In our last two conversations with Ronald Krauss, M.D., an expert in lipidology and a member of our editorial board, we discussed how to assess your risk of cardiovascular disease (CVD) and the role of diet in reducing that risk. Here, we present the third and last part of our conversation with Dr. Krauss about pharmaceutical treatment.
Wellness Letter: In terms of pharmaceutical treatment, what is the role of statins?
Dr. Ronald Krauss: When it comes to having the greatest impact on people at highest risk for CVD, cholesterol-lowering statins are really the central focus. A large body of evidence supports this. These drugs have been studied for 30-plus years. That’s why clinical guidelines recommend statins as the initial pharmacological treatment for patients whose risk of CVD is still sufficiently high even after they are on a healthy diet. Diet is important for many reasons, but dietary changes often don’t have sufficient impact on cholesterol levels. So statins are the mainstay, but we also have additional medications available if statins alone do not reduce CVD risk sufficiently or if a patient can’t tolerate statins.
In a few situations, statins are indicated immediately—if someone has a coronary event like a heart attack, for example, or they suffer an acute syndrome that clearly indicates the presence of severe coronary disease. When people are hospitalized for a heart attack or go in for an angioplasty, they are discharged on statin treatment right off the bat.
WL: Do statins reduce death rates?
RK: Presumably by reducing CVD risk, you’re going to reduce the risk of death from CVD. That has been demonstrated in trials with statins in individuals at high risk—those who already had CVD or who have very high risk of CVD. In these groups, the risk of death is reduced in conjunction with the risk of having a heart attack. It’s been most robustly shown in people who have already had CVD, but the evidence for those at high risk for CVD is also strong.
The literature does leave some issues that are not fully resolved. For example, fewer studies have been carried out in women than in men, and there are legitimate questions as to whether statins may be overprescribed in younger women who have high cholesterol levels but are otherwise at low risk for CVD.
Another question is whether we should be treating people over age 75 with statins to lower their risk of CVD. Studies looking at statin use in this age group are just starting to appear. The consensus based on available data is that age should not be a criterion for withholding statins for people who have high risk based on overall assessment of risk factors.
WL: What kinds of side effects can people experience from statins?
RK: I’m a specialist, so I see a fair number of patients who have side effects from statins—not because side effects are that common among the population, but people who do have them come to me to see what alternatives there might be. They have a condition that has been formally designated statin intolerance. These patients can have muscle symptoms, they can have a variety of aches and pains, or they might feel a little bit fuzzy. Not all these reactions can be clearly demonstrated to be due to the statins, but nevertheless, patients feel they cannot tolerate them. And in some patients, statin use can cause modest increases in blood sugar that can lead to development of diabetes in those who already have borderline high sugar levels.
There are well-established medications that we can use in addition to statins, and they can also be used on their own for lowering cholesterol levels in patients with statin intolerance. One is a medication called ezetimibe. Statins lower LDL levels by improving the ability of the liver to clear these particles from the blood. Ezetimibe works by blocking cholesterol absorption in the intestines. That’s a completely different mechanism, and the drug doesn’t have the side effects of statins.
Another type of drug for lowering LDL levels is called a PCSK9 inhibitor. This is an antibody that’s given by injection either once or twice a month, and there may soon be an oral PCSK9 inhibitor available. These drugs can dramatically lower cholesterol levels, even more than ezetimibe. They also can lower Lp(a) levels moderately. And even though statins don’t lower Lp(a), it’s been found that the CVD risk associated with high Lp(a) can be minimized by achieving a maximal reduction of LDL levels.
WL: Haven’t there also been concerns about cognitive effects from statins, especially with prolonged use?
RK: Yes. Statins carry a warning label that in rare cases they can cause a temporary loss of memory or confusion. When the statin is stopped, the condition improves. However, the more general question is an important one—are there risks for brain function, such as development of Alzheimer’s disease, with the use of statins—or possibly even benefits?
Many clinical trials of statins have measured cognitive function, and overall they have shown that statins don’t have a significant effect either way. But those trials are relatively short term, so they do not necessarily give the full story. When people go on statins, they are often taking them for 10 or 20 or 30 years. There is current research to see whether we can detect longer-term effects that are either adverse or beneficial. One of the studies I’m involved with is looking at outcomes for tens of thousands of patients who have been on statins for decades. So, the short answer to the question is that the issue is under study, but there is no conclusive evidence yet either way.
WL: Given the issue of side effects, why not wait to treat people until they already have symptoms or signs of CVD rather than just being at high risk of CVD?
RK: The problem with adopting that as a strategy for implementing treatment is that the first symptom or sign of CVD is often death from a heart attack or stroke. So, you don’t want to wait until that first symptom to prescribe medication. What I’ve been deeply involved with is trying to sharpen our ability to discriminate those at risk and for whom the benefits can be reasonably expected to outweigh the competing possibility of adverse effects from those for whom the risks outweigh the benefits. And that is where the rubber hits the road. That’s because this is a work in progress, and there’s still a lot to be learned about how to predict benefit versus risk in a more finely tuned way than is now possible from algorithms based on population studies or large clinical trials. That population perspective doesn’t consider individual factors and differences.
One thing that’s often overlooked in this discussion is that preventing a heart attack or stroke prevents not just the events but also the terrible medical consequences that can occur in patients who survive them. That’s a huge growing health burden in the population—people who have had heart attacks or strokes and survived. They haven’t died, but their heart or brain function has been severely compromised. The mortality data don’t capture that. Prevention in this field means you’re also preventing the likelihood of people developing devastating chronic vascular conditions that can drastically decrease quality of life, often for the rest of their lives.
