{
  "abstract": "Introduction Acetazolamide (ACZ) may be a useful adjunctive diuretic in people hospitalised with heart failure (HF). However, some patients fail to respond to treatment. We performed a post-hoc analysis of the ADA-HF trial (ACZ as a chloride-sparing diuretic in patients hospitalised with HF - ISRCTN13060336) to assess the clinical characteristics and outcomes of patients who did, and did not respond to treatment with ACZ.Methods ADA-HF was a single centre, open-label trial of oral ACZ 200 mg twice daily alongside high-dose intravenous (IV) furosemide (starting dose 240 mg per day via continuous IV infusion – ‘usual care’ (UC)) compared to usual care alone. The co-primary endpoints were difference in net fluid loss and change in serum chloride after four days of treatment. ACZ was not associated with a difference in net fluid loss, but serum chloride was significantly higher in the ACZ arm. In this analysis, we defined ‘response’ to treatment as urine output of ≥2400 mL on two or more consecutive days based on European Society of Cardiology HF guidelines. Patients were split into responders and non-responders, and differences in baseline characteristics and outcomes were assessed.Results 46 patients were enrolled (N=23 per group), of whom 26 patients (57%) were responders (N=14 (61%) in ACZ arm vs N=12 (52%) in UC arm; P=0.55). Responders had greater blood pressure, haemoglobin, and estimated glomerular filtration rate at baseline, and received lower cumulative doses of IV furosemide prior to randomisation compared to non-responders ( table 1). Pre-admission diuretic dose was not associated with response. On univariable logistic regression, only baseline systolic blood pressure was associated with response in those taking acetazolamide (table 2). Predictors of response to treatment were the same regardless of treatment allocation. All-cause mortality was higher in non-responders (35% Vs 7.7%, P= 0.029) after 180 day follow up (figure 1), as was the proportion of participants experiencing a serious adverse event during the four day trial period (30% Vs 0%, P=0.004).Conclusion Response to ACZ is not dependent on baseline values, or change in serum electrolyte concentrations with treatment. Pre-enrolment loop diuretic dosing may influence response to diuretic treatment after enrolment; this may have implications for the design of diuretic trials in people hospitalised with HF.Table 1 – Baseline characteristics of responders and non-responders to diuretic therapy. Results are displayed as median (IQR). P-values were generated using the Mann-Whitney U test. Days to randomisation = time interval between hospital admission and randomisation, eGFR = estimated glomerular filtration rate.Table 2 – Univariable logistic regression analysis showing the relationship of baseline characteristics to response in those receiving ACZ. Results are displayed as odds ratio (95% confidence interval). P-values were generated using the Wald Chi-Squared test. eGFR = estimated glomerular filtration rate.Figure 1 – Time to all-cause mortality is shown for responders and non-responders. Survival time was calculated from randomisation to death, with patients without events censored at six months. Log rank P = 0.016.Abstract 505 Figure 1Kaplan-meier estimate of all-cause mortalityAbstract 505 Table 1Baseline characteristicsBaseline CharacteristicsNon-respondersN=20RespondersN=26P-valueDays to randomisation2 (1-4)2 (1-3)0.367Age (years) 77 (70-85)76 (71-79)0.579Haemoglobin (g/L)108 (97-118)127 (114-144)0.012Systolic blood pressure (mmHg)109 (103-128)121 (114-136)0.030Pre-admission loop diuretic dose (mg) 50 (20-80)40 (20-80)0.882Pre-randomisation cumulative IV loop diuretic dose (mg)315 (160-445)105 (40-280)0.013eGFR (ml/min/1.73m2)50 (39-54)62 (45-70)0.021Chloride (mmol/L)98 (94-103)95 (94-100)0.317Bicarbonate (mmol/L)30 (20-31)32 (27-34)0.132Abstract 505 Table 2Univariable logistic regression for variables associated with response to ACZ therapyBaseline Characteristics Adjusted Odds RatioWald χ2P-valueSystolic blood pressure (mmHg)1.10 (1.01-1.20)4.380.036Pre-admission loop diuretic dose (mg)1.00 (0.99-1.02)0.060.803Pre-randomisation cumulative IV loop diuretic dose (mg)1.00 (1.00-1.00)1.120.290eGFR (ml/min/1.73m2)1.07 (0.99-1.15)2.700.101Change in eGFR D1-D4 (ml/min/1.73m2)0.99 (0.89-1.10)0.050.817Chloride (mmol/L)0.94 (0.76-1.17)0.270.605Change in serum chloride D1-D4 (mmol/L)0.99 (0.73-1.32)0.010.920Serum bicarbonate (mmol/L)1.08 (0.88-1.31)0.530.469Change in serum bicarbonate D1-D4 (mmol/L)0.97 (0.81-1.15)0.150.695",
  "authors": [
    {
      "affiliations": [
        "Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Cottingham Road, Kingston-Upon-Hull, HU6 7RX"
      ],
      "name": "T Huetson"
    },
    {
      "affiliations": [
        "Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Cottingham Road, Kingston-Upon-Hull, HU6 7RX"
      ],
      "name": "E Sanyaolu"
    },
    {
      "affiliations": [
        "Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, HU16 5JQ"
      ],
      "name": "E Luo"
    },
    {
      "affiliations": [
        "Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, HU16 5JQ"
      ],
      "name": "ASM Ahmed"
    },
    {
      "affiliations": [
        "Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, HU16 5JQ"
      ],
      "name": "M Ajith"
    },
    {
      "affiliations": [
        "Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, HU16 5JQ"
      ],
      "name": "H Butt"
    },
    {
      "affiliations": [
        "Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, HU16 5JQ"
      ],
      "name": "H Pinhol"
    },
    {
      "affiliations": [
        "Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, HU16 5JQ"
      ],
      "name": "F Baffour Korsah"
    },
    {
      "affiliations": [
        "Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, HU16 5JQ"
      ],
      "name": "J Bulemfu"
    },
    {
      "affiliations": [
        "Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, HU16 5JQ"
      ],
      "name": "S Ford"
    },
    {
      "affiliations": [
        "Research and Development, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, HU16 5JQ"
      ],
      "name": "G Constable"
    },
    {
      "affiliations": [
        "Research and Development, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, HU16 5JQ"
      ],
      "name": "L Cox"
    },
    {
      "affiliations": [
        "Hull York Medical School, University of Hull, Cottingham Road, Kingston-Upon-Hull, HU6 7RX"
      ],
      "name": "AS Rigby"
    },
    {
      "affiliations": [
        "Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, HU16 5JQ"
      ],
      "name": "AL Clark"
    },
    {
      "affiliations": [
        "Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Cottingham Road, Kingston-Upon-Hull, HU6 7RX",
        "Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, HU16 5JQ"
      ],
      "name": "JJ Cuthbert"
    }
  ],
  "title": "505 Factors which govern diuretic response to acetazolamide – a post-hoc analysis of the ADA-HF trial",
  "uid": "bf01e4bd-4114-5515-8bc4-70ec9038cc3f"
}