This week, Dr. Aju Mathew writes on the most important keyword in coronary artery disease management- lipids. He highlights major studies on lipid-lowering therapies such as statins and PCSK9 inhibitors and quotes a few instances of using them in his practice.

I don’t think there is a medical student in India who has not been impacted by Dr Eugene Braunwald, most likely unknowingly. For those who do not recognise this name, he is a legend in cardiology. He is 92 years old and still writing scientific manuscripts. I recently stumbled on a provocative opinion piece written by him. The title was eye-catching – How to live to 100 before developing clinical coronary artery disease.[1] What is the holy grail according to him?

Answer: Its lipids

Lipids

I am reminded of the movie The Graduate, where a young Dustin Hoffman plays the role of a 21-year-old who just graduated from college. At a party, his father’s friend, Mr McGuire, walks up to him and offers unsolicited career advice. “I’ve got one word for you Benjamin; it’s plastics”, he says. That was the era when there was a revolution in plastic products being manufactured. Mr McGuire implied several things when he said those words.[2]

Well, what Dr Braunwald wrote about lipids, is more straightforward. He points to the direct causal relationship between higher LDL levels and greater risk for coronary artery disease. So today, I will discuss a couple of articles on lipids that caught my eye.

Network meta-analysis of adverse effects of statins when given for primary prevention

Dr Braunwald’s evidence-based hypothesis implies that there’s a role for statins in the primary prevention of coronary artery disease in patients with no history of coronary disease (by reducing LDL cholesterol level). The BMJ meta-analysis evaluated 62 trials with 1,20,000 participants, none of whom had a history of coronary disease.[3] The study showed that there is a greater risk for adverse events, but cumulatively, the risk does not outweigh the benefit.

If you have prescribed statins to people, make sure you pay attention to the adverse effects like muscle pain, liver dysfunction, renal insufficiency and eye problems. For instance, one of my patients, a young man with Fanconi anaemia and hyperferritinemia had multiple ER visits for generalised body aches.

When I saw him in the clinic after one such visit, I asked him for medication reconciliation. I was unaware that he was taking a statin. Upon discontinuing statin, his pain syndrome resolved. In the last 2 months, he had zero ER visits when compared to around 4 in the previous 2 months. One other patient of mine who was on a statin for more than a decade complained of vague pain in the calf. I was concerned about DVT, but there was no oedema. I discontinued his statin and his pain completely resolved.

In the initial years of clinical trials on statins, the hypothesis was that nocebo was the contributory phenomenon for a greater reporting of muscle discomfort. [4] Now we know it is real. We just need to pay attention to it. But it is reassuring that the use of statins does not come with more harm than the benefit it offers.

PCSK9 inhibitors and Lipoprotein (a)

One way to reduce LDL levels in the body is to block the circulating PCSK9, a protein that causes the degradation of LDL receptors. These receptors are responsible for the clearance of LDL cholesterol. Inhibiting the PCSK9 with monoclonal antibody drugs such as alirocumab will therefore reduce LDL cholesterol levels.

A recent secondary analysis of the ODYSSEY trial provides credibility to the hypothesis that in patients with very low LDL cholesterol levels, higher lipoprotein (a) level [Lp (a)] may be a surrogate for identifying individuals who may benefit from the addition of PCSK9 inhibitors.[5]

The lipoprotein (a) level has been investigated as a target for intervention for quite some time now. I am reminded of my friend who was the first author of a high impact manuscript on Lp (a) and yet failed to get an interview spot for residency training. Thankfully, our program director was gracious enough to rectify the mistake and offer him an interview. He matched in the program and the rest, as they say, is history. He is a top cardiologist scientist in an Ivy league program now. Even though the best brains have worked on it, in my opinion, we are yet to see much forward movement in the Lp (a) field.

Where do you stand? Email me at cancerkerala@gmail.com with your comments.

To read Dr. Aju Mathew's previous articles, click here: Dr Aju Mathew picks 3 clinical updates you should not miss, Dr. Aju Mathew lists 4 new updates in diabetes treatment, Dr. Aju Mathew presents top 3 updates on antibiotics, A hidden side effect of COVID-19 on children: Dr. Aju Mathew & Dr. Aju Mathew reviews 3 crucial studies on liver disease

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

Dr Aju Mathew is a medical oncologist, haematologist, internist and epidemiologist practising in Kochi.