PATHWAY-2 (spironolactone vs. placebo)
Trial question
What is the role of add-on spironolactone 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=274 placebo (matching placebo daily for 12 weeks).
Primary outcome
Reduction in home systolic blood pressure through week 6 to week 12
12.8 mmHg
4.1 mmHg
12.8 mmHg
9.6 mmHg
6.4 mmHg
3.2 mmHg
0.0 mmHg
Spironolactone
Placebo
Significant
increase ▲
Significantly greater reduction in home SBP through week 6 to week 12 (12.8 mmHg vs. 4.1 mmHg; AD 8.7 mmHg, 95% CI 7.69 to 9.72).
Secondary outcomes
Significantly greater reduction in home SBP at week 12 (14.4 mmHg vs. 4.2 mmHg; AD 10.2 mmHg, 95% CI 8.74 to 11.7).
Significantly greater reduction in seated clinic SBP through week 6 to week 12 (20.7 mmHg vs. 10.8 mmHg; AD 9.92 mmHg, 95% CI 8.59 to 11.3).
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 placebo 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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