Anyone taking PCSK9 inhibitors (i.e. Repatha)?

[mcs]

I have a scrip for Repatha but haven't yet started. Covered by insurance so cost not an issue. Was concerned that LDL would go too low and cause issues. Also, side effects. Read that it can cause hyperglycemia (diabetes). Any input would be greatly appreciated.

 

[testiculus]

PCSK9 inibitors are the best option for reducing lipids. Highly effective and pretty much side effect free. It has not been my experience that they cause hyperglycemia and a I'm not aware of any evidence that they do. Since PCSK9 inhibitors were developed to mimic a genetic mutation that results in low levels of PCSK9, we know from studies of those with the mutation that there does not appear to be any long term adverse affect from lifelong reduced PCSK9. Too low of LDL is unlikely and generally would require multiple lipid reducing agents before that becomes a concern. Infants have LDL levels of ~20 mg/dl, so it takes really low levels of LDL before you're likely to have any adverse effects.

 

[mcs]

PCSK9 inibitors are the best option for reducing lipids. Highly effective and pretty much side effect free. It has not been my experience that they cause hyperglycemia and a I'm not aware of any evidence that they do. Since PCSK9 inhibitors were developed to mimic a genetic mutation that results in low levels of PCSK9, we know from studies of those with the mutation that there does not appear to be any long term adverse affect from lifelong reduced PCSK9. Too low of LDL is unlikely and generally would require multiple lipid reducing agents before that becomes a concern. Infants have LDL levels of ~20 mg/dl, so it takes really low levels of LDL before you're likely to have any adverse effects.

Thanks. Here are some links of concern:

Doubling of Hemoglobin A1c on PCSK9 Inhibitor Therapy​

Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data​

The latter study casts further doubt and the usefulness of PCSK9 inhibitors. Yes, they can push numbers around but do they REALLY provide any benefit?

 

[testiculus]

This first link is of no concern. A single case report of a diabetic whose diabetes got worse with no effort to eliminate other confounding variables. This sort of thing happens frequently with diabetics. Something a simple as an infection could cause the hyperglycemia in an insulin dependent diabetic like this.

The second link I hadn't seen before. This is obviously concerning. Fraud is a major problem in medical research and this has all the hallmarks of fraud. It's hard to draw any conclusions when the data is faked. The only other things I can point to that may alleviate your concern is there is the Odyssey trial which had a little bit longer follow-up period (2.8 years) and showed improvement in mortality (of course there's always the possibility that this data was faked too). Then there's post-marketing experience which hasn't identified any major issues. PCSK9 inhibitors have been used for 7 years now, which is enough time for an issue to be exposed. Vioxx being a good example, it became well known that it was causing cardiovascular issues after about 5 years of use.

 

[mcs]

This first link is of no concern. A single case report of a diabetic whose diabetes got worse with no effort to eliminate other confounding variables. This sort of thing happens frequently with diabetics. Something a simple as an infection could cause the hyperglycemia in an insulin dependent diabetic like this.

The second link I hadn't seen before. This is obviously concerning. Fraud is a major problem in medical research and this has all the hallmarks of fraud. It's hard to draw any conclusions when the data is faked. The only other things I can point to that may alleviate your concern is there is the Odyssey trial which had a little bit longer follow-up period (2.8 years) and showed improvement in mortality (of course there's always the possibility that this data was faked too). Then there's post-marketing experience which hasn't identified any major issues. PCSK9 inhibitors have been used for 7 years now, which is enough time for an issue to be exposed. Vioxx being a good example, it became well known that it was causing cardiovascular issues after about 5 years of use.

A followup to the Fourier Trial: Study Alleges Mortality Miscount in FOURIER Trial; TIMI Group Disagrees

Recount of FOURIER Data Finds Higher Mortality With Evolocumab

A readjudication of mortality data from the FOURIER trial by outside researchers concludes CV death was higher with evolocumab than originally reported. But FOURIER trialists stand by their conclusions.

www.medscape.com

Doesn't give me much confidence.

 

[KevinS]

I have been on Rapatha and just had 6 month labs:
LDL Calculated: 39 from 129 and higher
HDL: 28 from 33, higher a couple years ago
Total Cholesterol: 91 from 193, but has been as high as 245

No obvious side effects.
Injection every 2 weeks.

Over the years I was off and on Statins, had joint and muscle pain so I would stop taking them for months or years, then the Dr kept trying to scare me into taking them. My high LPa is what convinced me to push to get the Rapatha.