Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2015

Open Access 01-12-2015 | Study protocol

Upstream therapeutic strategies of Valsartan and Fluvastatin on Hypertensive patients with non-permanent Atrial Fibrillation (VF-HT-AF): study protocol for a randomized controlled trial

Authors: Wen-Wei Qi, Tong Liu, Gang Xu, Li-Feng Li, Ying-Zi Liang, Lan Ye, Guang-Ping Li

Published in: Trials | Issue 1/2015

Login to get access

Abstract

Background

Previous studies regarding rhythm control in patients with atrial fibrillation (AF) could not sufficiently demonstrate the efficacy of available anti-arrhythmic drugs. ‘Upstream therapy’ has emerged as a potential strategy for the prevention and treatment of AF. The use of angiotensin II receptor blockers and statins has been suggested to decrease new-onset AF, but which remains inadequately explored. This study was designed to examine whether valsartan or fluvastatin can reduce the risk of non-permanent AF in patients with hypertension.

Methods/design

The VF-HT-AF study is a multicenter, randomized, open-label, four-arm parallel group study with comparative evaluation of valsartan and fluvastatin as upstream therapies for the treatment of non-permanent AF complicated by hypertension. The primary outcome measure is change in the development of paroxysmal AF into persistent or permanent AF, the development of persistent AF to permanent AF, and change in incidence of overall and persistent AF recurrence, as evaluated by 7-days ambulatory electrocardiograph monitoring (Holter) and patients’ diaries during 2 years’ follow-up. Secondary outcome measures of this study include the occurrence of: (1) fatal and nonfatal myocardial infarction; (2) heart failure (New York Heart Association stage III or IV); (3) cardiogenic shock; (4) serious bleeding necessitating hospitalization; (5) malignant ventricular arrhythmia; (6) revascularization therapy; (7) radiofrequency catheter ablation of AF; (8) changes of left atrial dimension, as measured by ultrasound echocardiography; (9) stroke; (10) cardiovascular mortality; and (11) all-cause mortality. A total of 1879 patients will be investigated from 15 medical centers throughout China to obtain the relevant information.

Discussion

This is the first study in hypertensive patients complicated non-permanent AF in the Chinese population. Results of this study will inform the use of upstream therapies of AF.

Trial registration

chictr.org, ChiCTR-TRC-12002642
Appendix
Available only for authorised users
Literature
1.
Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011;123:269–367.CrossRef
2.
Benjamin EJ, Chen PS, Bild DE, Mascette AM, Albert CM, Alonso A, et al. Prevention of atrial fibrillation: report from a national heart, lung, and blood institute workshop. Circulation. 2009;119:606–18.CrossRefPubMedPubMedCentral
3.
Schmieder RE, Kjeldsen SE, Julius S, McInnes GT, Zanchetti A, Hua TA. Reduced incidence of new-onset atrial fibrillation with angiotensin II receptor blockade: the VALUE trial. J Hypertens. 2008;26:403–11.CrossRefPubMed
4.
Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347:1825–33.CrossRefPubMed
5.
Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002;347:1834–40.CrossRefPubMed
6.
Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation – Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet. 2000;356:1789–94.CrossRefPubMed
7.
Carlsson J, Miketic S, Windeler J, Cuneo A, Haun S, Micus S, et al. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. J Am Coll Cardiol. 2003;41:1690–6.CrossRefPubMed
8.
Lafuente-Lafuente C, Mouly S, Longas-Tejero MA, Mahe I, Bergmann JF. Antiarrhythmic drugs for maintaining sinus rhythm after cardioversion of atrial fibrillation: a systematic review of randomized controlled trials. Arch Intern Med. 2006;166:719–78.CrossRefPubMed
9.
Savelieva I, Kakouros N, Kourliouros A, Camm AJ. Upstream therapies for management of atrial fibrillation: review of clinical evidence and implications for European Society of Cardiology guidelines. Part I: primary prevention. Europace. 2011;13:308–28.CrossRefPubMed
10.
Goette A, Schon N, Kirchhof P, Breithardt G, Fetsch T, Hausler KG, et al. Angiotensin II-antagonist in paroxysmal atrial fibrillation (ANTIPAF) trial. Circ Arrhythm Electrophysiol. 2012;5(1):43–51.CrossRefPubMed
11.
Yamashita T, Inoue H, Okumura K, Kodama I, Aizawa Y, Atarashi H, et al. Randomized trial of angiotensin II-receptor blocker vs. dihydropiridine calcium channel blocker in the treatment of paroxysmal atrial fibrillation with hypertension (J-RHYTHM II study). Europace. 2011;13:473–9.CrossRefPubMed
12.
Liu T, Li L, Korantzopoulos P, Liu E, Li G. Statin use and development of atrial fibrillation: a systematic review and meta-analysis of randomized clinical trials and observational studies. Int J Cardiol. 2008;126:160–70.CrossRefPubMed
13.
Winchester DE, Wen X, Xie L, Bavry AA. Evidence of pre-procedural statin therapy a meta-analysis of randomized trials. J Am Coll Cardiol. 2010;56:1099–109.CrossRefPubMed
14.
Rahimi K, Emberson J, McGale P, Majoni W, Merhi A, Asselbergs FW. Effect of statins on atrial fibrillation: collaborative meta-analysis of published and unpublished evidence from randomised controlled trials. BMJ. 2011;342:1250.CrossRef
15.
Liu T, Korantzopoulos P, Li L, Li G. Preventive effects of rosuvastatin on atrial fibrillation: a meta-analysis of randomized controlled trials. Int J Cardiol. 2013;167:3058–60.CrossRefPubMed
16.
Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Heart Rhythm. 2012;9:632–96.CrossRefPubMed
17.
Kato T, Yamashita T, Sagara K, Iinuma H, Fu LT. Progressive nature of paroxysmal atrial fibrillation: observations from a 14-year follow-up study. Circ J. 2004;68:568–72.CrossRefPubMed
18.
Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL, et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation. 2004;109:1509–13.CrossRefPubMed
19.
Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation: a study in awake chronically instrumented goats. Circulation. 1995;92:1954–68.CrossRefPubMed
20.
Fang WT, Li HJ, Zhang H, Jiang S. The role of statin therapy in the prevention of atrial fibrillation: a meta-analysis of randomized controlled trials. Br J Clin Pharmacol. 2012;74:744–56.CrossRefPubMedPubMedCentral
21.
Fauchier L, Pierre B, de Labriolle A, Grimard C, Zannad N, Babuty D. Antiarrhythmic effect of statin therapy and atrial fibrillation a meta-analysis of randomized controlled trials. J Am Coll Cardiol. 2008;51:828–35.CrossRefPubMed
22.
Fauchier L, Clementy N, Babuty D. Statin therapy and atrial fibrillation: systematic review and updated meta-analysis of published randomized controlled trials. Curr Opin Cardiol. 2013;28:7–18.CrossRefPubMed
23.
Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof EL, Fleischmann KE, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery. J Am Coll Cardiol. 2007;50:1707–32.CrossRefPubMed
24.
Liu T, Li G, Li L, Korantzopoulos P. Association between C-reactive protein and recurrence of atrial fibrillation after successful electrical cardioversion: a meta-analysis. J Am Coll Cardiol. 2007;49:1642–8.CrossRefPubMed
25.
Bellosta S, Ferri N, Bernini F, Paoletti R, Corsini A. Non-lipid-related effects of statins. Ann Med. 2000;32:164–76.CrossRefPubMed
26.
Dernellis J, Panaretou M. Effect of C-reactive protein reduction on paroxysmal atrial fibrillation. Am Heart J. 2005;150:1064.CrossRefPubMed
27.
Negi S, Shukrullah I, Veledar E, Bloom HL, Jones DP, Dudley SC. Statin therapy for the prevention of atrial fibrillation trial (SToP AF trial). J Cardiovasc Electrophysiol. 2011;22:414–9.CrossRefPubMed
28.
Liu T, Korantzopoulos P, Li G. Antioxidant therapies for the management of atrial fibrillation. Cardiovasc Diagn Ther. 2012;2:298–307.PubMedPubMedCentral
29.
Watanabe T, Yasunari K, Nakamura M. Antioxidative actions of statins: potential mechanisms for antiathersclerotic effects. Mini Rev Med Chem. 2006;6:505–8.CrossRefPubMed
30.
Marin F, Pascual DA, Roldan V, Arribas JM, Ahumada M, Tornel PL, et al. Statins and postoperative risk of atrial fibrillation following coronary artery bypass grafting. Am J Cardiol. 2006;97:55–60.CrossRefPubMed
31.
Okazaki S, Yokoyama T, Miyauchi K, Shimada K, Kurata T, Sato H, et al. Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study. Circulation. 2004;110:1061–8.CrossRefPubMed
32.
Vlachopoulos C, Aznaouridis K, Dagre A, Vasiliadou C, Masoura C, Stefanadi E, et al. Protective effect of atorvastatin on acute systemic inflammation-induced endothelial dysfunction in hypercholesterolaemic subjects. Eur Heart J. 2007;28:2102–9.CrossRefPubMed
33.
Kostapanos MS, Liberopoulos EN, Goudevenos JA, Mikhailidis DP, Elisaf MS. Do statins have an antiarrhythmic activity? Cardiovasc Res. 2007;75:10–20.CrossRefPubMed
34.
Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31:2369–429.CrossRefPubMed
35.
Lee YL, Blaha MJ, Jones SR. Statin therapy in the prevention and treatment of atrial fibrillation. J Clin Lipidol. 2011;5:18–29.CrossRefPubMed
36.
Hirayama Y, Atarashi H, Kobayashi Y, Iwasaki Y, Miyauchi Y, Ohara T, et al. Long-term effects of upstream therapy on paroxysmal atrial fibrillation in patients without overt heart diseases. Int Heart J. 2009;50:141–51.CrossRefPubMed
37.
Ehrlich JR, Hohnloser SH, Nattel S. Role of angiotensin system and effects of its inhibition in atrial fibrillation: clinical and experimental evidence. Eur Heart J. 2006;27:512–8.CrossRefPubMed
38.
Boos CJ, Anderson RA, Lip GY. Is atrial fibrillation an inflammatory disorder? Eur Heart J. 2006;27:136–49.CrossRefPubMed
39.
Engelmann MD, Svendsen JH. Inflammation in the genesis and perpetuation of atrial fibrillation. Eur Heart J. 2005;26:2083–92.CrossRefPubMed
40.
Dernellis J, Panaretou M. Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation. Eur Heart J. 2004;25:1100–7.CrossRefPubMed
Metadata
Title
Upstream therapeutic strategies of Valsartan and Fluvastatin on Hypertensive patients with non-permanent Atrial Fibrillation (VF-HT-AF): study protocol for a randomized controlled trial
Authors
Wen-Wei Qi
Tong Liu
Gang Xu
Li-Feng Li
Ying-Zi Liang
Lan Ye
Guang-Ping Li
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Trials / Issue 1/2015
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-015-0836-5

Other articles of this Issue 1/2015

Trials 1/2015 Go to the issue

Study protocol

Cognitive Rehabilitation for Attention and Memory in people with Multiple Sclerosis: study protocol for a randomised controlled trial (CRAMMS)

Research

Exploring the role and function of trial steering committees: results of an expert panel meeting

Study protocol

Head Position in Stroke Trial (HeadPoST) – sitting-up vs lying-flat positioning of patients with acute stroke: study protocol for a cluster randomised controlled trial

Study protocol

Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase iii trial of treatment effectiveness (PROMOTE): study protocol for a randomized controlled trial

Study protocol

Core outcome sets for use in effectiveness trials involving people with bipolar and schizophrenia in a community-based setting (PARTNERS2): study protocol for the development of two core outcome sets

Study protocol

Comparing three forms of early intervention for youth with borderline personality disorder (the MOBY study): study protocol for a randomised controlled trial