a magnified benefit of high-dose statin therapy in patients with high CRP levels lends support for a mechanism involving anti-inflammatory effects, the authors note. However, patients with lower CRP levels also benefited, suggesting that “other mechanisms may be at play that may ultimately influence outcome during or after PCI,” they add.

David D. Waters, MD, of the University of California, San Francisco (San Francisco, CA), explained that the anti-inflammatory effects with high-dose statins—and not LDL-cholesterol lowering—are probably felt more in the earlier, periprocedural period. “You’re reducing the inflammation within the vessel wall where you’re blowing up the balloon and popping open the stent and you’re probably reducing the inflammation around the little platelet packages that go down the arteries and cause micro occlusions of the microvasculature,” he told TCTMD in a telephone interview. “You’re probably making those micro injuries less inflammatory, so it’s partly myocardial and partially arterial, but we really don’t know.”

By contrast, LDL-cholesterol lowering may be more involved later on in reducing adverse outcomes, Dr. Waters added.

Either way, “this is a treatment that interventional cardiologists should be using,” he stressed. “Many of them are already, but there’s no reason that they all don’t.”

Large Randomized Trial Not Necessary?

Dr. Waters acknowledged that although a randomized trial may carry more weight than a meta-analysis, such an investigation may not be necessary.

“The only reason you need a large clinical trial to prove something is if a small clinical trial doesn’t prove it. Here, we have several small studies that are showing a statistically significant benefit, and I think that’s as good as one large trial,” he said. “I’m skeptical of a meta-analysis when the P value is a slice below 0.05, but when it’s got several zeroes in it, there has to be a huge bias that’s pervasive through all the studies or else it has to be true, and in this case it’s obviously true. It just goes with everything else that we know.”

Not to mention the fact that the high-dose statin regimen is inexpensive and side-effect free, he added. “Something simple like this, it seems like an easy decision,” Dr. Waters said.

 

Source:

Patti G, Cannon CP, Murphy SA, et al. Clinical benefit of statin pretreatment in patients undergoing percutaneous coronary intervention. A collaborative patient-level meta-analysis of 13 randomized trials. Circulation. 2011;Epub ahead of print.

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Disclosures
  • Drs. Patti and Di Sciascio report no relevant conflicts of interest.
  • Dr. Waters reports serving on steering committees and data safety monitoring boards for trials funded by Merck/Schering-Plough and Pfizer and receiving lecture fees from Bristol-Myers Squibb.

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