On 2015 Oct 25, Brendan Everett commented:

We appreciate and agree with Dr. Gortler’s comments about the long-term benefits and safety of statin therapy in preventing important clinical cardiovascular events. We expressed concern in our Perspective that PCSK9 inhibitors might be broadly substituted for statins, when statins have a substantial body of evidence supporting their role in cardiovascular event reduction, as well as an excellent safety profile. This is of particular concern among patients with statin intolerance, which remains a difficult condition to define. For example, approximately 70% of patients who were considered unable to take statins prior to enrolling in a blinded alirocumab study who were randomized to the statin arm were able to tolerate atorvastatin 20 mg for 24 weeks. Nonetheless, many patients cannot tolerate the intensity of statin therapy that would be indicated based on their own specific clinical situation, even after switching statins or trying alternate-day dosing, as suggested by Dr. Gortler. While many non-statin treatments for hyperlipidemia have demonstrated safety, very few of these medications have shown evidence for cardiovascular event reduction when added to ongoing statin therapy, even when those statins are not at goal intensity. For patients and physicians caught in this clinical bind, PCSK9 inhibitors may represent a reasonable adjunctive therapy, particularly if the ongoing studies show evidence of cardiovascular event reduction with a tolerable safety profile. - Brendan M. Everett, Robert J. Smith, and William R. Hiatt

On 2015 Oct 11, David Gortler commented:

Unlike PCSK9 inhibitors alirocumab and evolocumab, long term findings from statins show that statins are unquestionably beneficial and safe for lowering LDL-cholesterol in hypercholesterolemic and hyperlipidemic patients. Prescribers are far too hasty to label their statin patients as intolerant, often grossly misdiagnosing and/or not differentiating between myopathy, myalgia and rhabdomyolysis due to a lack of established critera. True statin intolerance is very rare -- and there are clear pharmacologic options in those cases. Most obvious: if a patient experiences statin intolerance with one particular statin, he may be eligible for dosing of any one of the six other FDA approved statins available on the market.

Statin intolerance may be attributed directly to drug levels in the body and good data in multiple clinical pharmacy publications have shown that QOD dosing of the Type 2 statins cuts down true and legitimate cases to about half. For those that are still statin intolerant, there are non-statin drug treatment options for hyperlipidemia, all of which have more long-term safety data as compared to PCSK9 inhibitors alirocumab and evolocumab.

There is a “niche” need for PCSK9 inhibitors alirocumab and evolocumab for patients who fail all statin and all other pharmacology treatments, or who are unable to meet their goals with all available pharmacological treatment options. This residual population represents a very small percentage of hyperlipidemic patients eligible for the PCSK9 class.

On 2015 Oct 11, David Gortler commented:

Unlike PCSK9 inhibitors alirocumab and evolocumab, long term findings from statins show that statins are unquestionably beneficial and safe for lowering LDL-cholesterol in hypercholesterolemic and hyperlipidemic patients. Prescribers are far too hasty to label their statin patients as intolerant, often grossly misdiagnosing and/or not differentiating between myopathy, myalgia and rhabdomyolysis due to a lack of established critera. True statin intolerance is very rare -- and there are clear pharmacologic options in those cases. Most obvious: if a patient experiences statin intolerance with one particular statin, he may be eligible for dosing of any one of the six other FDA approved statins available on the market.

Statin intolerance may be attributed directly to drug levels in the body and good data in multiple clinical pharmacy publications have shown that QOD dosing of the Type 2 statins cuts down true and legitimate cases to about half. For those that are still statin intolerant, there are non-statin drug treatment options for hyperlipidemia, all of which have more long-term safety data as compared to PCSK9 inhibitors alirocumab and evolocumab.

There is a “niche” need for PCSK9 inhibitors alirocumab and evolocumab for patients who fail all statin and all other pharmacology treatments, or who are unable to meet their goals with all available pharmacological treatment options. This residual population represents a very small percentage of hyperlipidemic patients eligible for the PCSK9 class.

On 2015 Oct 25, Brendan Everett commented:

We appreciate and agree with Dr. Gortler’s comments about the long-term benefits and safety of statin therapy in preventing important clinical cardiovascular events. We expressed concern in our Perspective that PCSK9 inhibitors might be broadly substituted for statins, when statins have a substantial body of evidence supporting their role in cardiovascular event reduction, as well as an excellent safety profile. This is of particular concern among patients with statin intolerance, which remains a difficult condition to define. For example, approximately 70% of patients who were considered unable to take statins prior to enrolling in a blinded alirocumab study who were randomized to the statin arm were able to tolerate atorvastatin 20 mg for 24 weeks. Nonetheless, many patients cannot tolerate the intensity of statin therapy that would be indicated based on their own specific clinical situation, even after switching statins or trying alternate-day dosing, as suggested by Dr. Gortler. While many non-statin treatments for hyperlipidemia have demonstrated safety, very few of these medications have shown evidence for cardiovascular event reduction when added to ongoing statin therapy, even when those statins are not at goal intensity. For patients and physicians caught in this clinical bind, PCSK9 inhibitors may represent a reasonable adjunctive therapy, particularly if the ongoing studies show evidence of cardiovascular event reduction with a tolerable safety profile. - Brendan M. Everett, Robert J. Smith, and William R. Hiatt