#165 Three drugs and still hypertensive: What’s Left?

CLINICAL QUESTION

QUESTION CLINIQUE

Which drug lowers blood pressure (BP) best in patients with resistant hypertension?

BOTTOM LINE

RÉSULTAT FINAL

Spironolactone provides the largest BP reduction for “4th line therapy” in resistant hypertension (10/4 mmHg), causing an additional one in every three patients treated to reach target. Potassium rises on average ~0.4 mmol/L (and should be monitored), causing around 2% to stop due to hyperkalemia (≥5.5 mmol/L). Hard outcome data is lacking.

Reading Tools for Practice Article can earn you MainPro+ Credits

La lecture d'articles d'outils de pratique peut vous permettre de gagner des crédits MainPro+

Join Now S’inscrire maintenant

Already a CFPCLearn Member? Log in

Déjà abonné à CMFCApprendre? Ouvrir une session

EVIDENCE

DONNÉES PROBANTES

Only data on BP (not hard outcomes).
- High-quality cross-over Randomized Controlled Trial (RCT)¹ of 348 patients with resistant hypertension. Each patient cycled through six weeks low-dose and six weeks high-dose of spironolactone 25-50 mg, doxazosin 4-8 mg, bisoprolol 5-10 mg, and placebo.
  - Over both doses, average reduction in office BP versus placebo: Spironolactone 10/4 mmHg, bisoprolol 5/5 mmHg, or doxazosin 5/3 mmHg.
    - High dose decreased systolic BP more than low dose: Spironolactone 5 mmHg, bisoprolol 2 mmHg, or doxazosin 1 mmHg.
  - Patients achieving target home systolic BP (<135 mmHg): Spironolactone 58%, bisoprolol 44%, doxazosin 42%, placebo 24%.
    - Number Needed to Treat (NNT) versus placebo: Spironolactone NNT=3, bisoprolol or doxazosin NNT=6.
  - Serum K >6.0 in 2% of patients with spironolactone.
  - Notes: Excluded patients with abnormal serum K or eGFR <45 mL/min.
- Three systematic reviews^2-4 missed studies and pooled inappropriately (heterogeneity ≥90%).
- Five remaining spironolactone (generally 25 mg/day) RCTs (17-167 patients, 4-16 weeks):^5-9
  - Two smallest trials (Iran and Cameroon) with randomization concerns had largest BP changes (19-21/10-17 mmHg): Likely unreliable.^8,9
  - Three remaining RCTS: Spironolactone reduced BP 10-16/3-7 mmHg^.^5-7
  - Serum K increases ~0.3-0.4 mmol/L^5-9 and ~2% stop due to hyperkalemia (K >5.5 mmol/L).^5,7

Context:

Resistant hypertension is defined as office BP >140/90 mmHg while receiving (and adherent to) >3 BP-lowering drugs of different classes at optimal doses.^10,11
- Thiazides, ACE/ARB, and dihydropyridine calcium channel blockers all have evidence for reducing cardiovascular endpoints.
Prevalence of resistant hypertension is likely around 13% or less.¹²
Lower baseline potassium may be associated with better response to spironolactone.^7,13