PATHWAY-2 (spironolactone vs. bisoprolol)
Trial question
Is spironolactone superior to add-on bisoprolol in patients with drug-resistant hypertension?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
31.0% female
69.0% male
N = 335
335 patients (105 female, 230 male).
Inclusion criteria: patients aged 18-79 years with seated clinic SBP ≥ 140 mmHg and home SBP ≥ 130 mmHg, despite treatment with maximally tolerated doses of 3 antihypertensive drugs for at least 3 months.
Key exclusion criteria: secondary/accelerated hypertension; T1DM; eGFR < 45 mL/min; sustained AF; non-adherence to antihypertensive treatment.
Interventions
N=285 spironolactone (at a dose of 25 mg/day through week 6, forced uptitration to 50 mg/day through week 12).
N=285 bisoprolol (at a dose of 5 mg/day through week 6, forced uptitration to 10 mg/day through week 12).
Primary outcome
Reduction in home systolic blood pressure through week 6 to week 12
12.8 mmHg
8.3 mmHg
12.8 mmHg
9.6 mmHg
6.4 mmHg
3.2 mmHg
0.0 mmHg
Spironolactone
Bisoprolol
Significant
increase ▲
Significantly greater reduction in home SBP through week 6 to week 12 (12.8 mmHg vs. 8.3 mmHg; AD 4.48 mmHg, 95% CI 3.46 to 5.5).
Secondary outcomes
Significantly greater reduction in home SBP at week 12 (14.4 mmHg vs. 8.4 mmHg; AD 5.98 mmHg, 95% CI 4.51 to 7.45).
Significantly greater reduction in seated clinic SBP through week 6 to week 12 (20.7 mmHg vs. 16.3 mmHg; AD 4.45 mmHg, 95% CI 3.11 to 5.8).
Safety outcomes
No significant difference in adverse and serious adverse events.
Conclusion
In patients aged 18-79 years with seated clinic SBP ≥ 140 mmHg and home SBP ≥ 130 mmHg, despite treatment with maximally tolerated doses of 3 antihypertensive drugs for at least 3 months, spironolactone was superior to bisoprolol with respect to reduction in home SBP through week 6 to week 12.
Reference
Bryan Williams, Thomas M MacDonald, Steve Morant 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. Lancet. 2015 Nov 21;386(10008):2059-2068.
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