Results

25-Year Markov Model

The addition of inclisiran to statins as first-line therapy in the target population was modelled to save 6401 non-fatal CVD events and gain 23,730 QALY's over 25 years at an additional cost of $1,158,188,332 (or $46,327,533/year) to the Australian healthcare system (Table 4). This would represent 0.32% of the total Australian governments' 2022 CVD expenditure [1]. The ICER was $48,808/QALY (Table 4). The WTPT of inclisiran dropped under the hypothetical Australian government PBAC $50,000AUD threshold at the 10th year, making it incrementally more cost-effective for the following 11 years thereafter (Fig. 2). Linear inclisiran price reduction linearly reduced the ICER (Fig. 3).

Outcomes | Inclisiran + standard therapy | Standard Therapy | Difference
Total non-fatal CVD events | 79,051 | 72,649 | (6401)
Total fatal CVD events | 6255 | 5185 | 1070
Total QALY's gained | 154,495 | 130,765 | (23,730)
Total Cost | $3,415,398,727 | $2,644,042,927 | $1,158,188,332 (or$46,327,533/year)
ICER | - | - | $48,808

Fig. 2: Sensitivity analysis – Yearly change in ICER per QALY for Inclisiran over 25-years.

Fig. 3: Sensitivity analysis – Change in ICER per QALY for Inclisiran with price reduction.

Sensitivity analysis

Deterministic sensitivity analysis was performed on key model inputs to assess their influence on the primary outcome (Table 5, Fig. 4). Unless otherwise specified, parameters were varied by ±5%, with the discount rate additionally examined at 3%. No ±5% variation altered the ICER by more than 5%, except for recurrent non-fatal CVD event rates, which increased the ICER by 11%. Utility for the no-event health state altered the ICER by ±4%, while all other parameters changed the ICER by ≤ 1%. Broader (±20%) scenario analyses confirmed that the ICER was most sensitive to recurrent non-fatal CVD event rates, health-state utility estimates, and inclisiran cost, with some scenarios crossing commonly cited Australian willingness-to-pay thresholds (Appendix 3). Probabilistic sensitivity analysis was not performed because robust variance estimates were unavailable for several key model parameters. Future studies should incorporate probabilistic sensitivity analysis once robust parameter uncertainty estimates become available to better characterise decision uncertainty.

 | New Value | New ICER per QALY | % Change from baseline ICER
Utility - No Event | +5% | $46,848 | −4%
−5% | $50,934 | 4%
Utility – Non-fatal CVD event | +5% | $48,352 | −1%
−5% | $49,272 | 1%
Cost – No event | +5% | $49,058 | 1%
−5% | $48,557 | −1%
Cost – Non-fatal CVD event | +5% | $48,693 | 0%
−5% | $48,516 | −1%
Cost – Fatal CVD event | +5% | $48,973 | 0%
−5% | $48,643 | 0%
Cost – Fatal other event | +5% | $48,879 | 0%
−5% | $48,797 | 0%
Discounting | Reduced to 3% | $48,767 | 0%
Transition probabilities – Non-fatal CVD event | −5% | $48,939 | 0%
+5% | $54,166 | 11%
Transition probabilities – Fatal CVD event | −5% | $48,577 | 0%
+5% | $49,044 | 0%

Fig. 4: Tornado diagram showing influence of model parameters on the ICER.