It’s a cardiologist’s dream come true.  A newly approved $1200/monthly-injectable drug that dramatically reduces circulating cholesterol levels may become the first $100-200 billion medicine. 

That would dwarf the record $9 billion annual sales for Lipitor, the statin cholesterol-lowering drug that was the best selling drug of all time until its patent recently expired.  And to add value to the equation, this newly FDA-approved drug may be the first cholesterol-lowering medication to actually save lives, but for different reasons than advertised. 

I say this because statin cholesterol-lowering drugs prevented non-mortal heart attacks, not drop-dead heart attacks that are mostly caused by electrical storms within the heart, not cholesterol buildup within coronary arteries that feed the heart with oxygen.

The newly approved medicine will fill cardiologist’s offices for monthly or bi-monthly injections.   [FDA.gov July 24,2015] Injections eliminate compliance problems with patient who forget to take their pills. 

Initially patients with familial high cholesterol (620,000 in U.S.) or other uncontrolled high cholesterol (1 million in U.S.) or who are intolerant to statin cholesterol-lowering drugs (3.5 million) will be candidates for this new class of drugs.  Another 15 million Americans may be placed on this drug that have a history of coronary artery disease.   [Health Affairs Blog Feb 17, 2015]

If these 18.5 million patients are evenly divided by the nation’s 23,000 cardiologists, that would amount to 804 patients per month or 40 patients a work day flooding into cardiologists offices for injections.  Even with a physician’s procedural fee of just $100/per injection that comes to $80,400/month new income, or nearly $1 million year per cardiologist!  A survey of 50 cardiologists indicates they are ready to incorporate PCSK9s into their practice regimens and make a killing billing health insurance. [Medical Marketing Media March 25, 2014]

Dollars and mis-sense over PCSK9 inhibitors

This new class of drugs that dramatically reduces LDL cholesterol is likely to add another $100-200 billion to the nation’s $4 trillion/year health care bill.  

Statin drugs have been the mainstay of modern cardiology since Mevacor gained FDA approval in 1987. Lipitor only reduces the risk for a non-mortal heart attack from 3.3% to 2.0% (in hard numbers only a 1.3% reduction).  [Knowledge of Health Aug 15, 2012]  Statin drugs avert 1 non-mortal heart attack among 200 healthy users and 1 out of 70 high-risk individuals over a 5-year period.   [Business Week Jan 16, 2008]

The problem is with cholesterol-lowering medications is that only a few patients will actually experience a heart attack.  The risk of a heart attack at age 40 is 4 in 10,000 over a 10-year period; over age 60, 37 in 10,000.  Over that time span you are three times more likely to die of another cause.  [Know Your Chances]

A long-term (23-year) study of 10,059 males age 40-65 years in Israel found survival was 87% among men with the highest total cholesterol (over 241) versus 93% among men with the lowest total cholesterol (below 176).  Mortality from all causes only rose significantly when cholesterol was above 240.  Cholesterol was less predictive of death from heart disease than smoking or high blood pressure.  [Arteriosclerosis Aug 1990] So cholesterol phobia has been overhyped. 

Will PCSK9 inhibitors raise or lower the cost of healthcare?

Regardless of the scientific and political battles surrounding cholesterol-lowering drugs, the public health burden associated with coronary heart disease remains enormous with approximately 525,000 people predicted to have a new heart attack (2013) and ~$125.4 million living with coronary heart disease and 1,346,000 million hospitalized for disease of the coronary arteries. [Journal American Heart Association Dec 3, 2014]

A 2010 CBS News report claims a severe heart attack now costs $1 million, a less severe heart attack about $760,000, or about $38,000-$50,000 a month if amortized.  [CBS NEWS April 23, 2010] The Heart Foundation reports the direct and indirect costs of heart disease total more than $320 billion each year.  [The Heart Foundation] 

It would seem to be financially irresponsible to over-utilize one drug that would add $100 billion to $200 billion a year to the nation’s healthcare bill for the potential benefit of an estimated 3.5 million to 18.5 million patients, to prevent 12,950 – 68,450 heart attacks, which would respectively amount to $7,722,007 to $2,921,840 per heart attack prevented.  So the new drugs will cost more than the heart attack itself.   This new class of drugs is destined to add to the cost of healthcare, not save healthcare dollars. 

What pharmacy benefits manager in his right mind is going to pay $2.9 to $7.7 million per patient to prevent a heart attack that only costs $760,000 to $1,000,000?

Unflattering facts about CSK9 inhibitors

Some eyebrow-raising facts about OCSK9 inhibitors need to be shared here:

First, a review of the scientific literature shows that statin cholesterol-lowering drugs actually raise PCSK9 levels.  [Diabetes Obesity Metabolism July 17, 2015]  This suggests a giant long-standing misdirection by modern medicine.

Second, already a PCSK9 inhibitor has been withdrawn from FDA application because of a “clinical development.” [Expert Opinion Investigative Drugs Aug 2015; Twitter July 23, 2015]

Why has the FDA granted early approval of PCSK9 inhibitors, while most human clinical studies are not scheduled to be reported till 2018?

A likely reason is for early approval is that preliminary data indicate PCSK9 inhibitors appear to reduce mortality.  [MedPage Today April 27, 2015]  The drug companies may have urged the FDA to approve their injectable medications based upon preliminary data, which gets the product on the market and makes it tough to withdraw should more conclusive data reveal a vanishing reduction in mortality.

Why PCSK9 inhibitors may save lives this time

The new class of LDL-lowering cholesterol drugs differ from statin drugs which interfere with the natural production of cholesterol in the liver.  This new class of drugs, called PCSK9 inhibitors, prevent the recirculation of LDL cholesterol and thus achieve unprecedented and striking reduction of LDL cholesterol of 50% to 70%!  [Journal American College Cardiology Jun 23, 2015]

Statin drugs were toxic to the liver and bring on a list of side effects that includes cataracts, diabetes, muscle aches and brain fog.

PCSK9 inhibitors are proposed as LDL (low-density lipoprotein) reducers.  However, there is more to this story.  A bit of scientific sleight of hand is underway.

PCSK9 inhibitors also lower another fraction of cholesterol called lipoprotein(a).  PCSK9 inhibitors lower LDL cholesterol by about 50% and up to 73% when combined with statin drugs or another drug (ezetimibe: trade name Zetia) that blocks the absorption of cholesterol from the diet. 

About a third of the subjects given PCSK9 inhibitors achieve LDL-C levels less than 25 milligrams per deciliter of blood.  Some subjects are expected to reach nearly un-measurable LDL levels. 

However, when blood lipid researchers refer to LDL cholesterol they are remiss in not mentioning lipoprotein(a), another important fraction of cholesterol is a part of that LDL measurement.  In fact, as LDL levels are driven down further lipoprotein(a) comprises more of LDL. 

Maybe 1.5 billion people on earth have lipoprotein(a) levels above 50.  Lipoprotein(a) is found in advanced and unstable plaques within coronary arteries.  It could be said that PCSK9 inhibitors are more lipoprotein(a) inhibitors than LDL reducers. 

A recent published paper says PCSK9 inhibitors may lead to the overestimation of LDL reduction while overlooking the importance of lipoprotein(a) in coronary heart disease mortality.  The authors of this paper say: “it is likely that individuals with elevated lipoprotein(a) will achieve low LDL in which the LDL will mostly reflect lipoprotein(a)…. The currently available methods of LDL determination used in clinical trials do not provide a true measurement of LDL.  Confounding this measurement is the contribution of lipoprotein(a).”   

Depending upon LDL level, lipoprotein(a) may comprise somewhere between 20-100% of the measured LDL fraction.  [Current Opinion Lipidology June 2015]

Another recently published paper confirms that PCSK9 inhibitors reduce LDL cholesterol that correlates with a decline in lipoprotein(a).  [Journal American College Cardiology 2014]

Linus Pauling returns

Modern cardiology has good reason to hide lipoprotein(a)’s contribution to mortal heart disease.  For it was Nobel Prize winning Linus Pauling and Matthias Rath, two investigators who published papers about the importance of lipoprotein(a) in heart disease in the 1990s. 

Pauling and Rath noted that lipoprotein(a) is more prevalent in the blood circulation of animals that do not naturally synthesize vitamin C such as  guinea pigs and that lipoprotein(a) becomes a sticky bandage that takes the place of vitamin C within the walls of damaged coronary arteries and then induces blood platelets to accumulate and create a blood clot.  That blockage is what results in a heart attack.

Animals that do secrete vitamin C naturally do not develop this form of heart attack.  Humans are in the same predicament as guinea pigs as Homo sapiens lost ability to synthesize vitamin C in the liver many generations ago due to a gene mutation that eliminated a key enzyme (gulonolactone oxidase) that converts blood sugar to ascorbate (vitamin C).  [Proceedings National Academy Science Dec 1990; Proceedings National Academy Science, August 1990] 

Dr. Pauling wrote a book entitled Vitamin C The Common Cold in 1970 and retrospective analysis finds the public consumption of vitamin C rose by 300% upon publication of that book which correlated with a sudden decline in death rates for coronary heart disease.  (Linus Pauling Institute] 

Lipoprotein(a) more predictive of death than cholesterol

There has been a resurgence of interest in lipoprotein(a) as scientific reports now indicate it is “the strongest genetic risk factor for coronary artery disease.” [Journal Internal Medicine Jan 2013]  In 2008 researchers said lipoprotein(a) represents a risk factor in adults that is “very high, considerably higher than blood pressure, blood serum cholesterol and C-reactive protein.”  [Archives Internal Medicine March 24, 2008] 

Lipoprotein(a) levels above 30 milligrams per deciliter of blood represent an elevated risk for coronary artery disease.  [European Heart Journal Nov 2013]  Another report says lipoprotein(a) levels above 21 are associated with coronary artery disease.  [Heart Views Jan 2013]  Yet another study claims a lipoprotein(a) level exceeding 20 mg/deciliter is associated with a more than 600% increase risk for cardiovascular mortality.  [Diabetes Care April 2005]  About 30% of Caucasians and 60-70% of African Americans have lipoprotein(a) levels above 25 mg/deciliter. 

It is well documented that injury to internal walls of arteries are milder in areas that have higher levels of vitamin C.  [Canadian Medical Association JournalApril 1, 1955]  However, supplemental vitamin C does not reduce circulating levels of lipoprotein(a).  Vitamin C simply prevents lipoprotein(a) from taking vitamin C’s place within artery walls.  A more expansive explanation is available to read. [Knowledge of Health]

There may be other non-pharmacological ways to reduce PCSKP9 levels.  One documented method is to activate the Sirtuin1 survival gene. [European Heart Journal Jan 1, 2015]  Resveratrol, a red wine molecule widely available in dietary supplements, is a profound Sirtuin1 activator.  [Nature Sept 11, 2003]  Resveratrol works to promote the natural elimination of cholesterol.  [European Journal Pharmacology Jan 2013; Atherosclerosis Dec 2009]

Unlike statin drugs that largely prevented non-mortal heart attacks, PCSK9 inhibitors may save lives this time, but not by their advertised method of LDL cholesterol reduction but rather by a decline in circulating levels of lipoprotein(a).  

The obvious comes to mind.  Big Pharma doesn’t want the public to know that their $1200/month injectable drug could be replaced by a $10/month supply of vitamin C.  A head-to-head study comparing vitamin C to PCSK9 inhibitors is not likely to ever happen.  However, if your insurance plan doesn’t pay for PCSK9 inhibitors there is always vitamin C.  That is, if you can overcome your fears and your cardiologist who will predictably say everything that has been shared with you in this article is unproven.

The Best of Bill Sardi