Pharmacotherapy of Hypertension in Chronic Dialysis Patients

Abstract

Among patients on dialysis, hypertension is highly prevalent and contributes to the high burden of cardiovascular morbidity and mortality. Strict volume control via sodium restriction and probing of dry weight are first-line approaches for the treatment of hypertension in this population; however, antihypertensive drug therapy is often needed to control BP. Few trials compare head-to-head the superiority of one antihypertensive drug class over another with respect to improving BP control or altering cardiovascular outcomes; accordingly, selection of the appropriate antihypertensive regimen should be individualized. To individualize therapy, consideration should be given to intra- and interdialytic pharmacokinetics, effect on cardiovascular reflexes, ability to treat comorbid illnesses, and adverse effect profile. β-Blockers followed by dihydropyridine calcium-channel blockers are our first- and second-line choices for antihypertensive drug use. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers seem to be reasonable third-line choices, because the evidence base to support their use in patients on dialysis is sparse. Add-on therapy with mineralocorticoid receptor antagonists in specific subgroups of patients on dialysis (i.e., those with severe congestive heart failure) seems to be another promising option in anticipation of the ongoing trials evaluating their efficacy and safety. Adequately powered, multicenter, randomized trials evaluating hard cardiovascular end points are urgently warranted to elucidate the comparative effectiveness of antihypertensive drug classes in patients on dialysis. In this review, we provide an overview of the randomized evidence on pharmacotherapy of hypertension in patients on dialysis, and we conclude with suggestions for future research to address critical gaps in this important area.

Blood pressure control in conventional hemodialysis

“…Choice of the appropriate antihypertensive regimen among those on hemodialysis should not rely on extrapolation of evidence derived from the general population or those with earlier stages of chronic kidney disease . To wit, trials that evaluated the efficacy of ACEIs/ARBs suggest that their use as first‐line antihypertensive therapy in hemodialysis patients is not supported by strong evidence of a cardiovascular benefit .…”

“…However, this approach requires stronger supportive evidence from a phase 3 trial. The use of CCBs as add‐on or combination therapy is supported by their potent and long‐lasting BP‐lowering efficacy that enables their once daily administration . In the absence of “hard” clinical‐trial evidence to elucidate the benefits and risks of MRAs, the wide use of spironolactone or eplerenone among hemodialysis patients should be avoided .…”

“…The dialyzability of antihypertensive drugs is another factor that should be taken into consideration . With the exception of the nondialyzable fosinopril, most of the other ACEIs are removed during dialysis.…”

“…Hypertension should be managed first by nonpharmacological strategies aiming to control sodium and volume overload. If BP remains unresponsive to volume management strategies, initiation of antihypertensive therapy is the next treatment consideration …”

Blood pressure in hemodialysis

“…This trial is a first step in the long road towards an optimal management of hypertension in hemodialysis. Additional research efforts, mainly RCTs using out-of-dialysis BP monitoring and evaluating different home BP targets in relation to clinical outcomes and mortality, are needed to fully elucidate this critical issue [49,50]. In the meantime and until compelling clinical-trial evidence become available, lowering self-measured home BP <140/90 mmHg appears to be a reasonable target for management of hypertension in hemodialysis.…”