The cost-effectiveness of PCSK9 inhibitors - The Australian healthcare perspective
Introduction
3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are highly efficacious at reducing low density lipoprotein cholesterol (LDL-C) levels and lowering CVD risk [1] and currently comprise first line therapy in the treatment of hyperlipidaemia and prevention of CVD [2]. Previous research has demonstrated that a decrease of 1 mmol/L of LDL-C results in an approximate 20% decrease in risk of CVD major vascular events [1,3].
However, statins are unsuitable for approximately 5 to 10% of individuals, predominantly due to intolerance or ineffectiveness as monotherapy [4]. For such people, the new class of lipid lowering agents, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), represents an alternative treatment option. Randomised controlled trials of PCSK9i thus far have demonstrated reductions in LDL-C levels by >50% compared to placebo [5]. More recently, the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial reported that on a background of statin therapy, the PCSK9i evolocumab reduced the risk of CVD outcomes [6]. Hence PCSK9i represent an important treatment option for patients with statin intolerance and/or ineffectiveness, but their cost-effectiveness is currently unknown.
This study sought to determine the long-term effectiveness and cost-effectiveness of PCSK9i from the Australian healthcare perspective.
Section snippets
Model structure
A Markov state-transition model was developed in Microsoft Excel to assess the cost-effectiveness of PCSK9i versus placebo in the prevention of CVD. The model structure is conceptualized in Fig. 1.
With each 5-year cycle, model subjects could develop non-fatal CVD events (myocardial infarction [MI] and/or stroke), fatal CVD or die from other causes. All events were assumed to occur half-way through the cycle. Individuals continued to cycle through the model for 25 years or until death.
The model
Results
Table 2 summarizes the simulated results of the effectiveness of PCSK9i compared to placebo, determined by the number of CVD events prevented. Seventy CVD events were prevented in 1000 individuals over a 25-year time horizon, equating to a number needed to treat of 14 over this period. In total, 210 years of life (discounted) and 236 QALYs (discounted) were saved in the cohort, at a net cost (discounted) of AU$72,946,713 (discounted). These equated to ICERs of AU$347,164 per year of life saved
Discussion
To the best of the authors' knowledge, this is the first cost-effectiveness analyses of PCSK9i for the prevention of CVD in the general Australian population. The analysis demonstrates PCSK9i would not be cost-effective at current acquisition costs of AU$8174 per person per annum.
Cost-effectiveness analyses of PCSK9i in the US have showed conflicting results. Gandra et al. [17] found that evolocumab, at a cost of US$14,100 per person per annum, met cost-effectiveness thresholds in patients with
Conclusions
Those with existing CVD disease or at high risk of CVD in whom statin therapy is ineffective would benefit from treatment with other lipid lowering therapies such as PCSK9i. However, at current acquisition costs (reimbursed for patients with homozygous familial hypercholesterolemia) in Australia, PCSK9i would not be considered cost-effective within the Australian healthcare system. Cost-effectiveness is much improved in high risk patients, such as those with PAD. As long-term data on the
Sources of funding
No funding was required for this publication.
Disclosures
AT and DL have received honoraria from Amgen, including pertaining to work on evolocumab.
Conflict of interest
AT and DL have received honoraria from Amgen, including pertaining to work on evolocumab. RK and EZ report no relationships that could be construed as a conflict of interest.
References (29)
- et al.
The relationship between reduction in low-density lipoprotein cholesterol by statins and reduction in risk of cardiovascular outcomes: an updated meta-analysis
Clin. Ther.
(2009) - et al.
Determining when to add nonstatin therapy. A quantitative approach
J. Am. Coll. Cardiol.
(2016) - et al.
Efficacy and safety of more intensive lowering LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials
Lancet
(2010) Statin use for the primary prevention of cardiovascular disease in adults
J. Am. Med. Assoc.
(2016)- et al.
Statin intolerance
Circulation
(2015) - et al.
Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia
Ann. Intern. Med.
(2015) - et al.
Evolocumab and clinical outcomes in patients with cardiovascular disease
N. Engl. J. Med.
(2017) - et al.
Improving the cost-effectiveness of cardiovascular disease prevention in Australia: a modelling study
BMC Public Health
(2012) - et al.
Long-term survival and recurrence after acute myocardial infarction in England, 2004 to 2010
Circ. Cardiovasc. Qual. Outcomes
(2012) - et al.
Ten-year survival after first-ever stroke in the Perth Community Stroke Study
Stroke
(2003)
Australian Institute of Health and Welfare
Estimated cost weights for AR-DRG version 7.0, Round 18 (2013–14)
Australian Government. Department of Health
Australian Institute of Health and Welfare. 2015
Cited by (0)
- 1
These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.