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Why Doesn’t Lowering LDL Cholesterol Save More Lives?

Many health care providers believe that lowering LDL cholesterol with drugs will prevent heart attacks and prolong life. What about the data?

Most cardiologists believe that elevated levels of “bad” LDL are the number one cause of heart disease. They are convinced that lowering LDL cholesterol with statins saves large numbers of lives. But three cardiologists have just challenged their colleagues in the journal BMJ Evidence-Based Medicine (online, Aug. 3, 2020).

Statins Have Achieved Super Star Status:

According to our calculations, the number one most prescribed drug in the U.S. is atorvastatin (Lipitor). At last count, over 100 million prescriptions were dispensed to more than 21 million patients. That doesn’t include simvastatin (Zocor). This drug is dispensed 57 million times to over 11 million patients. Millions more take pravastatin (Pravachol), rosuvastatin (Crestor) and lovastatin (Mevacor).

Statins have become the sacred cows of medicine. Most physicians and many patients believe that cholesterol is our enemy. It is an article of faith that lowering LDL cholesterol (LDL-C) with statin-type drugs is essential for reducing the risk of dying prematurely from heart disease. Anyone who challenges this belief is considered a heretic.

Cardiologists Challenge Colleagues:

Three prominent cardiologists have challenged their colleagues to reexamine the evidence that lowering LDL cholesterol will prevent cardiovascular disease. They performed a systematic review of randomized controlled trials (RCTs) of a variety of cholesterol-lowering medicines (BMJ Evidence-Based Medicine, Aug. 3, 2020). 

If lowering LDL cholesterol with medications saves lives, these studies should show a clear and consistent relationship between reduced LDL and lower mortality. They do not.

Show Us the Data!

We know that seems heretical. But here is what they did. They reviewed all RCTs involving patients at moderate to high risk of atherosclerotic cardiovascular disease (ASCVD) and three classes of cholesterol-lowering drugs. They were 1) statins, 2) cholesterol-absorption inhibitors (ezetimibe) and 3) PCSK9 inhibitors.

According to the authors:

“This analysis highlights the discordance between a well-researched clinical guideline written by experts and empirical evidence gleaned from dozens of clinical trials of cholesterol reduction. It further underscores the ongoing debate about lowering cholesterol in general and the use of statins in particular. In this analysis over three-quarters of the cholesterol lowering trials reported no mortality benefit and nearly half reported no cardiovascular benefit at all.”

Why Hasn’t Lowering LDL Cholesterol Saved More Lives?

These cardiologists point out that greatly increased statin use over the last 20 years has not resulted in a commensurate reduction in deaths from cardiovascular disease. Stop! Read that sentence one more time and then pause to digest the meaning, please.

The use of statin drugs has increased dramatically over the last few decades. According to our calculations, at least 44 million people in the US take statins every day. And that’s just atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin. There are other statins too.

Lowering LDL Cholesterol and Mortality Stats:

We suspect that most patients who take a statin believe that it will protect them from having a heart attack. Of course, the real goal is a longer and healthier life. The implicit promise from health professionals is that if you take cholesterol-lowering drugs, your life will be substantially extended and the quality improved.

Although some studies do show a mortality benefit, the majority do not.

The cardiologists who analyzed the RCT data add that:

“Cardiovascular disease continues to be the leading cause of death worldwide. Between 2002 and 2013 statin use in the US nearly doubled, cholesterol levels are falling, yet cardiovascular deaths appear to be on the rise. In Sweden, recent widespread and increasing utilisation of statins did not correlate with any significant reduction in acute myocardial infarction or mortality, while in Belgium a very modest reduction in cardiovascular events was reported between 1999 and 2005, but primarily in elderly individuals not taking statins. These population studies suggest that, despite the widespread use of statins, there has been no accompanying decline in the risk of cardiovascular events or cardiovascular mortality. In fact, there is some evidence that statin usage may lead to unhealthy behaviours that may actually increase the risk of cardiovascular disease.”

Lowering LDL Cholesterol and Longevity:

How long will statins prolong life? That question has been asked before. A different group of physicians  wrote an article titled (BMJ Open, Sept. 24, 2015):

“The Effect of Statins on Average Survival in Randomized Trials, An Analysis of End Point Postponement”

Here is what the authors reported:

“Death was postponed between -5 and 19 days in primary preventions trials and between -10 and 27 days in secondary prevention trials.”

“The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively.”

They go on to say:

“The survival gains we found are surprisingly small.”

If you would like to read our overview of this research, here is a link

Statins Are NOT a Magic Bullet for Longer Life
Doctors may tell patients that statins will save their lives, but they don’t say how much longer that life will be. New data shows you can count it in days.

How The Media Reports Lowering LDL Cholesterol:

Several weeks ago there were lots of headlines about older people and the benefits of statins for lowering LDL cholesterol and prolonging life. This referred to a very large observational study of older veterans published in JAMA (July 7, 2020).  The investigators tracked 326,981 participants for about seven years. Of that total, 57,178 took a statin-type drug.

Headlines at the time of this publication noted a 25 percent lower risk of dying during that time among statin users. That is referred to as “all-cause mortality.” In other words, people who died from traffic accidents, cancer or dementia were counted along with those who died from heart attacks.

When it came to deaths due to heart attacks and strokes specifically, there were 22.6 deaths per 1000 person-years among those taking statins. For people not on statins, there were 25.7 deaths per thousand person-years. That works out to about three fewer deaths per thousand person-years. Not quite as impressive as reducing the risk by 25 percent.

Lowering LDL Cholesterol Did Not Prevent Heart Attacks and Strokes:

Even more puzzling, however, were the statistics on actual heart attacks and strokes. Statins did not reduce the risk of either outcome significantly. 

Stop! Read that last sentence one more time. After seven years the veterans taking statins did not have significantly fewer heart attacks or strokes than the veterans who weren’t taking statins. And yet there is little doubt that statins are very effective at lowering LDL cholesterol. The authors of this research did not highlight this finding and the reporters who featured the 25% lower all-cause mortality failed to note this surprising outcome.

No one seriously doubts that people with diagnosed heart disease should be taking a cholesterol-lowering drug. Those who can’t tolerate statins may need to be on one of the newer PCSK9 inhibitors such as alirocumab (Praluent) or evolocumab (Repatha).

But the evidence is far less compelling for people who don’t have diagnosed heart disease. Of course, no one should EVER stop taking any medicine without careful consultation with the prescriber. And we hope that prescribers will take time to read the most recent analysis published in BMJ Evidence-Based Medicine (online, Aug. 3, 2020). You could always print the article and offer it to your health care provider to make that process easier.

Lowering LDL Cholesterol vs Lp(a)

Have you ever had your Lp(a) levels measured? We didn’t think so. And chances are good that your health care provider has never mentioned this risk factor. We recently wrote about the importance of Lp little a. You might be surprised to learn that statins may actually raise this lipoprotein. Read more at this link:

Is Lp(a) the Best Kept Secret in Heart Disease?
Most people have had their LDL cholesterol measured. Have you ever had your Lp(a) tested? Did you know that statins may actually raise this key risk factor?

Lowering LDL Cholesterol With Other Strategies:

There are many lifestyle interventions that are important whether or not a person is taking medicine to lower cholesterol. Physical activity, stress reduction and a diet that focuses on plants and minimizes processed foods are crucial.

We cannot say that lowering LDL cholesterol with dietary interventions will reduce the risk of heart attacks and strokes or prolong life. There are data, however, that pomegranate juice, grapefruit, cinnamon, psyllium and red yeast rice can all lower LDL cholesterol.

So can a “portfolio” vegetarian diet. It includes foods such as almonds, barley, eggplant, oats, okra and soy. You can learn more about these nondrug approaches in our eGuide to Cholesterol Control and Heart. It is available in the Health eGuides section of PeoplesPharmacy.com.

Share your own experience with statins in the comment section below. If you think this article is of interest, please share it by scrolling to the top of the page and clicking on the icons for email, Facebook or Twitter. Thank you. 

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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