Resistant' hypertension: how to treat it successfully and what's on the horizon

But once the field has been cleared of secondary forms or resistant pseudo-hypertension, how should a truly 'resistant' hypertensive person behave? The lifestyle measures to be adopted are always the same: little, indeed very little salt in the diet (< 1500 mg of sodium per day), reduce or better abolish alcohol, do regular physical activity (at least 150 minutes per week of aerobic activity), lose the extra kilos, avoid drugs (cocaine, amphetamines) and, if possible, drugs known to increase blood pressure (NSAIDs, cortisone, some psychiatric drugs such as Snri). Beware also of sneaky sleep apnoea (if your partner snores a lot and then stops breathing for a few seconds during sleep, take him to the doctor), which should be detected and treated.

Having done all this, one moves on to optimising the actual drug therapy. Since several molecules have to be used, one way to simplify life for the patient (and increase acceptance of the therapy) is to use 'Swiss army knife' pills, i.e. the 2-3 in one, i.e. those with several active ingredients contained in the same tablet (it is recent news that 4-in-1, containing perindopril, indapamide, amlodipine, bisoprolol in the same pill, could also arrive soon). Crucially, one of the ingredients of the therapeutic 'cocktail' for the resistant hypertensive is a thiazide (such as chlorthalidone) or thiazide-like diuretic (such as indapamide). For patients with good renal function, a game changer in therapy are anti-aldosteronic diuretics (such as spironolactone or eplerenone).

Finally, for cases that just do not respond even to optimal drug therapy, one can resort to the 'renal denervation' procedure, which consists of destroying the sympathetic nerves inside the renal arteries through a special catheter (it is a minimally invasive procedure). The procedure involves inserting a thin vascular catheter through the femoral artery, which is then guided to the renal arteries. Once in place, this special catheter delivers radiofrequency or ultrasound energy to interrupt the sympathetic nerves in the outermost layer of the renal arteries. This procedure reduces sympathetic nerve activity both entering and leaving the kidneys, helping to lower blood pressure by reducing renin secretion, increasing sodium elimination with urine, and decreasing central sympathetic activity.

But the search for pharmacological solutions to the hypertension problem continues. Selective inhibitors of aldosterone synthesis (baxdrostat or lorundrostat) already loom in the near future. Then there is the whole sophisticated chapter of siRNA (small interfering RNA), such as zilebesiran, a drug that blocks the production of messenger RNA, the 'template' that the liver needs to manufacture angiotensinogen, almost completely reducing its production (angiotensinogen is the precursor of angiotensin I, which is then transformed into angiotensin II, one of the most powerful vasoconstrictors existing in nature, capable of greatly increasing pressure).

In short, the future will be a harbinger of many innovations and ever more intelligent and powerful drugs. But in the meantime, it is important for hypertensives to (re)start with the basics: take the antihypertensive therapy prescribed by the doctor and never settle for an intermediate result. The goal to be achieved is to get permanently below 130/80 mmHg.