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Combination medications for Resistant hypertension
Are there any particular recommended drug treatment add ons or combination regimens for Resistant hypertension?
The PATHWAY-2 trial showed spironolactone to be the best choice as the fourth-line drug, except in those whose renin level is extremely elevated. In patients with CKD, there is concern regarding hyperkalemia.
In CKD stages 1 to 3, if the initial potassium is less than 4.5 when adding 25 mg of spironolactone, hyperkalemia is rare; nevertheless, it is mandatory to check the potassium at 1 and 4 weeks after the initiation of treatment. It is also important to forewarn patients that if they become ill or stop eating and drinking, to discontinue spironolactone and proceed to an emergency room for a potassium measurement.
Although a small observational trial showed improved BP in CKD stage 4, the risk of hyperkalemia precludes further recommending it. There is currently interest in the use of novel oral potassium binders (e.g., patiromer in combination with spironolactone) to control hyperkalemia while offering the benefit of a mineralocorticoid antagonist. This is being studied in patients with RH in the AMBER trial.
Combination calcium channel blocker regimens (from dihydropyridine and non-dihydropyridine groups) have been demonstrated to be synergistic for BP control in this population. Decreasing the total pill burden with combination therapy may improve adherence.
In CKD, activation of the sympathetic nervous system is present, and clonidine twice daily or once daily guanfacine may be a helpful add-on after spironolactone. Somnolence and bradycardia can occur with these drugs, as well as rebound hypertension from abrupt cessation.
