title: Combined angiotensin-converting enzyme inhibition and receptor blockade associate with increased risk of cardiovascular death in hemodialysis patients.
abstract: To compare the relative effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in reducing cardiovascular mortality in chronic hemodialysis patients, we conducted an observational analysis of all patients initiated on ACEI or ARB therapy undergoing chronic hemodialysis at a large dialysis provider. Survival curves with mortality hazard ratios (HRs) were generated using the Kaplan-Meier method and Cox regression. Outcomes were compared using inverse probability of treatment weighting and propensity score matching. Over 6 years, 22,800 patients were newly initiated on an ACEI and 5828 on an ARB after at least 60 days of chronic hemodialysis. After adjustment for baseline cardiovascular risk factors, there was no significant difference in the risk of cardiovascular, all-cause, or cerebrovascular mortality in patients initiated on an ARB compared with an ACEI (HR of 0.96). A third of 28,628 patients, newly started on an ACEI or ARB, went on to another antihypertensive medication in succession. After adjustment for risk factors, 701 patients initiated on combined ACEI and ARB therapy (HR of 1.45) or 6866 patients on ACEI and non-ARB antihypertensive agent (HR of 1.27) were at increased risk of cardiovascular death compared with 1758 patients initiated on an ARB and non-ACEI antihypertensive therapy. Thus, an ARB, in combination with another antihypertensive medication (but not an ACEI), may have a beneficial effect on cardiovascular mortality. As observational studies may be confounded by indication, even when adjusted, randomized clinical trials are needed to confirm these findings.
authors.affiliation: Fresenius Medical Care NA, Waltham, Massachusetts, USA.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Chan
authors.affiliation: Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: T Alp
authors.initials: TA
authors.lastname: Ikizler
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Gamboa
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.affiliation: Fresenius Medical Care NA, Waltham, Massachusetts, USA.
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Hakim
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. Electronic address: nancy.j.brown@vanderbilt.edu.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
mesh_terms: D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D000959:Antihypertensive Agents / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000401:mortality*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents