Prevention And Treatment of Hypertension With Algorithm based therapY-2 - PATHWAY 2

Description:

The goal of the trial was to evaluate treatment with spironolactone compared with doxazosin or bisoprolol or placebo among subjects with resistant hypertension.

Contribution to the Literature: The PATHWAY-2 trial showed that spironolactone was the most effective add-on treatment for resistant hypertension.

Study Design

  • Randomized
  • Parallel
  • Blinded
  • Crossover

Subjects with resistant hypertension were randomized to each of the four different add-on study medications, each for a 12-week period. Study medications included spironolactone 25-50 mg daily, doxazosin 4-8 mg daily, bisoprolol 5-10 mg daily, or placebo.

  • Total number of enrollees: 335
  • Mean patient age: 61 years
  • Percentage female: 31%
  • Percentage diabetics: 14%

Other salient features/characteristics:

  • Home blood pressure: 148/84 mm Hg
  • Clinic blood pressure: 157/90 mm Hg

Inclusion criteria:

  • Resistant hypertension defined as uncontrolled blood pressure despite three antihypertensive agents (angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker + calcium antagonist + thiazide diuretic)

Exclusion criteria:

  • Noncompliance as cause for resistant hypertension
  • White coat hypertension
  • Secondary hypertension

Principal Findings:

The primary outcome:

  • ∆ in home systolic blood pressure (SBP) between spironolactone and placebo: -8.70 mm Hg (p < 0.001)
  • ∆ in home SBP between spironolactone and bisoprolol/doxazosin: -4.26 mm Hg (p < 0.001)
  • ∆ in home SBP between spironolactone and doxazosin: -4.03 mm Hg (p < 0.001)
  • ∆ in home SBP between spironolactone and bisoprolol: -4.48 mm Hg (p < 0.001)

Secondary outcomes:

  • Home SBP with spironolactone: 135 mm Hg (-12.8 mm Hg ∆ from baseline)
  • Home SBP with doxazosin: 139 mm Hg (-8.7 mm Hg ∆ from baseline)
  • Home SBP with bisoprolol: 139 mm Hg (-8.3 mm Hg ∆ from baseline)
  • Home SBP with placebo: 144 mm Hg (-4.1 mm Hg ∆ from baseline)

Serious adverse events were 2.3% with spironolactone, 1.7% with doxazosin, 2.6% with bisoprolol, and 1.7% with placebo.

Interpretation:

Among subjects with resistant hypertension, spironolactone was the most effective add-on agent for improved blood pressure control. Spironolactone resulted in a nearly 9 mm Hg reduction in SBP compared with placebo and an approximate 4 mm reduction compared with active antihypertensive agents. Spironolactone was well-tolerated with a low/similar frequency of serious adverse events. Spironolactone should be considered in the treatment algorithm for resistant hypertension.

References:

Williams, B, MacDonald TM, Morant S., et al. Spironolactone Versus Placebo, Bisoprolol, and Doxazosin to Determine the Optimal Treatment for Drug-Resistant Hypertension (PATHWAY-2): a Randomised, Double-Blind, Crossover Trial. The Lancet 2015;386:2059-2068.

Presented by Dr. Bryan Williams at the European Society of Cardiology Congress, London, August 31, 2015.

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Hypertension

Keywords: Algorithms, Antihypertensive Agents, Bisoprolol, Blood Pressure, Doxazosin, Hypertension, Metabolic Syndrome X, Primary Prevention, Sodium Chloride Symporter Inhibitors, Spironolactone, ESC Congress


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