Cost-effectiveness of zofenopril in patients with left ventricular systolic dysfunction after acute myocardial infarction: a post hoc analysis of SMILE-4

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Left ventricular systolic dysfunction following acute myocardial infarction (n=716). Intervention: Zofenopril + acetylsalicylic acid vs. Ramipril 5 mg twice daily (10 mg/day) + ASA 100 mg once daily. Primary outcome: 1-year combined occurrence of cardiovascular death or hospitalization for cardiovascular causes (including congestive heart failure, acute myocardial infarction, angina, revascularization, or a decline in LVEF >15%) and incremental cost-effectiveness ratio (ICER) (RRR 30%, NNT 13, ICER 2125.45 Euros per event prevented, 95% CI 4%-49%, p=0.028).

Q: What does this research mean for the field?

Zofenopril reduces the one-year risk of cardiovascular death or hospitalization by 30% compared with ramipril in post-myocardial infarction patients with left ventricular dysfunction, with an incremental cost-effectiveness ratio of 2,125.45 Euros per event prevented. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Stefano Omboni; Claudio Borghi; Ambrosioni; Arrigo F.G. Cicero; Stefano Bacchelli; Daniela Degli Esposti; Salvatore Novo; Dragoş Vinereanu; Giuseppe Ambrosio; Giorgio Reggiardo; Dario Zava

doi:10.2147/ceor.s43138

July 1, 2013ClinicoEconomics and Outcomes ResearchOpen Access

Cost-effectiveness of zofenopril in patients with left ventricular systolic dysfunction after acute myocardial infarction: a post hoc analysis of SMILE-4

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Key result

Zofenopril cuts 1-year cardiovascular death or hospitalization ~30% vs. ramipril.

RRR 30%, NNT 13, ICER 2125.45 Euros per event prevented
95% CI 4%-49%
P=0.028
NNT 13
n=716

Why the study?

Is zofenopril 60 mg/day plus acetylsalicylic acid 100 mg/day cost-effective compared with ramipril 10 mg/day plus acetylsalicylic acid 100 mg/day for preventing cardiovascular death or cardiovascular hospitalization at 1 year in patients with left ventricular dysfunction after acute myocardial infarction?

Key Points

To compare the cost-effectiveness of zofenopril versus ramipril in patients with left ventricular systolic dysfunction following acute myocardial infarction.
Post hoc economic evaluation of the SMILE-4 double-blind trial, which randomized 771 post-acute myocardial infarction patients with left ventricular dysfunction to zofenopril 60 mg/day (n = 389) or ramipril 10 mg/day (n = 382), each plus acetylsalicylic acid 100 mg/day, for one year.
The primary endpoint was the one-year combined incidence of death or hospitalization for cardiovascular causes.
Economic analysis evaluated drug and hospitalization costs using National Health Service databases from participating European countries in the intention-to-treat population (n = 716).
Zofenopril significantly reduced the primary combined endpoint by 30% compared with ramipril (95% CI, 4%-49%; P = 0.028), occurring in 29% (105/365) versus 37% (128/351) of patients, resulting in a number needed to treat of 13.
Average annual medication costs were 328.78 Euros per patient for zofenopril and 165.12 Euros for ramipril, while hospitalization costs averaged 4983.64 Euros and 4850.01 Euros, respectively.
The incremental cost-effectiveness ratio for zofenopril versus ramipril was 2125.45 Euros per event prevented, with worst- and best-case sensitivity analysis scenarios of 3590.09 and 3243.96 Euros, respectively.

Study Design

Type

RCT (n=716)

Blinding

Double-blind

Randomization

1:1 randomization

Multicenter

Yes

Structured PICO

Is zofenopril 60 mg/day plus acetylsalicylic acid 100 mg/day cost-effective compared with ramipril 10 mg/day plus acetylsalicylic acid 100 mg/day for preventing cardiovascular death or cardiovascular hospitalization at 1 year in patients with left ventricular dysfunction after acute myocardial infarction?

P

Population

716 adults aged 18-85 years in the intention-to-treat population (from 771 randomized) with left ventricular dysfunction (Killip class >1 or LVEF <45%) following acute myocardial infarction not treated with primary angioplasty across 8 European countries, followed for 12 months.

I

Intervention

Zofenopril 30 mg twice daily (60 mg/day) + acetylsalicylic acid (ASA) 100 mg once daily for 12 months (following a 4-day open-label uptitration phase of zofenopril 7.5 mg twice daily on days 1-2 and 15 mg twice daily on days 3-4 plus ASA 100 mg/day), administered in combination with standard recommended AMI treatments.

C

Comparator

Ramipril 5 mg twice daily (10 mg/day) + acetylsalicylic acid (ASA) 100 mg once daily for 12 months (following the same 4-day open-label zofenopril uptitration run-in phase), administered in combination with standard recommended AMI treatments.

O

Outcome

One-year combined occurrence of cardiovascular death or hospitalization for cardiovascular causes (congestive heart failure, acute myocardial infarction, angina, revascularization, or a decline in left ventricular ejection fraction > 15%) and incremental cost-effectiveness ratio (ICER, cost per event prevented in 2012 Euros).composite

Main Result

Number Needed to Treat: 13

Absolute Event Rate: 29% vs 37%

Number Needed to Treat: 13

p-value: p=0.028

In patients with left ventricular dysfunction after acute myocardial infarction, zofenopril plus aspirin is both clinically superior and highly cost-effective compared with ramipril plus aspirin, costing 2,125.45 Euros per additional major cardiovascular event prevented over one year.

Limitations

Post hoc cost-effectiveness analysis conducted after the randomized trial was completed, limiting variables available for detailed healthcare utilization measurement (e.g., quality of life or life-years gained were not assessed).
Third-party payer perspective (integrated public healthcare system) was used instead of a broader societal perspective.
One cost item (decline in left ventricular ejection fraction >15%) was missing from reference payment lists and had to be conservatively estimated as one-third the cost of a heart failure hospitalization.
Relatively limited time horizon of one year, preventing quantification of benefits or cost-effectiveness beyond the trial follow-up period.
Cost calculations were limited to direct medical costs of drugs and hospitalizations, excluding nonmedical, indirect (productivity losses), rehabilitation, and long-term care costs.
Post hoc cost analysis conducted after completion of the randomized trial, lacking assessment of quality of life or life-years gained
Restricted to a third-party payer perspective rather than a societal perspective
Missing reference payment cost for decline in left ventricular ejection fraction >15%, requiring an estimated cost assumption
Limited one-year time horizon with inability to quantify long-term cost-effectiveness beyond trial follow-up
Excluded nonmedical, indirect (productivity loss), rehabilitation, and long-term care costs

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Implication

Zofenopril plus aspirin may be preferred post-MI with LV dysfunction; extends randomized ACE inhibitor comparisons with favorable ICER.

Abstract

BACKGROUND: In SMILE-4 (the Survival of Myocardial Infarction Long-term Evaluation 4 study), zofenopril + acetylsalicylic acid (ASA) was superior to ramipril + ASA in reducing the occurrence of major cardiovascular events in patients with left ventricular dysfunction following acute myocardial infarction. The present post hoc analysis was performed to compare the cost-effectiveness of zofenopril and ramipril. METHODS: In total, 771 patients with left ventricular dysfunction and acute myocardial infarction were randomized in a double-blind manner to receive zofenopril 60 mg/day (n = 389) or ramipril 10 mg/day (n = 382) + ASA 100 mg/day and were followed up for one year. The primary study endpoint was the one-year combined occurrence of death or hospitalization for cardiovascular causes. The economic analysis was based on evaluation of cost of medications and hospitalizations and was applied to the intention-to-treat population (n = 716). Cost data were drawn from the National Health Service databases of the European countries participating in the study. The incremental cost-effectiveness ratio was used to quantify the cost per event prevented with zofenopril versus ramipril. RESULTS: Zofenopril significantly (P = 0.028) reduced the risk of the primary study endpoint by 30% as compared with ramipril (95% confidence interval, 4%-49%). The number needed to treat to prevent a major cardiovascular event with zofenopril was 13 less than with ramipril. The cost of drug therapies was higher with zofenopril (328.78 Euros per patient per year, n = 365) than with ramipril (165.12 Euros per patient per year, n = 351). The cost related to the occurrence of major cardiovascular events requiring hospitalization averaged 4983.64 Euros for zofenopril and 4850.01 Euros for ramipril. The incremental cost-effectiveness ratio for zofenopril versus ramipril was 2125.45 Euros per event prevented (worst and best case scenario in the sensitivity analysis was 3590.09 and 3243.96 Euros, respectively). CONCLUSION: Zofenopril is a viable and cost-effective treatment for managing patients with left ventricular dysfunction after acute myocardial infarction.

Discussion

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Cite This Study

Omboni et al. (2013) conducted an RCT in Left ventricular systolic dysfunction following acute myocardial infarction (n=716). Zofenopril + acetylsalicylic acid vs. Ramipril 5 mg twice daily (10 mg/day) + ASA 100 mg once daily was evaluated on 1-year combined occurrence of cardiovascular death or hospitalization for cardiovascular causes (including congestive heart failure, acute myocardial infarction, angina, revascularization, or a decline in LVEF >15%) and incremental cost-effectiveness ratio (ICER) (RRR 30%, NNT 13, ICER 2125.45 Euros per event prevented, 95% CI 4%-49%, p=0.028). Zofenopril reduced the 1-year risk of cardiovascular death or hospitalization by 30% compared with ramipril (p=0.028, NNT=13), yielding an ICER of 2,125.45 Euros per event prevented.

synapsesocial.com/papers/6a7749cba7498e5110ae731f https://doi.org/10.2147/ceor.s43138

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Cost-effectiveness of zofenopril in patients with left ventricular systolic dysfunction after acute myocardial infarction: a post hoc analysis of SMILE-4

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Cost-effectiveness of zofenopril in patients with left ventricular systolic dysfunction after acute myocardial infarction: a post hoc analysis of SMILE-4

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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