Title of Trial
Rhythm or Rate Control in Atrial Fibrillation - Pharmacologic Intervention in Atrial Fibrillation (PIAF): A Randomized Trial
Date and Citation of Primary Publication(s) or References
Hohnloser SH. Kuck KH. Lilienthal J. Rhythm or rate control in atrial fibrillation--Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet. 356(9244):1789-94, 2000 Nov 25
Purpose of the Trial
The purpose of this study was to compare a strategy of rate control versus rhythm control in patients with symptomatic persistent atrial fibrillation.
Study Category
Atrial Fibrillation. Open, randomized, multicenter trial.
Patient Population
Patients at 21 investigational sites in Germany.
Inclusion Criteria
In order to be eligible for enrollment in this study patients had be 18-75 years of age and have symptomatic & persistent atrial fibrillation for 7-360 days.
Exclusion Criteria
Patients were excluded from the trial if they met any of the following: Class IV NYHA congestive heart failure, unstable angina, acute MI within 30 days, ventricular response of less than 50bpm while in atrial fibrillation, known sick sinus syndrome, Wolff-Parkinson-White syndrome, CABG or valve surgery in the preceding 3 months, intracardiac thrombus on echocardiogram, embolic events in the preceding 3 months, amiodarone therapy in the prior 6 months, an acute thyroid disorder, an existing pacemaker, contraindications to anticoagulation, pregnancy.
Study design
Patients were randomly assigned to one of two strategies. In the rate control strategy, no attempt was made to restore sinus rhythm. Ventricular rate control was achieved first with diltiazem and, if diltiazem was not successful in achieving adequate rate control, other agents could be added at the discretion of the physician. In the rhythm control group, amiodarone was given at a daily dose of 600 mg for 3 weeks. If conversion to sinus rhythm had not occurred at the end of 3 weeks, electrical cardioversion was performed. After 3 weeks of 600 mg of amiodarone, the dose was decreased to 200 mg daily. If atrial fibrillation recurred, further action to restore sinus rhythm was left up to the treating physician. Patients were followed for 12 months with visits at 3 weeks, and 3, 6, and 12 months.
All patients in both strategies were anticoagulated to achieve an INR of 2.0-3.0.
Primary Endpoints
The primary endpoints of this study were symptoms related to atrial fibrillation, specifically, palpitations, dyspnea and dizziness as assessed by detailed interviews.
Secondary Endpoints
Secondary endpoints included a 6 minute walk test, change in mean heart rate during atrial fibrillation, number of hospital admissions and a quality of life questionnaire.
Baseline Characteristics
| | Rate Control Group
n=125 | Rhythm Control Group
n=127 |
| Male (%) | 74 | 72 |
| Mean age (years) | 61 | 60 |
| HTN (%) | 54 | 46 |
| CAD (%) | 26 | 20 |
| Prior MI (%) | 15 | 9 |
| Valve Disease (%) | 15 | 17 |
| DCM (%) | 15 | 18 |
| CHF (%) | 2.0 | 5.8 |
| No Underlying Cardiac Disease (%) | 17 | 14 |
| Persistent AF (%) | 7.8 | 6.4 |
| Mean LVEDD (mm) | 53 | 53 |
| Mean LA size (mm) | 46 | 45 |
| Mean AF duration (days) | 118 | 103 |
Time to Follow-up
In the rate control group 122 of 127 followed up at 12 months, with 2 deaths and one patient lost to follow-up. In the rhythm control group, 120 of 127 patients followed up at 12 months, with 2 deaths and 5 patients lost to follow-up.
Results
There was no difference in the primary endpoint, with similar symptomatic improvement reported in both groups. At the fourth follow up visit (12 months) there was a significant difference in the distance walked during a 6 minute walk test with the rhythm group having a longer walking distance than the rate control group (p=0.008). 56% of patients in the rhythm control group were in sinus rhythm at last follow up, compared to 10% of the rate control group (p<0.001). More patients in the rhythm control group were hospitalized at least once than the rate control group (69% vs. 24%, p=0.001). 67% of those hospitalizations in the rhythm control group were for cardioversions, and 27% were for side effects of amiodarone. More patients in the rhythm control (amiodarone) group experienced adverse medication side effects (64% vs. 47%, p=0.011). There was no difference in a quality of life questionnaire between the two groups at the end of the study.
Sponsor
Sanofil Synthelabo Research, Germany
Parke Davis Research, Germany
Trial Status: Completed
