We know the value of reducing high LDL cholesterol, the cholesterol that deposits plaque in your arteries. Studies done using the cholesterol-reducing drugs called statins have found that for every 40-point reduction in LDL, the risk for heart attack or stroke goes down by 22%. And the goal for a “healthy” level has been to reduce LDL to between 70 milligrams per deciliter (mg/dL) and 100 mg/dL.

Now the goalposts are on the move, in part because of a new type of biologic drug called PCSK9 inhibitors. By inactivating a protein in the liver, these man-made antibodies can bring LDL down to 20 mg/dL…or to virtually any level you want, possibly setting a new standard for low LDL cholesterol. They’re also an effective alternative for people who cannot tolerate statins or whose cholesterol isn’t reduced enough by statins. But, unlike daily statin pills, PCSK9s are injectable drugs that most patients self-administer every two weeks. Side effects are mild—including colds and itching in some people when injected.


Regardless of the drug used, when it comes to LDL cholesterol, the big question is, how low should a given person go? And related—does going lower because of drugs start to present a safety risk at some point? These are some of the questions that researchers at Brigham and Women’s Hospital and Harvard Medical School hoped to answer as they reviewed four large statin and non-statin drug trials involving people with cardiovascular disease at risk for heart attacks and strokes. All the participants started with LDL levels that were 70 mg/dL or below and took medication to further reduce them…down to 20 mg/dL for some.

The researchers looked at the frequency of heart attacks and strokes among patients with the standard low LDL and those with LDL below 70 mg/dL and found that going below 70 mg/dL (sometimes considerably lower than that) was good for patients.

For example, reducing LDL from 70 mg/dL to 30 mg/dL reduced cardiovascular events by another 20%, in essence doubling the benefits found in previous statin-only studies. And this was equally true for statins and statins plus PCSK9 inhibitors or other nonstatin drugs. This demonstrates that people who can’t take or don’t benefit from statins can get statinlike benefits from PCSK9 inhibitors. This includes people with very high LDL due to an inherited condition called familial hypercholesterolemia—for many of these people, heart attack risk remains high even with statin therapy.

Not every question has been answered. Most importantly, the “best” low LDL level really hasn’t been determined, and yet studies like this one may lead doctors to push for lower and lower levels. Indeed, new guidelines for cholesterol management are being worked on by the American Heart Association and the American College of Cardiology. They could include a drop in what’s considered a healthy LDL level to below 70 mg/dL now that it’s been shown this can be achieved without incremental side effects—but there are still existing side effects from statins. For a detailed look at statin side effects, see “What You Don’t Know About Statins (Could Hurt You)” and “Little-Known Side Effects of Taking Statins.”

Also, consider that the latest study took place over about two years, so any longer-term risks of taking doses that are higher than what’s currently being prescribed are as yet unknown—remember that it took 20 years to find out that statins can increase the risk for type 2 diabetes.

For now, talk to your doctor to better understand your personal risk for cardiovascular disease, heart attack and stroke. If a statin is not reducing your LDL to a safe level or if its adverse effects are interfering with your life, a PCSK9 inhibitor could be for you if you have established heart disease or are in a high-risk category. But in terms of going to new lower levels of LDL, regardless of the drug you take to get there, you need to weigh the unknowns as well as the benefits.

There’s one more important caution: No drug can fully compensate for not making lifestyle changes to reduce LDL, and they bear repeating…

  • A diet low in saturated and trans fats
  • Weight management
  • Physical activity
  • Stress reduction
  • Not smoking

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