At the current price of the drug, and lacking sufficient mortality data, treating patients for longer periods of time with expensive PCSK9 inhibitors is likely to result in increasing the financial burden on our high-risk patients with minimal clinical benefit in reducing non-fatal MI and stroke but unknown mortality benefit.​

There is no doubt that, based on the available data, PCSK9 inhibitors do decrease LDL levels more significantly than any other drug currently available in our arsenal, and they do decrease the incidence of non-fatal MI and stroke ​over high dose statin’s alone.


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However, with an estimated price tag of around $14,000 per year,would treating all high-risk patients who simply do not meet their lipid goals by adding a PCSK9 inhibitor to their treatment be cost effective — especially for an absolute risk reduction for a composite endpoint of only 1.5% and ​thus far ​no significant reduction in risk for cardiovascular death. With that said, there is no evidence that a patient without coronary heart disease or familial hypercholesterolemia should even be considered for this drug.

With the trial’s reported number needed to treat (NNT) of 74 individuals over a 2 year period, it would cost an estimated $2,072,000 to prevent one event based on the study authors’ secondary composite endpoint, an estimated $2,333,333 to prevent one nonfatal MI, and approximately $7,000,000 over 2 years to prevent a stroke.

Just for comparison, the cost to prevent one cardiovascular death with a statin would cost anywhere between $85,000 to $300,000 depending on the risk levels of the individuals being treated.4

Needless to say, despite their efficacy at lowering LDL, PCSK9 inhibitors are probably not yet ​a cost-effective solution. Widespread adoption of this drug would be costly and would significantly add to the economic burden of our patients and the struggling American healthcare system.

While this trial does make​ progress toward answering some of the crucial questions surrounding PCSK9 inhibitors, the trial was not designed to show mortality benefits in patients already at high risk. Trials involving longer outcomes are still needed to evaluate whether adopting the widespread use of PCSK9 inhibitors in high-risk patients with clinical atherosclerosis and suboptimal LDL levels will result in clinically significant reductions in cardiovascular mortality.

Further, while the reduction of LDL levels to 30 mg/dL in this study appeared to be safe, longer trials are still needed to test this conclusion. As the authors suggested — it takes time to see a clinical benefit. Likewise, if there are significant consequences to having such low LDL levels, I imagine those would take some time to become clinically evident as well.

Editor’s Note: The original version of this article was updated to clarify that the study’s primary or secondary endpoint was not cardiovascular mortality. Because cardiovascular mortality was not an endpoint, the study did not “fail.” It was successful in showing a risk reduction in composite endpoints. The original article emphasized the lack of mortality data, but ignored the improvement in composite endpoints. The article was updated on April 17, 2017, to reflect this.

References

  1. Nissen SE. “Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound.” GLAGOV. ACC Abstract. Updated November 2016.
  2. Sabatine MS, et al. “Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease.”  N Engl J Med.. doi: 10.1056/NEJMoa1615664. [Epub ahead of print]
  3. Kazi D, Moran A, Coxson P, et al. “Cost-Effectiveness of PCSK9 Inhibitor Therapy in Patients with Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease.” JAMA. 2016;316(7): 743-753.
  4. Thompson A, Temple NJ. “The Case for Statins: Has It Really Been Made?” J R Soc Med. 2004;97: 461–464. doi:10.1258/jrsm.97.10.461