Tag Archives: #ACC15

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,


Reporting From the American College of Cardiology Meetings 2015: Let the Science and Marketing Begin!

As part of his relentless pursuit of cardiologic knowledge, the skeptical cardiologist is in San Diego preparing to report on the 64th annual Scientific Sessions of the American College of Cardiology.

At last year’s meetings in Washington, DC, there were over ten thousand physicians attending, about two-thirds of whom were in clinical practice and one-third primarily involved in research.

These cardiologists will be listening to the latest presentations on scientific findings in cardiology and reviewing the best practice and guidelines in clinical cardiology.

They will also be interacting with almost three-hundred exhibitors. The exhibitors consist of companies that want to sell their wares to cardiologists.

Here is an interactive map of all the exhibitors in the “expo.”

If you move your cursor over the largest rectangle in the map you see that this 7800 square foot space belongs to Astra Zeneca, a British multinational pharmaceutical and biologics company. Astra Zeneca sells drugs in a lot of areas but I know that their major focus here at the ACC meeting will be on their new anti platelet drug known as Brilinta (ticagrelor).

They have been aggressively promoting this to cardiologists at my hospital through a combination of company sponsored dinner talks and pharmaceutical rep office lunch visits. When I began using the app for the ACC2015 meetings one of the first things to pop up was a stealth advertisement for this drug.

I moved my cursor over one of the smallest boxes I could find and up popped United Biologics, Inc. who have 100 square feet. Apparently they are “engaged in designing and manufacturing silicone replications of human vasculature, including common pathologies.”

I will be posting about the science and the marketing that goes on here over the next few days.

I’ll focus on the areas I am an expert in, including echocardiography and imaging, along with the new developments in fields like atrial fibrillation, valvular heart disease, prevention of coronary disease and heart failure that can help my patients.

If any of my readers have a particular topic you would like me to report on, let me know.

Yours in skepticism, ACP

Addendum: I have been to lots of ACC meetings in cities like Dallas, Atlanta and Orlando. The convention centers are usually located in very boring parts of the downtown area and are not particularly aesthetically pleasing. The San Diego convention center on the other hand is wonderful.IMG_3406

It is immediately adjacent to Embarcadero Marine Park, a very nice section of the harbor with boats and walking trails and exotic vegetation.


The building itself it a joy to behold, an architectural gem with features suggesting sails and spires from the nautical world. I can’t wait to get inside and start learning.