title: Differences in mean and variability of heart rate and ambulatory rate-pressure product when valsartan or carvedilol is added to lisinopril.
abstract: Guidelines recommend combining β-blockers and angiotensin-converting enzyme (ACE) inhibitors in high-risk heart disease but not in the initial treatment of hypertension. The mechanism of this benefit has not been determined. After 3 weeks of lisinopril (L, 40 mg/day) run-in, 30 subjects entered a single-blinded, forced-titration, crossover study in which carvedilol (C, 20 then 40 mg/day) or a control renin-angiotensin blocker, valsartan (V, 160 then 320 mg/day) were added to L. Ambulatory blood pressure (ABP) and heart rate monitoring was performed at the end of each period. Rate-pressure product (RPP, systolic BP × heart rate, an indicator of cardiac oxygen consumption) was measured over 24 hours, daytime (6 am to midnight), and nighttime (midnight to 6 am) periods. Variability (standard deviation and range) of RPP, BP, and heart rate was also investigated. After 4 weeks, mean 24-hour systolic BP was about 8 mm Hg lower when either V or C was added to L (P < .01 each). Heart rate was consistently lower with C (8 beats/min over 24 hours, P < .000) but was slightly increased with V (about 2 beats/min, P = NS). Consequently, C lowered RPP to a greater degree than V over 24 hours (about 8% vs. 2%, P < .000) and during daytime and nighttime periods (P < .000 each). In addition, RPP variability (SD but not range) was consistently lower on C than V. When added to L, C reduces the mean and variability (SD) of 24-hour heart rate and cardiac workload to a greater degree than valsartan. These effects may contribute to the outcome benefits observed with β-blocker-ACE inhibitor combinations.
authors.affiliation: Department of Medicine, State University of New York at Buffalo, Erie County Medical Center, Buffalo, NY, USA. jizzo@buffalo.edu
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Izzo
authors.forename: Siva H
authors.initials: SH
authors.lastname: Yedlapati
authors.forename: Sheikh M
authors.initials: SM
authors.lastname: Faheem
authors.forename: Usman
authors.initials: U
authors.lastname: Younus
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Osmond
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D018660:Blood Pressure Monitoring, Ambulatory; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017706:Lisinopril / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage*; D016037:Single-Blind Method; D013777:Tetrazoles / Q000008:administration & dosage*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D013777:Tetrazoles; D000077261:Carvedilol; D000068756:Valsartan; D017706:Lisinopril; D014633:Valine