Hyperkalaemia and ACE inhibitors: increased risk if poor renal function or on lisinopril or enalapril.

Clinical bottom line (level 3b)

  1. A tenth of patients on ACE inhibitors had raised potassium levels , though few had severe hyperkalaemia.
  2. Patients were at an increased risk of developing hyperkalaemia if they: had creatinine > 138 mmol/l (NNH = 4 at 12 months) ; on long-acting ACE inhibitor (NNH = 7 at 12 months) ; have urea > 6.5 mmol/l (NNH = 8 at 12 months) ; have congestive heart failure (NNH = 8 at 12 months) .
  3. Patients were at a decreased risk of developing hyperkalaemia if they: were on a loop diuretic (NNT = 16 at 12 months) ; on a thiazide diuretic (NNT = 16 at 12 months) .
  4. Patients were at an increased risk of developing severe hyperkalaemia (>6.9 mmol/l) if they: were aged >70 (NNH = 140 at 12 months) ; had urea > 9 mmol/l (NNH = 170 at 12 months) .
Reardon and MacPherson: Archives of Internal Medicine 1998; 158: 26-32
Expires February 2004

The study

Case-control study with objective outcomes, adjusted for confounding factors, not validated in an independent set of patients.

Setting: internal medicine clinic and Veterans' Affairs medical centre, USA

388 patients (aged mean 67 years, ?% male) receiving angiotensin converting enzyme inhibitors

Excluded if
  • haemolysed sample


    • Cases: 194 patients (% male, mean age ): potassium level > or = 5.1 mmol/l on same day as outpatient appointment. Patients mainly prescribed lisinopril (89%), and alternatives were captopril or enalapril
    Controls: 194 patients (% male, mean age ): potassium level <5.1 mmol/l on same day as outpatient appointment and did not rise above this during the study period


    Multivariate regression analysis was performed to adjust for confounding factors.

    Outcomes studied:
  • hyperkalaemia = 5.1 mmol/l
  • severe hyperkalaemia >6.0 mmol/l

    • The evidence

    Patient expected event rate for hyperkalaemia =5.1 mmol/l: 11.0%
    risk factor for
    hyperkalaemia = 5.1 mmol/l     		adjusted OR
    (95% CI)    		 NNH
    (95% CI)
    creatinine >138 micromol/l 4.60
    (1.80 to 12.0)     		4
    (2 to 14)
    use of long-acting ACE inhibitor (eg. lisinopril or enalapril) 2.80
    (1.30 to 6.00)     		7
    (3 to 35)
    urea >6.5 mmol/l 2.50
    (1.50 to 4.40)     		8
    (4 to 22)
    congestive heart failure 2.60
    (1.40 to 5.10)     		8
    (4 to 27)
    use of loop diuretic 0.40
    (0.20 to 0.80)     		-16
    (-50 to -12)
    use of thiazide diuretic 0.40
    (0.20 to 0.90)     		-16
    (-101 to -12)

    Patient expected event rate for severe hyperkalaemia >6.0 mmol/l: 0.20%
    risk factor for
    severe hyperkalaemia >6.0 mmol/l     		adjusted OR
    (95% CI)    		 NNH
    (95% CI)
    age >70 5.40
    (1.50 to 19.0)     		115
    (29 to 1003)
    urea >9 mmol/l 4.50
    (1.30 to 15.0)     		144
    (37 to 1671)
    baseline bicarbonate level >28 mmol/l 0.20
    (0.06 to 0.80)     		-625
    (-2504 to -532)

    • Increased risk of death was associated with (by univariate analysis only: no odds ratios given): potassium >6.4 mmol/l; creatinine >138 mmol/l; urea > or = 10 mmol/l; peripheral vascular disease; pulmonary disease; use of digoxin.
    • Patients with severe hyperkalaemia are at an increased risk of dying.

    Comments

    1. Study consisted of mainly elderly men.
    2. Not all patients on ACE inhibitors had follow-up potassium levels taken- so prevalence figures may be an underestimate.
    3. Risk factors need to be validated in another set of patients.

    Citation

    1. Reardon LC, and MacPherson DC: Hyperkalemia in outpatients using angiotensin-converting enzyme inhibitors: how much should we worry?. Archives of Internal Medicine 1998; 158: 26-32
    Contributor: Chris Ball and Clare Wotton, February 2000
    Reviewer:

    Clinical Question.
    Patient receiving ACE inhibitors
    Intervention or Exposure presence of risk factors
    Comparison absence of risk factors
    Outcome hyperkalaemia