A simulation model of U.S. adults found that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were not cost-effective in patients with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease (ASCVD).
Lead researcher Dhruv S. Kazi, MD, MSc, MS, of the University of California, San Francisco, and colleagues published their findings online in JAMA on Aug. 16.
The FDA approved the first two PCSK9 inhibitors in 2015: alirocumab (Praluent) from Regeneron Pharmaceuticals and Sanofi Aventis and evolocumab (Repatha) from Amgen. During clinical trials, the drugs lowered mean low-density lipoprotein (LDL) cholesterol levels by 47.5 percent. The medications are indicated as an adjunct to diet and exercise for patients with HeFH or ASCVD who require additional LDL cholesterol lowering despite maximally tolerated doses of statins.
Although alirocumab and evolocumab have been shown to lower LDL cholesterol, the medications are also expensive with a wholesale acquisition cost of more than $14,000 per year.
“In the face of limited health care resources, payers must consider the potential trade-off between paying for new drug treatments like PCSK9 inhibitors and investing in interventions known to improve access, physician prescription rates and patient adherence to statin therapy among those at high ASCVD risk,” the researchers wrote.
For this analysis, the researchers used the Cardiovascular Disease Policy Model, a simulation model of coronary heart disease and stroke incidence, prevalence, mortality and costs in U.S. adults. They used a wholesale acquisition cost of $14,350 for the medications, adopted a health system perspective, incorporated a lifetime horizon and included probabilistic sensitivity analyses to evaluate uncertainty.
The model included U.S. adults from 35 to 74 years old in 2015 and followed them until death or until they turned 95. The researchers estimated the prevalence of cardiovascular risk factors from population-weighted National Health and Nutrition Examination Surveys from 2005 to 2012.
The target populations were patients with HeFH or preexisting ASCVD, which the researchers defined as a history of angina, MI or stroke with LDL cholesterol of at least 70 mg/dL despite maximally tolerated statin therapy.
Of the 1.7 million adults who met the eligibility criteria for HeFH, 61 percent were taking a statin or designated as statin intolerant. The mean age was 51, while the mean LDL cholesterol level was 207 mg/dL.
Of the 13.0 million adults with ASCVD, 65 percent were taking a statin or were statin intolerant. The mean age was 61, while the mean LDL cholesterol level was 109 mg/dL.
Adding the PCSK9 inhibitors to statins for patients with HeFH would prevent an estimated 316,300 major adverse cardiovascular events at a cost of $503,000 per quality-adjusted life-year (QALY) compared with adding ezetimibe to statins, according to the researchers.
For patients with ASCVD, adding PCSK9 inhibitors to statins would prevent an estimated 4.3 million major adverse cardiovascular events at a cost of $414,000 per QALY.
For PCSK9 inhibitors to be cost-effective at less than $100,000 per QALY, annual drug costs would have to be reduced to $4,536 per patient or less, which is much less than the $14,000 current annual costs.
If all eligible patients received PCSK9 inhibitors at 2015 prices, cardiovascular care costs would decrease by $29 billion over five years. However, drug costs would increase by $125 billion during that same time period, which is a 38 percent increase from the approximately $329 billion spent on prescription medications in 2015. In addition, U.S. healthcare expenditures would increase by an estimated $120 billion, up 4 percent from the $2.8 trillion spent in 2015.
Meanwhile, if high-risk patients who are not currently taking statins start taking statins, it would save an estimated $12 billion, according to the model.
The researchers cited a few limitations of the study, including that there was no long-term data on clinical outcomes with PCSK9 inhibitors. They mentioned that the model might have overestimated the cost-effectiveness of PCSK9 inhibitors if long-term trials demonstrate the drugs do not improve clinical outcomes. They added that the effect of PCSK9 inhibitors on healthcare spending depends on how many people take the drugs and adhere to them.
“Although new, expensive therapies indicated for short duration or for treatment of rare conditions have thus far been absorbed by the budgets of health systems, the high cost of PCSK9 inhibitors is uniquely challenging,” the researchers wrote. “This is because PCSK9 inhibitors are meant to be lifelong therapy not only for the relatively small number of patients with FH but also for a large and growing population with ASCVD. As a result, the potential increase in health care expenditures at current or even moderately discounted prices could be staggering, despite cost savings from averted ASCVD events.”