Are Statins Worth It? (Part 1)

LDL cholesterol, also known as bad cholesterol, is unequivocally recognized as the principal driving force in the development of atherosclerotic cardiovascular disease, our leading cause of death. Over the decades, we have seen the guidelines shift to lower and lower LDL targets on the basis of clinical trials demonstrating that lower is better––starting in the 1980s with an LDL target of 130 mg/dL, then down to 100 in the 90s, and maybe down to 70 for those at really high risk, and then maybe even down to 55, 40, or 30 over the last decade. Those more recent targets might actually be closer to normal for the human species. Even after we learned to use tools so we could hunt, normal LDL has been in the 50 to 70 range. But today, the average in the Western world is more like 120 mg/dL. No wonder heart disease is our leading cause of death in men and women.

Recently, guidelines started scrapping targets in favor of just pushing for LDL levels to be as low as possible, because the lower the better. No threshold seems to exist below which LDL cholesterol-lowering does not further reduce risk. When it comes to LDL, it’s possible that lower is better for longer—even if you start out at low risk. The risk reduction of major vascular events is independent of the starting LDL cholesterol, meaning that even people starting out with an LDL under 80 had about the same relative risk reduction.

So, even if your LDL is “normal,” even if other heart disease risk factors are considered optimal, it is considered of utmost importance to control it. So, why not just put cholesterol-lowering drugs like statins in the drinking water, like we do fluoride? Why aren’t statins prescribed for everyone? Because of the downsides. There’s the risk of side effects, plus the burden of having to take a pill every day for the rest of your life. So, that’s why these drugs are only recommended for people at relatively high risk of having a heart attack, for whom the pros of cholesterol-lowering outweigh the cons of taking the drug.

Okay, but when it comes to LDL, if “lower is better for longer, and the earlier the better,” and the only reason we’re not giving more drugs is the downsides, what if there were safe, simple, side-effect-free solutions to lowering our cholesterol––for example, eating specific types of healthy foods every day? Well, in that case, regardless if we’re on drugs or not, shouldn’t we utilize every safe no-downside strategy there is to get our LDL down as low as possible? Before I get to all those strategies, let’s answer the on-drugs-or-not question.

According to the latest cholesterol clinical practice guidelines from the American Heart Association and the American College of Cardiology, the number one take-home message is a lifelong heart-healthy lifestyle. Okay, but when do they also recommend drugs? If you have been diagnosed with heart disease, like if you’ve already had a heart attack and are trying to prevent another one, then drugs are considered non-negotiable. Okay, but what about primary prevention––meaning preventing that first heart attack? Well, if you have an LDL of 190 or more, then “Don’t pass go, don’t collect $200,” and go straight to statins. Similarly, if you’re between 40 and 75 and have diabetes, then an LDL of even 70 gets you a statin recommendation. Now, if you don’t have known cardiovascular disease or diabetes, and your LDL is between 70 and 190, then statins are generally recommended if your risk of having a cardiovascular event, like a heart attack or stroke, is 7.5% or more over the next 10 years.

Even at a 10-year risk as low as 5%, a statin may be recommended if you have risk-enhancing factors such as high triglycerides or a bad family history. And, if you’re in that intermediate risk category where statins are recommended, but you’re still on the fence, a coronary calcium scan imaging test can be done to help you decide.

How do you figure out what your 10-year risk is? In a previous video I did on the topic, I recommended three common risk calculators, but I have a new favorite, u-prevent.com. That’s just the letter u, dash, prevent (p-r-e-v-e-n-t) dot com. It’s free and endorsed by the European Society of Cardiology. Not only does it give you a 10-year risk estimate, and a lifetime risk estimate, but it estimates how long you may have before the event and, best of all, you can then toggle various treatment options to see what may happen to your risk if you follow them, like what happens if you stop smoking or increase your step count or start a statin.

But whether or not the overall benefit-harm balance justifies the use of a medication for an individual patient cannot be determined by a guidelines committee, a health care system, or even the attending physician. Instead, it is the individual patient who has a fundamental right to decide whether or not to take a drug is worthwhile. It’s your body, your choice; so, let’s go through the pros and cons so you can decide for yourself, next.

In my video on how doctors paternalistically mislead patients about statin risks and benefits for their own good, I talk about how, for the majority of patients surveyed, the expectation of benefit from drugs like statins is higher than the actual benefit the drugs provide. So, this creates tension between a patient’s right to know and the likely reduction in the chance they’d agree to take it if they knew how little benefit the drug offered. On a population scale, that would be devastating. For example, statins probably prevent tens of thousands of deaths a year in the United States. However, if patients were routinely told the truth, as many as 75% of patients might stop treatment. So, unless we keep everyone in the dark, 30,000 people could die. So, what should doctors do? I agree with these doctors that we have to tell the truth, even if it means the patient doesn’t take it and potentially dies as a result. It’s their body, their choice. Of course, I wish this fully-informed consent would extend to telling people about the beneficial role a healthy diet. But before we get to that, let’s answer the statins question. Are they worth it? Maybe you’re in the 25% of people who would still take it, even knowing the whole truth. So, what is the whole truth?

We’ve all seen the drug ads, like this one touting atorvastatin—lipitor—as reducing the risk of a heart attack by about a third., “That means in a large clinical study, 3% of patients taking a sugar pill had a heart attack compared to 2% of patients taking Lipitor.” Going from 3 to 2 is indeed a drop by a third in relative risk, but the drop in absolute risk was only 1%, which sounds less impressive. This is common even in the medical literature—no surprise, since journal articles are often written by drug manufacturers. Now, the 3 to 2% Lipitor drop was over a period of only about three years. These are drugs to be taken over a lifetime; so, the benefits accrue. Over four or five years, the absolute risk reduction might reach 1.3%, but you can see why many patients are not very moved. Even in the studies where people were presented with an idealized tablet with no side effects, more than a third stated they would not consider taking a medication that would drop their five-year absolute risk by 5% or more.

Only about 50% of people would consider taking preventive medications that prolonged their life by less than eight months. The average expected longevity benefit from statins ranges from a few months to a few years, depending on risk. About a third said—three months? I’ll take it, whereas about one in 10 said they wouldn’t take pills even if they got to live an extra 10 years or more. That’s why it’s such a personal decision, because we are all over the place in terms of what we’re willing to accept.

Your doctor may not care, though. Physicians were presented with the case of a man with a 7 to 10% risk of dying from cardiovascular disease over the next decade who explicitly told the doctor they only wanted to take a statin if it would increase their lifespan by a certain amount. Some doctors were told the patient demanded at least eight years of life, and others were told the patient only asked for a matter of months, which is actually what they’d gain in real life. Yet 83% of the doctors said they’d prescribe it to the patients who unrealistically demanded eight years, which is almost exactly the same percentage recommended by the doctors who were told the patient only wanted a few months. In other words, the doctors were insensitive to patient preferences regarding survival gain.

Now, for primary prevention, trying to prevent your first heart attack, no overall survival benefits have been found. Indeed, only one of eight studies showed that statins actually make people live longer, but presumably that’s because the studies only lasted a few years, and for low-risk populations, the risk of dying from cardiovascular disease in that time may just be a few percent anyway. But such trials do show fewer events, heart attacks and strokes. So, on a public health scale, it would make sense not to just wait for people to have a heart attack before starting them on cholesterol-lowering drugs.

Critics counter that yes, that sounds good, and if statins had these benefits without side effects, then perhaps the decision to start them is understandable. But look, because statins increase our risk of diabetes, these drugs might give as many people diabetes as it does prevent them from having a heart attack or stroke. But the stat they cite is from a combination of primary and secondary prevention trials.

In primary prevention trials, like trying to prevent your first heart attack, there is no increased diabetes risk. You only see that in the secondary prevention trials, where people are trying to prevent their second heart attack, for instance. This might be because their risk of diabetes is higher in general, or they’re using higher doses of statins. Intensive-dose statin therapy is associated with a greater increased risk of new-onset diabetes compared to moderate-dose statin therapy. Of course, intensive therapy also offers more benefits in terms of cardiovascular protection.

Then, if you separate out the primary prevention trials by the populations who have low or high rates of diabetes, regardless of the drug, statins only seem to increase risk among those with high baseline rates. Again, this could be a consequence of running shorter-term trials in low-risk populations. The big benefit—preventing death—may not show up, but the big downside—like the drug giving you diabetes—may also not show up. But even in the trials that do show increased diabetes, the risk of getting diabetes may be vastly offset by the cardiovascular protection offered from statin therapy.