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Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study

BMJ 1997; 315 doi: https://doi.org/10.1136/bmj.315.7101.154 (Published 19 July 1997) Cite this as: BMJ 1997;315:154
  1. Thomas Philipp, directora,
  2. Manfred Anlauf, professorb,
  3. Armin Distler, directorc,
  4. Heinrich Holzgreve, professord,
  5. Joerg Michaelis, directore,
  6. Stefan Wellek, director the HANE Trial Research Groupf
  1. a Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122, Essen, Germany
  2. b Zentralkrankenhaus Reinkenheide, D-27574 Bremerhaven, Germany
  3. c Medizinische Klinik and Poliklinik, Benjamin Franklin Klinikum, Freie Universität Berlin, D-12203 Berlin, Germany
  4. d Medizinische Poliklinik, University of Munich, D-80336 Munich, Germany
  5. e Institut fur Medizinische Statistik, University of Mainz, D-55131 Mainz, Germany
  6. f Abteilung Biostatistik, ZI Seelische Gesundheit, D68072 Mannheim, Germany
  1. Correspondence to: Dr Philipp
  • Accepted 15 April 1997

Abstract

Objective: To compare the effectiveness and tolerability of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in patients with mild to moderate hypertension.

Design: Randomised multicentre trial over 48 weeks with double blind comparison of treatments.

Setting: 48 centres in four countries.

Patients: 868 patients with essential hypertension (diastolic blood pressure 95-120 mm Hg)

Interventions: Initial treatment (step 1) consisted of 12.5 mg hydrochlorothiazide (n=215), 25 mg atenolol (n=215), 10 mg nitrendipine (n=218), or 5 mg enalapril (n=220) once daily. If diastolic blood pressure was not reduced to <90 mm Hg within four weeks, doses were increased to 25 mg, 50 mg, 20 mg, 10 mg, respectively, once daily (step 2) and after two more weeks to twice daily (step 3). The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure.

Main outcome measure: Blood pressure by means of an automatic device with repeated measurements.

Results: After eight weeks the response rate for atenolol (63.7%) was significantly higher than for enalapril (50.0%), hydrochlorothiazide (44.7%), or nitrendipine (44.5%). After one year atenolol was still more effective (48.0%) than hydrochlorothiazide (35.4%) and nitrendipine (32.9%), but not significantly better than enalapril (42.7%). The treatment related dropout rate was higher (P<0.001) in the nitrendipine group (n=28).

Conclusions: There is no evidence of superiority for antihypertensive effectiveness or tolerability of the “new” classes of antihypertensives (calcium channel blockers and angiotensin converting enzyme inhibitors). As these drugs are now widely used as treatment of first choice, our results further emphasise the need for studies confirming that they also reduce morbidity and mortality, as has been shown for diuretics and ß blockers.

Key messages

  • Calcium channel blockers and angiotensin converting enzyme inhibitors as initial monotherapy in the treatment of hypertension

  • Reduction in mortality has been shown only with established ß blockers and diuretics

  • Comparison of treatment with hydrochlorothiazide, atenolol, nitrendipine, and enalapril showed no superiority of the new drug classes

  • Atenolol was the most effective drug, while nitrendipine showed the highest drop out rat

  • Elderly patients respond better to hydrochlorothiazide and nitrendipine, and women better to enalapril, although in both subgroups the highest rate of response was with atenolol

Footnotes

    • Accepted 15 April 1997
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