February 25th, 2014
Is Post-MI Statin Therapy Appropriately Intensive?
Suzanne V. Arnold, MD, MHA
CardioExchange’s Harlan M. Krumholz interviews Suzanne V. Arnold about her research group’s study of statin initiation, intensification, and maximization after acute myocardial infarction. The study is published in Circulation.
Researchers assessed statin use at admission and discharge for 4340 patients with acute MI at 24 U.S. hospitals from 2005 to 2008. Maximal therapy was defined as a statin with expected LDL-cholesterol lowering of at least 50%. Among statin-naive patients, 87% without a contraindication were prescribed a statin, with almost no variability across sites (median rate ratio, 1.02). Among patients who arrived on submaximal statins, 26% had their statin therapy intensified with modest site variability (median rate ratio, 1.47). Among all patients without a contraindication, 23% were discharged on maximal statin therapy, with substantial hospital variability (median rate ratio, 2.79).
Krumholz: Which of your study’s findings was most surprising to you?
Arnold: Very little of what we found was surprising. As a cardiology community, we have focused a lot on LDL numbers, to measure risk and the need for statins. I think with the MI performance measures, we at least were able to understand that all MI patients need a statin, regardless of LDL level — and our study documented high rates of statin initiation. Moving beyond just initiating statins to intensifying and maximizing statins required a deeper understanding of the statin trials, which were not as well known by clinical cardiologists. As such, physicians tended to make treatment decisions according to their perception of the patient’s risk — intensifying and maximizing statins in patients with high LDL levels and those with STEMI (despite no evidence that these patients were more likely to benefit from intensive statins). We also observed a lot of site-level variability in intensification and maximization, which again was not surprising, as such clinical decisions often follow local practice patterns. We are hopeful that the new lipid guidelines will emphasize the evidence-based imperative to get all MI patients on intensive statins during the MI hospitalization.
Krumholz: Why do you think intensification is not occurring?
Arnold: I think this primarily stems from a misperception about which patients are most likely to benefit from intensive statins. The prior trials showed that all MI patients were equally likely to benefit, regardless of patient characteristics. However, I think there is a misperception that patients who present with STEMI need more aggressive secondary prevention, which is why their statin regimens were more likely to be intensified. Similarly, patients with high LDL levels were thought to need more intensive statin therapy. However, LDL levels can be falsely low in a patient with acute MI, particularly in patients with severe MIs, which is one likely reason why we have not observed any association between LDL levels during MI and a differential benefit from statins. Again, I think the new guidelines will highlight the evidence for the general cardiology community.
Krumholz: Could it be patient choice? How do you present this decision to patients?
Arnold: Possibly, although I suspect this matters very little in the decision to prescribe intensive statins. When I talk to patients and go over the medications I will be prescribing them to take at home, some say, “But I don’t have high cholesterol. Why do I need that?” What I usually then discuss is that for a patient with an MI, cholesterol is deposited in the vessels of the heart, regardless of what the blood numbers read. Statins are the best medications we have for treating those cholesterol plaques in the heart —stabilizing them so they don’t grow and reducing the risk that they will rupture and cause another heart attack. So for patients who have heart attacks, it is really important to be on intensive doses of these medications, regardless of the blood numbers. I try to get patients to understand that the statin is treating the cholesterol plaques in the heart — not the blood numbers. This change of focus on what the medication is targeting seems to make patients more likely to accept taking it. It is a similar conversation for beta-blockers in patients without hypertension.
Krumholz: What is your sense of the trade-off in statin intensification (additional benefit and additional risk)?
Arnold: I think that intensive statins have a clear additional benefit over moderate statins in reducing the risks for recurrent MI and cardiovascular death, although to show an effect on mortality required combining the two major trials. Our pooled analysis documented an NNT of 95 patients with intensive statins to prevent 1 death — that is a fairly small NNT compared with many other secondary-prevention therapies. The more-intensive statins also increase the risk for myalgias, which cannot be ignored. The logical solution would be to start an intensive statin and, if myalgias occur, change to moderate statin therapy. However, if a patient gets myalgias with an intensive statin, he or she may be less willing to try moderate statins. Generally, I have had good luck with getting such patients to try moderate statins. However, I also admit that my personal practice is to use atorvastatin 40 mg in elderly patients who may be more likely to get a side effect (or, at least, whose mobility would be more compromised by a side effect).
I think the decision is more difficult in a patient with a remote cardiac event. The trials studied patients just after an MI, when event rates are highest and the expected benefit of aggressive secondary prevention would probably be greatest. Is there a time period after which the benefit of intensive statin therapy does not outweigh potential risks? We have already seen a suggestion of this with beta-blockers after MI. In the first few years after an MI, I think the case for intensive statins (or at least a trial of intensive statins) is strong. After that, questions remain. Certainly, if a patient has tolerated an intensive statin for a time after an MI, there seems to be no good reason to down-titrate. The question remains as to whether or not to intensify a statin in a patient with a more remote event.
JOIN THE DISCUSSION
In light of Dr. Arnold’s comments, share your thoughts on how well statin therapy is being delivered to patients after myocardial infarction.
Cost is also an issue, even with generic atorvastatin.
Although statin therapy seems to be effectively delivered at the time of an Acute MI – intensification of therapy in the outpatient setting seems to be hit or miss – this is often due to poor hospital follow up, lack of education of the primary care physician and often time due to medication cost which results in changing potent statins for less potent alternatives covered by a patients insurance – statin therapy has proven time an time again it’s resilience and benefit in CAD regardless of the presentation and should become mainstay and affordable even for the most undeserved population…
Thanks for that great scientific dialogue ..I wish to ask Dr/Arnold whether evidence now is the same regarding need for Statin therapy intensification in the different scenarios of unstable angina/NSTEMI/STEMI/Stable CAD…especially after LDL numbers and goals are no longer marks in the road of the therapy of these patients as it used to be last year.In those with renal impairment can intensified Statin therapy still be used?.Thanks a lot for your kindness
Thanks for your question. I do not think the evidence has changed in the last few years–PROVE IT and A to Z were both published in 2004–but what has changed are the guidelines. Our analysis looked specifically at following the evidence at the time, which fortunately, is also now reflected in the guidelines. What to do with the post-ACS patient is pretty straight-forward to me. For me, the big question is the stable CAD patient, as I do not think we have as much evidence to support intensive statins in this population. The guidelines now say to treat all of these patients with intensive statins, and while I think this likely has some benefit, I suspect the NNT would be much larger for the stable CAD population than what was seen in the post-ACS popualation.
Regarding your question about renal impairment, I do not know of any concern about using intensive statins in these patients. Renal patients with coronary disease are very high risk for adverse cardiovascular outcomes, so I suspect they would benefit at least as much (if not more) from the most aggressive secondary prevention, including intensive statins. While admittedly I do not know this literature well, I do not believe intensive statins have been shown to worsen renal function, and thus should be used in CKD patients with coronary disease, particularly after an ACS.
Thanks alot Dr/Arnold for clarifying things in a great scientific manner.