Treating hypertension by rational use of diuretics: results of the Russian ARGUS-2 study

ABSTRACT

Objective: Insufficient use of diuretics in combination antihypertensive therapy is a main cause of poor blood pressure (BP) control in Russia. The objective of the ARGUS-2 study was to demonstrate that a rational use of a thiazide-like diuretic, indapamide sustained release (SR), alone or in combination, improves BP control in patients with arterial hypertension difficult to control due to isolated systolic hypertension (ISH), diabetes mellitus (DM), chronic nephropathy, or metabolic syndrome.

Methods: The open-label, non-comparative, 3-month study without preliminary washout included 1438 hypertensive patients (mean age: 57.3 ± 10.7 years, mean BP: 158.8 ± 14.2/93.4 ± 10.0 mmHg), with difficult-to-control arterial hypertension and who had never been treated with diuretics previously. Throughout the study, patients received indapamide SR 1.5 mg OD. BP control was defined as <140/90 mmHg for all patients and <130/80 mmHg for those with diabetes mellitus or chronic nephropathy.

Results: Indapamide SR was given as initiation monotherapy to 13.7% of the patients, as substitutive monotherapy to 6.8% of the patients uncontrolled by a previous monotherapy, as additive therapy to 31.9% of the patients uncontrolled by previous monotherapy, and as additive therapy to 47.6% uncontrolled by previous combination therapy without a diuretic. Among included patients 75.7% received also an ACE inhibitor or an angiotensin II receptors blocker, 43.9% a calcium channel blocker, and 32.8% a beta-blocker. In 3 months after indapamide SR administration, average BP level decreased to 131.8 ± 9.7/80.5 ± 6.9 mmHg and 84.5% of the study population achieved BP control. BP was controlled in 91.9% of patients with ISH (n = 477), 74.8% of those with diabetes (n = 214), 75.6% of those with chronic nephropathy (n = 82), and 85.1% of patients with metabolic syndrome (n = 745). No case of hypokalemia was reported.

Conclusion: The study demonstrates the value of including the thiazide-like diuretic indapamide SR in a combined antihypertensive regimen to control BP in hypertensive patients with added cardiovascular risk factors whose hypertension is difficult to treat. Methodological limitations of this study are its open-label design and the possibility of a change in concomitant antihypertensive treatment during the study.

Keywords: :

• Chronic nephropathy
• Diuretics
• Hypertension
• Indapamide SR
• Isolated systolic hypertension
• Metabolic syndrome
• Uncontrolled hypertension

Transparency

Declaration of funding

This study was supported by an investigational grant from Servier. Servier has had no role in the preparation and/or reviewing of this article.

Declaration of financial/other relationships

Z.D.K. has disclosed that she has been the recipient of honoraria for faculty participation in accredited CME activity from Abbot, AstraZeneca, Berlin-Chemi, Boehringer Ingelheim, KRKA, MSD, Novartis, Pfizer and Servier. Y.V.K. has disclosed that she has been the recipient of honoraria for faculty participation in an accredited CME activity from Abbot, AstraZeneca, Boehringer Ingelheim, Novartis and Servier. S.V.V. has disclosed that she has been the recipient of honoraria for faculty participation in an accredited CME activity from AstraZeneca and Servier. V.S.M. has disclosed that he has been the recipient of honoraria for faculty participation in an accredited CME activity from Orion and Servier.

All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 and Peer Reviewer 2 have disclosed that they have no relevant financial relationships.

Acknowledgements

The authors express their gratitude to the following regional ARGUS-2 study coordinators: E. Baranova (Saint-Petersburg), R. Bogachev (Smolensk), N. Volkova (Rostov-na-Donu), S. Drozdetsky (Nizhniy Novgorod), M. Freidlina (Yekaterinburg), R. Khokhlov (Voronezh), O. Kisliak (Moscow), N. Koziolova (Perm), I. Kolina (Omsk), Y. Lopatin (Volgograd), S. Nedogoda (Volgograd), L. Nekrutenko (Perm), E. Tarlovskaya (Kirov), L. Tiukalova (Tomsk) and statistician E. Lukianova (Moscow).