6/29/23, 1:37 AM PATHWAY-2 (spironolactone vs. doxazosin) Pathway Feedback Search Clinical Topics Home Studies PATHWAY 2 (spironolactone vs. doxazosin) PATHWAY 2 (spironolactone vs. doxazosin) DiseaseHypertension Trial question Is spironolactone superior to add-on doxazosin in patients with drug-resistant hypertension? Study design Multi-center Double blinded RCT Population Characteristics of study participants 31.0% female N = 335 69.0% male 335 patients (105 female, 230 male) Inclusion criteria: patients aged 18-79 years with seated clinic systolic BP 140 mmHg and home systolic BP 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=282 doxazosin (at a dose of 4 mg/day through week 6, forced uptitration to 8 mg/day through week 12) https://web.pathway.md/studies/recfEl7A9aHjWykQD 1/2 6/29/23, 1:37 AM PATHWAY-2 (spironolactone vs. doxazosin) Pathway Primary outcome Reduction in home systolic blood pressure through week 6 to week 12 12.8 mmHg 12.8 9.6 mmHg 8.7 6.4 mmHg 3.2 mmHg Significant increase 0.0 mmHg Spironolactone Doxazosin Significant increase in reduction in home systolic BP through week 6 to week 12 (12.8 mmHg vs. 8.7 mmHg; AD 4.03 mmHg, 95% CI 3.02 to 5.04) Secondary outcomes Significant increase in reduction in home systolic BP at week 12 (14.4 mmHg vs. 9.1 mmHg; AD 5.3 mmHg, 95% CI 3.83 to 6.77) Significant increase in reduction in seated clinic systolic BP through week 6 to week 12 (20.7 mmHg vs. 16.3 mmHg; AD 4.42 mmHg, 95% CI 3.09 to 5.75) Safety outcomes No significant difference in adverse and serious adverse events. Conclusion In patients aged 18-79 years with seated clinic systolic BP 140 mmHg and home systolic BP 130 mmHg, despite treatment with maximally tolerated doses of 3 antihypertensive drugs for at least 3 months, spironolactone was superior to doxazosin with respect to reduction in home systolic BP 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. Open reference URL https://web.pathway.md/studies/recfEl7A9aHjWykQD 2/2