title: Pulse pressure lowering effect of dual blockade with candesartan and lisinopril vs. high-dose ACE inhibition in hypertensive type 2 diabetic subjects: a CALM II study post-hoc analysis.
abstract: BACKGROUND
  Elevated pulse pressure (PP) is strongly associated with micro- and macrovascular complications in type 2 diabetic patients. We examined the effect of 12 months of dual blockade with candesartan and lisinopril vs. high-dose lisinopril monotherapy on ambulatory PP in hypertensive type 2 diabetic patients from the CALM (Candesartan and Lisinopril Microalbuminuria Trial) II study.
  
  
  METHODS
  The CALM II study was a 12-month prospective, randomized, parallel-group, double-masked study that included 75 type 1 and type 2 diabetic subjects with hypertension. Participants were randomized for treatment with either high-dose lisinopril (40 mg once daily (o.d.)) or for dual blockade treatment with candesartan (16 mg o.d.) and lisinopril (20 mg o.d.). In this article, we present data from the post-hoc subgroup of 51 type 2 diabetic subjects who completed the full 12-month study period with successful ambulatory blood pressure (BP) measurements at both baseline and follow-up visits.
  
  
  RESULTS
  Baseline 24-h BP values were similar in the two groups (24-h systolic BP (SBP) 130 +/- 12 vs. 127 +/- 9, 24-h diastolic BP (DBP) 77 +/- 8 vs. 74 +/- 7, and 24-h PP 53 +/- 8 vs. 53 +/- 7 mm Hg, for the lisinopril and dual blockade groups, respectively, P > 0.2 for all). Compared with lisinopril monotherapy, dual blockade treatment caused a highly significant reduction in 24-h PP levels (-5 +/- 5 mm Hg, P = 0.003), albeit the difference in the BP lowering effect between the treatment groups did not differ significantly for 24-h systolic (P = 0.21) or diastolic (P = 0.49) BP. Dual blockade treatment significantly lowered 24-h SBP (-5 +/- 11 mm Hg, P = 0.03), but not 24-h DBP (-2 +/- 7 mm Hg, P = 0.29), whereas in the lisinopril group, the opposite effect was observed (24-h SBP -1 +/- 9 mm Hg, P = 0.45, 24-h SBP -3 +/- 7 mm Hg, P = 0.03).
  
  
  CONCLUSIONS
  Twelve months of dual blockade with candesartan and lisinopril significantly reduced PP when compared with high-dose monotherapy with lisinopril. Larger studies are needed to confirm this observation, and to evaluate whether this effect translates into a greater degree of end-organ protection from dual blockade treatment than from conventional angiotensin-converting enzyme (ACE) inhibition.
authors.affiliation: Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus, Denmark. stk@dadlnet.dk
authors.forename: Søren T
authors.initials: ST
authors.lastname: Knudsen
authors.forename: Niels H
authors.initials: NH
authors.lastname: Andersen
authors.forename: Steen H
authors.initials: SH
authors.lastname: Poulsen
authors.forename: Hans
authors.initials: H
authors.lastname: Eiskjaer
authors.forename: Klavs W
authors.initials: KW
authors.lastname: Hansen
authors.forename: Kjeld
authors.initials: K
authors.lastname: Helleberg
authors.forename: Per L
authors.initials: PL
authors.lastname: Poulsen
authors.forename: Carl E
authors.initials: CE
authors.lastname: Mogensen
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000150:complications; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D017706:Lisinopril; C081643:candesartan