Efficacy of Perindopril to Prevent Recurrence of Atrial Fibrillation in Patients With Essential Hypertension (CTAF-2)

University of Montreal

Status and phase

Completed

Phase 3

Conditions

Atrial Fibrillation

Essential Hypertension

Treatments

Drug: Perindopril

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00461903

IC4-9490-123-CAN

Details and patient eligibility

About

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.

Full 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.

Enrollment

316 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.