Angiotensins May Not Protect Heart in Dialysis

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By Crystal Phend, Senior Staff Writer, MedPage TodayPublished: April 10, 2012
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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Action Points

• ACE inhibitors or angiotensin-receptor blockers are among the most commonly used drugs in dialysis patients.
• This non-randomized study showed no beneficial cardiovascular outcomes with the use of these drugs in dialysis patients when compared with statins or calcium channel blockers, agents which have not been shown to have beneficial outcomes.

Older dialysis patients may not get the expected cardioprotective effect from ACE inhibitors and angiotensin-receptor blockers (ARBs), researchers warned.
Major cardiovascular adverse events were no less likely on an ARB than with a calcium channel blocker (HR 0.97, 95% CI 0.84 to 1.13), Andrew T. Yan, MD, of St Michael's Hospital in Toronto, and colleagues found.
Likewise, an ACE inhibitor or ARB was no better at cutting that risk than a statin (HR 1.08, 95% CI 0.91 to 1.22) in the population-based study reported as a research letter in the April 9 issue of the Archives of Internal Medicine.
ACE inhibitors have been shown to be effective, but the trials have largely excluded the dialysis population, Kirsten L. Johansen, MD, of the University of California San Francisco, wrote in an editor's note.
Yan and colleagues' real-world findings are particularly relevant despite the limitations of observational data because ACE inhibitors are so commonly used to manage high blood pressure and heart failure in dialysis patients, she pointed out.
For example, lisinopril was the seventh-most prescribed drug of any kind in this population as of 2008, based on U.S. national registry data.
"Given the substantial cardiovascular morbidity and mortality in the expanding chronic dialysis patient population, a large definitive randomized controlled trial of ACE inhibitors/ARBs is warranted," the researchers recommended, and Johansen seconded.
The study used linked healthcare databases in Ontario to compare 1,950 chronic dialysis patients 66 or older who started taking an ACE inhibitor or ARB, calcium channel blocker, or statin as mutually exclusive groups from July 1991 to July 2007.
During up to five years of follow-up, none of the components of the primary composite endpoint showed a consistent significant reduction in risk with ACE inhibitors or ARBs. Multivariate-adjusted hazard ratios were:

• For all-cause mortality, 0.92 versus calcium channel blockers (95% CI 0.79 to 1.06) and 1.05 versus statins (95% CI 0.91 to 1.22)
• For hospitalization for myocardial infarction, 1.02 versus calcium channel blockers (95% CI 0.72 to 1.46) and 1.05 versus statins (95% CI 0.76 to 1.50)
• For hospitalization for stroke, 0.97 versus calcium channel blockers (95% CI 0.56 to 1.70) and 1.08 versus statins (95% CI 0.62 to 1.88)
• For hospitalization for heart failure, 0.83 versus calcium channel blockers (95% CI 0.63 to 1.09) and 0.73 (95% CI 0.55 to 0.96)
• For hospitalization for coronary revascularization, 0.87 versus calcium channel blockers (95% CI 0.46 to 1.69) and 1.08 versus statins (95% CI 0.57 to 2.07)

Calcium channel blockers and statins were chosen as comparators to minimize confounding by indication and because they have not been shown to be clearly beneficial in the dialysis population.
"If statin or calcium channel blocker use can indeed confer cardiovascular protection in chronic dialysis patients, our comparative analysis may have attenuated any observed benefit of ACE inhibitors/ARBs," Yan's group noted.
The researchers also cautioned that, although the three groups didn't differ systematically in baseline characteristics, their study didn't randomly assign patients to drug therapy and that it looked at drugs by class rather than individually.

The researchers reported having no conflicts of interest to disclose.
Yan reported support by an award from the Heart and Stroke Foundation of Canada.

Primary source: Archives of Internal Medicine
Source reference:
Bajaj RR, et al "Use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and cardiovascular outcomes in chronic dialysis patients: a population-based cohort study" Arch Intern Med 2012; 172: 591-93; DOI: 10.1001/archinternmed.2012.139.
Additional source: Archives of Internal Medicine
Source reference:
Johansen KL "Do the benefits of medications outweigh the burdens for hemodialysis patients?" Arch Intern Med 2012; 172: 593-94; DOI: 10.1001/archinte.172.7.593.