Study | Country | Study period | Setting | Duration of follow-up | Follow-up schedule | BNP/NT-proBNP target | Clinical target | Primary endpoint | Treatment algorithm |
---|---|---|---|---|---|---|---|---|---|
Studies that provided IPD | |||||||||
Anguita [20] | Spain | 2006–2008 | HF clinic | 18 months | 1, 2, 3, 6, 12, and 18 months | BNP level < 100 pg/ml | Framingham HF score of < 2 | Composite of all-cause mortality and cardiovascular hospital admission | BNP group: therapy intensified to achieve target BNP Control group: therapy intensified to achieve target congestion score. |
Northstar [27] | Denmark | 2005–2009 | HF clinic | 2.5 years | Every 1–3 months at the discretion of the investigator | No set target | Clinical assessment | Composite of all-cause mortality and cardiovascular hospital admission | BNP group: checklist to evaluate need for further investigation or intensification of therapy when NT-BNP was > 30% from randomisation visit Control group: therapy evaluated and intensified at clinician discretion |
Shochat [32] Published as abstract only | Israel | 2007–2010 | HF clinic | Median 11 months (IQR 3–22) | Every 1–2 months | No set target | Not known | All-cause mortality | BNP group: therapy intensified if NT-BNP was higher by > 30% from previous clinic visit Control group: not stated in abstract |
Starbrite [31] | USA | 2003–2005 | HF clinic | 4 months | Week 1 and then 1, 2, 3, and 4 months | Individual BNP at discharge | Individual congestion score | Composite of 90-day survival and hospital-free survival | BNP group: therapy intensified if BNP levels were 2 times greater than or less than the target BNP Control group: therapy intensified to achieve target congestion score |
Upstep [24] | Sweden and Norway | 2006–2009 | HF clinic | ≥ 12 months | Weeks 2, 6, 10, 16, 24, 36, 48, and then every 6 months | < 75 years: BNP level < 150 pg/ml ≥ 75 years: BNP level < 300 pg/ml | Clinical assessment | Composite of all-cause mortality, hospitalisation and worsening HF | BNP group: therapy intensified according to stepwise algorithm to achieve maximally tolerated or guideline recommended target doses Control group: therapy intensified at clinician discretion |
Studies that provided aggregate data [33] | |||||||||
Christchurch Pilot [29] | New Zealand | 1998–1999 | HF clinic | 9.5 months | Every 3 months unless treatment targets not met | NT-proBNP level < 1700 pg/ml | Framingham HF score of < 2 | Total cardiovascular events (mortality, hospital admission, new HF-related outpatient episode) | BNP group: therapy intensified according to stepwise algorithm to achieve target NT-BNP Control group: therapy intensified according to stepwise algorithm to achieve target HF score |
Switzerland and Germany | 2003–2006 | HF clinic | 18 months | 1, 3, 6, 12, and 18 months | NT-proBNP less than 2× upper limit of normal: (< 400 pg/ml for patients < 75 yrs.; < 800 pg/ml for patients > = 75 years) | NYHA ≤II | Hospital-free survival | BNP group: therapy intensified according to stepwise algorithm to achieve target NT-BNP Control group: therapy intensified according to stepwise algorithm to achieve NYHA ≤II | |
Berger [21] | Austria | 2003–2004 | HF clinic | 15 months | 2 weekly, then 1, 3, 6, and 12 months | NT-proBNP < 2200 pg/L | Clinical assessment | Composite of all-cause mortality and HF re-hospitalisation | BNP group: therapy intensified according to set protocol to maintain target NT-BNP Control group: therapy intensified at clinician discretion |
Prima [22] | Netherlands | 2004–2007 | HF clinic | 24 months | 2 weeks, 1 month, then 3 monthly for 2 years | Individual NT-proBNP level (lowest level at discharge or at 2 weeks follow-up) | Clinical assessment | Survival and hospital-free survival | BNP group: therapy intensified according to clinical guidelines to maintain target NT-BNP Control group: therapy intensified at clinician discretion |
Signal-HF [25] | Sweden | 2006–2009 | Primary care | 9 months | 1, 3, 6, and 9 months | Individual NT-proBNP level (reduction of 50% from baseline) | Clinical assessment | Composite of survival, hospital-free survival and symptoms score | BNP group: stepwise algorithm to increase therapy to achieve target NT-BNP Control group: therapy intensified at clinician discretion |
Battlescarred [28] | New Zealand | 2001–2006 | HF clinic | 3 years | 2 weekly until treatment target met then 3 monthly | NT-proBNP < 1300 pg/ml | Framingham HF score of < 2 | All-cause mortality | BNP group: therapy intensified according to stepwise algorithm to achieve target NT-BNP and congestion score < 2 Control group: therapy intensified to achieve target congestion score < 2 |
Stars-BNP [23] | France | Not stated | HF clinic | 15 months | Months 1, 2, and 3, and then 3 monthly thereafter | BNP level < 100 pg/ml | Clinical assessment | Composite of HF mortality or HF hospitalisation | BNP group: therapy intensified according to clinical guidelines to maintain target NT-BNP Control group: therapy intensified at clinician discretion |
Protect [30] | USA | 2006–2010 | HF clinic | At least 6 months | As required to meet treatment target and then 3 monthly (for max 12 months) | NT-proBNP ≤ 1000 pg/ml | Clinical assessment | Composite of worsening HF, HF hospitalisation and cardiovascular events | BNP group: therapy intensified according to clinical guidelines to maintain target NT-BNP Control group: therapy intensified at clinician discretion |
Guide-IT [11] | USA | 2013–2016 | HF clinic | 15 months | Initial visits at 2 and 6 weeks and then every 3 months. A follow-up visit 2 weeks after any therapy adjustment | NT-proBNP < 1000 pg/ml | Clinical assessment | Composite of cardiovascular death and HF hospitalisation | BNP group: therapy intensified at clinician discretion but in line with clinical guidelines to achieve target NT-BNP Control group: therapy intensified at clinician discretion but in line with clinical guidelines |
Eligible studies that did not provide IPD or aggregate data | |||||||||
Karavidas [45] Published as abstract only | Greece | Not stated | Not stated | 12Â months | Not stated | Not stated but likely no set target | Clinical assessment | Not clear. Composite of all-cause mortality cardiovascular hospitalisation? | Not stated |
Home [46] Clinical trial registration only | Ireland, UK, Australia and Canada | 2011–2014 | Not stated | 6 months | 1, 3, and 6 months | Not stated but likely no set target | Not stated | Average number of ‘hard’ events per subject (HF mortality, hospitalisation for HF, unplanned outpatient episodes for decompensated HF (including change in diuretic therapy) | BNP group: therapy intensified at clinician discretion using BNP information Control group: As above but without the BNP information |
Optima [47] Published as poster only | Czech Republic | Not stated | Not stated | Not stated | Not stated | Not stated but likely a BNP lowering strategy | Clinical assessment | Composite of cardiovascular mortality, HF hospitalisation and outpatient episodes of worsening HF requiring an increase in diuretic by at least 50% | BNP group: therapy intensified to ‘normalise’ plasma BNP levels. Control group: therapy intensified at clinician discretion according to guidelines. |
Koshkina et al. [48] Published as abstract only | Russian Federation | Not stated | HF clinic | Mean (SD) 10 ± 2.5 months | Not stated | NT-proBNP < 1000 pg/ml or at least 50% of the initial | Clinical assessment | Total cardiovascular events | Not stated |
Ex Improve CHF [49] Study ongoing | Canada | 2007–ongoing | HF clinic | Minimum 12 months | Not stated | No set target | Clinical assessment | Composite of all-cause mortality and HF hospitalisation | BNP group: therapy intensified at clinician discretion using BNP information Control group: As above but without the BNP information |