Characteristics of the Validation Cohort
The 2580 participants had a mean age of 72 years, 38% were female, and 22% had suffered a prior stroke or TIA .
The most frequent risk factor was hypertension, which was present in 46%, and the least common was diabetes, with a 13% prevalence. Participants were followed up for a mean of 1.9 years (maximum 6.6 years). During 4887 patient-years of follow-up, there were 207 ischemic strokes, for an overall
incidence rate of 4.2 strokes per 100 patient-years during aspirin therapy. The rate among the 2014 primary prevention participants without prior cerebral ischemia was 2.5 strokes
per 100 patient-years of aspirin; for the 566 participants with a prior stroke or TIA, the rate was 10.8 per 100 patient-years of aspirin.
Stroke Rates According to Predicted Risk for Each Scheme
All schemes stratified the risk of ischemic stroke significantly better than chance (log-rank P0.001 for all schemes), but the number of AF patients categorized as at high, moderate,
and low risk varied substantially. The agreement between schemes was variable, with weighted -values ranging from a low of 0.13 (ACCP versus Framingham) to a high of 0.58 (ACCP versus AFI).
Comparison of the Classification Schemes The stroke rates (95% CI) per 100 patient-years of aspirin
rose with increasing CHADS 2 scores: 0.8 (0.4 to 1.7; n- 469) with 0 points; 2.2 (1.6 to 3.1; n- 752) with 1 point; 4.5 (3.5 to 5.9; n- 670) with 2 points; 8.6 (6.8 to 11.0; n - 428) with 3 points; 10.9 (7.8 to 15.2; n -200) with 4 points; 12.3 (6.6 to 22.9; n- 56) with 5 points; and 13.7 (2 to 97; n- 5) with 6 points. Rates (95% CI) per 100 patient-years of aspirin in other high-risk patients were lower than in the highest CHADS 2 cohorts: 6.1 (5.3 to 7.1) by AFI criterion, 6.5 (5.6 to 7.6) by SPAF, 5.1 (4.4 to 5.8) by ACCP, and 7.9 (6.5 to 9.7) for Framingham score 13. Among primary prevention participants, CHADS 2 identified participants at high risk for stroke: primary prevention participants with 3 or 4 points averaged 5.3 (95% CI 3.3 to 8.4) strokes per 100 patient-years. In contrast, patients iden tified by other schemes as high risk had rates of 3.0 to 4.2 strokes per 100 patient-years. The use of a higher Framingham threshold (15 rather than 13 points; Table 3) identified 144 participants whose stroke rate was only 3.9.
A Cox proportional hazards model quantified the ability to discriminate between low- and high-risk patients by the likelihood ratio 2 test. The 2 (SD) was 67 (16) for AFI, 73 (16) for SPAF, 44 (11) for ACCP, 98 (19) for CHADS 2 , and 89 (20) for Framingham (P 0.001 for CHADS 2 versus the other schemes). Collapsing CHADS 2 into 3 strata (0, 1 to 2, and 3 to 6) yielded a 2 value of 86, and collapsing Framingham into 3 strata (0 to 7, 8 to 13, and 13) yielded a value of 69. When only primary prevention patients were analyzed, 2 values were lower, but the pattern was similar: AFI 18, SPAF 17, ACCP 17, CHADS 2 22 (20 with 3 strata), and Framingham 16 (P 0.001 for CHADS 2 versus other schemes).
|
|
|
The c-statistics (SD) were 0.63 (0.01) for AFI, 0.64 (0.01) for SPAF, 0.58 (0.01) for ACCP, 0.70 (0.02) for CHADS 2 , and 0.69 (0.02) for Framingham (P 0.001 for CHADS 2 versus other schemes). When participants with a prior stroke or TIA were excluded, c-statistics (SD) were 0.61 (0.02) for
AFI, 0.61 (0.02) for SPAF, 0.58 (0.02) for ACCP, 0.63 (0.03) for CHADS 2 , and 0.62 (0.03) for Framingham.
Identification of Patients Whose Stroke Rate Was Low With Aspirin Therapy
ACCP criteria classified the fewest participants as low risk
(n 182). In contrast, SPAF classified 668 participants as low risk (Table 3). Primary prevention participants with a Framingham score of 4 or less (n-502) or 7 or less (n- 983) both
averaged 1.4 strokes per 100 patient-years. Primary prevention participants with 7 or fewer Framingham points who were not considered low risk by SPAF averaged 2.2 strokes per 100 patient-years; primary prevention participants with 7 or fewer Framingham points who had 1 or more CHADS 2
points averaged 1.9 strokes per 100 patient-years.
Discussion
This study of 2580 participants to whom aspirin had been prescribed confirms that AF populations with high and low stroke risks can be identified prospectively. Patients with a prior stroke or TIA averaged 10.8 strokes per 100 patientyears despite aspirin therapy. For these patients, it is clear that
the benefits of anticoagulant therapy outweigh the risks. Primary prevention patients whose stroke risk exceeds 4 per100 patient-years of aspirin also benefit from warfarin therapy. These patients were reliably identified by a CHADS 2 score 3. Such patients averaged 5.3 strokes per 100 patient-years of aspirin. The number needed to treat with warfarin instead of aspirin for 1 year to prevent 1 stroke would be 30 for
|
|
|
these patients.
High-risk primary prevention patients identified by the other schemes had stroke rates of only 3.0 to 4.2. In contrast, all schemes successfully identified low-risk patients whose stroke rate was 1.4 or lower per 100 patient-years of aspirin, but the agreement between schemes was poor. Experts
and patients typically prefer aspirin to warfarin when the risk is less than 2 strokes per 100 patient-years of aspirin. 9–11 For these AF patients, the number needed to treat with warfarin for
1 year to prevent 1 stroke exceeds 100. The ability to characterize low-risk AF patients with confidence allows clinicians to identify patients who can safely be treated with aspirin, sparing
them the risk of bleeding, cost, and inconvenience from anticoagulant therapy. 39,40 Although the Framingham scheme identified the largest fraction of low-risk patients (almost half of the
primary prevention cohort had a Framingham score of 7 or less), the additional low-risk patients identified had 2 strokes per 100 patient-years, a rate substantially greater than other low-risk
cohorts.
For patients whose stroke risk is 2 to 4 per 100 patient-years of aspirin therapy, many experts offer warfarin, 41,42 whereas others offer aspirin, depending on risk of hemorrhage and patient preferences. In clinical trials, warfarin increased the risk of major hemorrhage 1.7-fold compared with aspirin. Outside of trials, the risk of hemorrhage was greater, depending on how warfarin was monitored 47 and risk factors for hemorrhage. How patients trade off the risk of stroke, risk of hemorrhage, and
the aggravation of taking and monitoring anticoagulant therapy depends on individual preferences.
The use of data from clinical trial cohorts confers both strengths and limitations to the present study. One strength is that similar sets of comorbid conditions were collected at baseline across different trials. A second strength is that ischemic strokes were identified prospectively by clinical examination and con-
|
|
|
firmed by computerized tomography. A third is that all patients received aspirin, which allowed us to quantify the stroke rate with this ubiquitous, inexpensive therapy. A fourth strength is
that none of the patients included in these analyses were included as part of the derivation cohorts for any of the schemes.
This work was supported by an award from the American Heart Association (AHA). The data used for this study were funded by a variety of sources. The National Institutes of Health (R01 NS 24224) funded the SPAF III studies (principal investigator: Dr Hart). The Danish Heart Foundation funded the Atrial Fibrillation, Aspirin, Anticoagulation I and II trials (principal investigators: Dr Petersen). The Zorg Onderzoek Nederland Prevention fund (grant 002817010) funded the Primary Prevention of Arterial Thromboembolism in patients with nonrheumatic Atrial Fibrillation (principal investigator: Dr Boode). The Netherlands Heart Foundation, Bayer Germany, the UK Stroke Association, University Hospital Utrecht, and University Hospital Rotterdam funded the European Atrial Fibrillation Trial (principal investigator: Dr Koudstaal). We thank Dr Andreas Laupacis for his leadership in combining the patient-level data from these trials. We thank Dr Gregory Albers for his comments on an earlier draft of this manuscript and Dr Elena Deych for performing the bootstrapping statistical analysis. The writing com-
mittee for this article consisted of the first 4 authors (Dr Gage, Dr van Walraven, L. Pearce, and Dr Hart); all authors provided critical review of the manuscript. We are grateful for the assistance of Dr
Annette Lemche.
Several of the authors were involved in the development of the risk stratification schemes tested in these analyses: AFI (Drs Hart and Petersen), SPAF (Drs Hart and L. Pearce), and CHADS 2 (Dr Gage).
Дата добавления: 2018-11-24; просмотров: 158; Мы поможем в написании вашей работы! |
Мы поможем в написании ваших работ!