, Volume 61, Issue 6, pp 867–896 | Cite as


An Updated Review of Its Use in Hypertension
  • Miriam Hurst
  • Blair Jarvis
Adis Drug Evaluation



Perindopril erbumine (perindopril) is a prodrug ester of perindoprilat, an angiotensin converting enzyme (ACE) inhibitor. Perindopril 4 to 8mg once daily significantly reduces supine systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline values in hypertensive patients. These reductions are maintained for at least 24 hours, as evidenced by trough/peak ratios of >50%.

Vascular abnormalities associated with hypertension were improved or normalised during perindopril treatment. Perindopril 4 to 8mg once daily significantly decreased carotid-femoral aortic pulse wave velocity (PWV), improved arterial compliance, reduced left ventricular mass index and, in patients with recent cerebral ischaemia and/or stroke, preserved cerebral blood flow despite significantly reducing SBP and DBP. Further research is needed to establish the significance of promising results showing that reductions in aortic PWV were associated with reduced mortality in patients with end-stage renal failure, a third of whom received perindopril.

Response rates (numbers of patients with supine DBP ≤90mm Hg) were significantly higher with perindopril 4 to 8mg once daily (67 to 80%) than with captopril 25 to 50mg twice daily (44 to 57%) in 3 randomised double-blind trials. In other clinical trials, the antihypertensive effects of perindopril were similar to those of other ACE inhibitors (including enalapril) and calcium-channel antagonists. Combination treatment with perindopril and an antihypertensive agent from another treatment class provided additional benefits, either as first-line treatment or in patients failing to respond to monotherapy. Perindopril monotherapy was also effective in the elderly and in patients with hypertension and concomitant disease.

Perindopril has a similar adverse event profile to that of other ACE inhibitors; cough is the most common event reported during treatment, and is also the most common adverse event responsible for treatment withdrawal.

Conclusions: Perindopril is a well tolerated ACE inhibitor that is significantly better than captopril (in terms of response rates) in the treatment of hypertension, and as effective as other ACE inhibitors. Perindopril appears to reverse some of the vascular abnormalities associated with hypertension, including arterial stiffness and left ventricular hypertrophy, although further research is needed to confirm promising results regarding its ability to decrease associated cardiovascular morbidity and mortality. Results from ongoing studies will help confirm the place of perindopril in the treatment of hypertension; currently, it is an effective and well tolerated treatment for patients with mild to moderate essential hypertension.

Pharmacodynamic Profile

Perindopril erbumine (perindopril) is a prodrug ester of perindoprilat, an angiotensin converting enzyme (ACE) inhibitor. Oral administration of perindopril dose-dependently decreases plasma ACE activity; the concentration of perindoprilat required to inhibit 50% of ACE activity (IC50) is 3.6 nmol/L at steady state. Maximal inhibition of ACE activity occurred 2 to 4 hours after perindopril 2,4 or 8mg at steady state, and inhibition of plasma ACE activity remained >70% 24 hours after single dose perindopril 4, 8 or 16mg. ACE inhibition was not affected by age or ethnicity, but was significantly increased compared with single dose values after multiple dose administration (15 days) in patients with severe renal failure.

In patients with hypertension, perindopril significantly reduces systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline levels, maintaining reductions for at least 24 hours (see Therapeutic Efficacy summary). Treatment with perindopril improved arterial and haemodynamic abnormalities associated with hypertension; carotid-femoral aortic pulse wave velocity (PWV) significantly decreased from baseline levels (−1.1 m/sec, p < 0.001) in a non-comparative 6-month study (n = 1703). Reductions in aortic PWV during anti-hypertensive treatment (71% of patients required medication, 46% of whom received perindopril 4 to 8mg every 48 hours alone or in combination with other antihypertensive agents) were associated with significant reductions in both cardiovascular and all-cause mortality in a cohort study involving 150 patients with end-stage renal failure. Treatment with perindopril, but not atenolol or nitrendipine, was positively correlated with survival.

Significant reductions in systemic vascular resistance and significant increases in arterial diameter, compliance and blood flow were seen during perindopril treatment in a number of studies. Intravenous perindoprilat 1mg restored the normal flow-dependent and cold-pressor test-induced dilatations in the coronary arteries of patients with hypertension. Perindopril did not significantly decrease cerebral blood flow in patients with hypertension and recent cerebral ischaemia or stroke (in 1 study, patients also had moderate to severe carotid stenosis or occlusion), although both SBP and DBP were significantly reduced.

Significant reductions from baseline values in left ventricular mass index (LVMI) were seen with perindopril 4 to 8 mg/day for 2 to 12 months in a number of clinical trials. LVMI decreased significantly from baseline by 13.55 g/m2 (p < 0.001) during treatment with perindopril 4 to 8mg once daily for 3 months in 741 patients with stable hypertension and moderate LV hypertrophy; smooth LV remodelling occurred, with the reduction in wall thickness matching the reduction in ventricular size. Other echocardiographic parameters were improved by perindopril in some studies, with significant decreases in diastolic wall and intraventricular septal thickness and increases in left ventricular relaxation.

Albuminuria in patients with hypertension and diabetes or nephropathy was significantly reduced during treatment with perindopril 2 to 8mg once daily. Perindopril did not adversely affect glycaemic control or lipid profiles.

Pharmacokinetic Profile

After oral administration, perindopril undergoes extensive metabolic changes that include the formation of perindoprilat by hydrolysis. The bioavailability of perindopril ranges between 65.6 and 95.1%; 16.8% of an oral dose of perindopril is present in plasma as perindoprilat. Perindopril is 74% plasma protein-bound at steady-state concentrations and perindoprilat is 15% bound to plasma proteins.

Perindopril is rapidly absorbed, with a peak plasma concentration (Cmax) of 64.2 µg/L achieved 0.7 to 0.9 hours after single dose perindopril 4mg. Perindoprilat reached a Cmax of 4.7 µg/L at 3.6 hours post-dose. At therapeutic doses, both perindopril and perindoprilat display linear pharmacokinetics. The volume of distribution of perindopril in humans is low, at 0.22 L/kg; animal data suggest that perindopril distributes primarily to tissues with high ACE activity.

After absorption, perindopril either undergoes first-pass metabolism to form perindopril glucuronide (subsequently hydrolysed to perindoprilat glucuronide) or is hydrolysed to perindoprilat (primarily in the liver). Plasma concentrations of perindopril were negligible within 8 hours of drug administration; elimination half-life (t½β) values for perindopril, perindoprilat and perindoprilat glucuronide were 2.9, 10.9 and 1.7 hours, respectively. Both perindoprilat and perindoprilat glucuronide are renally cleared. In 1 study, within 96 hours of oral administration of radioactively labelled perindopril (dosage not stated), 75% of the dose was recovered in the urine and 25% in the faeces.

The pharmacokinetics of perindopril were not significantly different in patients with hypertension, compared with those in healthy volunteers. Significantly increased perindoprilat bioavailability was observed in the elderly. Perindoprilat Cmax, area under the plasma concentration-time curve and half life were significantly increased in patients with renal impairment, and reduced perindopril dosages are recommended in this patient group; in contrast, no clinically significant changes in pharmacokinetic parameters were seen in patients with hepatic impairment.

Therapeutic Efficacy

Perindopril significantly reduced SBP and DBP from baseline values in clinical trials involving patients with hypertension, with a dose-response effect for doses of ≤8mg. Rates of supine DBP ≤90mm Hg ranged from 67 to 80% in perindopril recipients, compared with 44 to 57% in captopril recipients (p ≤ 0.02), in 3 randomised double-blind 3-month trials. In other comparative trials, perindopril 4 to 8mg once daily produced similar mean reductions from baseline DBP and SBP to those seen with enalapril, ramipril, lisinopril and fosinopril.

Mean reductions from baseline supine SBP and DBP values did not differ significantly between perindopril recipients and those who received the calcium antagonists verapamil, diltiazem, isradipine and amlodipine in 4 randomised trials lasting for 2 to 6 months. Perindopril reduced supine DBP from baseline values significantly more than metoprolol in an 8-week trial in patients with left ventricular hypertrophy (by 13.2 vs 5.3%, respectively, p < 0.05). Response rates were significantly higher with perindopril than with atenolol in a 3-month double-blind study involving 171 patients (78 vs 58%, p < 0.05), although 1 small study (n = 25) found significantly greater reductions in supine SBP and DBP with atenolol.

Response rates and reductions from baseline supine SBP and DBP values did not significantly differ between patients who received perindopril and those who received combination therapy with amiloride/hydrochlorothiazide 5/50 to 10/100 mg/day in a 3-month randomised double-blind study (n = 165), although mean reductions in standing SBP were significantly greater with diuretic therapy (31.1 vs 24.6mm Hg with perindopril, p = 0.01). Mean reductions from baseline supine DBP values were significantly greater with perindopril than with combination therapy with amiloride and hydrochlorothiazide (7.9 vs 3.5%, p < 0.05) in another study, although dosages for amiloride/hydrochlorothiazide (2.5/25 and 5/50 mg/day) were lower.

Combining perindopril with hydrochlorothiazide 25 mg/day or indapamide 1.25 mg/day resulted in higher response rates and greater reductions in BP than those observed with any agent alone. Patients who failed to respond to perindopril monotherapy experienced significant reductions in supine SBP and DBP with the addition of hydrochlorothiazide 12.5 to 50 mg/day, nifedipine sustained release 10mg twice daily or indapamide 1.25 mg/day.

In large noncomparative trials, mean SBP/DBP fell by 28/18mm Hg in 43 245 patients who completed 1 year of treatment with perindopril 2 to 8 mg/day alone or in combination with other antihypertensive agents, and normalisation of BP (supine DBP ≤90mm Hg) was achieved in 95.7% of 23 460 outpatients who received perindopril-based treatment for 6 months. Most patients (≥80%) were receiving perindopril monotherapy.

Trough/peak ratios for supine DBP were >70% for perindopril 2, 4, 8 or 16mg once daily in a dose-finding study involving 293 patients with hypertension. Although data are limited, trough/peak ratios for perindopril appeared to be as good as or better than those for other antihypertensive agents and are >50% for doses ≥4mg, as recommended by the US Food and Drug Administration for once daily administration of antihypertensives.

In patients aged ≥70 years (n = 2927), perindopril 2 to 8 mg/day (alone or in combination with other antihypertensive agents) significantly reduced mean supine SBP and DBP in a 6-month noncomparative study, with 94.2% of patients achieving a mean DBP ≤90mm Hg. Response rates (DBP <90mm Hg) were 59% in a similar 1-year study involving 2256 patients aged ≥80 years.

Perindopril was also effective in the treatment of patients with hypertension and a range of concomitant diseases, including type 2 diabetes mellitus, ischaemic heart disease and nephropathy with proteinuria. Parameters of concomitant disease were either improved or were not adversely affected during treatment with perindopril.


Perindopril is well tolerated, with a similar adverse effect profile to that of other ACE inhibitors. The most common adverse events reported during treatment with perindopril 2 to 8mg once daily for 1 year were cough, GI upset/dyspepsia and asthenia in a postmarketing surveillance study involving 47 351 patients with hypertension; 16.3% of patients spontaneously reported an adverse event. 8.5% of patients withdrew from treatment; the majority (59%) did so because of suspected adverse reactions (most often cough). Perindopril 4 to 8 mg/day was at least as well tolerated as captopril 50 to 100 mg/day, diltiazem 60 to 180mg twice daily, amlodipine 5 to 10 mg/day or combination therapy with amiloride 5 to 10 mg/day and hydrochlorothiazide 50 to 100 mg/day in clinical trials.

Dosage and Administration

The recommended starting dosage of perindopril in patients with hypertension is 2mg once daily, increased as necessary to a maximum recommended daily dosage of 8mg according to European guidelines (dosage guidelines may differ in other countries). As perindoprilat is renally excreted, dosage reductions are necessary in patients with renal impairment. No dosage adjustments are necessary in the elderly or in patients with hepatic impairment.

Perindopril is contraindicated in pregnancy and in patients with a history of angioneurotic oedema in association with ACE inhibitor therapy. Potassium supplements and potassium-sparing diuretics should not be used in combination with perindopril.


Angiotensin Converting Enzyme Pulse Wave Velocity Angiotensin Convert Enzyme Inhibitor Perindopril Left Ventricular Mass Index 
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  1. 1.
    Oparil S. Management of the hypertensive patient with coronary artery disease. Am J Hypertens 1999 Feb; 12 (Pt 2): 56S–62SPubMedCrossRefGoogle Scholar
  2. 2.
    Alderman M, Arakawa K, Beilin L, et al. 1999 World Health Organization — International Society of Hypertension Guidelines for the Management of Hypertension. Blood Press 1999; 8 Suppl. 1: 9–43Google Scholar
  3. 3.
    The sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1997 Nov 24; 157: 2413–46CrossRefGoogle Scholar
  4. 4.
    Todd PA, Fitton A. Perindopril: a review of its pharmacological properties and therapeutic use in cardiovascular disorders. Drugs 1991; 42(1): 90–114PubMedCrossRefGoogle Scholar
  5. 5.
    Louis WJ, Workman BS, Conway EL, et al. Single-dose and steady-state pharmacokinetics and pharmacodynamics of perindopril in hypertensive subjects. J Cardiovasc Pharmacol 1992 Sep; 20: 505–11PubMedCrossRefGoogle Scholar
  6. 6.
    Zacharieva S, Torbova S, Orbetzova M, et al. Effects of perindopril treatment on plasma and urine of kallikrein activity and the stable metabolite of prostaglandin E2 in patients with essential hypertension. Methods Find Exp Clin Pharmacol 1996 Apr; 18: 205–9PubMedGoogle Scholar
  7. 7.
    Grandi AM, Bignotti M, Gaudio G, et al. Ambulatory blood pressure and left ventricular changes during antihypertensive treatment: perindopril versus isradipine. J Cardiovasc Pharmacol 1995 Nov; 26: 737–41PubMedCrossRefGoogle Scholar
  8. 8.
    Grekas D, Dioudis C, Kalevrosoglou I, et al. Management of moderate to severe hypertension and proteinuria by nifedipine retard and perindopril after renal transplantation. Clin Nephrol 1995 Nov; 44: 299–302PubMedGoogle Scholar
  9. 9.
    Hui Y, Dai Z, Chen X, et al. Effect of perindopril and metoprolol on left ventricular hypertrophy and performance in essential hypertension. Chin Med J Engl 1995 Sep; 108: 678–81PubMedGoogle Scholar
  10. 10.
    Sihm I, Schroeder AP, Aalkjaer C, et al. Normalization of structural cardiovascular changes during antihypertensive treatment with a regimen based on the ACE-inhibitor perindopril. Blood Press 1995 Jul; 4: 241–8PubMedCrossRefGoogle Scholar
  11. 11.
    Sukonthasarn A, Ratanaprakarn R, Koanantakul B, et al. Efficacy and acceptability of perindopril in essential hypertension. J Med Assoc Thai 1994 Jun; 77: 281–7PubMedGoogle Scholar
  12. 12.
    Overlack A, Adamczak M, Bachmann W, et al. ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases. Perindopril Therapeutic Safety Collaborative Research Group. Am J Med 1994 Aug; 97: 126–34PubMedCrossRefGoogle Scholar
  13. 13.
    Jandrain B, Herbaut C, Depoorter J-C, et al. Long-term (1 year) acceptability of perindopril in type II diabetic patients with hypertension. Am J Med 1992 Apr 27; 92: 91S–4SPubMedCrossRefGoogle Scholar
  14. 14.
    Agabiti-Rosei E, Ambrosioni E, Finardi G, et al. Perindopril versus captopril: efficacy and acceptability in an Italian multicenter trial. Am J Med 1992 Apr 27; 92: 79S–83SPubMedCrossRefGoogle Scholar
  15. 15.
    Andrejak M, Santoni JP, Carré A, et al. A double-blind comparison of perindopril and hydrochlorothiazide-amiloride in mild to moderate essential hypertension. Fundam Clin Pharmacol 1991; 5: 185–92PubMedCrossRefGoogle Scholar
  16. 16.
    Grandi AM, Venco A, Barzizza F, et al. Double-blind comparison of perindopril and captopril in hypertension: effects on left ventricular morphology and function. Am J Hypertens 1991 Jun; 4: 516–20PubMedGoogle Scholar
  17. 17.
    Erdem Y, Usalan C, Haznedaroglu IC, et al. Effects of angiotensin converting enzyme and angiotensin II receptor inhibition on impaired fibrinolysis in systemic hypertension. Am J Hypertens 1999 Nov; 12 (11 Pt 1): 1071–6PubMedCrossRefGoogle Scholar
  18. 18.
    Allen T, Cooper M, Jerums G, et al. Comparison between perindopril and nifedipine in hypertensive and normotensive diabetic patients with microalbuminuria. Br Med J 1991; 302(6770): 210–6CrossRefGoogle Scholar
  19. 19.
    Fogari R, Zoppi A, Lazzari P, et al. ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and insulin resistance in overweight hypertensive patients. J Cardiovasc Pharmacol 1998; 32(4): 616–20PubMedCrossRefGoogle Scholar
  20. 20.
    Agabiti Rosei E, Corea L, Leonetti G, et al. A double-blind assessment, perindopril vs verapamil, of the effects on office and 24 HR ambulatory blood pressure and on left ventricular morphology [abstract no. 708]. European Society of Hypertension; 7th European Meeting on Hypertension; 1995 Jun 9–12, Milan, ItalyGoogle Scholar
  21. 21.
    London GM, Pannier B, Guerin AP, et al. Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease: comparative effects of ACE inhibition and calcium channel blockade. Circulation 1994 Dec; 90: 2786–96PubMedCrossRefGoogle Scholar
  22. 22.
    Thybo NK, Stephens N, Cooper A, et al. Effect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension. Hypertension 1995 Apr; 25 (Pt 1): 474–81PubMedCrossRefGoogle Scholar
  23. 23.
    Galiavitch A, Shlyakhto E, Konradi A, et al. Effects of antihypertensive treatment on heart structure in mild essential hypertension [abstract]. J Hypertens 1998 Jun; 16 Suppl. 2: S242Google Scholar
  24. 24.
    Fogari R, Mugellini A, Zoppi A, et al. Effect of losartan and perindopril on plasma PAI-1 and fibrinogen in hypertensive type 2 diabetic patients [abstract]. Cardiovasc Drugs Ther 1999 Mar; 13: 12CrossRefGoogle Scholar
  25. 25.
    Asmar RG, Pannier B, Santoni JP, et al. Reversion of cardiac hypertrophy and reduced arterial compliance after converting enzyme inhibition in essential hypertension. Circulation 1988 Oct; 78(4): 941–50PubMedCrossRefGoogle Scholar
  26. 26.
    Asmar R, Topouchian J, Pannier B, et al. Pulse wave velocity as endpoint in large-scale intervention trial. The Complior study. J Hypertens 2001; 19: 813–8CrossRefGoogle Scholar
  27. 27.
    Richer C, Thuillez C, Giudicelli JF. Perindopril, converting enzyme blockade, and peripheral arterial hemodynamics in the healthy volunteer. J Cardiovasc Pharmacol 1987; 9: 94–102PubMedGoogle Scholar
  28. 28.
    Guerin AP, Blacher J, Pannier B, et al. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation 2001 Feb 20: 987–92CrossRefGoogle Scholar
  29. 29.
    Gisclon LG, Moyer M. Pharmacokinetics (PK) and pharmacodynamics (PD) of perindopril (P) and its active metabolite, perindoprilat (PL) in healthy subjects [abstract]. Clin Pharmacol Ther 1992 Feb; 51: 153Google Scholar
  30. 30.
    Louis WJ, Conway EL, Krum H, et al. Comparison of the pharmacokinetics and pharmacodynamics of perindopril, cilazapril and enalapril. Clin Exp Pharmacol Physiol 1992; 19 Suppl. 19: 55–60CrossRefGoogle Scholar
  31. 31.
    Bussien J-P, d’Amore TF, Perret L, et al. Single and repeated dosing of the converting enzyme inhibitor perindopril to normal subjects. Clin Pharmacol Ther 1986 May; 39(5): 554–8PubMedCrossRefGoogle Scholar
  32. 32.
    Lees KR, Reid JL. Haemodynamic and humoral effects of oral perindopril, an angiotensin converting enzyme inhibitor, in man. Br J Clin Pharmacol 1987; 23: 159–64PubMedCrossRefGoogle Scholar
  33. 33.
    Plouin P-F, Alhenc-Gélas F, Aldigier J-C, et al. Effect of perindopril (S-9490) on blood pressure and renin-angiotensin aldosterone system in hypertensive men [poster abstract]. Clin Exp Hypertens A 1987; A9(11): 1988Google Scholar
  34. 34.
    Lees KR, Green ST, Reid JL. Influence of age on the pharmacokinetics and pharmacodynamics of perindopril. Clin Pharmacol Ther 1988 Oct; 44(4): 418–25PubMedCrossRefGoogle Scholar
  35. 35.
    Anderson PJ, Critchley J, Tomlinson B, et al. Comparison of the pharmacokinetics and pharmacodynamics of oral doses of perindopril in normotensive Chinese and Caucasian volunteers. Br J Clin Pharmacol 1995 Apr; 39: 361–8PubMedCrossRefGoogle Scholar
  36. 36.
    Sennesael J, Ali A, Sweny P, et al. The pharmacokinetics of perindopril and its effects on serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure. Br J Clin Pharmacol 1992 Jan; 33: 93–9PubMedCrossRefGoogle Scholar
  37. 37.
    Gerbrandt KR, Yedinak KC. Formulary management of ACE inhibitors. Pharmacoeconomics 1996; 10(6): 594–613PubMedCrossRefGoogle Scholar
  38. 38.
    Mendelsohn FAO, Pupic V, Jackson B, et al. Acute and chronic effects of perindopril on tissue angiotensin converting enzyme activity. Am J Hypertens 1991; 4(3) Pt 2: 220S–5SPubMedGoogle Scholar
  39. 39.
    Zhuo JL, Froomes P, Casley D, et al. Perindopril chronically inhibits angiotensin-converting enzyme in both the endothelium and adventitia of the internal mammary artery in patients with ischemic heart disease. Circulation 1997 Jul 1; 96: 174–82PubMedGoogle Scholar
  40. 40.
    Littler WA, West JW. Twenty-four hour action of ACE inhibitors. J Hum Hypertens 1990; 4 Suppl. 4: 13–6PubMedGoogle Scholar
  41. 41.
    Savi L, Mettimano M, Montebelli MR, et al. Effects of perindopril on left ventricular mass and on diastolic function in mild-to-moderate hypertension. J Drug Dev Clin Pract 1995 Jun; 7: 85–90Google Scholar
  42. 42.
    Grandi AM, Venco A, Sessa F, et al. Determinants of left ventricular function before and after regression of myocardial hypertrophy in hypertension. Am J Hypertens 1993; 6(8): 708–12PubMedGoogle Scholar
  43. 43.
    Klug EQ, Joffe BI, Panz VR, et al. Perindopril and physiologic responses to exercise. J Cardiovasc Pharmacol 1994 Jun; 23: 864–8PubMedCrossRefGoogle Scholar
  44. 44.
    Kuwajima I, Fujisawa A, Mitani K, et al. Effect of perindopril on 24-hour blood pressure levels and hemodynamic responses to physical and mental stress in elderly hypertensive patients. Clin Ther 1994 Nov-Dec; 16: 962–71PubMedGoogle Scholar
  45. 45.
    Asmar RG, Topouchian JA, Benetos A, et al. Non-invasive evaluation of arterial abnormalities in hypertensive patients. J Hypertens 1997; 15 Suppl. 2: S99–107Google Scholar
  46. 46.
    Benetos A, Cambien F, Gautier S, et al. Influence of the angiotensin II type 1 receptor gene polymorphism on the effects of perindopril and nitrendipine on arterial stiffness in hypertensive individuals. Hypertension 1996 Dec; 28: 1081–4PubMedCrossRefGoogle Scholar
  47. 47.
    Kool MJ, Lustermans FA, Breed JC, et al. Effect of perindopril and amiloride/hydrochlorothiazide on haemodynamics and vessel wall properties of large arteries. J Hypertens 1993; 11 Suppl. 5: S362–3CrossRefGoogle Scholar
  48. 48.
    Girerd X, Giannattasio C, Moulin C, et al. Regression of radial artery wall hypertrophy and improvement of carotid artery compliance after long-term antihypertensive treatment in elderly patients. J Am Coll Cardiol 1998 Apr; 31: 1064–73PubMedCrossRefGoogle Scholar
  49. 49.
    Schwartzkopff B, Brehm M, Mundhenke M, et al. Repair of coronary arterioles after treatment with perindopril in hypertensive heart disease. Hypertension 2000 Aug; 36: 220–5PubMedCrossRefGoogle Scholar
  50. 50.
    Antony I, Lerebours G, Nitenberg A. Angiotensin-converting enzyme inhibition restores flow-dependent and cold pressor test-induced dilations in coronary arteries of hypertensive patients. Circulation 1996 Dec 15; 94(12): 3115–22PubMedCrossRefGoogle Scholar
  51. 51.
    Meyer C, Nielsen FS, Sato A, et al. Beneficial effect of acute ACE inhibition on vasomotion and myocardial perfusion in type II diabetics with left ventricular hypertrophy [abstract no. 914]. Circulation 1997 Oct 21; 96(8) Suppl.: 1–166Google Scholar
  52. 52.
    Dyker AG, Grosset DG, Lees K. Perindopril reduces blood pressure but not cerebral blood flow in patients with recent cerebral ischemic stroke. Stroke 1997 Mar; 28: 580–3PubMedCrossRefGoogle Scholar
  53. 53.
    Walters MR, Bolster A, Dyker AG, et al. Effect of perindopril on cerebral and renal perfusion in stroke patients with carotid disease. Stroke 2001; 32: 473–8PubMedCrossRefGoogle Scholar
  54. 54.
    Kuperstein R, Sasson Z. Effects of antihypertensive therapy on glucose and insulin metabolism and on left ventricular mass: a randomized, double-blind, controlled study of 21 obese hypertensives. Circulation 2000 Oct 10; 102: 1802–6PubMedCrossRefGoogle Scholar
  55. 55.
    Revel F, Gallois H, Le-Coz Y, et al. Course of the left ventricular mass in a population of 893 hypertensive patients: effects of therapeutic intervention with perindopril. Ann Cardiol Angeiol Paris 1994 Dec; 43: 594–9. in FrenchPubMedGoogle Scholar
  56. 56.
    Sihm I, Schroeder AP, Aalkjaer C, et al. Regression of media-to-lumen ratio of human subcutaneous arteries and left ventricular hypertrophy during treatment with an angiotensinconverting enzyme inhibitor-based regimen in hypertensive patients. Am J Cardiol 1995 Nov 24; 76: 38E–40EPubMedCrossRefGoogle Scholar
  57. 57.
    Bonner G, Lederle RM, Scholze J, et al. Therapeutic safety of perindopril in the treatment of mild hypertension with concomitant nephropathy. Arzneim Forsch Drug Res 1993; 43(8): 852–5Google Scholar
  58. 58.
    Stumpe KO, Overlack A. A new trial of the efficacy, tolerability, and safety of angiotensin-converting enzyme inhibition in mild systemic hypertension with concomitant diseases and therapies. Perindopril Therapeutic Safety Study Group (PUTS). Am J Cardiol 1993 Jun 24; 71: 32E–7EGoogle Scholar
  59. 59.
    Ha S-K, Lee SY, Park HS, et al. ACE DD genotype is more susceptible than ACE II and ID genotypes to the antiproteinuric effect of ACE inhibitors in patients with proteinuric non-insulin-dependent diabetes mellitus. Nephrol Dial Transplant 2000; 15: 1617–23PubMedCrossRefGoogle Scholar
  60. 60.
    Tykarski A, Kopatka P, Posadzy-Malaczynska A, et al. Comparison of the effects of angiotensin II antagonists and ACE inhibitors on renal handling of uric acid in hypertensive patients [abstract]. Nephrol Dial Transplant 1999 Sep; 14: A62Google Scholar
  61. 61.
    Seedat YK, Randeree IGH. Antihypertensive effect and tolerability of perindopril in Indian hypertensive and type 2 diabetic patients: 1-year randomised, double-blind, parallel study vs atenolol. Clin Drug Invest 1998; 16(3): 229–40CrossRefGoogle Scholar
  62. 62.
    Woo J, Woo KS, Or KH, et al. A double-blind randomised comparison of perindopril and ketanserin in the treatment of hypertension in elderly diabetic patients. Drugs Aging 1993 Nov–Dec; 3: 525–31PubMedCrossRefGoogle Scholar
  63. 63.
    Giuntoli F, Gabbani S, Natali A, et al. Effects of perindopril on carbohydrate and lipoprotein metabolism in essential hypertension. Am J Med 1992 Apr 27; 92: 95S–7SPubMedCrossRefGoogle Scholar
  64. 64.
    Morgan TO, Louis WJ, MacDonald GJ, et al. Antihypertensive efficacy and safety of perindopril in mild-to-moderate essential hypertension: results of a double-blind multicenter study versus atenolol. Am J Med 1992 Apr 27; 92 Suppl. 4B: 73S–8SPubMedCrossRefGoogle Scholar
  65. 65.
    Bak JF, Gerdes LU, Sorensen NS, et al. Effects of perindopril on insulin sensitivity and plasma lipid profile in hypertensive non-insulin-dependent diabetic patients. Am J Med 1992; 92 Suppl. 4B: 69S–72SPubMedCrossRefGoogle Scholar
  66. 66.
    Oksa A, Gajdos M, Fedelesová V, et al. Effects of angiotensinconverting enzyme inhibitors on glucose and lipid metabolism in essential hypertension. J Cardiovasc Pharmacol 1994 Jan; 23: 79–86PubMedCrossRefGoogle Scholar
  67. 67.
    Uchida K, Azukizawa S, Kigoshi T, et al. Effects of perindopril on glucose and lipid metabolism in patients with mild-to-moderate essential hypertension and glucose intolerance. Clin Ther 1994 May–Jun; 16: 466–70PubMedGoogle Scholar
  68. 68.
    Fogari R, Corradi L, Malamani GD, et al. Effect of perindopril and of nitrendipine on plasma fibrinogen in overweight hypertensive patients [abstract]. Am J Hypertens 1997 Apr; 10 Pt 2: 136ACrossRefGoogle Scholar
  69. 69.
    Middeke M, Krone W. Effects of perindopril on serum lipids in hypertensive patients with hyperlipidemia. J Cardiovasc Pharmacol 1994 Apr; 23: 629–31PubMedCrossRefGoogle Scholar
  70. 70.
    Fennessy PA, Campbell JH, Campbell GR. Perindopril inhibits both the development of atherosclerosis in the cholesterol-fed rabbit and lipoprotein binding to smooth muscle cells in culture. Atherosclerosis 1994; 106: 29–41PubMedCrossRefGoogle Scholar
  71. 71.
    Squire IB, O’Kane KPJ, Anderson N, et al. Bradykinin B2 receptor antagonism attenuates blood pressure response to acute angiotensin-converting enzyme inhibition in normal men. Hypertension 2000 Jul; 36: 132–6PubMedCrossRefGoogle Scholar
  72. 72.
    Lecocq B, Funck-Brentano C, Lecocq V, et al. Influence of food on the pharmacokinetics of perindopril and the time course of angiotensin-converting enzyme inhibition in serum. Clin Pharmacol Ther 1990 Mar; 47(3): 397–402PubMedCrossRefGoogle Scholar
  73. 73.
    Brown CL, Backhouse CI, Grippat JC, et al. The effect of perindopril and hydrochlorothiazide alone and in combination on blood pressure and on the renin-angiotensin system in hypertensive subjects. Eur J Clin Pharmacol 1990; 39: 327–32PubMedCrossRefGoogle Scholar
  74. 74.
    Devissaguet JP, Ammoury N, Devissaguet M, et al. Pharmacokinetics of perindopril and its metabolites in healthy volunteers. Fundam Clin Pharmacol 1990; 4: 175–89PubMedCrossRefGoogle Scholar
  75. 75.
    Bree F, Nguyen P, Urien S, et al. Specific and high affinity binding of perindoprilat, but not of perindopril to blood ACE. Int J Clin Pharmacol Ther Toxicol 1992 Sep; 30: 325–30PubMedGoogle Scholar
  76. 76.
    Funck-Brentano C, Lecocq B, Jaillon P, et al. Effects of food on the pharmacokinetics and ACE-inhibition of perindopril in healthy volunteers. In: Velasco M, Israel A, Romero E, et al., editors. Recent advances in pharmacology and therapeutics. Amsterdam: Elsevier Science Publishers BV, 1989: 277–80Google Scholar
  77. 77.
    Guérin A, Resplandy G, Marchais S, et al. The effect of haemodialysis on the pharmacokinetics of perindoprilat after long-term perindopril. Eur J Clin Pharmacol 1993; 44(2): 183–7PubMedCrossRefGoogle Scholar
  78. 78.
    Thiollet M, Funck-Brentano C, Grange J-D, et al. The pharmacokinetics of perindopril in patients with liver cirrhosis. Br J Clin Pharmacol 1992 Mar; 33: 326–8PubMedCrossRefGoogle Scholar
  79. 79.
    2001 Mosby’s GenRx [online]. 2001 Mosby’s Gen Rx. Available from [Accessed 2000 Nov 13]
  80. 80.
    Mignat C, Unger T. ACE inhibitors: drug interactions of clinical significance. Drug Saf 1995; 12(5): 334–47PubMedCrossRefGoogle Scholar
  81. 81.
    Chrysant SG, McDonald RH, Wright JT, et al. Perindopril as monotherapy in hypertension: a multicenter comparison of two dosing regimens. Perindopril Study Group. Clin Pharmacol Ther 1993 Apr; 53: 479–84PubMedCrossRefGoogle Scholar
  82. 82.
    Myers MG. A dose-response study of perindopril in hypertension: effects on blood pressure 6 and 24 h after dosing. Perindopril Multicentre Dose-Response Study Group. Can J Cardioll 1996 Nov; 12: 1191–6Google Scholar
  83. 83.
    Zannad F, Bernaud CM, Fay R. Double-blind, randomized, multicentre comparison of the effects of amlodipine and perindopril on 24 h therapeutic coverage and beyond in patients with mild to moderate hypertension. General Physicians Investigators’ Group. J Hypertens 1999 Jan; 17: 137–46PubMedCrossRefGoogle Scholar
  84. 84.
    Mallion J-M, Chastang C, Unger P. Efficacy and safety of a fixed low-dose perindopril/indapamide combination in essential hypertension. A randomised controlled study. Clin Exp Hypertens 2000 Jan; 22: 23–32PubMedCrossRefGoogle Scholar
  85. 85.
    Safar M, Salzman V, Brault Y, et al. Safety and efficacy of perindopril/indapamide fixed combination in mild-to-moderate hypertension [abstract]. J Hypertens 1996 Jun; 14 Suppl. 1: S225Google Scholar
  86. 86.
    Lees KR, Reid JL, Scott MG, et al. Captopril versus perindopril: a double blind study in essential hypertension. J Hum Hypertens 1989 Feb; 3: 17–22PubMedGoogle Scholar
  87. 87.
    Alcocer L, Campos C, Bahena JH, et al. Clinical acceptability of ACE inhibitor therapy in mild to moderate hypertension, a comparison between perindopril and enalapril. Cardiovasc Drugs Ther 1995 Jun; 9: 431–6PubMedCrossRefGoogle Scholar
  88. 88.
    Nedogoda SV, Petrov VI. The differences between ACE inhibitors trough to peak ratios at 24-hour ambulatory monitoring (cross-over study) [abstract]. J Hypertens 1998 Jun; 16 Suppl. 2: S247Google Scholar
  89. 89.
    Polónia J, Pego M, Calaça J, et al. A double-blind comparison of perindopril and enalapril on 24-h control of blood pressure in hypertensive patients [abstract]. Am J Hypertens 1996 Apr; 9 Pt: 162CrossRefGoogle Scholar
  90. 90.
    Yoshinaga K, Saruta T, Abe K, et al. Clinical evaluation of monotherapy with perindopril, an ACE inhibitor, in the treatment of essential hypertension: double-blind parallel comparison with enalapril. Rinsholyaku 1997; 13: 4259–97Google Scholar
  91. 91.
    Yusoff K, Razak TA, Yusof N, et al. Comparative efficacy of perindopril and enalapril once daily using 24-hour ambulatory blood pressure monitoring [see comments]. Int J Clin Pract 1999 Jun; 53: 277–80PubMedGoogle Scholar
  92. 92.
    Honos G, Gossard D, Auger P, et al. Once daily perindopril versus slow release diltiazem in the treatment of mild to moderate essential hypertension. Canadian Study Group on Perindopril. Can J Cardiol 1994 Nov; 10 Suppl. D: 8D–12DGoogle Scholar
  93. 93.
    Thurston H, Mimran A, Zanchetti A, et al. A double blind comparison of perindopril and atenolol in essential hypertension. J Hum Hypertens 1990; 4: 547–52PubMedGoogle Scholar
  94. 94.
    Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998 June 13; 351 (1755–1762)PubMedCrossRefGoogle Scholar
  95. 95.
    Black HR, Saunders E. Efficacy and safety of perindopril and hydrochlorothiazide in stage I–III hypertension. Perindopril PE Study Group. J Vasc Med Biol 1994; 5(5-6): 191–8Google Scholar
  96. 96.
    Letellier P, Overlack A, Agnes E, et al. Perindopril plus nifedipine versus perindopril plus hydrochlorothiazide in mild to severe hypertension: a double-blind multicentre study. Multicentre Study Group on Treatment Association with Perindopril. J Hum Hypertens 1994 Feb; 8: 145–9PubMedGoogle Scholar
  97. 97.
    Wing LMH, Arnolda LF, Harvey PJ, et al. Low-dose diuretic and/or dietary sodium restriction when blood pressure is resistant to ACE inhibitor. Blood Press 1998 Nov; 7: 299–307PubMedCrossRefGoogle Scholar
  98. 98.
    McClellan KJ, Markham A. Perindopril 2mg/indapamide 0.625mg: fixed low-dose combination. Drugs 1999 Aug; 58: 297–302. [discussion 303-4]PubMedCrossRefGoogle Scholar
  99. 99.
    Speirs C, Wagniart F, Poggi L. Perindopril postmarketing surveillance: a 12 month study in 47 351 hypertensive patients. Br J Clin Pharmacol 1998 Jul; 46: 63–70PubMedCrossRefGoogle Scholar
  100. 100.
    Poggi L, Renucci J-F, Denolle T. Treatment of essential hypertension in general practice: an open-label study of 47,351 French hypertensive patients treated for one year with perindopril. Can J Cardiol 1994 Nov; 10 Suppl. D: 21D–4DPubMedGoogle Scholar
  101. 101.
    Fressinaud P, Berrut G, Gallois H. Antihypertensive activity and acceptability based on clinical and laboratory parameters of perindopril: chief results in 23,460 mild to moderate hypertension patients treated for 6 months in general practice [in French]. Ann Cardiol Angeiol Paris 1993 Jan; 42: 51–9PubMedGoogle Scholar
  102. 102.
    Morgan T, Anderson A. How important is 24-hour control of blood pressure? Drug Saf 1996; 15(4): 243–8PubMedCrossRefGoogle Scholar
  103. 103.
    Morgan T, Anderson A, Jones E. The effect on 24 h blood pressure control of an angiotensin converting enzyme inhibitor (perindopril) administered in the morning or at night. J Hypertens 1997; 15(2): 205–11PubMedCrossRefGoogle Scholar
  104. 104.
    Morgan TO, Morgan O, Anderson A. Effect of dose on trough peak ratio of antihypertensive drugs in elderly hypertensive males. Clin Exp Pharmacol Physiol 1995; 22(10): 778–80PubMedCrossRefGoogle Scholar
  105. 105.
    Leonetti G, Cuspidi C. Choosing the right ACE inhibitor: a guide to selection. Drugs 1995; 49(4): 516–35PubMedCrossRefGoogle Scholar
  106. 106.
    Tan KW, Leenen FH. Persistence of anti-hypertensive effect after missed dose of perindopril. Br J Clin Pharmacol 1999 Oct; 48: 628–30PubMedCrossRefGoogle Scholar
  107. 107.
    Suraniti S, Berrut G, Marre M, et al. Antihypertensive efficacy and acceptability of perindopril in elderly hypertensive patients. Am J Cardiol 1993 Jun 24; 71: 28E–31EPubMedCrossRefGoogle Scholar
  108. 108.
    Denolle T, Rennuci J-F, Poggi L, et al. Efficacy and tolerance of a angiotensin converting enzyme, perindopril, in 2256 hypertensive patients aged 80 years or over treated for one year [abstract]. Am J Hypertens 1994 Apr; 7 (Pt 2): 50AGoogle Scholar
  109. 109.
    Leenen FHH, Tanner J, McNally CF. Antihypertensive efficacy of the ACE-inhibitor perindopril in the elderly. J Hum Hypertens 2000 May; 14: 321–5PubMedCrossRefGoogle Scholar
  110. 110.
    Nalbantgil S, Gürün C, Yilmaz H, et al. The effect of antihypertensive treatment with Perindopril and Lacidipine on the incidence of silent ischemia in patients with hypertension [abstract]. Cardiovasc Drugs Ther 1999 Mar; 13: 56Google Scholar
  111. 111.
    PROGRESS: Perindopril Protection Against Recurrent Stroke Study. ESH 1999, Milan, Italy (Data on file)Google Scholar
  112. 112.
    ABPI compendium of data sheets and summaries of product characteristics. 1999–2000 edition, 1999–2000Google Scholar
  113. 113.
    Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke and coronary heart disease: Part 2, short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990 Apr 7; 335: 827–38PubMedCrossRefGoogle Scholar
  114. 114.
    Ramsay LE, Williams B, Johnston GD, et al. British Hypertension Society guidelines for hypertension management 1999: summary. BMJ 1999 Sep 4; 319: 630–5PubMedCrossRefGoogle Scholar
  115. 115.
    Blacher J, Asmar R, Djane S, et al. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 1999 May; 33: 1111–7PubMedCrossRefGoogle Scholar
  116. 116.
    Blacher J, Guerin AP, Pannier B, et al. Impact of aortic stiffness on survival in end-stage renal disease. Circulation 1999 May 11; 99: 2434–9PubMedCrossRefGoogle Scholar
  117. 117.
    O’Leary DH, Polak JF, Kronmal RA, et al. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med 1999 Jan 7; 340(1): 14–22PubMedCrossRefGoogle Scholar
  118. 118.
    Liao D, Arnett DK, Tyroler HA, et al. Arterial stiffness and the development of hypertension: the ARIC study. Hypertension 1999 Aug; 34: 201–6PubMedCrossRefGoogle Scholar
  119. 119.
    Van Bortel LMAB, Kool MJF, Spek JJ. Disparate effects of antihypertensive drugs on large artery distensibility and compliance in hypertension. Am J Cardiol 1995 Nov 24; 76: 46–9CrossRefGoogle Scholar
  120. 120.
    Schiffrin EL. Vascular remodeling and endothelial function in hypertensive patients: Effects of antihypertensive therapy. Scand Cardiovasc J 1998; 32 Suppl. 47: 15–21CrossRefGoogle Scholar
  121. 121.
    van Zwieten PA. The influence of antihypertensive drug treatment on the prevention and regression of left ventricular hypertrophy. Cardiovasc Res 2000; 45(1): 82–91PubMedCrossRefGoogle Scholar
  122. 122.
    Dahlof B, Pennert K, Hansson L. Reversal of left ventricular hypertrophy in hypertensive patients; a meta-analysis of 109 treatment studies. Am J Hypertens 1992; 5: 95–110PubMedGoogle Scholar
  123. 123.
    Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin-converting enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet 1999 Feb 20; 353: 611–6PubMedCrossRefGoogle Scholar
  124. 124.
    Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000 Jan 20; 342(3): 145–53CrossRefGoogle Scholar
  125. 125.
    Henderson JR, Gomma AH, Fox KM. European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease. In: Fox K, Remme WJ, editors. ACE inhibition and ischaemic heart disease. London: Science Press, Ltd, 1999:51–8Google Scholar
  126. 126.
    Sever PS, Dahlof B, Poulter NR, et al. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT): baseline demography of randomised subjects and BP changes after 18 months follow-up. J Hum Hypertens 2000; 14: 847CrossRefGoogle Scholar

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© Adis International Limited 2001

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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