ACS? Start My Statins!

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Buried in the 2014 AHA/ACC NSTEMI guidelines is a strong recommendation for EPs to start treating ACS with a quick regimen of high-dose statins. According to the research, this a low risk treatment with a high potential of benefit.

When it comes to Acute Coronary Syndrome (ACS), usually it’s the cardiologist who decides which patients get heparin, which get platelet inhibitors other than aspirin, and which receive beta blockers and calcium channel blockers.

As an emergency physician, even if you’re up on the literature and are aware of the indications and contraindications for these drugs, the fact is that it’s a moving target. The literature seems to be ever changing about which drugs should be given to which patients with ACS and the treating cardiologist may have their favorite, though not necessarily evidence-based, regimen.


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Enter the AHA/ACC 2014 NSTEMI guidelines, which sidelined some common treatments, and elevated others. Oxygen, for example, used to be given in a knee-jerk manner, but now it seems the prudent physician will avoid hyperoxemia (there are some theoretical concerns about increasing coronary artery resistance and some other negative physiologic effects) and simply maintain the O2 saturation in the mid-90’s.  In fact, most ACS patients, unless in pulmonary edema, cardiogenic shock or with pre-existent COPD are likely to have normal oxygen saturation and in these cases no supplemental oxygen is indicated. Can you imagine an ACS patient not getting oxygen?  Well, that’s the recommendation of the AHA/ACC NSTEMI guidelines.  Specifically they advise to “administer supplemental oxygen only with oxygen desaturation < 90%, respiratory distress, or other high-risk feature of hypoxemia.”

More interesting than the devaluing of oxygen for ACS, however, is the role of statins in the treatment of ACS. How many emergency physicians routinely start ACS patients on high-dose statins (in patients not already on them)?

What do the AHA/ACC guidelines say about statins in NSTEMI?  Buried in 43 pages are these two small sentences:


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“High-intensity statin therapy should be initiated or continued in all patients with NSTE-ACS and no contraindications to its use” – Four references are cited and the Level of Evidence is A. All references were published between 1996 and 2010.

“It is reasonable to obtain a fasting lipid profile in patients with NSTE-ACS, preferably within 24 hours of presentation.”  No references are cited. Level of Evidence is C.

That’s it – certainly no banner headlines, certainly easily overlooked – yet, important for every emergency physician to know – despite the fact that the AHA/ACC never gets specific about when statins should be initiated or how much.

Well, here are two papers that will hopefully allow emergency physicians to feel comfortable initiating high-dose statins in the ED.  No, it’s not about commando lowering of blood lipids – not at all.  It’s about other, less well-understood effects of statins generally described as their “pleiotropic effects.”  Generically, pleiotropic effects of a drug are effects, usually unanticipated, other than those for which the agent was specifically developed.


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More than 10 years ago articles started describing potentially beneficial effects of statins seemingly unrelated to their ability to alter lipid levels.  Beneficial effects on endothelial function, stabilization of atherosclerotic plaques, decreasing oxidative stress and inflammation and inhibition of thrombogenesis have all been noted.  Although studies didn’t seem to focus on the benefits of statins in ACS in general, many studies started popping up regarding the potential benefits in patients having a percutaneous coronary intervention (PCI) – ACS or not.

So the question for emergency physicians is whether statins should be given to all suspected ACS patients recognizing that, at least some significant fraction will be getting a PCI and there is no harm in a single dose if a PCI is not performed (just like there is no harm if aspirin is given and a patient doesn’t have an ACS).

So here are two studies, one very recent, addressing statins in the setting of PCIs.  The first noted that there are about a million percutaneous coronary interventions performed annually in the United States and that, depending on the definitions used and populations examined, peri-procedural MIs have been shown to occur in 8-25% of patients getting a PCI.

The authors of the first study, in justifying their meta-analysis, noted that a large series of trials has suggested that statins may decrease the rate of peri-procedural MIs in those getting PCIs, but most of the prospective trials reporting a benefit of statins were small in size, with varying endpoints and varying statin regimen and collectively these studies lacked the power to demonstrate a clinical difference.

Although the authors of the first study specifically choose to examine outcomes according to the type of presenting coronary complaints (specifically, stable angina and NSTEMI), they excluded STEMIs! The rationale for not attempting to determine the effect of statins in STEMI patients about to receive a PCI is baffling. They say STEMI patients were excluded because “they felt that in these cases there would be insufficient time from loading with a statin to treatment with emergency PCI to allow for the statin medication to be absorbed by the patient and exhibit its pleiotropic effect ‘prior to’ PCI.”  Although this may be the case, it would have been great to avoid the assumption they made and just do the study.  The authors also excluded patients who were already on statin therapy (seems reasonable).

So, despite the very positive effects on peri-procedural MIs (the primary study end-point) ascertained in their 14-study meta-analysis, emergency physicians technically can’t say anything about the use of statins in STEMIs.  However, the meta-analysis demonstrated that only in the subset of NSTEMI patients did statins reduce the composite end-point of death, spontaneous MI and target vessel revascularization (OR 0.59, 95% CI 0.38-0.92, p=0.02).  More specifically, in the statin-loaded group, the combined end-point occurred in 0.9% of the statin patients vs 5.7% of the controls (NNT = 16).

Given the significant reduction in adverse clinical outcomes in NSTEMI patients getting a PCI, why would we not assume, given the frequency of PCIs in ACS, that there is at least theoretical benefits in giving statins just as soon as an ACS is suspected – just like we give aspirin?

Dosing of statins in potential ACS patients is another issue. The Benjo study below noted that in the subset of NSTEMI patients, the dosing of statins used was atorvastatin (80mg) or rosuvastatin (20mg or 40mg).

If you’re still not convinced about initiating statin therapy for suspected ACS, here are two additional points to consider: First, it will be the rare patient with an ACS who is not started on a statin during their hospitalization — independent of their lipid levels – so beginning therapy in the ED should not be an issue. Second, there are conflicting studies indicating that statins may reduce the incidence of contrast-induced nephrotoxicity associated with the IV contrast material used when a PCI is performed. See Statins for the Prevention of Contrast-Induced Nephropathy After Coronary Angiography/Percutaneous Intervention: A Meta-Analysis of Randomized Controlled Trials by Liu, Y.H., et al, J Cardiovasc Pharm Ther, March 2015.

HIGH DOSE STATIN LOADING PRIOR TO PERCUTANEOUS CORONARY INTERVENTION DECREASES CARDIOVASCULAR EVENTS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Benjo, A.M., et al, Cath Cardiovasc Interv 85(1):53, January 1, 2015

BACKGROUND: Studies have reported that peri-procedural myocardial infarction (MI) occurs in up to 25% of patients undergoing percutaneous coronary intervention (PCI). Some have suggested that statin loading prior to PCI reduces this risk.

METHODS: These multicentered authors, coordinated at Columbia University, performed a meta-analysis of 14 randomized, placebo-controlled trials of the effects of a pre-procedural loading dose of a statin prior to PCI in 3,146 statin-naïve patients with stable angina, non-ST-elevation acute coronary syndrome (NSTE-ACS) or mixed indications. Patients with ST-elevation MI referred for primary PCI were excluded. All patients were treated with statins post-PCI.

RESULTS: Peri-procedural MI (the primary endpoint) occurred in 7.5% of patients randomized to pre-PCI statin loading vs. 15.8% of controls (odds ratio [OR] 0.44, 95% CI 0.35-0.56, p<0.00001). Significant reductions in peri-procedural MI were observed in patients with stable angina (OR 0.33, p<0.00001) or NSTE-ACS (OR 0.32, p<0.0001) and in mixed populations (OR 0.66, p=0.02). Statin loading was also associated with a reduction in the combined endpoint of death, spontaneous MI and target vessel revascularization ((OR 0.59, 95% CI 0.38-0.92, p=0.02), but this benefit was observed only in the subgroup of patients undergoing PCI for NSTE-ACS (OR 0.18, p=0.0005).

CONCLUSIONS: These results are consistent with a significant short-term clinical benefit of pre-PCI statin loading in statin-naïve patients with NSTE-ACS followed by standard statin dosing after the procedure. 35 references (jtamis@chpnet.org – no reprints)
Copyright 2015 by Emergency Medical Abstracts – All Rights Reserved 5/15 – #2

Here’s a prior meta-analysis that was also positive regarding the effect of statins in the setting of PCIs.

CLINICAL BENEFIT OF STATIN PRETREATMENT IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION: A COLLABORATIVE PATIENT-LEVEL META-ANALYSIS OF 13 RANDOMIZED STUDIES
Patti, G., et al, Circulation 123(15):1622, April 19, 2011

BACKGROUND: The rate of periprocedural myocardial infarction (MI) in patients undergoing percutaneous coronary intervention (PCI) has been reported to range from 5% to 40%, depending upon the definition. Animal studies and limited human trials have reported that statin pretreatment might prevent this complication.

METHODS: These multinational authors, coordinated in Italy, performed a patient-level meta-analysis of 3,341 participants in 13 randomized controlled trials of high-dose statin pretreatment vs. low-dose or no statins (controls) prior to PCI (one was an ED-based study using 80mg of atorvastatin). There were no differences in periprocedural antithrombotic treatment, and all of the patients received post-procedure statins.

RESULTS: Rates of periprocedural MI were 6.8% in the intervention group receiving high-dose statin pretreatment vs. 11.9% in controls (odds ratio [OR] 0.54, p<0.00001), and corresponding rates of periprocedural myocardial injury, based on post-PCI troponin levels, were 34.9% vs. 47.7%, respectively (OR 0.59, p<0.00001), and 5.9% vs. 9.0% in the subgroup undergoing PCI for acute coronary syndrome (OR 0.64, p=0.06). Rates of major adverse cardiac events (defined as death, MI or target vessel revascularization) at 30 days were 7.4% in the intervention group vs. 12.6% in controls (OR 0.56, p<0.00001) when periprocedural MI was included as an outcome, and 0.6% vs. 1.4%, respectively (OR 0.44, p=0.05) when periprocedural MIs were excluded. The number-needed-to-pretreat (NNT) with high-dose statins to prevent one periprocedural MI was 20.

CONCLUSIONS: These findings support routine high-dose statin pretreatment for patients undergoing PCI. 48 references (g.patti@unicampus.it – no reprints)
Copyright 2011 by Emergency Medical Abstracts – All Rights Reserved 11/11 – #2

So, when I come into your ED with my ACS, please, please – just give me the ASA and a high-dose statin as I hit the door.  This is a situation where I can’t see any harm and there is the potential for some clinically significant benefits.  I’m not interested in waiting for the definitive trial.

ABOUT THE AUTHOR

EXECUTIVE EDITOR
Dr. Bukata is the Editor of Emergency Medical Abstracts.

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