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PATHWAY-2 Spironolactone Fourth-line — EECC MCQ

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ModerateHypertension & Preventive CardiologyPATHWAY-2 Spironolactone Fourth-lineEECC

A 60-year-old man with treatment-resistant hypertension (office BP 155/95 on ACEi + CCB + chlorthalidone at maximum tolerated doses, confirmed by ABPM and adherence testing) has his fourth agent selected. The PATHWAY-2 trial guides this decision. What did it show?

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Correct answer: E — PATHWAY-2 showed spironolactone was the most effective fourth agent for resistant hypertension (mean SBP reduction ~9 mmHg vs doxazosin ~4 mmHg vs bisoprolol ~6 mmHg) — supporting the role of excess aldosterone/sodium retention as the predominant mechanism in resistant HTN

The PATHWAY-2 trial (2015) was a double-blind crossover trial comparing spironolactone 25-50 mg, doxazosin, bisoprolol, and placebo as fourth-line agents in patients with resistant hypertension. Results: spironolactone was clearly superior (mean home SBP reduction ~9 mmHg vs doxazosin ~4 mmHg, bisoprolol ~6 mmHg, placebo ~1 mmHg). This confirmed that excess sodium retention (aldosterone-mediated) is the dominant mechanism in most resistant hypertension. The 2024 ESC Hypertension Guidelines recommend: spironolactone 25-50 mg as the preferred fourth agent (Class I, LOE A). If spironolactone is not tolerated (hyperkalaemia, gynaecomastia), alternatives include: eplerenone, amiloride, doxazosin, or bisoprolol. The trial also highlighted that 'resistant' hypertension often responds dramatically to MRA, suggesting undiagnosed primary aldosteronism in many cases.

Reference: ESC (2024): Hypertension Guidelines; PATHWAY-2 Trial