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Archive for February, 2012

Journal Club 29 February 2012

February 29, 2012 3 comments

Article:


Development and validation of a risk score to predict early mortality in recipients of implantable cardioverter-defibrillators

Presenter

KC

PICO

An observational study in recipients of implantable cardioverter defibrillators to determine correlates of one-year mortality using stepwise logistic

regression. A derivation set was chosen and then a validation set used to assess the goodness of fit of the model.

Population:

Patients receiving implantable cardioverter defibrilllators (new implants)

Intervention

Not applicable

Comparator

Not applicable

Outcome

One-year mortality

Findings
The total cohort included 2717 ICD patients (mean age = 64.6 ± 14.5, male = 77.2%, primary prevention = 74.7%). A simple risk score incorporating peripheral

arterial disease, age ≥ 70 years, creatinine ≥ 2.0 mg/dL, and ejection fraction ≤20% (PACE) accurately predicted 1-year mortality in the VG. Patients with a

risk score of ≥3 had a >4-fold excess 1-year mortality compared with patients with a risk score of ❤ (16.5% vs 3.5%; P <.0001).

Discussion Summary 

  • The paper is hypothesis generating. The issue of trying to develop criteria for futility are laudable from a patient interest and resourcing.
  • The limitations of risk scores were discussed in general, and consistent with other risk scores there was a poor positive predictive value.
  • The selection bias of cardiologists chosing patients who they perceived had reasonable survival had impacts such as narrowing the age range in the patient group. Age appears to have been a forced variable in the stepwise regression model. It was somewhat reassuring that even in the highest risk (from this model) 80% of patients survived one year.
  • Information regarding the appropriate discharge rate would have provided insight into the benefit in the high risk group. A control group without device with same risk score would have also provided insight. Dr. Atherton observed that patients with similar characteristics in the heart failure with LV systolic dysfunction had a 7% annual mortality.

Background Materials

Dr. Karin Chia kindly provided background material for this paper.

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Journal Club 22 February 2012

Article:


Subclinical Atrial Fibrillation and the Risk of Stroke

Presenter

KF

PICO

An observational study of patients with recent pacemaker of defibrillator implantation

Population:

65 years of age or older, with hypertension and no history
of atrial fibrillation, in whom a pacemaker or defibrillator had recently been implanted

Intervention

Longitudinal observation of sublcinical atrial arrhtyhmias and risk of stroke or systemic embolism.
Subclinical atrial arrhythmia was defined as atrial arrhythmia with rate greater than 190 beats per minute for greater than 6 minutes at 3 month device assessment. Mean follow was for 2.5 years.

Comparator

An observational studies. The outcomes of patients with and without subclinical atrial arrhythmias was assessed.
Patients with pacemakers were randomly assigned to receive or not
to receive continuous atrial overdrive pacing

Outcome

Risk of ischemic stroke or systemic embolism.

Findings

Results

By 3 months, subclinical atrial tachyarrhythmias detected by implanted devices had
occurred in 261 patients (10.1%). Subclinical atrial tachyarrhythmias were associated
with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence
interval [CI], 3.78 to 8.17; P (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P = 0.007).

Of 51 patients who had a primary outcome event, 11 had had subclinical atrial tachyarrhythmias detected by 3 months,
and none had had clinical atrial fibrillation by 3 months. The population attributable
risk of stroke or systemic embolism associated with subclinical atrial tachyarrhythmias
was 13%. Subclinical atrial tachyarrhythmias remained predictive of the primary
outcome after adjustment for predictors of stroke (hazard ratio, 2.50; 95% CI, 1.28 to
4.89; P = 0.008).

Continuous atrial overdrive pacing did not prevent atrial fibrillation.

Conclusions

Subclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred frequently
in patients with pacemakers and were associated with a significantly increased
risk of ischemic stroke or systemic embolism.

Discussion Summary 

  • Although the risk of ischemic stroke and systemic embolism was higher in patients with subclinical atrial arrhtyhmias this is based on 11 patients. The majority of events occurred in patients without subclinical atrial arrhythmias
  • CHADS2 point estimates of risk were consistent with gradient of risk. However, small event numbers limit conclusions
  • There was greater prevalence of anticoagulant use in follow up in the subclinical atrial arrhythmia group. This, therefore, may lead to underestimation of the risk,
  • There is limited information regarding the burden of arrhythmia and risk. The highest quartile of duration of arrhythmia (hours) had approximately four fold increase in event rate compared with the lowest quartile. Again this is based on 11 patients.
  • Continuous atrial overdrive pacing did not reduce frequency of follow up atrial fibrillation. This was low frequency event.

Journal Club 15 February 2012

Article:

Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial

Presenter

DBC

PICO

Population:

Patients with atrial fibrillation at increased of stroke unsuitable for vitamin K antagonists

Intervention

Apixaban 5 mg bd oral (2.5 mg bd for age >80 years, body mass < 60 kg,  creatinine >1.g mg/dL)

Comparator

Aspirin 81 to 324 mg per day oral

Outcome

Primary efficacy end-point: stroke or systemic embolism (1 year)

Primary safety end-point: major bleeding (decrease in HB >2g/dL over 24 hours; transfusion of 2 units or more; bleeding that occurs in critical sites [intracranial, intraspinal, intraocular, pericardial, intra-articular,intra-muscular with compartment syndrome, or retroperitoneal]

Study examines effect of prior TIA/stroke status.

Findings

In patients with previous stroke or TIA, ten events of stroke or systemic embolism occurred in the apixaban group (n=390, cumulative hazard 2·39% per year) compared with 33 in the aspirin group (n=374, 9·16% per year; hazard ratio [HR] 0·29, 95% CI 0·15—0·60). In those without previous stroke or TIA, 41 events occurred in the apixaban group (n=2417, 1·68% per year) compared with 80 in the aspirin group (n=2415, 3·06% per year; HR 0·51, 95% CI 0·35—0·74). The p value for interaction of the effects of aspirin and apixaban with previous cerebrovascular events was 0·17. Major bleeding was more frequent in patients with history of stroke or TIA than in patients without (HR 2·88, 95% CI 1·77—4·55) but risk of this event did not differ between treatment groups.

Discussion Summary 

  • Apixaban (similar to dabigatran and rivoraxaban) has been demonstrated to have efficacy in reduction of stroke and system embolism  compared with warfarin. The newer agents appear to have consistently lower rates of intracranial hemorrhage compared to warfarin (not covered in the presented paper: background information).
  • AVERROES provided insights into the risks of aspirin (under-appreciated). The evidence fro efficacy in this context of atrial fibrillation is limited and the magnitude of benefit modest: 20% relative risk reduction
  • Patients with prior TIA or stroke are at higher risk of recurrent stroke or systemic embolism as well as bleeding complications.
  • Although there was insufficient grounds to reject the hypothesis of homogeneity of effect for those with and without prior stroke, the relatively small number of events in the subgroups limit the power to detect differential responses.