Treatment of Hypertension in Patients Requiring Dialysis

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Treatment of Hypertension in Patients Requiring Dialysis

Lynda A. Szczech, MD, MSCE

Published: 04/23/2009
Effect of Lowering Blood Pressure on Cardiovascular Events and Mortality in Patients on Dialysis: A Systematic Review and Meta-analysis of Randomised Controlled Trials

Heerspink HJ, Ninomiya T, Zoungas S, et al
Lancet. 2009;373:1009-1015. Epub 2009 Feb 25.
Summary

Multiple studies have been performed and are available to guide us in the treatment of hypertension in our patients with normal kidney function. These studies have tested a variety of agents in the setting of a series of different blood pressure goals and have provided comparative efficacy in the prevention of end organ damage as well as mortality. The treatment of hypertension in patients requiring dialysis, however, has not been investigated as rigorously. The current study attempts to rectify this.

Heerspink and colleagues' meta-analysis combined the data from the 8 available randomized controlled trials of blood pressure lowering in patients on dialysis. These studies were all published recently (2003-2008), enrolled 60-397 patients each (N = 1679; 495 cardiovascular events), and measured the rate of cardiovascular events in the different treatment groups.[1-8] Each trial compared a single agent (ie, carvedilol, ramipril, telmisartan, candesartan, fosinopril, or amlodipine) with either placebo or "conventional therapy" but did not compare blood pressure goals. The studies achieved an overall difference of -4.5 mm Hg systolic and -2.3 mm Hg diastolic in the treated groups vs controls. Per meta-analytic methods, in these 8 studies the use of blood pressure lowering medication was associated with lower risk for cardiovascular events (risk ratio, 0.71; 95% confidence interval, 0.55-0.92) compared with controls.
Viewpoint

The meta-analysis was performed using sound methods, and its conclusions reflect the design of the studies that were available to combine. The study's publication in a high-impact journal such as The Lancet ought to indicate to the medical community -- as well as to pharmaceutical companies with an interest in the treatment of hypertension -- that dialysis patients represent a population of increasing concern. Furthermore, this population is far behind other groups in terms of rigorous trials to truly establish best practices.

As we draw conclusions from the present meta-analysis, however, we should carefully consider the design of the trials that were available to combine. This meta-analysis demonstrates that the use of one of the antihypertensives listed above results in better outcomes than not using one of those medications. Arguably, these trials did not directly test the lowering of blood pressure using a particular agent or goal. When considering how to apply these results, the questions that remain are: In whom should blood pressure be lowered? Which agent is appropriate? And to what level should we use it?

Hypertension control in dialysis patients is notoriously complicated: Which blood pressure parameter is most reflective of the mediator of risk (systolic, diastolic, pulse)? When should that parameter be assessed to best capture risk (predialysis, postdialysis, or on a nondialysis day)? What goals are appropriate to test? And how should the inherent risk for elevated blood pressure (which is associated with withholding antihypertensives in the predialysis period to minimize intradialytic hypotension) affect trial design and the ultimate comparison of treatment arms?

These questions will likely result in the most challenging trial design to date. Heerspink and colleagues' meta-analysis indicates an issue of growing concern that we now need to tackle.

Abstract
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References

1. Cice G, Ferrara L, D'Andrea A, et al. Carvedilol increases two-year survival in dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial. J Am Coll Cardiol. 2003;41:1438-1444. Abstract
2. Zannad F, Kessler M, Lehert P, et al. Prevention of cardiovascular events in end-stage renal disease: results of a randomized trial of fosinopril and implications for future studies. Kidney Int. 2006;70:1318-1324. Abstract
3. Moher D, Cook DJ, Eastwood Li PK, et al. Effects of an angiotensin-converting enzyme inhibitor on residual renal function in patients receiving peritoneal dialysis. A randomized, controlled study. Ann Intern Med. 2003;139:105-112. Abstract
4. Cice G, Di Benedetto A, D'Isa S, D'Andrea A, De Gregoria P, Calabro R. Effect of telmisartan added to angiotensin converting enzyme inhibitors in reducing morbidity and mortality in haemodialysis patients with chronic heart failure. J Hypertens Suppl. 2006;24:S56.
5. Takahashi A, Takase H, Toriyama T, et al. Candesartan, an angiotensin II type-1 receptor blocker, reduces cardiovascular events in patients on chronic haemodialysis--a randomized study. Nephrol Dial Transplant. 2006;21:2507-2512. Abstract
6. Suzuki H, Kanno Y, Sugahara S, et al. Effect of angiotensin receptor blockers on cardiovascular events in patients undergoing hemodialysis: an open-label randomized controlled trial. Am J Kidney Dis. 2008;52:501-506. Abstract
7. Tepel M, Hopfenmueller W, Scholze A, Maier A, Zidek W. Effect of amlodipine on cardiovascular events in hypertensive haemodialysis patients. Nephrol Dial Transplant. 2008;23:3605-3612. Abstract
8. Nakao N, Hasegawa H, Fujimori A, Seno H, Toriyama T, Kawahare H. Effects of combined â-blockade and anti-aldosterone antagonist treatment for cardiovascular prevention in patients receiving maintenance dialysis. J Am Soc Nephrol. 2007;18(suppl):709A.

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Authors and Disclosures
Author
Lynda A. Szczech, MD

MSCE, Associate Professor, Duke University Medical Center, Durham, North Carolina

Disclosure: Lynda A. Szczech, MD, MSCE, has disclosed that she has received grants for clinical research from Pfizer Inc., GlaxoSmithKline, and Genzyme Corporation. She has also disclosed that she has received grants for educational activities from Gilead Sciences, Inc., GlaxoSmithKline, Fresenius Medical Care North America, and AMAG Pharmaceuticals. Dr. Szczech has also disclosed that she served as an advisor or consultant to Affymax, Inc., Pharmasset, Inc., and Roche Laboratories Inc.

http://www.medscape.com/viewarticle/590057