PATHWAY-2: Optimal treatment of drug resistant hypertension
Resistant hypertension can be defined as blood pressure not controlled to target despite treatment with maximal recommended and tolerated doses of A + C + D. The current NICE/BHS guidelines advise that such patients can be managed using a further diuretic, an alpha-blocker, or a beta-blocker, or that specialist advice is sought.
Which of these 4th line drugs is most likely to be effective is unclear however. Three possibilities are:
- It doesn’t matter – on average all drug classes will be the same
- One class of drug will always be better – the same mechanism
underpins all resistant hypertension
- One commonly proposed mechanism is that patients with resistant hypertension invariably have salt retention; a diuretic would therefore be expected to be the most effective drug
- The best class of drug will vary between patients
- The hypertension unit in Cambridge routinely check renin
levels in these patients, and base treatment on the results:
- The hypertension unit in Cambridge routinely check renin levels in these patients, and base treatment on the results:
PATHWAY-2 has the following two objectives:
- to evaluate whether resistant hypertension is invariably due to excessive sodium retention, and if further diuretic will be the most effective treatment
- to evaluate if plasma renin will predict the most effective 4th line drug
The protocol for PATHWAY-2 is shown above. Patients will be recruited if they have BP above target despite treatment with ACE inhibitor (or angiotensin receptor blocker), calcium channel blocker and diuretic. Patients will cycle through 4 therapeutic options, in a randomised order: additional diuretic (spironolactone), beta-blocker (bisoprolol), alpha-blocker (doxazosin), or a placebo. Each drug will be given at a lower dose for 6 weeks, and then increased for a further 6 weeks. Blood pressure and biochemical measurements will be made at the start of the study, and at the end of each 12 week period.