Ambulatory blood pressure parameters after canrenone addition to existing treatment regimens with maximum tolerated dose of angiotensin-converting enzyme inhibitors/angiotensin II type 1 receptor blockers plus hydrochlorothiazide in uncontrolled hypertensive patients

Drug Des Devel Ther. 2017 Aug 4:11:2293-2300. doi: 10.2147/DDDT.S134826. eCollection 2017.

Abstract

Background: Blockade of the renin-angiotensin-aldosterone system is a cornerstone in cardiovascular disease prevention and hypertension treatment. The relevance of ambulatory blood pressure monitoring (ABPM) has been widely confirmed for both increasing the accuracy of blood pressure (BP) measurements, particularly in pharmacological trials, and focusing on 24 h BP prognostic parameters. The aim of this study was to assess the effects of canrenone addition on ambulatory BP in uncontrolled hypertensive patients already treated with the highest tolerated dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor (AT1R) antagonists plus hydrochlorothiazide (HCT).

Methods: ABPM was performed at baseline and after 3 months of combination therapy in 158 outpatients with stage 1 or 2 hypertension who were randomized to add canrenone (50 or 100 mg) to the pre-existing therapy with ACE inhibitors or AT1R antagonists plus HCT. Twenty-four-hour systolic and diastolic BPs were considered normalized when the values were <130 and <80 mmHg, respectively.

Results: The addition of canrenone was associated with a reduction in systolic and diastolic BPs (24 h and daytime and nighttime; P<0.001), mean arterial pressures (P<0.001), and pulse pressures (P<0.01). The Δ 24 h systolic/diastolic BPs were -13.5±11.2/-8±8 mmHg and -16.1±13.5/-11.2±8.3 mmHg (50 and 100 mg/day, respectively). In the 50 mg arm, the 24 h systolic and diastolic BPs were normalized in 67.5% and 74% of the patients, respectively, and in 61.6% and 68.5% of the patients in the 100 mg arm, respectively (P<0.05; P= not significant for 50 vs 100 mg). The percentage of patients whose nocturnal decrease was >10% with respect to diurnal values did not change during combination therapy.

Conclusion: Canrenone addition to ACE inhibitors or AT1R antagonists plus HCT was associated with a significant reduction of 24 h BP and to an increased number of patients meeting 24 h ABPM targets in a clinical setting of uncontrolled stage 1 or 2 hypertension.

Keywords: ACE inhibitors; AT1R antagonist; RAAS; ambulatory blood pressure; canrenone.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / adverse effects
  • Blood Pressure / drug effects
  • Blood Pressure Monitoring, Ambulatory
  • Canrenone / administration & dosage*
  • Canrenone / pharmacology
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydrochlorothiazide / administration & dosage
  • Hydrochlorothiazide / adverse effects
  • Hypertension / drug therapy*
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / administration & dosage*
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Renin-Angiotensin System / drug effects
  • Treatment Outcome

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Mineralocorticoid Receptor Antagonists
  • Hydrochlorothiazide
  • Canrenone