Table 1PICO characteristics of review question

PopulationAdults (aged 18 years and older) with primary hypertension who are taking the maximally tolerated doses of at least 3 drugs (including a diuretic) and their blood pressure is still not controlled.
InterventionStep 4 antihypertensive pharmacological treatment received for a minimum of 1 year. Examples include:
  • Alpha-blockers
  • Beta-blockers
  • Other or further diuretics such as amiloride and spironolactone
  • Aliskiren (direct renin inhibitors)
  • Clonidine, minoxidil, methyldopa, moxonidine (centrally acting antihypertensive)
ComparisonCompared against each other (class comparisons) Compared to placebo (class compared to placebo)
Outcomes

All outcomes to be measured at a minimum of 12 months. Where multiple time points are reported within each study, the longest time point only will be extracted.

Critical

  • All-cause mortality
  • Health-related quality of life
  • Stroke (ischaemic or haemorrhagic)
  • Myocardial infarction (MI)

Important

  • Heart failure needing hospitalisation
  • Vascular procedures (including lower limb, coronary and carotid artery procedures)
  • Angina needing hospitalisation
  • Discontinuation or dose reduction due to side effects
  • Side effect 1: Acute kidney injury
  • Side effect 2: New onset diabetes
  • Side effect 3: Change in creatinine or eGFR
  • Side effect 4: Hypotension (dizziness)
  • [Combined cardiovascular disease outcomes in the absence of MI and stroke data]
  • [Coronary heart disease outcome in the absence of MI data]

Study designRandomised controlled trials (RCT) and systematic reviews (SR)

From: Evidence review for step 4 treatment

Cover of Evidence review for step 4 treatment
Evidence review for step 4 treatment: Hypertension in adults: diagnosis and management: Evidence review G.
NICE Guideline, No. 136.
National Guideline Centre (UK).
Copyright © NICE 2019.

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