Further evidence that chronic perindopril treatment maintains neurohormonal suppression but does not lower blood pressure in chronic cardiac failure.
OBJECTIVE
Previous studies in heart failure (CHF) after temporary diuretic withdrawal have suggested that perindopril is associated with no first dose hypotension in comparison with other ACE inhibitors (ACEI) or placebo. The aim of this study was to explore further the profile of perindopril during chronic dosing.


METHODS
We report the effects of acute and chronic (8 weeks) treatment with the ACE inhibitor perindopril (Per, 2-->4 mg daily) or placebo (P) in a double-blind parallel group study of 24 diuretic treated patients (17M; 67 +/- 8 years, 80 +/- 17 kg) with ischaemic cardiomyopathy (fractional shortening, 19 +/- 5%; radionuclide ejection fraction, 31 +/- 3%). Baseline biochemical, hormonal (ACE, Ang I, Ang II), isotopic renal function (GFR, ERPF, ECFV), pretreatment diuretic dose and heart failure scores were similar between groups. Concomitant cardiac treatments remained unchanged and diuretic withdrawal was not used to introduce treatment.


RESULTS
There were no significant effects on electrolytes, liver function tests, serum or erythrocyte magnesium. There was no significant first dose fall in SBP over 6 h) (P, baseline 137 +/- 18; min 115 +/- 16 mmHg; Per, baseline 137 +/- 15; min 118 +/- 17 mmHg). Neither supine nor erect BP was significantly affected by chronic treatment (P, erect baseline 134 +/- 23/76 +/- 10 to 124 +/- 41/74 +/- 10 mmHg; Per, baseline 135 +/- 21/76 +/- 14 to 128 +/- 22/70 +/- 12 mmHg, P=NS). Active treatment was associated with significant ACE inhibition (P, baseline 47 +/- 17 to 43 +/- 17; Per baseline 49 +/- 15 to 14 +/- 7); aldosterone (P, baseline 337 +/- 179 to 375 +/- 306; Per, baseline 335 +/- 357 to 293 +/- 155 pg ml(-1)) and Ang II suppression (P, baseline 9 +/- 9 to 20 +/- 39; Per baseline 10 +/- 9 to 3 +/- 3 pM). Isotopic renal function was unaffected by either treatment.


CONCLUSIONS
At this dose (2-4 mg orally) chronic perindopril therapy has no significant effect on blood pressure or renal function. Sustained neurohormonal suppression of ACE and AII occurred without evidence of AII reactivation. A lack of effect on BP at these doses may make perindopril suitable for study in unstable patients with acute HF or useful in those patients where there are concerns over ACEI induced hypotension.
MacFadyen
R J
RJ
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, UK.
Barr
C S
CS
Sturrock
N D
ND
Fenwick
M
M
Struthers
A D
AD
D000368:Aged; D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002303:Cardiac Output, Low / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D002908:Chronic Disease; D003864:Depression, Chemical; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D020913:Perindopril
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D000804:Angiotensin II; D000450:Aldosterone; D000803:Angiotensin I; D020913:Perindopril