DOCSLIB.ORG

Single-Pill Combination of Perindopril/Indapamide/ Amlodipine in Patients with Uncontrolled Hypertension: a Randomized Controlled Trial

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Single-Pill Combination of Perindopril/Indapamide/ Amlodipine in Patients with Uncontrolled Hypertension: a Randomized Controlled Trial Cardiol Ther DOI 10.1007/s40119-017-0085-7 ORIGINAL RESEARCH Single-Pill Combination of Perindopril/Indapamide/ Amlodipine in Patients with Uncontrolled Hypertension: A Randomized Controlled Trial Sergey V. Nedogoda . Vesna J. Stojanov Received: October 13, 2016 Ó The Author(s) 2017. This article is published with open access at Springerlink.com ABSTRACT (SBP C140 and \160 mmHg and DBP C90 and\100 mmHg), uncontrolled on maximal Introduction: Patients with hypertension often dose antihypertensive monotherapy or with a require a combination of three antihypertensive single dose of dual therapy. Patients were ran- agents to achieve blood pressure control, but domly assigned to: single-pill triple combina- very few single-pill triple combinations are tion of perindopril 5 mg/indapamide 1.25 mg/ available. The aim of this study was to deter- amlodipine 5 mg (Per/Ind/Aml) or dual-pill mine whether a single-pill triple combination of combination perindopril 5 mg/indapamide perindopril, indapamide, and amlodipine was 1.25 mg ? amlodipine 5 mg (Per/Ind ? Aml) as effective as a dual-pill combination of once daily for 12 weeks. The primary endpoint perindopril/indapamide plus separate amlodip- was change in office supine SBP and DBP from ine at reducing blood pressure in patients with baseline to week 12. The proportion of respon- uncontrolled, essential hypertension. ders defined as those with normalized BP Methods: This international, multicenter, (SBP\140 mmHg and DBP\90 mmHg), and/or open-label, randomized controlled trial was decrease of SBP C20 mmHg, and/or decrease of conducted in men or women aged C18 years old DBP C10 mmHg at week 12 (W12) compared with confirmed essential hypertension with baseline was also assessed. Secondary effi- cacy endpoints included change in office supine SBP and DBP, response, and BP control at weeks Enhanced content To view enhanced content for this article go to http://www.medengine.com/Redeem/ 4 and 8. The tolerability of the treatments was A487F0607C763559. also assessed. Results: A total of 148 patients were random- Electronic supplementary material The online version of this article (doi:10.1007/s40119-017-0085-7) ized: 75 to Per/Ind/Aml and 73 to Per/ contains supplementary material, which is available to Ind ? Aml. Mean supine SBP and DBP were authorized users. 149.1 ± 4.7 and 94.1 ± 3.1 mmHg, respectively, with no relevant between-group difference. At S. V. Nedogoda (&) week 12, both triple-therapy regimens were Department Volgograd Medical State University, associated with clinically significant reductions Volgograd, Russia e-mail: [email protected] in SBP compared with baseline (-21.5 ± 11.7 and -20.0 ± 12.9 mmHg, respectively). Reduc- V. J. Stojanov tions in office supine DBP were also clinically Center for Hypertension, Clinical Center of Serbia, significant (-15.3 ± 7.8 and -14.8 ± 9.0 Medical School University of Belgrade, Belgrade, Serbia mmHg, respectively). The proportion of Cardiol Ther treatment responders was high in both groups: increasingly used to provide optimal BP control 89.2 and 87.1%, respectively. The reduction in [8–13] with fewer dose-related adverse office supine SBP/DBP was already evident at effects. In addition, each agent in the combi- week 4 and maintained for the duration of the nation can lessen adverse effects of other com- study in both groups. The majority of patients ponents [14]. This may counteract the tendency were treatment responders at week 4 (89.2 and of some physicians to prescribe lower than 82.9%, respectively) and had achieved BP con- guideline-recommended doses of anti-hyper- trol (87.8 vs. 78.6%, respectively), which was tensive drugs because of concerns over tolera- maintained until week 12 in both treatment bility, and the inevitable suboptimal dosing and groups. Both treatments were well tolerated inadequate dose titration required to achieve with no between-group differences. target BP goals [15, 16]. Conclusions: In adult patients with uncon- When triple-combination therapy is trolled essential hypertension on treat- required, the European Society of Cardiology/ ment, single-pill triple-combination therapy European Society of Hypertension guidelines [1] with Per/Ind/Aml is as effective as the same dose and other guidelines [3, 17–20] recommend the dual-pill combination of Per/Ind ? Aml. Both use of an angiotensin-converting enzyme (ACE) treatments were associated with clinically sig- system inhibitor or angiotensin II receptor nificant BP reductions compared with baseline blocker (ARB) with a calcium channel blocker and were well tolerated.Clinical trials number: (CCB) and a diuretic as rational and effective. http://www.controlled-trials.com ISRCTN: One such combination is perindopril, inda- 16442558.Funding: Les Laboratoires Servier. pamide, and amlodipine. In addition to addi- tive effects on BP control, each component of Keywords: Amlodipine; Antihypertensive; this combination has demonstrated protection Indapamide; Perindopril; Single-pill of target organs at risk from hypertension combination; Uncontrolled essential including the heart, renal system, brain, and hypertension vasculature, in a wide range of patients with hypertension. The three components are also complementary in terms of tolerability: INTRODUCTION perindopril reduces the peripheral edema that is a dose-limiting side effect of CCBs [14]; Hypertension is a major modifiable risk factor for amlodipine reduces ACE inhibitor-related cardiovascular disease and stroke and there is cough by decreasing prostaglandin synthesis global agreement among current hypertension that is induced by bradykinin [21]; and inda- management guidelines that the majority of pamide is a metabolically neutral diuretic [22]. patients with uncomplicated hypertension Each individual component is associated with a should be treated to a blood pressure (BP) goal of large evidence base of use in arterial hyperten- systolic blood pressure (SBP)\140 mmHg and sion, and single-pill combinations have also diastolic blood pressure (DBP)\90 mmHg [1–6]. been extensively evaluated: perindopril/inda- Monotherapy can effectively reduce BP in pamide has shown efficacy in patients with only a limited number of patients and the recurrent stroke [23], diabetes mellitus [24], and majority will therefore require treatment with in octogenarians with hypertension [25]; two or more agents to reach target levels [7]. In a perindopril/amlodipine combination has been meta-analysis of SBP reductions in 42 trials studied in detail in patients with hypertension (N = 10,698), the combination of any two med- at high cardiovascular risk [26]. ications from different BP-lowering drug classes Given the extensive experience with these was approximately five times more effective than agents as mono and dual therapy it was doubling the dose of a single drug [8]. hypothesized that combining the three agents The use of triple-combination therapy, tar- into a single-pill would maintain the estab- geting three different mechanisms of arterial lished efficacy and safety of these agents while hypertension pathogenesis, is becoming reducing dosing complexity. Knowing that Cardiol Ther some physicians may be reluctant to prescribe confirmed at the inclusion visit. Patients were fixed-dose triple-therapy combinations due to excluded if they had any contraindications to concerns over tolerability, the aim of the pre- perindopril, indapamide or amlodipine, or any of sent study was to evaluate the clinical efficacy the following conditions: complicated hyperten- and safety of a triple combination of perindopril sion (known stage III or IV hypertensive retinopa- 5 mg/indapamide 1.25 mg/amlodipine 5 mg in thy); macroalbuminuria; diabetes; moderate or a single-pill versus dual-pill combination severe renal failure (creatinine clearance 30–59 and perindopril 5 mg/indapamide 1.25 mg plus \30 ml/min, respectively); known complicated amlodipine 5 mg over 12 weeks, in treated liver disease; recent disease (previous 6 months) patients with uncontrolled hypertension. such as cerebrovascular disease (ischemic stroke, cerebral hemorrhage, transient ischemic attack); recent ventricular rhythm disorders (except iso- METHODS lated extrasystoles); and known or suspected symptomatic orthostatic hypotension (defined as a Study Design reductioninSBPC20 mmHg and/or in DBP C10 mmHg from supine to standing-up, The study was an international, multicenter, maintained for the first 3 min of standing-up). open-label, randomized controlled trial con- ducted at 13 centers in Russia and four centers Intervention in Serbia. The study protocol was approved by independent Ethics Committees, in accordance At the inclusion visit, patients were randomly with the local regulations in each of the coun- assigned to one of the following treatment tries and complied with the Declaration of groups: a single-pill triple combination of Helsinki, current Good Clinical Practice guide- perindopril 5 mg/indapamide 1.25 mg/am- lines (including source documents archiving), lodipine 5 mg (1 tablet/day orally in the morn- and local laws and regulations (ISRCTN regis- ing before breakfast), or a dual-pill combination tration number: 16442558). All participants of perindopril 5 mg/indapamide 1.25 mg ? am- provided informed consent before enrolment. lodipine 5 mg (1 tablet each/day orally in the Patients were randomized 1:1 to treatment by a morning before breakfast) (Fig. 1). Treatment computer-generated allocation schedule using a allocation was balanced, non-centralized, permuted block method (with a block
Load more

Recommended publications
  • Annual Report 2019/2020
    1 ANNUAL REPORT 2019/2020 SERVIER 2019/2020 ANNUAL REPORT 04 THE YEAR IN PICTURES 16 EDITORIAL BY OLIVIER LAUREAU 19 PROFILE 20 AMBITIOUS STRATEGIC OBJECTIVES 22 SERVIER, AN INDEPENDENT GROUP — Governance — Financial results — A comprehensive range of health care solutions — Global footprint 32 ACCELERATING THERAPEUTIC INNOVATION — A new agile and integrated R&D model — High aspirations in oncology — Open and collaborative R&D — A pipeline full of promise 42 ACTING FOR AND WITH PATIENTS — Involving patients throughout the life cycle of a medicine — Providing health care professionals with the medical information they need 48 GUARANTEEING ACCESS TO HEALTH CARE FOR ALL — A solid geographic footprint, building proximity with patients — Generic medicines, an opportunity for the health care system and an asset for Servier 54 PREPARING PRODUCTION FACILITIES OF TOMORROW — High quality production — Preparing production facilities to drive the Group’s transformation 60 NURTURING ENGAGEMENT — Boosting engagement among a united collective — Charitable initiatives around the world in response to Covid-19 — Increased social and environmental contribution — Mécénat Servier: committed to solidarity SERVIER 2019/2020 ANNUAL REPORT FOREWORD 03 AS THE WORLD FACES THIS UNPRECEDENTED HEALTH CRISIS, I FIRST OF ALL WOULD LIKE TO EXPRESS MY RESPECT AND ADMIRATION FOR ALL THOSE WHO SPARE NO EFFORT IN TREATING AND SAVING THE LIVES OF PEOPLE WITH COVID-19 OR OTHER CONDITIONS. SINCE THE VERY BEGINNING OF THE PANDEMIC, OUR GROUP HAS FOCUSED ON TWO PRIORITIES—TO CONTINUE SUPPLYING OUR MEDICINES TO PATIENTS THAT NEED THEM AND GUARANTEEING EMPLOYEE HEALTH AND SAFETY. I AM PROUD OF AND GRATEFUL TO EVERYONE AT SERVIER FOR THEIR UNWAVERING COMMITMENT AS THEY CONTINUE TO CARRY OUT THEIR DUTIES AT THIS TIME.
    [Show full text]
  • SPC Triplixam 0516.Pdf
    SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET 1 SUMMARY OF PRODUCT CHARACTERISTICS 2 1. NAME OF THE MEDICINAL PRODUCT Triplixam 2.5mg/0.625mg/5mg film-coated tablets [Triplixam 5mg/1.25mg/5mg film-coated tablets] [Triplixam 5mg/1.25mg/10mg film-coated tablets] [Triplixam 10mg/2.5mg/5mg film-coated tablets] [Triplixam 10mg/2.5mg/10mg film-coated tablets] 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One film-coated tablet contains 1.6975 mg perindopril equivalent to 2.5 mg perindopril arginine, 0.625 mg indapamide and 6.935 mg amlodipine besilate equivalent to 5 mg of amlodipine. [One film-coated tablet contains 3.395 mg perindopril equivalent to 5 mg perindopril arginine, 1.25 mg indapamide and 6.935 mg amlodipine besilate equivalent to 5 mg of amlodipine]. [One film-coated tablet contains 3.395 mg perindopril equivalent to 5 mg perindopril arginine, 1.25 mg indapamide and 13.870 mg amlodipine besilate equivalent to 10mg of amlodipine]. [One film-coated tablet contains 6.790 mg perindopril equivalent to 10 mg perindopril arginine, 2.5 mg indapamide and 6.935 mg amlodipine besilate equivalent to 5 mg of amlodipine]. [One film-coated tablet contains 6.790 mg perindopril equivalent to 10 mg perindopril arginine, 2.5 mg indapamide and 13.870 mg amlodipine besilate equivalent to 10 mg of amlodipine]. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet. Triplixam 2.5/0.625/5 mg: white, oblong, film-coated tablet, 8.5 mm long and 4.5 mm wide engraved with on one face and on the other face.
    [Show full text]
  • 4. Redefining Diuretics Use in Hypertension-Why Select a Thiazide
    Review Redefining diuretics use in hypertension: why select a thiazide-like diuretic? Michel Burniera,b, George Bakrisc, and Bryan Williamsd when compared with placebo or no treatment, blood Diuretics are listed in hypertension guidelines as one of pressure lowering by these antihypertensive drug classes three equally weighted first-line treatment options. In is accompanied by significant reductions of stroke and order to differentiate between antihypertensives, a lot of major cardiovascular events [9]. In order to differentiate discussion has been directed at side effect profiles and as a between the three options, a lot of discussion has been result, has created a perhaps disproportionate fear of the directed at side effect profiles. Multiple meta-analyses, for metabolic effects that can be associated with diuretics. instance, have documented concerns that treatment with Data, however, show that the risk of a clinically diuretics could lead to disruptions in electrolyte levels, to meaningful change in laboratory parameters is very low, unfavorable metabolic effects, and to an increased risk of whereas the benefits of volume control and natriuresis are developing type 2 diabetes mellitus [10–15]. These data, high and the reductions in morbidity and mortality are though important, have generated a perhaps dispropor- clinically significant. Moreover, as clinically significant tionate fear of the side effects that can be associated with differences in safety and efficacy profiles exist among diuretic treatment. diuretics, several international guidelines have started Understanding the place of diuretics in the treatment of making a distinction between thiazides hypertension is complicated by the fact that in many (hydrochlorothiazide) and thiazide-like (chlorthalidone, countries, diuretics are more commonly used in combina- indapamide) diuretics; and some of them now recommend tion with other classes rather than alone as a first-line longer acting thiazide-like diuretics.
    [Show full text]
  • Summary of Product Characteristics
    SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT PRETERIAN 5mg/1.25mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One film-coated tablet contains 3.395 mg perindopril corresponding to 5 mg perindopril arginine and 1.25 mg indapamide. Excipient : 71.33 mg lactose monohydrate For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet. White, rod-shaped film-coated tablet. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Treatment of essential hypertension, PRETERIAN 5mg/1.25mg film-coated tablet is indicated in patients whose blood pressure is not adequately controlled on perindopril alone. 4.2 Posology and method of administration Oral route One PRETERIAN 5mg/1.25mg film-coated tablet per day as a single dose, preferably to be taken in the morning, and before a meal. When possible individual dose titration with the components is recommended. PRETERIAN 5mg/1.25mg film-coated tablet should be used when blood pressure is not adequately controlled on PRETERIAN 2.5mg/0.625mg film-coated tablet (where available).When clinically appropriate, direct change from monotherapy to PRETERIAN 5mg/1.25mg film-coated tablet may be considered. Elderly (see section 4.4) Treatment should be initiated after considering blood pressure response and renal function. Patients with renal impairment (see section 4.4) In severe renal impairment (creatinine clearance below 30 ml/min), treatment is contraindicated. In patients with moderate renal impairment (creatinine clearance 30-60 ml/min), it is recommended to start treatment with the adequate dosage of the free combination. In patients with creatinine clearance greater than or equal to 60 ml/min, no dose modification is required.
    [Show full text]
  • Annual Report
    1 - 2 0 9 1 8 0 2 ANNUAL REPORT AN INDEPENDENT GROUP COMMITTED TO THERAPEUTIC PROGRESS TO SERVE PATIENT NEEDS - 1 - Because life is precious and caring means acting with compassion, patient health is our priority. Because seeking scientific excellence and discovering new treatments is all about improving patients’ lives, we are committed to therapeutic progress. Because meeting tomorrow’s challenges requires innovation, and our independence makes us unique and drives us to perform, we dare to innovate and succeed. Because the unity of men and women is the story of a collective commitment and is our strength, we grow by sharing. Because passing on to future generations a world that can ensure access to quality health care for all is our vision for the future, at Servier, all over the world, we are ready to meet the health care challenges of tomorrow, for and with patients. - 2 - TABLE OF CONTENTS SERVIER GROUP 2018/2019 ACHIEVEMENTS SERVIER ANNUAL - 2018/2019 REPORT P. 04 Editorial by Olivier Laureau P. 07 The basis for our actions P. 08 An independent Group P. 10 Preparing for the future P. 12 Financial results P. 14 An international Group P. 34 with strong roots in France Promoting access to P. 16 Servier R&D: meeting patient health care needs as effectively as possible for all P. 20 A comprehensive health care offering P. 30 P. 22 HR: mobilizing around the Group’s performance Acting for and with the patient P. 26 Committed to a safe, responsible, and transparent industry - 3 - P. 46 P. 54 Becoming a Developing recognized player generic in oncology activities P.
    [Show full text]
  • Australian Public Assessment Report for Perindopril Arginine/Amlodipine (As Besylate)
    Australian Public Assessment Report for Perindopril arginine/amlodipine (as besylate) Proprietary Product Name: Coveram Sponsor: Servier Laboratories (Aust) Pty Ltd December 2009 Therapeutic Goods Administration About the Therapeutic Goods Administration (TGA) · The TGA is a division of the Australian Government Department of Health and Ageing, and is responsible for regulating medicines and medical devices. · TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance), when necessary. · The work of the TGA is based on applying scientific and clinical expertise to decision-making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines and medical devices. · The TGA relies on the public, healthcare professionals and industry to report problems with medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action. · To report a problem with a medicine or medical device, please see the information on the TGA website. About AusPARs · An Australian Public Assessment Record (AusPAR) provides information about the evaluation of a prescription medicine and the considerations that led the TGA to approve or not approve a prescription medicine submission. · AusPARs are prepared and published by the TGA. · An AusPAR is prepared for submissions that relate to new chemical entities, generic medicines, major variations, and extensions of indications. · An AusPAR is a static document, in that it will provide information that relates to a submission at a particular point in time. · A new AusPAR will be developed to reflect changes to indications and/or major variations to a prescription medicine subject to evaluation by the TGA.
    [Show full text]
  • Coversyl Referral Art 6 12 En
    ANNEX I LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTHS OF THE MEDICINAL PRODUCTS, ROUTE OF ADMINISTRATION, MARKETING AUTHORISATION HOLDERS IN THE MEMBER STATES 1 EMEA 2005 Marketing Authorisation Member State Invented name Strength Pharmaceutical form Route of administration Holder Austria Servier Austria GmbH COVERSUM 2 mg Tablets Oral use Austria Servier Austria GmbH COVERSUM 4 mg Tablets Oral use Belgium Servier Benelux S.A. COVERSYL 2 mg Tablets Oral use Belgium Servier Benelux S.A. COVERSYL 4 mg Tablets Oral use Denmark Les Laboratoires Servier COVERSYL 2 mg Tablets Oral use Denmark Les Laboratoires Servier COVERSYL 4 mg Tablets Oral use Finland Les Laboratoires Servier COVERSYL 2 mg Tablets Oral use Finland Les Laboratoires Servier COVERSYL 4 mg Tablets Oral use France Les Laboratoires Servier COVERSYL 2 mg Tablets Oral use France Les Laboratoires Servier COVERSYL 4 mg Tablets Oral use Germany Les Laboratoires Servier COVERSUM COR 2 mg Tablets Oral use Germany Les Laboratoires Servier COVERSUM 4 mg Tablets Oral use Greece Servier Hellas Pharmaceuticals COVERSYL 2 mg Tablets Oral use S.A. Greece Servier Hellas Pharmaceuticals COVERSYL 4 mg Tablets Oral use S.A. Iceland Les Laboratoires Servier COVERSYL 2 mg Tablets Oral use Iceland Les Laboratoires Servier COVERSYL 4 mg Tablets Oral use 2 EMEA 2005 Marketing Authorisation Member State Invented name Strength Pharmaceutical form Route of administration Holder Ireland Les Laboratoires Servier COVERSYL 2 mg Tablets Oral use Ireland Les Laboratoires Servier COVERSYL 4 mg Tablets Oral use Italy Les Laboratoires Servier COVERSYL 4 mg Tablets Oral use Luxembourg Servier Benelux S.A. COVERSYL 2 mg Tablets Oral use Luxembourg Servier Benelux S.A.
    [Show full text]
  • Version 10 February 2012
    Public Assessment Report Scientific discussion Decentralised Procedure Prestalia perindopril arginine/ amlodipine Applicant: Les Laboratoires Servier IT/H/0375/001-003/DC Date: 19/04/2015 TABLE OF CONTENTS Module 1: Information about the initial procedure Page 3 Module 2: Summary of Product Characteristics Page 5 Module 3: Package Leaflets Page 34 Module 4: Labelling Page 46 Module 5: Scientific discussion during the initial procedure Page 58 I Introduction Page 58 II. Scientific Overview and discussion Page 58 III. Quality aspects Page 59 III. Non-clinical aspects Page 63 III. Clinical aspects Page 63 IV. Overall conclusions and benefit-risk assessment Page 66 Viacoram IT/H/375/001-003/DC 2/66 Module 1 Information about the Initial Procedure Based on the review of the quality, safety and efficacy data, the Member States have granted a marketing authorisation for : Name of the medicinal product in the Prestalia RMS: Name of the drug substance (INN Perindopril arginine/Amlodipine name): Pharmaco-therapeutic group C09BB04 (ATC Code): Pharmaceutical form(s) and Tablet 3.5 mg /2.5 mg strength(s): Tablet 7 mg /5 mg Reference Number for the IT/H/0375/001-002/DC Decentralised Procedure: Reference Member State: IT Concerned Member States: AT, CZ, EE, EL, ES, FI, FR, HU, LV, NL, PT IT/H/0374/001-003/DC Applicant (name and address): Les Laboratoires Servier 50 Rue Carnot, 92284 Suresnes cedex France The marketing authorisation has been granted pursuant to Article 8(3) application of Directive 2001/83/EC. Viacoram IT/H/375/001-003/DC 3/66 Based
    [Show full text]