Atrial Fibrillation, Stroke
Conditions
Keywords
atrial fibrillation, stroke, TIA, trans ischemic attack, warfarin, Coumadin
Brief summary
This was a prospective, randomized, multicenter study to provide additional information on the safety and efficacy of the WATCHMAN LAA Closure Technology. The purpose of the PREVAIL study was to confirm the efficacy endpoint as demonstrated in the PROTECT AF pivotal study and to further demonstrate that the WATCHMAN LAA Closure Technology is safe and effective in subjects with non-valvular atrial fibrillation who require anticoagulation therapy for potential thrombus formation.
Interventions
DEVICEWATCHMAN Device
WATCHMAN Left Atrial Appendage Closure Technology
DRUGWarfarin
Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Paroxysmal, persistent or permanent non-valvular AF * Eligible for long-term warfarin therapy * Eligible to come off warfarin therapy * Calculated CHADS2 score of 2 or greater. Also patients with a CHADS2 score of 1 may be included if any of the following apply: * Female age 75 or older * Baseline LVEF ≥ 30 and \< 35% * Aged 65-74 and has diabetes or coronary artery disease * Aged 65 or greater and has congestive heart failure Key
Exclusion criteria
* Contraindicated/allergic to aspirin * Indicated for clopidogrel therapy or has taken clopidogrel within 7 days prior to enrollment * History of atrial septal repair or has an ASD/PFO device * Implanted mechanical valve prosthesis * NYHA Class IV CHF * Resting heart rate \> 110 bpm * Participated previously in the PROTECT AF or CAP Registry studies Key Echo
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Endpoint (Device Group Only) | 7-Day | 7-Day procedure rate of death, ischemic stroke, systemic embolism and complications requiring major cardiovascular or endovascular intervention. |
| Composite of Stroke, Systemic Embolism, and Death (Cardiovascular and Unknown) | 18 month rate | The endpoint was analyzed using a Bayesian piecewise exponential model with the historical priors based on data from the previous pivotal study PROTECT AF. This was a non-inferiority design with comparison of rate ratio of 18-month event rates of the Device and Control groups. The 18-month rate represents the probability of an event occurring within 18 months, and the 18-month rate ratio is a mean of the rate ratios. The primary endpoint was based on a calculation of the probability of events at 18 months but the statistical piecewise hazards model does not require the observation of any subjects out to 18-months. |
| Composite of Ischemic Stroke or Systemic Embolism | Day 8 to 18-months | Composite of ischemic stroke or systemic embolism excluding events that occurred in the first 7 days following randomization |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| WATCHMAN Subjects assigned to receive the WATCHMAN device.
WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology | 269 |
| Warfarin Subjects assigned to warfarin therapy.
Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0 | 138 |
| Total | 407 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Death | 37 | 25 |
| Overall Study | Implant Attempt Unsuccessful | 13 | 0 |
| Overall Study | Implant Not Attempted | 4 | 0 |
| Overall Study | Lost to Follow-up | 5 | 8 |
| Overall Study | Patient Still in Follow-up | 152 | 72 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 13 |
Baseline characteristics
| Characteristic | WATCHMAN | Warfarin | Total |
|---|---|---|---|
| Age, Continuous | 74.0 years STANDARD_DEVIATION 7.4 | 74.9 years STANDARD_DEVIATION 7.2 | 74.3 years STANDARD_DEVIATION 7.4 |
| CHADS2 Stroke Risk Score | 2.6 scores on a scale STANDARD_DEVIATION 1 | 2.6 scores on a scale STANDARD_DEVIATION 1 | 2.6 scores on a scale STANDARD_DEVIATION 1 |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black/Aftrican American | 6 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Caucasian | 253 Participants | 131 Participants | 384 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 6 Participants | 5 Participants | 11 Participants |
| Race/Ethnicity, Customized Native American Indian/Alaskan Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 269 participants | 138 participants | 407 participants |
| Sex: Female, Male Female | 87 Participants | 35 Participants | 122 Participants |
| Sex: Female, Male Male | 182 Participants | 103 Participants | 285 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 37 / 269 | 25 / 138 |
| other Total, other adverse events | 38 / 269 | 10 / 138 |
| serious Total, serious adverse events | 86 / 269 | 44 / 138 |
Outcome results
Primary
Composite of Ischemic Stroke or Systemic Embolism
Composite of ischemic stroke or systemic embolism excluding events that occurred in the first 7 days following randomization
Time frame: Day 8 to 18-months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WATCHMAN | Composite of Ischemic Stroke or Systemic Embolism | 0.0253 Probability of events within 18-months |
| Warfarin | Composite of Ischemic Stroke or Systemic Embolism | 0.0200 Probability of events within 18-months |
Comparison: A Bayesian piecewise exponential model was used to model the 18-month event rates. Historical priors for each interval were based on PROTECT AF. Hazards were modeled for 0-7 day, 7-60 day, 60-182 day, and 182+ day intervals. Event rates were estimated separately for the WATCHMAN and Warfarin groups. The posterior distribution for the 18-month event rate ratio (WATCHMAN vs. Warfarin), and the corresponding equitailed 95% credible interval, were determined via Monte Carlo simulations.95% CI: [-0.019, 0.0273]
Comparison: A Bayesian piecewise exponential model was used to model the 18-month event rates. Historical priors for each interval were based on PROTECT AF. Hazards were modeled for 0-7 day, 7-60 day, 60-182 day, and 182+ day intervals. Event rates were estimated separately for the WATCHMAN and Warfarin groups. The posterior distribution for the 18-month event rate ratio (WATCHMAN vs. Warfarin), and the corresponding equitailed 95% credible interval, were determined via Monte Carlo simulations.95% CI: [0.5, 4.2]
Primary
Composite of Stroke, Systemic Embolism, and Death (Cardiovascular and Unknown)
The endpoint was analyzed using a Bayesian piecewise exponential model with the historical priors based on data from the previous pivotal study PROTECT AF. This was a non-inferiority design with comparison of rate ratio of 18-month event rates of the Device and Control groups. The 18-month rate represents the probability of an event occurring within 18 months, and the 18-month rate ratio is a mean of the rate ratios. The primary endpoint was based on a calculation of the probability of events at 18 months but the statistical piecewise hazards model does not require the observation of any subjects out to 18-months.
Time frame: 18 month rate
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WATCHMAN | Composite of Stroke, Systemic Embolism, and Death (Cardiovascular and Unknown) | 0.064 Probability of events within 18 months |
| Warfarin | Composite of Stroke, Systemic Embolism, and Death (Cardiovascular and Unknown) | 0.063 Probability of events within 18 months |
Comparison: A Bayesian piecewise exponential model was used to model the 18-month event rates. Historical priors for each interval model were based on PROTECT AF. Hazards were modeled for 0-7 day, 7-60 day, 60-182 day, and 182+ day intervals. Event rates were estimated separately by treatment group and event type. The posterior distribution for the 18-month event rate ratio (WATCHMAN vs. Warfarin), and the corresponding equitailed 95% credible interval, were determined via Monte Carlo simulations.95% CI: [0.57, 1.89]
Primary
Primary Safety Endpoint (Device Group Only)
7-Day procedure rate of death, ischemic stroke, systemic embolism and complications requiring major cardiovascular or endovascular intervention.
Time frame: 7-Day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WATCHMAN | Primary Safety Endpoint (Device Group Only) | 6 Participants |
Comparison: Bayesian calculations were used to incorporate the data from PROTECT AF CAP Registry through a conjugate beta-binomial model. A one-sided upper 95% credible interval for the event rate was calculated based off this posterior distribution.