In the Journals

High-risk patients unable to take PCSK9 inhibitors have poor outcomes

Daniel J. Rader
Daniel J. Rader

Among high-risk patients prescribed PCSK9 inhibitors, those whose prescriptions were rejected by payers or who abandoned their prescriptions had worse outcomes compared with those whose prescriptions were paid for and picked up, researchers reported.

“Two years ago, the FH Foundation published a study looking at individuals who likely had [familial hypercholesterolemia and atherosclerotic CVD] and found that they were being rejected for these therapies at the same rate as the general public,” researcher Kelly D. Myers, FH Foundation chief technology officer, told Cardiology Today. “In that analysis, we had an observation that it looked like they were having more cardiovascular events as well. After that publication came out, the FH Foundation made the conscious decision to look at that objectively, to see if there were differences in cardiovascular events” depending on access to the medications.

The researchers analyzed 139,036 patients who were prescribed a PCSK9 inhibitor between August 2015 and December 2017, who had a claims history and who had known prescription status of paid, rejected or abandoned.

The researchers conducted propensity matching to reduce differences in baseline characteristics. In the propensity-matched cohort, mean follow-up was 411.5 days for the paid group, 337 for the rejected group and 310.5 for the abandoned group.

The primary outcome was a composite of CV events, defined as MI, unstable angina, acute ischemic heart disease, ischemic stroke, PCI, CABG and cardiac arrest, after final adjudication status date.

Differences in outcomes

Compared with the paid group, the rejected group had higher risk for the primary outcome (HR = 1.1; 95% CI, 1.01-1.19), as did the abandoned group (HR = 1.12; 95% CI, 1.01-1.24), according to the researchers.

The results did not change when the paid group included only those who received at least 338 days of therapy within 12 months (HR for rejected vs. paid = 1.16; 95% CI, 1.02-1.3; HR for abandoned vs. paid = 1.21; 95% CI, 1.04-1.38).

Rejection/abandonment rates were higher in women compared with men, in racial minorities compared with white patients and in lower-income patients compared with higher-income patients.

Among high-risk patients prescribed PCSK9 inhibitors, those whose prescriptions were rejected by payers or who abandoned their prescriptions had worse outcomes compared with those whose prescriptions were paid for and picked up, researchers reported.
Source: Adobe Stock

Myers and colleagues found that patients with familial hypercholesterolemia (FH) were at particularly high risk.

In particular, those with FH and atherosclerotic CVD were five times more likely to have a CV event than those with neither, but those with both had their PCKS9 inhibitor prescription rejected two-thirds of the time.

“One of the most important take-home messages is that individuals who are being denied or are abandoning their prescriptions for PCSK9 inhibitors are more likely to have heart attacks and go on to serious events as a result of not having access to their PCSK9 inhibitors,” Daniel J. Rader, MD, chair of the department of genetics in the Perelman School of Medicine at the University of Pennsylvania and chief scientific adviser of the FH Foundation, said in an interview. “This is something we suspected was going to be the case, but the data unequivocally suggest that the denial or abandonment of a PCSK9 inhibitor results in worse outcomes for those individuals.”

The manufacturers of PCSK9 inhibitors reduced prices in 2018, and “there are two global trends on the 2018 data vs. the study period data,” Myers told Cardiology Today. “Rejections by plans are down a little but not dramatically, but what’s troubling is that prescriptions that are abandoned or unfilled by patients is going up.”

Cost to the patient is likely a major factor behind abandonment, as abandoned prescriptions cost $234 per month to the patient compared with $100 per month for prescriptions that were filled and picked up, Myers said.

Khurram Nasir
Khurram Nasir

Evidence-based recommendations

In a related editorial, Khurram Nasir, MD, MPH, MSc, and colleagues wrote that price reductions to PCSK9 inhibitors implemented in 2018 should reduce some of the barriers to access, but challenges remain.

“While we strongly advocate redesigning the [prior authorization] documentation process, at the same time, we also encourage the clinical community to align prescribing practices with existing evidence-based recommendations,” Nasir, associate professor of internal medicine at Yale School of Medicine and director of population health and health systems research at the Center for Outcomes Research and Evaluation, and colleagues wrote. “For example, in the current study, more than a quarter of patients prescribed PCSK9 [inhibitors] reported no use of statin, with nearly six out of every 10 patients prescribed not reporting high-intensity statin therapy use in the last 12 months. While one can speculate that most of these patients may have severe statin-associated side effects allowing no use, the general consensus is that a great majority of these patients can tolerate some dose of statin therapy. Therefore, every effort should be made to document statin-associated side effects to at least two different statins with one at the lowest therapeutic daily dose of a statin before prescribing PCSK9 [inhibitors] specifically for statin-associated side effects in high-risk patients. ... We have recently demonstrated that maximizing and optimizing use of statins and ezetimibe could lead to a nearly 60% reduction in PCSK9 [inhibitor] eligibility with significant cost savings to health systems.”

Rader noted that another major challenge is that “there is a whole group of patients who are not being prescribed the medications in the first place. I would argue that this group is even larger than the group who were denied their medication or abandoned their prescription. Cost is one reason why these patients are not being prescribed the medication, as all the discussion around the cost has discouraged many physicians from even prescribing in the first place, but a second reason is that many physicians still are not seriously considering these medications. I think that is especially true for patients with familial hypercholesterolemia who may not be diagnosed or, despite their high cholesterol, may not have existing heart disease, and therefore physicians don’t really consider these medications for them. Increasing awareness of the importance of these medications is important in reducing risk not just in patients with heart disease whose cholesterol levels are too high, but also in patients with familial hypercholesterolemia, even if they don’t have heart disease.” – by Erik Swain

Disclosures: The study was funded by the FH Foundation. Myers reports he is a paid consultant for the FH Foundation. Rader reports he is an unpaid adviser for the FH Foundation. Please see the study for the other authors’ relevant financial disclosures. The editorial authors report no relevant financial disclosures.

 

Daniel J. Rader
Daniel J. Rader

Among high-risk patients prescribed PCSK9 inhibitors, those whose prescriptions were rejected by payers or who abandoned their prescriptions had worse outcomes compared with those whose prescriptions were paid for and picked up, researchers reported.

“Two years ago, the FH Foundation published a study looking at individuals who likely had [familial hypercholesterolemia and atherosclerotic CVD] and found that they were being rejected for these therapies at the same rate as the general public,” researcher Kelly D. Myers, FH Foundation chief technology officer, told Cardiology Today. “In that analysis, we had an observation that it looked like they were having more cardiovascular events as well. After that publication came out, the FH Foundation made the conscious decision to look at that objectively, to see if there were differences in cardiovascular events” depending on access to the medications.

The researchers analyzed 139,036 patients who were prescribed a PCSK9 inhibitor between August 2015 and December 2017, who had a claims history and who had known prescription status of paid, rejected or abandoned.

The researchers conducted propensity matching to reduce differences in baseline characteristics. In the propensity-matched cohort, mean follow-up was 411.5 days for the paid group, 337 for the rejected group and 310.5 for the abandoned group.

The primary outcome was a composite of CV events, defined as MI, unstable angina, acute ischemic heart disease, ischemic stroke, PCI, CABG and cardiac arrest, after final adjudication status date.

Differences in outcomes

Compared with the paid group, the rejected group had higher risk for the primary outcome (HR = 1.1; 95% CI, 1.01-1.19), as did the abandoned group (HR = 1.12; 95% CI, 1.01-1.24), according to the researchers.

The results did not change when the paid group included only those who received at least 338 days of therapy within 12 months (HR for rejected vs. paid = 1.16; 95% CI, 1.02-1.3; HR for abandoned vs. paid = 1.21; 95% CI, 1.04-1.38).

Rejection/abandonment rates were higher in women compared with men, in racial minorities compared with white patients and in lower-income patients compared with higher-income patients.

Among high-risk patients prescribed PCSK9 inhibitors, those whose prescriptions were rejected by payers or who abandoned their prescriptions had worse outcomes compared with those whose prescriptions were paid for and picked up, researchers reported.
Source: Adobe Stock

Myers and colleagues found that patients with familial hypercholesterolemia (FH) were at particularly high risk.

In particular, those with FH and atherosclerotic CVD were five times more likely to have a CV event than those with neither, but those with both had their PCKS9 inhibitor prescription rejected two-thirds of the time.

“One of the most important take-home messages is that individuals who are being denied or are abandoning their prescriptions for PCSK9 inhibitors are more likely to have heart attacks and go on to serious events as a result of not having access to their PCSK9 inhibitors,” Daniel J. Rader, MD, chair of the department of genetics in the Perelman School of Medicine at the University of Pennsylvania and chief scientific adviser of the FH Foundation, said in an interview. “This is something we suspected was going to be the case, but the data unequivocally suggest that the denial or abandonment of a PCSK9 inhibitor results in worse outcomes for those individuals.”

The manufacturers of PCSK9 inhibitors reduced prices in 2018, and “there are two global trends on the 2018 data vs. the study period data,” Myers told Cardiology Today. “Rejections by plans are down a little but not dramatically, but what’s troubling is that prescriptions that are abandoned or unfilled by patients is going up.”

Cost to the patient is likely a major factor behind abandonment, as abandoned prescriptions cost $234 per month to the patient compared with $100 per month for prescriptions that were filled and picked up, Myers said.

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Khurram Nasir
Khurram Nasir

Evidence-based recommendations

In a related editorial, Khurram Nasir, MD, MPH, MSc, and colleagues wrote that price reductions to PCSK9 inhibitors implemented in 2018 should reduce some of the barriers to access, but challenges remain.

“While we strongly advocate redesigning the [prior authorization] documentation process, at the same time, we also encourage the clinical community to align prescribing practices with existing evidence-based recommendations,” Nasir, associate professor of internal medicine at Yale School of Medicine and director of population health and health systems research at the Center for Outcomes Research and Evaluation, and colleagues wrote. “For example, in the current study, more than a quarter of patients prescribed PCSK9 [inhibitors] reported no use of statin, with nearly six out of every 10 patients prescribed not reporting high-intensity statin therapy use in the last 12 months. While one can speculate that most of these patients may have severe statin-associated side effects allowing no use, the general consensus is that a great majority of these patients can tolerate some dose of statin therapy. Therefore, every effort should be made to document statin-associated side effects to at least two different statins with one at the lowest therapeutic daily dose of a statin before prescribing PCSK9 [inhibitors] specifically for statin-associated side effects in high-risk patients. ... We have recently demonstrated that maximizing and optimizing use of statins and ezetimibe could lead to a nearly 60% reduction in PCSK9 [inhibitor] eligibility with significant cost savings to health systems.”

Rader noted that another major challenge is that “there is a whole group of patients who are not being prescribed the medications in the first place. I would argue that this group is even larger than the group who were denied their medication or abandoned their prescription. Cost is one reason why these patients are not being prescribed the medication, as all the discussion around the cost has discouraged many physicians from even prescribing in the first place, but a second reason is that many physicians still are not seriously considering these medications. I think that is especially true for patients with familial hypercholesterolemia who may not be diagnosed or, despite their high cholesterol, may not have existing heart disease, and therefore physicians don’t really consider these medications for them. Increasing awareness of the importance of these medications is important in reducing risk not just in patients with heart disease whose cholesterol levels are too high, but also in patients with familial hypercholesterolemia, even if they don’t have heart disease.” – by Erik Swain

Disclosures: The study was funded by the FH Foundation. Myers reports he is a paid consultant for the FH Foundation. Rader reports he is an unpaid adviser for the FH Foundation. Please see the study for the other authors’ relevant financial disclosures. The editorial authors report no relevant financial disclosures.