Summary of findings 1. Usual care with ivabradine compared to placebo, usual care, or no treatment in participants with HFrEF (long‐term treatment (≥ 6 months) with ivabradine).
Usual care with ivabradine compared to placebo, usual care, or no treatment in participants with HFrEF (long‐term treatment (≥ 6 months) with ivabradine) | ||||||
Patient or population: adults (≥ 18 years of age) with a diagnosis of chronic heart failure with reduced ejection fraction (HFrEF) Setting: hospital or outpatient care Intervention: long‐term treatment (≥ 6 months) with ivabradine Comparison: placebo, usual care, or no treatment | ||||||
Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
Risk with placebo | Risk with usual care with ivabradine compared to placebo, usual care, or no treatment in participants with HFrEF (long‐term treatment (≥ 6 months) with ivabradine) | |||||
Mortality from cardiovascular causes (follow‐up range 19 to 23 months) | 106 per 1000 | 105 per 1000 (93 to 117) | RR 0.99 (0.88 to 1.11) | 17,676 (3 RCTs) | ⊕⊕⊕⊝ MODERATE1 | Evidence of no difference as the effect is close to 1 and the CI is narrow. |
Quality of life |
Swedberg 2010: Treatment with ivabradine improved Kansas City Cardiomyopathy Questionnaire (KCCQ) by 1.8 (95% CI 0.30 to 3.24) for clinical summary score (CSS) and by 2.4 (95% CI 0.91 to 3.85) for overall summary score (OSS) (placebo‐corrected, P = 0.018 and P < 0.001, respectively). Chaudhari 2014: Significant improvement (P = 0.004, no further details available) |
2102 (2 RCTs) |
⊕⊕⊝⊝ LOW2, 4 |
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Time to first hospitalisation for heart failure during follow‐up | Not reported in studies that met the inclusion criteria for this comparison | |||||
Number of days spent in hospital due to heart failure during follow‐up | Not reported in studies that met the inclusion criteria for this comparison | |||||
Rate of serious adverse events | 321 per 1000 | 308 per 1000 (296 to 321) | RR 0.96 (0.92 to 1.00) | 17,399 (2 RCTs) | ⊕⊕⊕⊝ MODERATE1 | 2 additional RCTs (207 participants) could not be pooled. Chaudhari 2014: Author reported that no significant adverse effects on ivabradine therapy were noted at the end of 6 months; no further details are provided. Potapenko 2011: Author reported that the addition of ivabradine to standard treatment promoted less fatal cardiovascular events; no further details are provided. |
Exercise capacity | Chaudhari 2014: No significant improvement for ivabradine group in exercise duration (320 ± 130.6 s vs 311.79 ± 103.60 s) (P = 0.663) | 158 (1 RCT) |
⊕⊕⊝⊝ LOW2, 3 |
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Economic costs | All data are based on the SHIFT trial by Swedberg 2010: Adena 2018: Ivabradine is likely to be cost‐effective in Australia (cost per QALY = AUS 14,905). Borer 2016: Ivabradine led to lower average annual treatment costs in the US (PMPM cost savings year 3: USD 0.04). Chang 2014: Ivabradine is likely to be cost‐effective in Taiwan (cost per QALY: GBP 14,832). Fernandez de Bobadilla 2014: Ivabradine is cost‐effective in Spain (cost per QALY: EUR 17,488/cost per LYG: EUR 13,044). Griffiths 2014: Ivabradine is likely to be cost‐effective in the UK (cost per QALY: GBP 8498 (≥ 75 bpm)/GBP 13,764 (≥ 70 bpm). Kansal 2016: Ivabradine is associated with cost savings in the USA (cost saving over 10‐year time horizon: USD 8594/QALY: 0.24/ICER per QALY: USD 24,920). Kourlaba 2014: Ivabradine is a cost‐effective option in Greece (cumulative lifetime total cost per patient EUR 8665 vs EUR 5837/ICER per QALY: EUR 9986). Krittayaphong 2019: The addition of ivabradine to standard treatment is a cost‐effective treatment strategy in HFrEF patients in Thailand with a heart rate ≥ 77 bpm (USD 6515.16/QALY). Polistena 2014: Results show social acceptability of ivabradine in Italy (cost per QALY: EUR 17,435/cost per LYG: EUR 15,557/HOS costs avoided: EUR 3420). Taheri 2018: From an Iranian healthcare system, the analysis indicates that the clinical benefit of ivabradine can be achieved at a reasonable cost in eligible hear failure patients (cost per QALY: USD 5437). |
6558 (1 RCT) |
⊕⊕⊕⊕ HIGH | |||
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). bpm: beats per minute; CI: confidence interval; HFrEF: heart failure with reduced ejection fraction; HOS: hospitalization; ICER: Incremental cost‐effectiveness ratio; LYG: life years gained;PMPM: per member per month; QALY: quality‐adjusted life year; RCT: randomised controlled trial; RR: risk ratio | ||||||
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. |
1Downgraded by one level due to indirectness (male predominance). 2Downgraded by one level due to risk of bias (allocation, blinding). 3Downgraded by one level due to imprecision (low number of participants). 4Downgraded by one level due to attrition bias (only around 30% of the overall trial participants contributed data).