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Back to the future in resistant hypertension

Spironolactone ‘overwhelmingly’ the most effective

A drug whose history goes back more than 50 years could revolutionise today’s treatment of resistant hypertension, a Hot Line session heard yesterday. The PATHWAY-2 study showed that spironolactone, first introduced in 1959 as a diuretic, controlled 60% of previously uncontrolled patients with resistant hypertension and was three times more likely than doxazosin or bisoprolol to exert control.


Bryan Williams, presented 'unequivocal' results from the PATHWAY-2 study of spironolactone in resistant hypertension, and from the PARAMETER study on arterial stiffness in the elderly‘Spironolactone is overwhelmingly the most effective drug treatment for resistant hypertension,’ said study presenter Bryan Williams, from University College London. ‘The result in favour of spironolactone is unequivocal and for the first time establishes a clear hierarchy for drug treatment of resistant hypertension which should influence future guidelines and clinical practice worldwide.’

The study, which has the global potential to influence treatment in 100 million people, offers a ‘spectacularly cost-effective’ approach, added Williams, since spironolactone is cheap and patients are at very high risk of cardiovascular events.

International guidelines recommend treating resistant hypertension with three BP-lowering agents - ACE inhibitors or ARBs, plus calcium channel blockers plus thiazide-like diuretics. ‘However,’ said Williams, ‘despite 50 years of research the optimal drug treatment is still undefined.’

The PATHWAY-2 study, funded by the British Heart Foundation, randomised 335 patients with resistant hypertension (already treated according to guidelines) to sequentially receive 12 weeks of spironolactone (25-50 mg), bisoprolol (5-10 mg), doxazosin (4-8 mg modified release) and placebo. The study design allowed drug comparisons in each patient, with 230 completing all cycles.

Results showed that spironolactone reduced home systolic BP by 8.70 mmHg more than placebo (p<0.001), 4.26 mmHg more than bisoprolol/doxazosin (p<0.001), 4.03 mmHg more than doxazosin (p<0.001), and by 4.48 mmHG more than bisoprolol (p<0.001).

By the end of the trial, said Williams, there would only be 15 patients considered eligible for renal denervation trials in uncontrolled hypertension. ‘PATHWAY-2,’ he added, will have significant implications for patient recruitment into other trials.’