Study to Determine the Efficacy of Perindopril to Prevent the Recurrence of Atrial Fibrillation in Patients With Essential Hypertension

Condition(s) targeted: Essential Hypertension; Atrial Fibrillation

Intervention: Coversyl (perindopril) (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: Montreal Heart Institute

Official(s) and/or principal investigator(s):
Mario Talajic, MD, Principal Investigator, Affiliation: Montreal Heart Institute

Overall contact:
Sonia Gagnon, BSc, Phone: 514-461-1300, Ext: 2038, Email: sonia.gagnon@mhicc.org

The purpose of this 7- to 13-month study is to determine the efficacy of 8 mg/day oral perindopril to prevent the recurrence of atrial fibrillation (AF) in patients with essential hypertension.

Official title: A Prospective, Randomized, Double-Blind Placebo-Controlled Study to Determine the Efficacy of 8 mg/Day Oral Perindopril to Prevent the Recurrence of Atrial Fibrillation in Patients With Essential Hypertension

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Primary outcome: The primary efficacy endpoint will be time to first sustained recurrence of AF.

Secondary outcome: Secondary efficacy endpoints will be the proportion of patients without AF throughout the 6 months of follow-up, number of documented relapses of AF, and health care resource utilization (including hospitalisations for AF and cardioversions).

Detailed description: Hypertension affects approximately 50 million individuals in the United States and approximately 1 billion individuals worldwide. As the population ages, the prevalence of hypertension is expected to increase even further unless broad and effective preventive measures are implemented. Recent data from the Framingham Heart Study suggest that individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension. The relationship between blood pressure (BP) and risk of cardiovascular disease (CVD) events is continuous, consistent, and independent of other risk factors. The higher the BP, the greater is the chance of myocardial infarction, heart failure (HF), stroke, and kidney disease.

Atrial fibrillation (AF) is also a major health problem and has been described as one of two emerging cardiovascular epidemics at the turn of the century. It is the most frequent cardiac arrhythmia, affecting 5% of individuals aged > 65 years, and it is associated with an increased risk of stroke and a doubling of all-cause mortality. The loss of effective atrial contraction may result in impaired cardiac performance, reduced exercise tolerance and congestive heart failure. In addition, patients with atrial fibrillation often have disabling palpitations.

Perindopril (Coversyl) is an angiotensin-converting enzyme (ACE) inhibitor with demonstrated efficacy in controlling hypertension. There are several lines of evidence suggesting that ACE inhibition may reduce the incidence of new-onset AF as well as AF recurrences.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients must be age 18 years or older.

- Patients may be either male or female without childbearing potential (or with

adequate contraception).

- Patients must have a current diagnosis of essential hypertension with systolic blood

pressure (SBP) ≤ 160 mmHg and diastolic blood pressure (DBP) ≤ 100 mmHg at the time of inclusion visit AND

- Patients must have had at least one episode of symptomatic paroxysmal or persistent

atrial fibrillation within the preceding six months:

- With an indication for cardioversion in the case of persistent AF

- With electrocardiogram (ECG) documentation of AF

- With duration of an AF episode of at least 10 minutes

Exclusion Criteria:

- Unlikely to co-operate in the study

- Pregnancy, breastfeeding, or possibility of becoming pregnant during the study

(patients must have adequate contraception as determined by the investigator).

- Alcoholism or drug abuse

- Participation in another study at the same time or within 30 days of randomisation.

- Left ventricular systolic dysfunction with an ejection fraction of 45% or less

- Myocardial infarction within the past month prior to the selection visit

- Cardiac or thoracic surgery within the past 3 months or likely to be performed during

the trial

- Chronic AF (continuously present for > 6 months)

- AF secondary to an acute reversible condition (e. g. post-operative atrial

fibrillation, hyperthyroidism)

- Currently requiring class I or class III anti-arrhythmic drug therapy (for atrial

fibrillation or any other arrhythmia)

- Any medical condition that makes the patient an unsuitable candidate in the

investigator’s opinion

- Any medical condition requiring ACE inhibitor or angiotensin-receptor blocker therapy

(e. g. diabetes, known proteinuria of more than 300 mg per day)

- Renal insufficiency with serum creatinine of 180 μmol/L or greater

- Known bilateral renal artery stenosis

- Serum potassium of 5. 0 mmol/L or greater on recent laboratory exam

- Positive pregnancy test (beta human chorionic gonadotropin [HCG] performed in women

of childbearing potential)

- Known intolerance to ACE inhibitor

- Impossibility to discontinue certain treatments at selection visit

- Known contraindication(s) to perindopril

- Severe known liver disease including cirrhosis, biliary obstruction or alanine

aminotransferase (ALT) or aspartate aminotransferase (AST) elevation more than 3 times the upper limit of normal

- Use of ACE inhibitor or angiotensin-receptor blocker in the 3 months before the

inclusion visit

- Severely uncontrolled hypertension with SBP > 160 mmHg or DBP > 100 mmHg at the

inclusion visit.

Sonia Gagnon, BSc, Phone: 514-461-1300, Ext: 2038, Email: sonia.gagnon@mhicc.org

Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada; Not yet recruiting
Mario Talajic, MD, Principal Investigator

Related publications:

Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002 Dec 14;360(9349):1903-13. Erratum in: Lancet. 2003 Mar 22;361(9362):1060.

Last updated: July 16, 2007