Which risk factors are more associated with ischemic stroke than intracerebral hemorrhage in patients with atrial fibrillation?

BACKGROUND AND PURPOSE: The decision to prescribe oral anticoagulant therapy in patients with atrial fibrillation is based on an assessment of the competing risks of ischemic stroke and major bleeding, of which intracerebral hemorrhage (ICH) is the most important type. We sought to determine the comparative importance of risk factors for ischemic stroke and ICH in patients with acute stroke and atrial fibrillation with particular emphasis on risk factors common to both stroke types. METHODS: Consecutive patients with acute ischemic stroke or ICH and atrial fibrillation included in the Registry of the Canadian Stroke Network constituted the cohort. Multivariable logistic regression analysis was used to determine the association between baseline risk factors and presentation with ICH versus ischemic stroke. Risk factors included: (1) those previously reported to be risk factors for both ischemic stroke and major bleeding (particularly ICH) ("shared" risk factors, including age, alcohol, hypertension, diabetes mellitus, renal impairment, prior stroke/transient ischemic attack and preadmission dementia); and (2) other risk factors associated with either stroke subtype alone. RESULTS: A total of 3197 patients presented with atrial fibrillation and acute stroke, of which 12.2% presented with ICH. Of the "shared" risk factors, age (OR, 1.19; 95% CI, 1.06-1.34 per decade) and prior stroke/transient ischemic attack (OR, 1.45; 95% CI, 1.12-1.87) were more associated with ischemic stroke than ICH, whereas a history of hypertension (OR, 0.89; 95% CI, 0.68-1.17), diabetes mellitus (OR 1.23; 95% CI, 0.92-1.64), renal impairment (OR, 1.28; 95% CI, 0.95-1.71), and alcohol intake were not more strongly associated with either stroke subtype. CONCLUSION: Of the risk factors known to be associated with both ischemic stroke and ICH in patients with atrial fibrillation, we found that none had a stronger association with ICH. Older age was more strongly associated with ischemic stroke than ICH.

Preventing cardiovascular disease in primary care: role of a national risk factor management program.

BACKGROUND: Heartwatch, a structured risk factor modification program for secondary prevention of cardiovascular (CV) disease (CVD) in primary care, is associated with improvements in CV risk factors in participating patients. However, it is not known whether Heartwatch translates into reductions in clinically important CV events. OBJECTIVE: The aim of the study was to determine the association between participation in Heartwatch and future risk of CV events in patients with CVD. METHODS: The study consisted of a prospective cohort of 1,609 patients with CVD in primary care practices. Of these, 97.5% had data available on Heartwatch participation status, of whom 15.2% were Heartwatch participants. Cox proportional hazards models were used to determine the association between Heartwatch participation and risk of the CV composite (CV death, nonfatal myocardial infarction, heart failure, and nonfatal stroke). All-cause mortality and CV mortality were secondary outcome measures. RESULTS: During follow-up, the CV composite occurred in 208 patients (13.6%). Of Heartwatch participants, 8.4% experienced the CV composite compared with 14.5% of nonparticipants (P = .003). Participation in Heartwatch was associated with a significantly reduced risk of the CV composite (hazard ratio [HR] 0.52, 95% CI, 0.31-0.87), CV mortality (HR 0.31, 95% CI, 0.11-0.89), and all-cause mortality (HR 0.32, 95% CI, 0.15-0.68). Heartwatch participation was also associated with greater reductions in mean systolic blood pressure (P = .047), mean diastolic blood pressure (P < .001), and greater use of secondary preventative therapies for CVD, such as lipid-lowering agents (P < .001), ß-blockers (P < .001), and angiotensin-converting enzyme inhibitors (P < .001). CONCLUSION: Heartwatch is associated with a reduced risk of major vascular events and improved risk factor modification, supporting its potential as a nationwide program for secondary prevention of CVD.

Effect of a Run-In Period on Estimated Treatment Effects in Cardiovascular Randomized Clinical Trials: A Meta-Analytic Review.

Background A run-in period may increase adherence to intervention and reduce loss to follow-up. Whether use of a run-in period affects the magnitude of treatment effects is unknown. Methods and Results We conducted a meta-analysis comparing treatment effects from 11 systematic reviews of cardiovascular prevention trials using a run-in period with matched trials not using a run-in period. We matched run-in with non-run-in trials by population, intervention, control, and outcome. We calculated a ratio of relative risks (RRRs) using a random-effects meta-analysis. Our primary outcome was a composite of cardiovascular events, and the primary analysis was a matched comparison of clinical trials using a run-in period versus without a run-in period. We identified 66 run-in trials and 111 non-run-in trials (n=668 901). On meta-analysis there was no statistically significant difference in the magnitude of treatment effect between run-in trials (relative risk [RR], 0.83 [95% CI, 0.80-0.87]) compared with non-run-in trials (RR, 0.88 [95% CI, 0.84-0.91]; RRR, 0.95 [95% CI, 0.90-1.01]). There was no significant difference in the RRR for secondary outcomes of all-cause mortality (RRR, 0.97 [95% CI, 0.91-1.03]) or medication discontinuation because of adverse events (RRR, 1.05 [95% CI, 0.85-1.21]). Post hoc exploratory univariate meta-regression showed that on average a run-in period is associated with a statistically significant difference in treatment effect (RRR, 0.94 [95% CI, 0.90-0.99]) for cardiovascular composite outcome, but this was not statistically significant on multivariable meta-regression analysis (RRR, 0.95 [95% CI, 0.90-1.0]). Conclusions The use of a run-in period was not associated with a difference in the magnitude of treatment effect among cardiovascular prevention trials.

Validity of composite outcomes in meta-analyses of stroke prevention trials: the case of aspirin.

BACKGROUND: Aspirin has been reported to be less effective for secondary vascular prevention in patients with ischaemic stroke, compared with other high-risk populations. This contention is largely based on results of meta-analyses that used a composite outcome of vascular death, myocardial infarction and stroke, reporting a 13% relative risk reduction. In this study, we explore whether the summary relative risk reduction for this composite outcome is representative of estimates for each of the individual components of the composite. STUDY SELECTION: All randomised controlled trials comparing aspirin with placebo/control in patients following ischaemic stroke or transient ischaemic attack, beyond the acute period (2 weeks). DATA ANALYSIS: A fixed-effects model was used and summary risk ratios were calculated for each of the outcomes: vascular mortality, recurrent non-fatal stroke, non-fatal myocardial infarction, composite of the latter three outcomes, all-cause mortality and non-vascular mortality. RESULTS: Ten trials (n = 9,168) were included. For the composite of non-fatal stroke, non-fatal myocardial infarction and vascular death, aspirin was associated with a 13% reduction in risk (risk ratio, RR: 0.87; 95% CI: 0.81-0.94). For individual components of the composite, aspirin reduced the risk of non-fatal ischaemic stroke (RR: 0.81; 95% CI: 0.72-0.90) and non-fatal myocardial infarction (RR: 0.68; 95% CI: 0.52-0.87), but not vascular death (RR: 0.97; 95% CI: 0.86-1.1). Aspirin did reduce the risk of non-vascular death (RR: 0.79; 95% CI: 0.66-0.95), though, and had a trend towards a reduced risk of all-cause mortality (RR: 0.91; 95% CI: 0.81-1.01). CONCLUSIONS: Following ischaemic stroke, aspirin does not reduce the risk of vascular death, but provides a significant reduction in non-fatal stroke, myocardial infarction and non-vascular death. Our findings would support presenting the effect of aspirin therapy on individual outcomes rather than a composite including vascular death.

Association of atrial fibrillation with mortality and disability after ischemic stroke.

OBJECTIVE: We determined whether patient characteristics (age, sex, comorbidities), stroke severity, and quality of care explained a proportion of the association between atrial fibrillation (AF) and increased disability and mortality in patients with acute ischemic stroke. METHODS: The study included a prospective cohort of consecutive patients admitted with acute ischemic stroke included in the Registry of the Canadian Stroke Network (July 1, 2003 to March 31, 2008). Multivariable logistic regression analyses were used to determine the magnitude of association between AF and modified Rankin score 4-5 at discharge, 30-day mortality, and 1-year mortality. RESULTS: There were 10,528 patients admitted with acute ischemic stroke. AF was associated with an increased risk of severe disability and mortality, but the magnitude of association was substantially attenuated in the full multivariable models: modified Rankin score 4-5 at discharge (univariate odds ratio [OR] 1.74, 95% confidence interval [CI] 1.57-1.93; multivariable OR 1.19, 95% CI 1.03-1.36), 30-day mortality (univariate OR 2.52, 95% CI 2.25-2.84; multivariable OR 1.36, 95% CI 1.17-1.58), and 1-year mortality (univariate OR 2.41, 95% CI 2.19-2.66; multivariable OR 1.25, 95% CI 1.10-1.42). Older age and increased stroke severity explained most of the association between AF and poor stroke outcomes. We found no association between AF and poor stroke outcomes in patients receiving therapeutic preadmission oral anticoagulant therapy. CONCLUSIONS: Older age and increased stroke severity explain most of the association between AF and poorer outcomes after acute ischemic stroke. Nonuse of oral anticoagulant therapy represents the most important modifiable care gap to mitigate the association between AF and poor outcomes after ischemic stroke.