Studies are being done to test whether hypertension therapy taken at bedtime results in improved cardiovascular disease (CVD) risk reduction compared with medication taken upon awakening. The Hygia Chronotherapy Trial, conducted in primary care, found that hypertensive patients taking ≥1 prescribed blood pressure (BP)-lowering medications at bedtime had improved ambulatory BP control compared with those who took their medications upon awakening, and they also had a reduced occurrence of major CVD events. These findings should be replicated in other populations before being routinely adopted in clinical practice.
Renal sympathetic denervation for treatment-resistant hypertension (experimental)
Activation of renal sympathetic nerves is a component of essential hypertension pathophysiology; however, renal denervation studies have reported variable efficacy results. [ ] Renal denervation may be considered in the context of clinical trials, but is not used in everyday clinical practice.
Baroreflex activation therapy
Electrical stimulation of the carotid sinus baroreflex system, also known as baroreflex activation therapy (BAT), may decrease blood pressure in patients with resistant hypertension. Electric stimulators directly activating afferent baroreflex nerves have previously failed in trials for technical reasons. However, a novel implantable device may overcome some of the previously experienced technical problems. The device stimulates the carotid sinus wall and has been shown to reduce BP in feasibility studies. In the Rheos Pivotal trial, which assessed long-term blood pressure control in resistant-hypertension patients receiving BAT, BP reduction was maintained over long-term follow-up of 22 to 53 months.
Oral supplementation with L-arginine, an amino acid and a substrate of nitric oxide synthase, has been shown to significantly lower both systolic and diastolic BP.
Vitamin C supplementation
Vitamin C supplementation has been shown to reduce systolic and diastolic BP in short-term trials. Long-term trials examining the effects of vitamin C supplementation on BP and clinical events are needed.
Vitamin D supplementation
Data from cross-sectional studies report that low levels of 25-hydroxy vitamin D are associated with higher systolic blood pressure and higher incidence of hypertension. Large observational studies show a weaker, yet similar, association. This effect is thought to be partly mediated through regulation of the renin-angiotensin-aldosterone axis. Randomised control trials conflict with observational data, probably due to differences in populations studied, doses of vitamin D used, and unmeasured confounders. A systematic review found that in studies to date, vitamin D supplementation was ineffective for blood pressure lowering. Large randomised trials focusing on patients with severe vitamin D deficiency and hypertension are needed before vitamin D can be recommended for the prevention or treatment of hypertension.
Preliminary data indicate that increased calcium intake slightly reduces systolic and diastolic blood pressure in people with normal blood pressure, particularly young people. This could have implications for prevention and public health, but more and larger studies are needed.
Sodium-glucose transporter-2 [SGLT-2] inhibitors in people with type 2 diabetes
SGLT-2 inhibitors have been found to have an antihypertensive effect. Empaglifozin has been found to lower blood pressure and cardiovascular risk in people with type 2 diabetes over up to 2.6 years. Canagliflozin has also been associated with reduced blood pressure in people with type 2 diabetes across a range of baseline BPs.
In the PATHWAY-2 study of resistant hypertension, the potassium-sparing diuretic amiloride was shown to be as effective at reducing blood pressure as spironolactone, suggesting it may be an alternative option for resistant hypertension.
In a phase 2 trial, firibastat, a first-in-class aminopeptidase A inhibitor, has demonstrated efficacy in lowering blood pressure in a high-risk diverse population, and may have future use in patients with difficult-to-treat or potentially resistant hypertension.
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