When Statins Aren’t Enough: Using Pharmacogenomics to Justify PCSK9 Inhibitors

Why Statins Matter 

Statins remain the cornerstone of lipid-lowering therapy in cardiovascular prevention. Whether you're prescribing simvastatin, atorvastatin, or rosuvastatin, these drugs are widely used and well-supported by NICE guidelines. They work by blocking HMG-CoA reductase (the key enzyme in cholesterol production) and prompting the liver to increase LDL clearance. 

They're effective. But not for everyone.

The Clinical Problem: When Good Drugs Fall Short 

Statins, including commonly prescribed options like rosuvastatin or atorvastatin, can cause side effects such as myalgia, fatigue, or even mild insulin resistance. Sometimes patients simply don’t respond, even when taking higher doses like atorvastatin 80 mg or rosuvastatin 20 mg. Some patients ask about switching, while others want to know, “Should rosuvastatin be taken at night?” or “Can I take atorvastatin in the morning?” 

These are common and valid concerns. But if a patient continues to show poor LDL response despite correct use, or side effects, pharmacogenetics may hold the key to a better treatment outcome.

The PGx Case: From Trial and Error to Tailored Strategy 

A pharmacogenomic (PGx) test can offer insight into whether a patient is likely to: 

• Absorb or metabolise statins like simvastatin or atorvastatin effectively 

• Be at higher risk of long-term side effects of rosuvastatin due to variants in the SLCO1B1 gene

• Have poor LDL response despite normal dosing, particularly with atorvastatin in patients who have a particular variant in the APOE gene (rs7412 C/C)

These findings can support decisions to: 

• Switch to another statin (e.g. hydrophilic vs lipophilic statins) 

• Move to non-statin therapy if response is predictably poor 

• Justify the use of evolocumab or alirocumab (expensive PCSK9 inhibitors) by demonstrating a clear genetic rationale 

Unlocking Access to Next-Line Therapy 

Both the NHS and private insurers expect evidence that a patient has failed first-line treatment. A PGx report supports that case with objective, genotype-based data. It shows that you're not just escalating because of symptoms, but because of molecular inefficacy. 

In patients who continue to have high cholesterol despite using rosuvastatin, atorvastatin, or simvastatin, PGx provides a personalised map for what to try next.

Final Word: When Pharmacogenomics Strengthens the Statin Story 

This isn’t about abandoning statins. It’s about understanding that for a minority of patients, even the best statin (whether rosuvastatin, simvastatin, or atorvastatin) might not work due to their genetic makeup. PGx allows doctors to personalise care, improve outcomes, and in some cases, unlock high-cost but more effective treatments that would otherwise be out of reach.