Statin Therapy: Risk for Future CV Events

Health care professionals caution on the persistent/residual cardiovascular risk that remains in patients who have their LDL well controlled on statin therapy.


Deepak L. Bhatt, MD, MPH: One thing that not all patients seem to realize, maybe not even their physicians, is that even if the LDL [low-density lipoprotein] is well controlled on statin therapy, there is still the potential for cardiovascular events. There’s still residual cardiovascular risk. I’ll ask Dr Navar for a brief comment on why that is. Why is it that there’s still persistent risk? If their LDL is lowered to the ranges you mentioned before, say below 50 mg/dL or so, why do events keep happening?

Ann Marie Navar, MD, PhD: I think this gets back to the pathophysiology of cardiovascular events. People who already have established atherosclerosis, who have cholesterol deposited in arterial walls, those plaques can still rupture. Thrombotic complications happen, and progression of atherosclerosis can still happen with low LDL cholesterol, requiring revascularization. As great as these therapies are, they’re not a panacea. This is probably an important message for us. We really should be doing a better job of preventing atherosclerosis in the first place.

One of the numbers that I think is pretty striking is if you look at clinical trials, which tend to recruit healthier participants who are adherent to therapy and are well treated, you still see high event rates. There was a trial that looked at post-ACS [acute coronary syndrome]. Almost everybody was on a high-intensity statin. There were high rates of appropriate antiplatelet, β-blocker, ACE [angiotensin-converting enzyme] inhibitor use. And in the placebo arm, at 3 years 10% of patients had a hard cardiovascular event—a stroke, MI [myocardial infarction], or cardiovascular death. And if you look at certain subgroups of those patients, like those with polyvascular disease, or CABG [coronary artery bypass grafting], or lots of other risk factors, those event rates are even higher. So it’s great that we have made the progress that we’ve made so far, but you still have plaque and that plaque can still rupture. And although LDL cholesterol reduction can reduce the risk, it doesn’t eliminate it.

Deepak L. Bhatt, MD, MPH: Yes, I think that’s such a critical point. When statins were first introduced, and then with all of the great outcomes data, there were some who said, “Oh, once we have statins and they’re in widespread use, acute coronary syndromes will go away.” And the same arguments were made when PCSK9 inhibitors were first being tested. But you know, acute coronary syndromes haven’t gone away. They haven’t really gone anywhere. There have been some shifts in terms of proportion of STEMI [ST-elevation myocardial infarction] going down and STEMI going up. But still, a lot of acute coronary syndromes and other morbidities of cardiovascular disease. So yes, LDL control is important, but that doesn’t end the discussion.

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