Category Archives: Cholesterol Treatment

Unsure About Taking A Statin For High Cholesterol? Consider A Compromise Approach

In an earlier post the skeptical cardiologist introduced Geo, a 61 year old male with no risk factors for heart attack or stroke other than a high cholesterol. His total cholesterol was 249, LDL (bad) 154, HDL (good) 72 and triglycerides 116.

His doctor had recommended that he take a statin drug but Geo balked at taking one due to concerns about side effects and requested my input. My first steps were to gather more information.

-I calculated his 10 year risk of stroke or heart attack at 8.4% (treatment with statin typically felt to benefit individuals with 10 year risk >7.5%) and as I have previously noted, this is not unusual for a man over age 60.

-I assessed him for any hidden  or subclinical atherosclerosis and found

The vascular ultrasound showed below normal carotid thickness and no plaque and his coronary calcium score was 18,  putting him at the 63rd  percentile. This is slightly higher than average white men his age.

So Geo definitely has atherosclerotic plaque in his coronary arteries. This puts him at risk for heart attack and stroke but not a lot higher risk than most men his age.

Strictly speaking, since he hasn’t already had a heart attack or stroke, treating him with a statin is a form of primary prevention. However, we know that atherosclerotic plaque has already developed in his arteries and at some point, perhaps years from now it will have consequences.

What is the best approach to reduce Geo’s risk?

It’s essential  to look closely at lifestyle changes in everyone to reduce cardiac risk.

The lifestyle components that influence risk are

  1. Cigarette Smoking (by far the strongest)
  2. Diet
  3. Exercise
  4. Obesity (Obviously related to #1 and #2)
  5. Stress
  6. Sleep

Patients who try to change to what they perceive as a heart healthy diet by switching to non-fat dairy and eliminating all red meat will not substantially lower risk (see here.) Even if you are possess the rock-hard discipline to stay on a radically low fat diet like the Esselstyn diet or the Pritikin diet there are no good data supporting their  efficacy in preventing cardiac disease.

Geo was not far from theMediterranean diet I recommend but would probably benefit from increased veggie and nut consumption. He was not overweight and he doesn’t smoke. I encouraged him to engage in 150 minutes of moderate exercise weekly.

Low Dose, Intermittent Rosuvastatin

I engaged in shared decision-making with Geo.  Informing him, as best I could, of the potential side effects and benefits of statin therapy.

After a long discussion we decided to try a compromise between no therapy and the guideline recommended moderate intensive dose statin therapy.

This approach utilizes a low dose of rosuvastatin taken intermittently with the goal of minimizing any statin side effect but obtaining some of the benefits of statin drugs on  cardiovascular risk reduction.

I have many patients who have been unable to tolerate other statin drugs in any dosage due to statin related muscle aches but who tolerate this particular  treatment and I  see substantial reductions in the LDL (bad) cholesterol with this approach.

Studies have shown that rosuvastatin 5–10 mg or atorvastatin 10–20 mg given every other day produce LDL-C reduction of 20–40 %

Studies have also shown that In patients with previous statin intolerance, rosuvastatin administered once or twice weekly (at a mean dose of 10 mg per week) achieved an LDL-C reduction of 23–29% and was well tolerated by 74–80 % of patients.

In a recent report from a specialized lipid clinic, 90 % of patients referred for intolerance to multiple statins were actually able to tolerate statin therapy, although the majority was at a reduced dose and less-than-daily dosing.

Results in Geo

After several months of taking 5 mg rosuvastatin twice weekly Geo felt fine with no discernible side effects. He obtained repeat cholesterol  levels:

His LDL had dropped 52% from 140 to 92.

Hopefully, this LDL reduction plus the non-cholesterol lowering beneficial properties of statins (see here) will substantially lower Geo’s risk of heart attack and stroke.

We need randomized studies testing long-term outcomes using this approach to make it evidence-based. But in medicine we frequently don’t have studies that apply to  specific patient situations. In these cases shared decision-making in order to find solutions that fit the individual patient’s concerns and experience becomes paramount.

Faithfully Yours,

-ACP

 

 

 

Are You Paying More For Rosuvastatin (Generic Crestor) Than Brand Name Crestor?

The skeptical cardiologist was shocked to hear from a patient last week that she would have to pay considerably more for generic rosuvastatin (GR) than Crestor, its brand name equivalent.

Crestor is the most potent statin we have at lowering LDL (bad) cholesterol, raising HDL (good) cholesterol, and  preventing strokes and heart attacks.  It is also the best tolerated statin in my experience; I use it frequently at low or intermittent dosages in patients who have developed muscle aches on other statins.

In comparison to atorvastatin (Lipitor, the most widely prescribed statin), Crestor is less likely to interact with other medications and (very important for a surprising number of my patients), you can consume grapefruit when taking it.

When a generic (rosuvastatin calcium) of Crestor became available last year I rejoiced, believing that the high cost of Crestor would now drop to the levels we have typically seen with other generic statins.

I have been giving Crestor sample packs like these to my patients for years. Alas, they will fade away. One downside to going generic.
I have been giving Crestor sample packs like these to my patients for years. Alas, they will fade away. One downside to going generic.

For example, when Lipitor (atorvastatin, the statin market leader for 20 years) went generic, patients no longer worried about its cost.

Initially it seemed GR was much more affordable for my patients than Crestor, however recently, I have had many of them report a rise in its cost.

Why Would The Generic Cost More Than Crestor?

The reasons for brand name versus generic pricing are many and complex, and they yield insight into the legal machinations that Big Pharma engages in to maintain high patient pharmaceutical costs.

This NY Times piece from July, 2016 reveals  how hard AstraZeneca fought to protect its exclusivity in selling Crestor and to prevent generics from entering the market. AstraZeneca’s last tactic involved a lawsuit claiming that their patent was protected by the orphan drug act. They lost and were heavily criticized:

“This case is not about the medical needs of a small population of pediatric patients with a rare disease,” the F.D.A. and Justice Department said in a brief filed in the lawsuit. “It is about AstraZeneca’s profit-driven desire to substantially extend its virtual monopoly on one of the world’s most popular medicines.”

There are other factors that slow the drop in generic prices. Consumer Reports, writing on the anticipated release of GR in May quoted an expert thusly:

“While some pharmacies drop the price as generics enter the market, others will hold it near the brand-name price as long as possible.” They get away with it, he says, because many customers who have health insurance pay a set co-pay regardless of the retail price. But those consumers who pay the entire cost of the drug themselves because they don’t have insurance or have a high deductible may not see the substantial savings that should come with generic availability.”

What an individual pays for drugs varies wildly depending on their insurance coverage. These costs are extremely hard for a physician to anticipate and rarely reflect the actual cost of drugs. Thus, in America, patients as consumers are often isolated from the true costs of pharmaceuticals to society.

Geo (he who was “on the fence” about taking a statin) asked me the following reasonable question about his GR prescription:

I did not pay anything for the 25 pills, however the paperwork states a cost of $220 if I had to buy this outside of a health insurance plan. Do you know if the health insurance company is being charged the $220, or do they negotiate a lower cost with the manufacturer?
I don’t have that answer, but would love to know it. This kind of information is hard to get at.
Send Me Your Observations On The Cost of Generic Rosuvastatin
I would like to get input from my patients and readers on their experience regarding the cost of GR to them and/or their insurance company.
I’d also appreciate input from those in the pharmaceutical or insurance portion of this equation (I know I have at least one patient who is in the pharmaceutical industry).
Finally, if any of you have experience with purchasing GR online from international pharmacies, please share it below. For example, this site claimed in May, 2016:
Ninety pills of generic rosuvastatin cost a whopping $795 at a Walgreens in Brooklyn, NY, but 90 pills of brand name Crestor is $45.65 at a low-cost international online pharmacy,
Specifically Yours,
-ACP

Are You On The Fence About Taking A Statin Drug?

The father of the eternal fiancee’ of the skeptical cardiologist (FOEFOSC, let’s call him “Geo”) is a typical 61 year old white male. A year ago his primary care physician informed him that he needed to start taking a statin drug because his cholesterol was high. The note accompanying this recommendation also stated “work harder on diet and exercise to get LDL<130.”  No particulars on how to change his current diet and exercise program were provided.

Neither of Geo’s parents and none of his siblings have had heart problems at an early age and Geo is very active without any symptoms. His diet is reasonably free of processed food and added sugar, he is not overweight and his blood pressures are fine. Due to concern about side effects he had read about on the internet and because he doesn’t like taking medications , Geo balked at taking the recommended statin,

Reluctance to start a new and likely life-long drug is understandable especially when combined with a constant stream of internet-based bashing of statins.

My advice was sought and I suggested a few things that would be helpful in making a more informed decision:

-Calculate Geo’s 10 year risk of heart attack and stroke using the ACC ASCVD Risk estimator app.

-Assess for early or advanced build-up of atherosclerotic or fatty plaque in the carotid arteries (vascular ultrasound) and coronary arteries (coronary calcium scan).

As I’ve pointed out before (here), the vast majority of men over the age of 60 move into a 10 year risk category >7.5%, no matter how great their lifestyle is, and Geo was no exception with a risk of 8.4%. His total cholesterol was 249, LDL (bad) 154, HDL (good) 72 and triglycerides 116.

The vascular ultrasound showed below normal carotid thickness and no plaque and his coronary calcium score was 18,  putting him at the 63rd  percentile. This is slightly higher than average white men his age.

When Geo presented these findings to his PCP, he seemed unaware of the ASCVD risk estimator (recommended by AHA/ACC guidelines first published in 2013), which no longer suggests LDL levels as goals. His PCP also seemed miffed that he had gotten the coronary calcium scan. Geo felt like the PCP’s attitude was “shut up and do what I tell you.”

Geo’s PCP’s approach exemplifies a not-uncommon traditional doctor-patient relationship, but a better approach is shared decision-making (see here). Geo, like many patients, welcomes more information on the risks and benefits of any recommended treatment so that he can participate in deciding the best course of action.

I steer patients who want more complete information towards my  evidence-based blog posts on statins (see here for discussion on statin side effects and here for statin benefits beyond cholesterol lowering.)

By giving patients more information on the risks, side effects, and benefits of the statin drugs along with a better understanding of their overall risk of heart disease and stroke, we can hopefully move more patients “off the fence” and onto the most appropriate treatment.

Stay tuned to find out what The Skeptical Cardiologist Recommended for Geo.

Decisively Yours

-ACP

For more discussion on the value of coronary artery calcification (CAC) and the value of statin in lower risk patients see this recent paper entitled “Refining Statin Prescribing in Lower-Risk Individuals: Informing Risk/Benefit Decisions”(PDF refining-statin-prescribing-in-lower-risk-individuals-informing-riskbenefit-decisions)

If you’d like to read the recently published recommendations of the US Preventive Services Task Force on statins for primary prevention of cardiovascular disease see here. Importantly this panel of unbiased experts concluded that statin therapy significantly reduced overall mortality and cardiovascular mortality. In addition, the review found no increased risk of diabetes overall with statin therapy. The only trial that identified an increased risk was using high intensity statin therapy (Crestor (rosuvastatin) >20 mg).

And,  since the internet is jammed with people who believe statins robbed them of their brain power, I would advise noting that the writers concluded  “These findings are consistent with those from a recent systematic review of randomized trials and observational studies that found no adverse associations of statins with incidence of Alzheimer disease, dementia, or decreased scores on tests of cognitive performance.”

 

 

Does Pravastatin Lower Your Risk of Diabetes?: The Joys of Continuing Education From Patients

One of the amazing perquisites of being a doctor is the opportunity to talk to a wide diversity of individuals with fascinating backgrounds and interests. I’ve always had some appreciation of this during my office interactions, but with age and ripening, I have come to relish and savor these conversations.

The skeptical cardiologist learns something from virtually every patient visit.  On a recent office day, I received patient pearls on topics ranging from Viking River cruises in Germany, to the method by which Express Scripts squeezes money from Walgreens and drug manufacturers, to certain novels of T. Coraghessan Boyle not centered on the maniacal vegetarian John Harvey Kellogg.

Not uncommonly, I’ll learn something about medicine or cardiology if I listen closely to my patients and keep an open mind.

I saw a 69 year old woman (we’ll call her Donna) the other day who had advanced plaque in her coronary arteries and with whom I had  initiated a discussion on the pros and cons of taking a statin drug to lower her risk of heart attack and stroke. This was not the first time we had talked about this topic; in previous visits she had shared with me her great fear of statin side effects and her desire to modify risk by dietary modification. On this visit, she came prepared with more research she had done on statins, and told me she was concerned about an increased  risk of diabetes with statin drugs.

I gave her my standard spiel:  statins, especially more potent ones like rosuvastatin and atorvastatin, appear to increase the risk of diabetes by 10-20%, however, this is offset by the benefits of statins, especially in someone with significant atherosclerosis, in reducing heart attack and stroke.

Donna then told me that she had read that pravastatin lowers the risk of diabetes. I hadn’t heard this (or more likely this slipped out of my ever-shrinking cerebral database) previously. Ten years ago, in the era before routine use of electronic health records (EHR), I would have had to just admit my ignorance and promise to look into that claim later (something that would not consistently happen due to time constraints and forgetfulness).  However, now I enter the patient exam room with my MacBook Air, primarily to access the patient’s EHR and look at old notes, cardiac tests etc.

Increasingly I also use the Mac to quickly look up information about a topic the patient has brought to my attention – either double checking what I believe to be true or researching claims I am unfamiliar with.

Often, the topic raised is the “snake oil du jour” (for example, is turmeric a cardiovascular panacea?), but in this case and many others, it is a relevant question about the nuances of disease or my proposed treatment.

A quick search (20 seconds) pulled up a 2009 meta-analysis of randomized trials of statins and the risk of diabetes. Sure enough, one of these trials (the West of Scotland Coronary Prevention Study) actually showed that patients treated with 40 mg of  pravastatin had a 30% lower risk of developing diabetes.  Four studies showed no effect of statins on risk of developing diabetes and only one, the JUPITER trial utilizing rosuvastatin (Crestor), showed a slight increase.

For some patients like Donna, a higher risk of diabetes may be a deal breaker for taking a life-saving medication. Although I can confidently tell her that the benefits outweigh the risks, if she has a specific fear of diabetes, perhaps related to a family member who had horrific complications of the disease, she could easily decline to take statins.

In Donna’s case, this new information about pravastatin, confirmed by the wonders of Google and a fast WiFi connection led to her giving statins (in the form of pravastatin) a chance.

I’ll remember this patient-triggered drop of wisdom for future discussions with patients whose  grave fear of diabetes makes them balk at taking statins.

Corasonically Yours,

-ACP

 

 

 

 

 

 

west of scotland

http://care.diabetesjournals.org/content/32/10/1941.full

Death Knell For Niacin For Lipids Sounded by FDA?

The skeptical cardiologist stopped writing new prescriptions for niacin extended release tablets in 2011. For any patient who was taking niacin, I recommended stopping it.

Because niacin had favorable effects on the cholesterol profile, physicians had been utilizing it for many years in high risk patients on statins who had low HDL  (good cholesterol) and/or high triglycerides.

The rationale was that, since high HDL was associated with lower risk of heart attacks, raising the HDL would lower that risk. Similarly, lowering the triglycerides would improve cardiovascular risks.

While niacin certainly improved the cholesterol profile, there was no good evidence that starting it in a patient already on statin would improve cardiovascular outcomes. The cholesterol profile is a surrogate endpoint: the actual treatment goal is reducing cardiovascular disease.

In 2011, the AIM-HIGH study proved there was no benefit to adding niacin to good statin therapy despite increasing HDL from 35 to 42 mg/dl, lowering triglycerides and lowering LDL. This and other studies showing no benefit of niacin therapy (and worrisome adverse effects) should have resulted in the total cessation of niacin prescriptions, especially  in patients on statins.

Unfortunately, old habits die hard amongst physicians, and the allure of raising HDL and lowering triglycerides with niacin persisted despite a lack of evidence of any benefit in lowering cardiovacular risk.

Yesterday, the FDA announced it was removing from the market two  drugs made by Abbvie, Advicor and Simcor, which are combinations of extended release niacin plus lovastatin or simvastatin, and removed its approved indication for niacin ER plus statin for lowering CHD risk stating:

“Based on the collective evidence from several large cardiovascular outcome trials (Refs. 1-3), the Agency has concluded that the totality of the scientific evidence no longer supports the conclusion that a drug-induced reduction in triglyceride levels and/or increase in HDL-cholesterol levels in statin-treated patients results in a reduction in the risk of cardiovascular events. Consistent with this conclusion, FDA has determined that the benefits of niacin ER tablets and fenofibric acid DR capsules for coadministration with statins no longer outweigh the risks, and the approvals for this indication should be withdrawn.”

This is good news for patients whose physicians were keeping them on the unproven brand name combination drugs, Advicor and Simcor.

There are still legitimate uses of niacin to prevent vitamin deficiencies but If you are still taking some form of niacin ER for the purpose of preventing heart disease with or without a statin I recommend presenting your doctor with the link to the FDA pronouncement above and having a good discussion with him about the rationale for staying on it.

The other drug mentioned in the announcement, fenofibric acid,  is far less often prescribed and is not available as a combination. It is the most effective drug we have for extremely high triglyceride levels over 500 mg/dl which can cause pancreatitis. I have a few patients on the generic fenofibric acid strictly for the purpose of lowering their dangerously high triglycerides but not for the indication of lowering their cardiovascular risk.

Nonsurrogateingly Yours

-ACP

 

Are You Sabotaging Your Heart With Statin Drugs?

No, you are not “sabotaging” your heart with statin drugs. Neither are you “wrecking” your heart.

But that title probably got your attention if you are taking a statin drug and thought that it was helping your heart.

Typical appearance of Newsmax Health. Note that  the offer to assess cardiac risk is a self-serving promo of the book on natural cardiac cures written by the author of the article on the left which summarizes only the negatives of bypass surgery
Typical appearance of Newsmax Health. Note that the offer to assess cardiac risk is a self-serving promo of the book on natural cardiac cures, written by the author of the article on the left, which summarizes only the negatives of bypass surgery

This question is prominently displayed on the Health portion of a news website called Newsmax, that somehow interrupted my web surfing today. If you click on the banner, you will get to listen to the words of Dr. David Brownstein, “America’s most popular family physician.”

Dr. Brownstein, in my opinion, should more properly be termed “one of America’s most popular quacks, charlatans and purveyors of misinformation in order to market useless junk.”

What Brownstein says can be found on multiple similar sites across the internet which are promoting “alternative” or “natural” approaches to high cholesterol.

His claims can be summarized as follows:

  • statin drugs do nothing to protect you from heart attacks
  • statin drugs “weaken your heart,” muscles, cause fatigue and lower your sex drive, damage your kidneys and liver
  • statin drugs prevent the formation of cholesterol which is essential for brain, sex hormone and vitamin D production
  • 1/2 of people with heart attacks have normal cholesterol levels
  • CHF is increasing in frequency and it is related to an increase in statins and consumption of sugar and refined carbohydrates
  • Big pharma has perpetrated the biggest fraud in medical history on the American public by brainwashing doctors, beginning in medical school, to prescribe statin drugs

These claims resonate with patients who are reluctant to take medications and who feel that “natural” approaches to prevention and treatment are superior.

Brownstein uses a combination of alarmist rhetoric and pseudoscientific jargon that appeals to those seeking alternatives.

Let’s look at his claims.

Do Statins Prevent heart Attacks?

Statins unequivocally prevent heart attacks in patients who have had heart attacks or have evidence of advanced vascular disease due to atherosclerosis. This is called secondary prevention and there are almost no cardiologists/scientists with any credibility who dispute the value of statins in secondary prevention.

The only specific study that Brownstein cites is the ASCOT-LLA study, published in 2003 which looked at ten thousand patients with hypertension, no heart disease and low or normal cholesterol levels, half of whom got 10 mg of atorvastatin and half a placebo.

This was a primary prevention study and showed such a benefit of the atorvastatin on reducing heart attack and coronary deaths that the study was stopped early, at 3.3 years at which time 154 patients receiving placebo versus 100 receiving atorvastatin had had heart attacks or died from coronary disease.

This was a highly significant reduction in events. There are several ways to look at this data and present it to patients; Brownstein implies that “Big pharma” presented the most favorable way, which is that there was a 36% reduction in relative risk.

The absolute risk of an event in the atorvastatin group was 1.7% (2.7% in the placebo group), so the absolute risk reduction was from 2.7% down to 1.7% or 1%.

To help better understand the data, we can also look at the number needed to treat (NNT). The NNT is the inverse of the absolute risk reduction. So for the ASCOT trial, the absolute risk reduction was 1%. 1 divided by 1% is 100 — 100 people would need to be treated with atorvastatin (the generic of Lipitor) over the study period to prevent one heart attack. (For more discussion on the NNT check out this blog post and this paper on its limitations)

lipitorUnderstandably, Pfizer, the makers of atorvastatin, prominently displayed the 36% relative risk reduction in their direct to consumer marketing campaigns (featuring Dr.Robert Jarvik (proclaiming himself a doctor in direct to consumer videos), although he was never a licensed physician (see here for interesting discussion on the controversy that ensued)).

Until, the FDA compels them to do otherwise, big pharma will project their products in the most favorable light possible.

However, it is debatable whether presenting data to patients using absolute risk reductions or NNT info plus relative risk reductions results in better choices. As Mcalister has pointed out:

“For example, many British patients with atrial fibrillation who were likely to benefit from anticoagulant therapy because of their risk profiles and their similarity to the participants in randomized trials supporting the efficacy of warfarin declined warfarin therapy when presented with the data about their absolute risks and benefits.”

ASCOT really makes a strong case for taking a statin drug to prevent heart attacks, even in those with normal or low cholesterol levels, not the opposite, as Brownstein has implied.

Do Statin Drugs “Weaken” The Heart Muscle Or Cause Heart Failure?

After criticizing the now infamous “Seven Nations Study” of Ancel Keys, which found high fat consumption in countries with high rates of heart attacks, Brownstein trots out the weakest imaginable argument for statins causing heart failure: heart failure has increased in the last decades, statin use has increased, therefore statins are causing heart failure. 

Correlation does not equal causation!

There is no compelling evidence that statins cause heart failure or weaken heart muscle.

In fact, a recent review of heart failure and statins concluded that statins, while not reducing mortality in heart failure, do have favorable effects on reducing the rate of hospitalization for heart failure and increasing the strength of the heart muscle.

Statins may not be as beneficial in patients with heart failure, but they definitely don’t cause heart failure.

Much of the misinformation about heart failure and statins arises from sites like Life Extension, which promotes sales of its own preferred brand of vitamin CoQ10, ubiquinol. (According to their website, though, this is for altruistic reasons: “We at the Life Extension Foundation take a different view. Keeping our members in a youthful state of longevity is the most efficient way of maintaining the revenue stream we need to fund our scientific research projects. We had no problem reducing our margins to provide members with the clearly superior ubiquinol form of CoQ10.”)

As is typical for this slick organization (see my previous post here), the writing has the veneer of science but is all pseudoscience with references that are outdated, irrelevant or meaningless.

Statin Side Effects

I’ve written about statin side effects and the decision to take them based on analysis of risks and benefits here and here.
By far, the most common thing we see is myalgia, aching of the muscles, and this is reversible.
The bottom line is that the benefits of statins far outweigh the risks if you are at very high risk for heart attack and stroke.  The risks outweigh the benefits if you are at very low risk.
For those in the middle, I advocate a search for subclinical atherosclerosis either by vascular screening or coronary calcium detection.

Misinformation and Scare Tactics on the Internet

Brownstone is not the only purveyor of dangerous misinformation on Newsmax’s Health website. There seems to be a concerted effort to promote quacks and charlatans and any information on this website is suspect.

A good rule of thumb if you are searching for credible health information on the web:

Avoid sites that use scare tactics and inflammatory rhetoric to induce you to stop your prescription medication and buy a health newsletter or nutraceutical.

By the way, Big Pharma has not brainwashed me.

I have no ties to industry.

I stopped taking any pharma food or money years ago.

Listen all y’all, it’s not a sabotage!

-Boyishly yours,

ACP

 

PCSK9: The canine that escalates Your LDL

Yes. PCSK9 is a factor in escalating LDL cholesterol levels. The point was brought home as I rode the escalator up from the first to the top pcsk9floor of the San Diego Convention Center at this year’s American College of Cardiology meetings. I suspsect if I had taken an elevator I would have seen a sign proclaming that PCSK9 is a factor in elevating cholesterol levels.
And PCSK9 signage is everywhere in this meeting.

 

 

Proprotein convertase subtilisin/kexin type 9, also known as PCSK9, is an enzyme that appears to degrade LDL receptors.

If you are born with a mutation that produces less active PCSK9 you have more LDL receptors and consequently more LDL is taken out of circulation leading to lower LDL levels.

Mutations leading to gain of PCSK9 function result in lower LDL receptors, higher LDL levels and substantial clinical evidence for premature atherosclerosis.

Amgen has produced all the PCSK9 signs that abound at the ACC meetings because they have produced a fully humanized monoclonal antibody (utilizing Chinese hamster ovaries) that inhibits PCSK9 and does a great job of lowering LDL without significant adverse effects.

At a late-breaking clinical trial session, results of longer term follow up of the company’s Osler randomized trials were presented and simultaneously published here.

The results were remarkably good. Not only did evolocumab drop LDL by 61% (from 120 down to 48) it showed significant improvement in cardiovascular outcomes.

“The rate of cardiovascular events at 1 year was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group (hazard ratio in the evolocumab group, 0.47; 95% confidence interval, 0.28 to 0.78; P=0.003).”

According to the biotech website fiercebiotech:

“The antibody is expected to win FDA approval by Aug. 27, trailing Sanofi ($SNY) and Regeneron’s ($REGN) alirocumab, which, thanks to some regulatory opportunism, is likely to hit the market a month or so before. Pfizer ($PFE) is in third place, working through Phase III with its bococizumab. Analysts say each treatment could bring in more than $3 billion a year at its peak…”

More study is needed of these drugs before approval in my opinion for a number of reasons. There is evidence of a small, but significant increase in neurocognitive side effects for one.

Although with evolocumab these were not related to the level of LDL achieved, there are concerns that extremely low LDL levels may interfere with neural development and such effects may not manifest for years.

The study authors did a good job of pointing out other limitations including small number of events, open-label design and patients selected who were free of adverse events. Hopefully, the FOURIER study will resolve these issues.

This post was also posted at SERMO, the physician social network. I would encourage physicians to join in the robust discussions on medicine and other topics at this site.

Skeptically Yours,

ACP

Ezetimibe (Zetia) Shown to Reduce Heart Attack and Stroke After Thirty Billion Dollars in Sales

Important findings from the IMPROVE-IT trial were presented at the American Heart Association meeting yesterday. They demonstrate for the first time that the cholesterol lowering drug ezetimibe (brand name Zetia) lowers the risk of heart attack and stroke when added to a statin drug in high risk patients (those who have sustained a heart attack or had unstable angina) over a statin drug plus placebo.

That study showed

 The primary endpoint of CV death/MI/UA/coronary revascularization beyond 30 days/stroke was significantly lower in the ezetimibe/simvastatin arm compared with the simvastatin arm over the duration of follow-up (32.7% vs. 34.7%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.89-0.99; p = 0.016).

Prior to this study, Zetia had been prescribed to millions of patients since 2002 garnering Merck, its maker, profits of 30 billion dollars despite there being no evidence that it reduced heart attack or stroke.

Dr. Melissa Walton-Shirley wrote an excellent article on the status of Zetia at the beginning of 2014, summarizing thusly:

Perhaps the lesson to be learned is that starting in 2014, let’s not put compounds on the market for human ingestion without knowing if they help or hurt. Let’s make it unacceptable for a company to make tens of billion dollars from the sale of a compound without knowing if it lowers mortality or improves quality of life

I have previously bashed Zetia on this site and I only prescribe it in very rare cases. These new data may change my approach.

Before embracing Zetia, though, I want to see the full paper in published form and examine the data in detail. Many questions need to be answered. For example, the addition of the drug to simvastatin lowered heart attack and stroke compared to simvastatin alone but there was no difference in overall death rates or cardiovascular death rates. That raises a red flag.

In addition, this study does not support the use of Zetia in patients who have not had heart attacks or near heart attacks (primary prevention).

Science moves slowly but inexorably toward the truth if done properly. It’s important that public policy and drug prescribing not get in front of the science as it did with this drug.