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Health technology assessment

A systematic review and economic evaluation of prasugrel compared to clopidogrel after PCI

Patients who have undergone percutaneous coronary intervention (PCI) for coronary artery disease usually get a platelet inhibitor (e.g. clopidogrel) for one year after the procedure. Prasugrel is a new platelet inhibitor which is available for patients with acute coronary syndrome (ACS) who undergo PCI in Norway.

Patients who have undergone percutaneous coronary intervention (PCI) for coronary artery disease usually get a platelet inhibitor (e.g. clopidogrel) for one year after the procedure. Prasugrel is a new platelet inhibitor which is available for patients with acute coronary syndrome (ACS) who undergo PCI in Norway.


Key message

Patients who have undergone percutaneous coronary intervention (PCI) for coronary artery disease usually get a platelet inhibitor (e.g. clopidogrel) for one year after the procedure. Prasugrel is a new platelet inhibitor which is available for patients with acute coronary syndrome (ACS) who undergo PCI in Norway.

We aimed to analyze the efficacy and cost-effectiveness of prasugrel compared to clopidogrel for ACS patients who have undergone PCI. This analysis was commissioned by the Norwegian Medicines Agency to support their decision on whether to give reimbursement to prasugrel as well as clopidogrel, which is reimbursed today.

We performed a systematic review of randomised controlled trials (RCTs) to estimate the efficacy of prasugrel compared to clopidogrel. Cost-effectiveness analyses were performed in a previously developed Markov model (MOCCA) which simulates clinical events after a PCI is performed. In the model, health and costs are calculated to give the remaining life expectancy and lifetime costs, which again are used to calculate incremental cost-effectiveness of prasugrel compared to clopidogrel.


Key messages

  • Prasugrel significantly reduces rates of myocardial infarction and urgent target vessel revascularization compared to clopidogrel in both short term (up to 1 month) and long term (up to 15 months). Quality of the evidence was high and moderate for myocardial infarction and low and moderate for urgent target vessel revascularization.
  • Prasugrel significantly increases rates of bleeding events compared to clopidogrel in both short term and long term data. Quality of the evidence for this outcome was high and low, respectively.
  • The analyses on short and long term effects on mortality revealed no statistically significant differences. Quality of the evidence for this outcome was low and moderate, respectively.
  • Prasugrel is cost-effective compared to clopidogrel for ACS patients who have undergone PCI. Our analyses indicate however that there is uncertainty surrounding the cost-effectiveness result.
  • Uncertainty related to efficacy on mortality and, hence also, cost-effectiveness could be reduced if new randomised controlled trials are performed.

Summary

Background
Patients who have undergone percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) usually get a platelet inhibitor (clopidogrel) for one year after operation. Prasugrel is a new platelet inhibitor which is available for ACS patients who undergo PCI in Norway.

Objective
To analyse the cost-effectiveness of prasugrel compared to clopidogrel for ACS patients who have undergone PCI.

Methods
We searched Medline and Embase for randomised controlled trials (RCTs) on efficacy of prasugrel compared to clopidogrel on 08.02.2010 and 15.03.2011. Trials were assessed by two independent reviewers and combined into meta-analyses on the outcomes cardiovascular death, acute myocardial infarction (AMI), urgent target vessel revascularization (UTVR) and bleeding events. The quality of the evidence was evaluated using GRADE (Grading of Recommendations, Assessment, Development and Evaluation).

We used a modified version of a Markov model (Model of cost-effectiveness of coronary artery disease (MOCCA)) previously developed by Norwegian Knowledge Centre for the Health Services, to model the cost-effectiveness of prasugrel compared to clopidogrel. Possible events in the model were UTVR, myocardial infarction, bleeding and death. Incidences of events were based on registries from Sweden and Denmark. Costs of prasugrel and clopidogrel were based on list prices from the Norwegian Medicines Agency.

In addition, we performed probabilistic sensitivity analyses, designed as a Monte Carlo simulation with 1 000 iterations, to get an impression of the uncertainty surrounding our analyses.

Results
We found three relevant trials with 14624 participants comparing prasugrel with clopidogrel. All three reported short-term outcomes (14-30 days) and one trial reported also long-term follow-up (15 months). Meta-analyses of short-term outcomes showed that prasugrel significantly lowered need for UTVR, relative risk (RR)=0,53 (95% confidence interval: 0,39-0,73) and AMI, RR=0,75 (0,65-0,86) compared to clopidogrel. However, prasugrel led to increased rates of bleeding (RR=1,24 (1,00-1,53)). Quality of the evidence for these three outcomes were regarded to be low, high and high, respectively.

On long term, prasugrel also had lower rates of UTVR and AMI at RR=0,67 (0,55-0,82) and RR=0,76 (0,68-0,86), respectively. As in short term, bleeding rates were also higher for prasugrel than clopidogrel RR=1,31 (1,10-1,55). These three outcomes were graded to be at moderate, moderate and low quality of evidence, respectively.

The meta-analyses failed to show any differences in mortality between the two drug regimens  (short term: RR=0,79 (0,57-1,10), long term: RR=0,88 (0,70-1,11)). Quality of the evidence on mortality was rated to be of low and moderate quality, respectively.

Our modelling resulted in an increase in both life expectancy and costs with prasugrel. This gave an incremental cost-effectiveness ratio of NOK 37 600 per life year gained for prasugrel compared with clopidogrel. The probabilistic sensitivity analyses demonstrated that prasugrel is cost-effective in 88% of the simulations. From our value of information analysis, it became evident that the decision depends mostly on the uncertainty in data on efficacy, and hence if new research should be conducted, this is the kind of data that has the highest potential to reduce the decision uncertainty.

Discussion
Efficacy data on the comparison of prasugrel and clopidogrel was scarce. Based on GRADE, only short term efficacy data on myocardial infarction and bleeding had high quality. Hence, this comparison would benefit from further research.

The incremental cost-effectiveness ratio of NOK 37 600 per life year gained, indicates that prasugrel is clearly cost-effective compared to clopidogrel if a threshold for cost-effectiveness is in the range of 350 000 to 1 000 000. Simulations indicated, however, that this result is uncertain. Further research on the efficacy and safety of prasugrel compared to clopidogrel is particularly likely to reduce uncertainty in conclusions of this analysis.

Conclusion
Prasugrel is likely to be more cost-effective than clopidogrel for ACS patients who have undergone PCI. This conclusion is, however, uncertain, and even for high levels of willingness to pay for health, there is a probability of clopidogrel being cost-effective.

    About this publication

  • Year: 2011
  • By: Norwegian Knowledge Centre for the Health Services
  • Authors Wisløff T, Ringerike T, Klemp M.
  • ISSN (digital): 1890-1298
  • ISBN (digital): 978-82-8121-401-9