Spironolactone appears to be the front-runner for preferred fourth-line pharmacotherapy in patients with resistant hypertension.
According to a review of the evidence, the mineralocorticoid receptor agonist is probably the best add-on therapy in patients with high blood pressure despite maximal doses of guideline-recommended triple therapy.
Co-author Professor Markus Schlaich, head of the Dobney Hypertension Centre at the Royal Perth Hospital, told the limbic the PATHWAY-2 trial provided the most convincing evidence to date.
“It highlights spironolactone is a very important and good drug but you have to use it with caution, and that too is an important message.”
Hyperkalaemia is a common and serious adverse effect.
The review also considered centrally acting antihypertensives such as moxonidine, adrenergic receptor blockers such as doxazosin and peripheral vasodilators such as hydralazine.
Professor Schlaich said there was still a lot of work to be done regarding fourth line therapy given resistant hypertension affected up to 30% of all hypertensive patients.
“Over the last few years, it became apparent that we have rates of blood pressure control which are quite low and we really started to appreciate that what we refer to as resistant hypertension is actually quite a common issue.”
“And what we’ve been focusing on, and rightly so, is determining the best first and second line choices because the majority of people will be controlled with two to three medications, and there is very clear evidence for the three major drug classes.”
Professor Schlaich, a renal physician, said device-based therapy would not be the mainstay of treatment but offered ‘a wonderful opportunity’ for patients whose blood pressure could not be controlled with medication and lifestyle modification.
He said renal denervation was experiencing a revival after the controversial failure of the SYMPLICITY HTN-3 trial.
And there were other strategies, including baroreflex activation therapy, reserved for people with resistant BP who did not tolerate or benefit from medications.
“These new interventional procedures are generally safe as well, but once you’ve done it there is no going back afterwards – so you really want to make sure you do it in the right people.”
Professor Schlaich added that lifestyle modification remained important in all patients with hypertension.
“So that should always be flanking any other kind of therapy. It’s never too late for that. Sometimes it’s amazing what you can achieve just with weight loss.”
Controversial US guidelines, which have dropped the threshold for hypertension from 140/90 to 130/80 mm Hg, will further drive the need to identify fourth and fifth line therapies.
“From one day to another they have increased the prevalence of hypertension in the US from around 36 to 44%. So people who were okay yesterday, today have hypertension.”