Compare Non-Statin Options for LDL Lowering

You’ll be asked which non-statin to use for LDL lowering...due to recent headlines about Nexletol (bempedoic acid).

So far, Nexletol is only approved for certain patients who need more LDL lowering...despite max tolerated statins.

Now new data suggest that Nexletol prevents 1 CV event for every 63 patients at high CV risk treated for about 3 years.

But this study is in statin-intolerant patients or those who only tolerate a very low dose...such as atorvastatin 5 mg/day.

Be aware of downsides. Nexletol costs about $400/month.

Plus it can bump up uric acid levels. Generally avoid it with gout...about 1 in 10 patients with gout on Nexletol report a flare.

And about 1 in 100 patients develop gallstones with Nexletol. Advise caution in patients with a history of gallbladder disease.

Continue to emphasize statins first for LDL lowering...based on established CV benefits, safety and tolerability, and low cost.

Then consider a non-statin if needed.

Additional LDL lowering. Weigh adding a non-statin for some patients...such as those at high CV risk (prior CV event, etc) if an optimized statin lowers LDL less than 50% from baseline.

Usually lean toward adding ezetimibe first. It reduces CV events in some high-risk patients also on a statin...lowers LDL another 20% or so when added to a statin...and costs about $10/month.

Or suggest adding an injectable PCSK9 inhibitor (Praluent, Repatha). These reduce CV events in high-risk patients on a statin...and lower LDL another 50% or so. But they cost about $550/month.

Evaluate pros and cons of adding Nexletol. There aren’t data yet to show improved CV outcomes when added to an optimized statin.

And avoid Nexletol with simvastatin doses over 20 mg or pravastatin over 40 mg...due to myopathy risk with these combos.

Statin intoleranceUse a stepwise approach for intolerance...assess for other causes, try multiple statins or lower doses, etc.

Consider Nexletol for high-risk patients who don’t tolerate a statin despite several attempts. In these cases, it reduces CV risk and lowers LDL about 20%. Plus it doesn’t seem to cause myalgia.

The combo of bempedoic acid and ezetimibe (Nexlizet) lowers LDL about 35%...but had limited use in the recent CV outcome trial.

Or think of ezetimibe or a PCSK9 inhibitor as options. But these lack CV outcomes data in patients who aren’t on a statin.

Use our resource, Non-Statin Lipid-Lowering Agents, for more comparisons...cholestyramine, fenofibrate, Leqvio (inclisiran), etc.

Key References

  • N Engl J Med. 2023 Mar 4. doi: 10.1056/NEJMoa2215024
  • J Am Coll Cardiol. 2022 Oct 4;80(14):1366-1418
  • J Clin Lipidol. 2022 Jul-Aug;16(4):361-375
  • Medication pricing by Elsevier, accessed Mar 2023
Pharmacist's Letter. April 2023, No. 390404

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