CLINICAL RESEARCH: HYPERTENSION
Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/Indapamide in hypertensive subjects: comparison with atenolol
Gérard M. London, MD*,
Roland G. Asmar, MD ,
Michaël F. O'Rourke, MD ,
Michel E. Safar, MD ,* REASON Project Investigators
* Hôpital Manhès, Fleury-Mèrogis, France
L'Institut Cardiovasculaire, Paris, France
St. Vincent Hospital, Darlinghurst, Australia
Hôtel-Dieu, Paris, France
Manuscript received February 4, 2003;
revised manuscript received July 28, 2003,
accepted July 28, 2003.
* Reprint requests and correspondence: Dr. Michel E. Safar, Centre de Diagnostic, Hôtel-Dieu, 1 Place du Paris Notre Dame, Paris, 75004 France.
michel.safar{at}brs.ap-hop-paris.fr
OBJECTIVES: The goal of this study was to determine if a low-dose combination of the angiotensin-converting enzyme inhibitor perindopril (Per) and the diuretic indapamide (Ind) reduces central (thoracic aorta, carotid artery) as well as brachial systolic blood pressure (SBP) more than the beta-blocker atenolol and to determine the hemodynamic factors influencing independently brachial and central SBP: pulse wave velocity (PWV) and pattern of wave reflections.
BACKGROUND: In high cardiovascular risk populations, angiotensin blockade improves survival without affecting brachial SBP and diastolic blood pressure (DBP). Whether central SBP, which is physiologically lower than brachial SBP, is significantly reduced has never been investigated.
METHODS: This study was a double-blind randomized trial for one year in patients with essential hypertension.
RESULTS: For a similar DBP reduction, Per/Ind decreased SBP significantly more than atenolol, with a more pronounced reduction for central than for brachial SBP. After one year, the difference between brachial and central SBP was maintained by Per/Ind (8.28 ± 1.53 mm Hg) and significantly attenuated by atenolol (0.29 ± 1.61 mm Hg). Under atenolol, the principal factor modulating SBP reduction was mean blood pressure. Under Per/Ind, this parameter played a minor role, and the central SBP reduction implied a major role for disturbed PWV and wave reflections.
CONCLUSIONS: Under Per/Ind, but not atenolol, normalization of brachial SBP is achieved with a significantly greater reduction of central SBP. This hemodynamic profile reflects changes of wave reflections issued from distal arterial and arteriolar territory, where Per/Ind, but not atenolol, is known to improve vessel wall structure.
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Abbreviations and Acronyms
| | ACEI | = angiotensin-converting enzyme inhibitor | | AIa | = augmentation index (aortic) | | AIc | = augmentation index (carotid) | | CV | = cardiovascular | | DBP | = diastolic blood pressure | | Ind | = indapamide | | ITT | = intention-to-treat | | LVET | = left ventricular ejection time | | MBP | = mean blood pressure | | M0, M6, M12 | = month 0, month 6, month 12 | | Per | = perindopril | | PP | = pulse pressure | | PWV | = pulse wave velocity | | SBP | = systolic blood pressure |
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