Renal Dysfunction as a Predictor of Stroke and Systemic Embolism in Patients wit

Renal Dysfunction as a Predictor of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation: Validation of the R2CHADS2 Index in the ROCKET AF and ATRIA Study Cohorts; Piccini JP, Stevens SR, Chang Y, Singer DE, Lokhnygina Y, Go AS, Patel MR, Mahaffey KW, Halperin JL, Breithardt G, Hankey GJ, Hacke W, Becker RC, Nessel CC, Fox KA, Califf RM; Circulation (Dec 2012)BACKGROUND: We sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial. METHODS AND RESULTS: In ROCKET AF, 14,264 patients with nonvalvular AF and creatinine clearance (CrCl) ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non-central nervous system (CNS) embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA, an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 (4.0%) patients experienced primary endpoint events. Reduced CrCl was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack (TIA). Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, and vascular disease of the heart and limbs (C-index 0.635). A model including CrCl (R(2)CHADS(2)) improved net reclassification index (NRI) by 6.2% when compared with CHA(2)DS(2)VASc (C-statistic=0.578) and 8.2% when compared with CHADS(2) (C-statistic=0.575). The inclusion of estimated glomerular filtration rate<60 and prior stroke or TIA in a model with no other covariates led to a C-statistic of 0.590. Validation of R(2)CHADS(2) in an external, separate population improved NRI by 17.4% (95% CI 12.1-22.5%) relative to CHADS(2). CONCLUSIONS: In patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients with AF should include renal function. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; Unique identifier: NCT00403767.

8

FDA: Don't use dabigatran with mechanical valves

ROCKVILLE, Md -- December 20, 2012 -- The US Food and Drug Administration (FDA) is informing healthcare professionals and the public that the anticoagulant dabigatran etexilate mesylate (Pradaxa) should not be used to prevent stroke or blood clots in patients with mechanical prosthetic heart valves.

A clinical trial in Europe (RE-ALIGN) was recently stopped because dabigatran users were more likely to experience strokes, heart attacks, and blood clots forming on the mechanical heart valves than were warfarin users. There was also more bleeding after valve surgery in the dabigatran group versus the warfarin group.

Dabigatran is not approved for patients with atrial fibrillation caused by heart valve problems.

The FDA is requiring a contraindication of dabigatran in patients with mechanical heart valves. Health care professionals should promptly transition any patient with a mechanical heart valve who is taking dabigatran to another medication.

The use of dabigatran in patients with bioprosthetic valves has not been evaluated and cannot be recommended.

Patients with all types of prosthetic heart valve replacements taking dabigatran should talk to their health care professional as soon as possible to determine the most appropriate anticoagulation treatment.

Data Summary
In the RE-ALIGN trial, patients with bileaflet mechanical prosthetic heart valves (recently implanted or implanted more than 3 months prior to enrolment) were randomised to receive warfarin or dabigatran (150, 220, or 300 mg twice-daily). Initial dosing of dabigatran was determined by renal function. In the warfarin group, the target international normalized ratio (INR) was 2 to 3 or 2.5 to 3.5, depending on the presence of risk factors and the position of the mechanical prosthetic heart valve.

The study was terminated early because the dabigatran arm had significantly more thromboembolic events (valve thrombosis, stroke, and myocardial infarction) and major bleeding (predominantly postoperative pericardial effusions requiring intervention for hemodynamic compromise) than did the warfarin arm. These bleeding and thromboembolic events were reported in patients who were initiated on dabigatran postoperatively within 3 days after mechanical bileaflet valve implantation and in patients whose valves had been implanted more than 3 months previously.

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Atenolol improves outcome in ICH

Is beta-blocker (atenolol) a preferred antihypertensive in acute intracerebral hemorrhage?; Kalita J, Misra UK, Kumar B; Neurological Sciences (Oct 2012)

 

The mortality in intracerebral hemorrhage (ICH) is mainly due to raised intracranial pressure, and its complications mediated by sympathetic overactivity. There is paucity of studies evaluating the role of beta-blockers in the outcome of ICH. This study reports the role of atenolol in reducing mortality, pneumonia, systemic inflammatory response syndrome (SIRS), and 3 months outcome in the patients with hypertensive ICH. 138 consecutive patients with hypertensive ICH were included and their stroke risk factors and clinical details were recorded. Consciousness was assessed by Glasgow Coma Scale and severity of stroke by Canadian Neurological Scale. Volume of hematoma was measures on CT scan and occurrence of SIRS and pneumonia were noted. 3 months outcome was categorized into good (Barthel index>12) and poor (BI < 12). The patients were categorized into those receiving atenolol and nonatenolol. The effects of atenolol on stroke outcome parameters were evaluated. Seventy-nine patients received atenolol and 59 did not and they mainly received amlodipine. There was no difference in the base line clinical characteristics between the two groups except smoking (P = 0.01) and baseline blood pressure (P = 0.007). Atenolol significantly reduced the mortality (11.4 vs 37.3 %, P < 0.0001), SIRS (16.4 vs 40.9 %, P = 0.007), and pneumonia (8.9 vs 30.5 %, P = 0.002) compared to those not receiving atenolol. At 3 months, patients with atenolol had insignificantly better outcome compared to nonatenolol group (49.1 vs 31.9 %, P = 0.11). Use of atenolol in hypertensive ICH results in reduction in mortality, SIRS, and pneumonia which may be due to its β-adrenergic blocking effect.

warfarin v. dabigatran RE-LY trial

Intracranial Hemorrhage in Atrial Fibrillation Patients During Anticoagulation With Warfarin or Dabigatran: The RE-LY Trial; Hart RG, Diener HC, Yang S, Connolly SJ, Wallentin L, Reilly PA, Ezekowitz MD, Yusuf S; Stroke (Apr 2012)

BACKGROUND AND PURPOSE: Intracranial hemorrhage is the most devastating complication of anticoagulation. Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined. METHODS: Analysis of 18 113 participants with atrial fibrillation in the Randomized Evaluation of Long-term anticoagulant therapY (RE-LY) trial assigned to adjusted-dose warfarin (target international normalized ratio, 2-3) or dabigatran (150 mg or 110 mg, both twice daily). RESULTS: During a mean of 2.0 years of follow-up, 154 intracranial hemorrhages occurred in 153 participants: 46% intracerebral (49% mortality), 45% subdural (24% mortality), and 8% subarachnoid (31% mortality). The rates of intracranial hemorrhage were 0.76%, 0.31%, and 0.23% per year among those assigned to warfarin, dabigatran 150 mg, and dabigatran 110 mg, respectively (P<0.001 for either dabigatran dose versus warfarin). Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg (n=13 and n=11, respectively) versus warfarin (n=32; P<0.01 for both). Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran (11 patients with each dose) compared with warfarin (24 patients; P<0.05 for both dabigatran doses versus warfarin). Independent predictors of intracranial hemorrhage were assignment to warfarin (relative risk, 2.9; P<0.001), aspirin use (relative risk, 1.6; P=0.01), age (relative risk, 1.1 per year; P<0.001), and previous stroke/transient ischemic attack (relative risk, 1.8; P=0.001). CONCLUSIONS: The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran. Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin. Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage.

212 Stars

Star

(no subject)

Dose-dependent effect of early antiplatelet therapy in acute ischaemic stroke; Meves SH, Overbeck U, Endres HG, Krogias C, Neubauer H; Thrombosis and Haemostasis 107 (1), (Dec 2011)

Antiplatelet agents are essential in treating patients with acute ischaemic stroke (AIS) to prevent recurrent ischaemic events. The aim of this study was to evaluate the effectiveness of early antiplatelet therapy with different aspirin (ASA) dosages in patients with AIS. This observational study included 454 patients with AIS in whom antiplatelet treatment was initiated. The antiplatelet effect was determined by whole blood aggregometry within 48 hours after antplatelet therapy was initiated. An impedance change exceeding 0 Ω after stimulation with arachidonic acid was defined as ASA low response (ALR) and ≥5 Ω in ADP-stimulated specimen as clopidogrel LR. Of the study group 53.5% patients were treated with 200 mg ASA orally, 27.5% with 500 mg ASA intravenously, 8.6% with 100 mg ASA orally, and 7.7% with 75 mg clopidogrel. A dose-dependent antiplatelet effect of ASA treatment was found: 18.4% of patients with 500 mg ASA intravenously were ALR, in contrast to 32.5% on 200 mg and 35.9% on 100 mg ASA orally. Clopidogrel treatment without a loading dose resulted in a high proportion of LR (45.7%). Using the propensity score method revealed a three times higher risk for ALR for patients treated with ASA 200 mg [odds ratio 2.99 (1.55-5.79)] compared to treatment with ASA 500 mg. In conclusion, initiating antiplatelet therapy in patients with AIS resulted in a dose-dependent insufficient platelet inhibitory effect. Our findings suggest using a loading dose of 500 mg ASA intravenously as this seems to be favourable when a sufficient early platelet inhibitory effect is wanted.

comment- debate over aspirin dose never ends.  However, we treat patients, not lab tests and it would be interesting to know if there were any clinical effects or side effects of high v. low dose aspirin

dual antiplatelet therapy for 7 days in intracranial occlusive disease

The effectiveness of dual antiplatelet treatment in acute ischemic stroke patients with intracranial arterial stenosis: a subgroup analysis of CLAIR study; the CLAIR Study Investigators; International Journal of Stroke (Aug 2012)

BACKGROUND: Dual antiplatelet therapy with clopidogrel and aspirin reduces the presence and number of microembolic signals in patients with large artery disease. However, whether it is effective in patients with intracranial disease alone remains uncertain. We performed a subgroup analysis of the The CLopidogrel plus Aspirin for Infarction Reduction (CLAIR in acute stroke or transient ischemic attack patients with large artery stenosis and microembolic signals) study of only patients with intracranial occlusive disease, excluding those with extra cranial disease. METHODS: CLAIR was a randomized-controlled, open-label, multicenter clinical trial with blinded outcome evaluation, which recruited patients with symptoms of ischemic stroke or transient ischemic attack within seven-days of onset, with large artery stenosis verified by transcranial Doppler and carotid ultrasound, and with microembolic signals detected by transcranial Doppler recording. All patients were randomized to receive clopidogrel plus aspirin daily for seven-days (dual treatment), or aspirin alone for seven-days (monotherapy). Repeated transcranial Doppler recordings for microembolic signals were made on day one, two, and seven. This subgroup study only analyzed the patients with purely intracranial large artery disease and excluded those with extra cranial stenosis. RESULTS: There were 70 patients recruited with purely intracranial stenosis, 34 in the dual treatment group and 36 in the monotherapy group. The proportion of the patients with positive emboli at day seven in the dual treatment group was significantly lower than that in the monotherapy group (relative risk reduction 56·5%, 95% confidence interval 2·5-80·6; P = 0·029). The number of emboli in the dual treatment group decreased significantly at day two (P = 0·043) and day seven (P = 0·018) compared with the monotherapy group. After adjustment for the number of emboli at day one, the effect of dual treatment was still significant for the reduction of presence (relative risk reduction 56·0%; 95% confidence interval 5·4-79·6; P = 0·036) and number (adjusted mean difference -0·9; 95% confidence interval -1·5 to -0·3; P = 0·004) of positive emboli at day seven. CONCLUSIONS: Dual treatment with clopidogrel and aspirin for seven-days is more effective than aspirin alone to reduce microembolic signals in patients with intracranial arterial stenosis.

Suggestion AGAINST warfarin after 3 months post maze procedure

The impact of CHADS(2) score on late stroke after the Cox maze procedure; Pet M, Robertson JO, Bailey M, Guthrie TJ, Moon MR, Lawton JS, Rinne A, Damiano RJ, Maniar HS; Journal of Thoracic and Cardiovascular Surgery (Jul 2012)

OBJECTIVE: The Heart Rhythm Society, European Heart Rhythm Association, and European Cardiac Arrhythmia Society jointly recommend indefinite warfarin anticoagulation in patients with CHADS(2) (congestive heart failure, hypertension, age, diabetes, and stroke) score of at least 2 who have undergone ablation for atrial fibrillation. This study determined the impact of CHADS(2) score on risk of late stroke or transient ischemic attack after the performance of a surgical Cox maze procedure. METHODS: A retrospective review of 433 patients who underwent a Cox maze procedure at our institution was conducted. Three months after surgery, warfarin was discontinued regardless of CHADS(2) score if the patient showed no evidence of atrial fibrillation, was off antiarrhythmic medications, and had no other indication for anticoagulation. A follow-up questionnaire was used to determine whether any neurologic event had occurred since surgery. RESULTS: Follow-up was obtained for 90% of the study group (389/433) at a mean of 6.6 ± 5.0 years. Among these patients, 32% (125/389) had a CHADS(2) score of at least 2, of whom only 40% (51/125) remained on long-term warfarin after surgery. Six patients had late neurologic events (annualized risk of 0.2%). Neither CHADS(2) score nor warfarin anticoagulation was significantly associated with the occurrence of late neurologic events. Among the individual CHADS(2) criteria, both diabetes mellitus and previous stroke or transient ischemic attack were predictive of late neurologic events. CONCLUSIONS: The risk of stroke or transient ischemic attack in patients after a surgical Cox maze procedure was low and not associated with CHADS(2) score or warfarin use. Given the known risks of warfarin, we recommend discontinuation of anticoagulation 3 months after the procedure if the patient has no evidence of atrial fibrillation, has discontinued antiarrhythmic medications, and is without any other indication for systemic anticoagulation.

19

asa + plavix decreased MI's, increases fatal hemorrhages, no effect on mortality

Effect of addition of clopidogrel to aspirin on mortality: systematic review of randomized trials; Palacio S, Hart RG, Pearce LA, Benavente OR; Stroke 43 (8), 2157-62 (Aug 2012)

 

BACKGROUND AND PURPOSE In the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, addition of clopidogrel to aspirin was associated with an unexpected increase in mortality in patients with lacunar strokes. We assessed the effect of the addition of clopidogrel to aspirin on mortality in a meta-analysis of published randomized trials. METHODSRandomized trials in which clopidogrel was added to aspirin in subjects with vascular disease or vascular risk factors were identified. Trials were restricted to those with a mean follow-up of ≥14 days in which both the combination of aspirin and clopidogrel was tested and mortality was reported. RESULTSTwelve trials included 90 934 participants (mean age, 63 years; 70% men; median follow-up, 1 year) with 6849 observed deaths. There was no significant increase in mortality with the combination therapy either in 4 short-term (14 days-3 months; OR, 0.93; 95% CI, 0.87-0.99) or in 7 long-term (>3 months; hazard ratio, 0.97; 95% CI, 0.91-1.04) trials after 1 long-term trial (the SPS3 trial) was excluded because of heterogeneity. Addition of clopidogrel was associated with an increase in fatal hemorrhage (OR, 1.35; 95% CI, 0.97-1.90) and a reduction in myocardial infarction (OR, 0.82; 95% CI, 0.74-0.91). CONCLUSIONSThe addition of clopidogrel to aspirin has no overall effect on mortality. The SPS3 trial results are outliers, possibly because of a lower prevalence of coronary artery ischemia. Addition of clopidogrel to aspirin increases fatal bleeding and reduces myocardial infarction. Clinical Trial Registration- URL: http//www.clinicaltrials.gov. Unique identifier: NCT00059306.

 

Comment -- metaanalysis improves our knowledge over SPS3 results which are outliers

Need for extended clopidogrel therapy after intracranial stenting

Incidence of cerebral ischemic events after discontinuation of clopidogrel in patients with intracranial aneurysms treated with stent-assisted techniques; Rossen JD, Chalouhi N, Wassef SN, Thomas J, Abel TJ, Jabbour PM, Kung DK, Hasan DM; Journal of Neurosurgery (Sep 2012)

Object: The optimal antiplatelet medication protocol for prevention of thrombotic complications after stent-assisted coil embolization of cerebral aneurysms is unclear. Early cessation of antiplatelet agents may be associated with an increased risk of cerebral ischemic events. In this study, the authors assess the incidence of stroke or transient ischemic attack (TIA) following discontinuation of a 6-week course of clopidogrel in patients with cerebral aneurysms treated with stent-assisted techniques. Methods A retrospective review was conducted in all patients with cerebral aneurysms undergoing stent-assisted coil embolization or stent-in-stent flow diversion at the University of Iowa during a 24-month period. The antiplatelet protocol was 81 mg aspirin and 75 mg clopidogrel daily for 6 weeks, followed by 325 mg aspirin daily indefinitely. The incidence of stroke or TIA was determined by a retrospective review of medical records generated during a 3-month period following discontinuation of clopidogrel. Results A total of 154 patients underwent aneurysm treatment with stent techniques during this interval. Documentation of neurological follow-up 3 months after discontinuation of a 6-week clopidogrel treatment was available in 121 (78.6%) of 154 patients. Of these 121 patients, 114 were treated with stent-assisted coil embolization and 7 with stent-in-stent flow diversion. Six patients (5%) suffered an ischemic event after cessation of clopidogrel, with 2 events occurring within the first 2 weeks. Specifically, the rate of ischemic events was 5 (4.3%) of 114 in the"stent-coil"treatment group and 1 (14.3%) of 7 in the stent-in-stent group. Treatment had been performed in the setting of a subarachnoid hemorrhage in 1 patient. Atypical aneurysm features and technical factors predisposing to thrombotic events were found in all but one of these patients. Similarly, cardiovascular risk factors were present in 5 of the 6 patients in whom ischemic events developed after clopidogrel discontinuation. Conclusions Clopidogrel discontinuation is associated with a 5% risk of ischemic events in patients treated with stent techniques. Any stroke related to clopidogrel discontinuation is avoidable, and longer treatment is therefore clearly necessary. Patients with cardiovascular risk factors, high-risk aneurysm features, and those undergoing stent-in-stent flow diversion might benefit the most from longer clopidogrel therapy.

details of preiprocedural strokes in SAMMPRIS

Detailed Analysis of Periprocedural Strokes in Patients Undergoing Intracranial Stenting in Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS); Fiorella D, Derdeyn CP, Lynn MJ, Barnwell SL, Hoh BL, Levy EI, Harrigan MR, Klucznik RP, McDougall CG, Pride GL, Zaidat OO, Lutsep HL, Waters MF, Hourihane JM, Alexandrov AV, Chiu D, Clark JM, Johnson MD, Torbey MT, Rumboldt Z, Cloft HJ, Turan TN, Lane BF, Janis LS, Chimowitz MI, for the SAMMPRIS Trial Investigators; Stroke (Sep 2012)

 

BACKGROUND AND PURPOSE: Enrollment in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial was halted due to the high risk of stroke or death within 30 days of enrollment in the percutaneous transluminal angioplasty and stenting arm relative to the medical arm. This analysis focuses on the patient and procedural factors that may have been associated with periprocedural cerebrovascular events in the trial. METHODS: Bivariate and multivariate analyses were performed to evaluate whether patient and procedural variables were associated with cerebral ischemic or hemorrhagic events occurring within 30 days of enrollment (termed periprocedural) in the percutaneous transluminal angioplasty and stenting arm. RESULTS: Of 224 patients randomized to percutaneous transluminal angioplasty and stenting, 213 underwent angioplasty alone (n=5) or with stenting (n=208). Of these, 13 had hemorrhagic strokes (7 parenchymal, 6 subarachnoid), 19 had ischemic stroke, and 2 had cerebral infarcts with temporary signs within the periprocedural period. Ischemic events were categorized as perforator occlusions (13), embolic (4), mixed perforator and embolic (2), and delayed stent occlusion (2). Multivariate analyses showed that higher percent stenosis, lower modified Rankin score, and clopidogrel load associated with an activated clotting time above the target range were associated (P≤0.05) with hemorrhagic stroke. Nonsmoking, basilar artery stenosis, diabetes, and older age were associated (P≤0.05) with ischemic events. CONCLUSIONS: Periprocedural strokes in SAMMPRIS had multiple causes with the most common being perforator occlusion. Although risk factors for periprocedural strokes could be identified, excluding patients with these features from undergoing percutaneous transluminal angioplasty and stenting to lower the procedural risk would limit percutaneous transluminal angioplasty and stenting to a small subset of patients. Moreover, given the small number of events, the present data should be used for hypothesis generation rather than to guide patient selection in clinical practice.Clinical Trial Registration Information

 

Comment

high risk for hemorrhagic stroke: higher percent stenosis, lower modified Rankin score, and clopidogrel loading dose.n=13

high risk for ischemic stroke:  nonsmoker, BA stenosis, DM, and older age n=19

Clinical Outcomes Using a Platelet Function-Guided Approach for Secondary Preven

Depta JP, Fowler J, Novak E, Katzan I, Bakdash S, Kottke-Marchant K, Bhatt DL; Stroke (Jun 2012)BACKGROUND AND PURPOSE: Antiplatelet therapy nonresponse is associated with worse clinical outcomes. We studied the clinical outcomes associated with platelet function-guided modifications in antiplatelet therapy in patients with ischemic stroke or transient ischemic attack. METHODS: From January 2005 to August 2007, 324 patients with ischemic stroke underwent platelet function testing using platelet aggregometry. Aspirin nonresponse was defined as a mean platelet aggregation ≥20% with 0.5 mg/mL arachidonic acid and/or ≥70% with 5 μmol/L adenosine diphosphate. Clopidogrel nonresponse was defined as a mean platelet aggregation ≥40% with 5 μmol/L adenosine diphosphate. A modification was any increase in antiplatelet therapy occurring after testing. Clinical outcomes were compared between patients with and without platelet function-guided antiplatelet therapy modifications using univariate and propensity score-adjusted analyses. RESULTS: In patients with ischemic stroke or transient ischemic attack, 43% (n=128) and 35% (n=54) were nonresponders to aspirin and clopidogrel, respectively. After platelet function testing, antiplatelet therapy was increased in 23% of patients (n=73). After propensity score matching (n=61 in each group), antiplatelet therapy modification was associated with significantly increased rates of death, ischemic events, or bleeding (hazard ratio, 2.24; 95% CI, 1.12-4.47; P=0.02) compared with no modification in antiplatelet therapy and a trend toward increased bleeding (hazard ratio, 3.56; 95% CI, 0.98-12.95; P=0.05). No differences in ischemic events were observed. CONCLUSIONS: Platelet function-guided modification in antiplatelet therapy after an ischemic stroke or transient ischemic attack was associated with significantly higher rates of adverse clinical outcomes.

32

Intracranial Hemorrhage in Atrial Fibrillation Patients During Anticoagulation W

Intracranial Hemorrhage in Atrial Fibrillation Patients During Anticoagulation With Warfarin or Dabigatran: The RE-LY Trial

Diener HC, Yang S, Connolly SJ, Wallentin L, Reilly PA, Ezekowitz MD, Yusuf S; Stroke (Apr 2012)

BACKGROUND AND PURPOSE: Intracranial hemorrhage is the most devastating complication of anticoagulation. Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined. METHODS: Analysis of 18 113 participants with atrial fibrillation in the Randomized Evaluation of Long-term anticoagulant therapY (RE-LY) trial assigned to adjusted-dose warfarin (target international normalized ratio, 2-3) or dabigatran (150 mg or 110 mg, both twice daily). RESULTS: During a mean of 2.0 years of follow-up, 154 intracranial hemorrhages occurred in 153 participants: 46% intracerebral (49% mortality), 45% subdural (24% mortality), and 8% subarachnoid (31% mortality). The rates of intracranial hemorrhage were 0.76%, 0.31%, and 0.23% per year among those assigned to warfarin, dabigatran 150 mg, and dabigatran 110 mg, respectively (P<0.001 for either dabigatran dose versus warfarin). Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg (n=13 and n=11, respectively) versus warfarin (n=32; P<0.01 for both). Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran (11 patients with each dose) compared with warfarin (24 patients; P<0.05 for both dabigatran doses versus warfarin). Independent predictors of intracranial hemorrhage were assignment to warfarin (relative risk, 2.9; P<0.001), aspirin use (relative risk, 1.6; P=0.01), age (relative risk, 1.1 per year; P<0.001), and previous stroke/transient ischemic attack (relative risk, 1.8; P=0.001). CONCLUSIONS: The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran. Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin. Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage.

 

Comment:  warfarin use by itself was more of a risk than dabagitran + asa, although the combination also increased risk.  Age was not a major risk factor. Fall risk was not looked at.

Old studies that panned the use of anticoagulation in stroke, including WASID might need to be restudied, with dabagatran, since in Wasid the real problem was keeping the INR's in range.  This point is likely to be incredibly controversial, yet the facts speak:  dabagatran has not been studied in the group of intracranial stensosis and the results of warfarin studies cannot be generalized as is clear from this trial.

Glaucoma and obstructive sleep apnea

Faridi O, Park SC, Liebmann JM, Ritch R; Clinical and Experimental Ophthalmology (Feb 2012)

 

Glaucoma is increasingly becoming recognized as a manifestation of both ocular and systemic risk factors. Risk factors in addition to intraocular pressure (IOP) are increasingly being identified and play a critical role in the development and/or progression of glaucoma. Particularly in the lower ranges of IOP, a number of disorders associated with reduced blood flow and ischemia, collectively termed vascular risk factors, such as migraine, Raynaud's phenomenon, atrial fibrillation, and reduced nocturnal blood pressure, lead to decreased ocular perfusion pressure. During sleep, alterations occur in cardiovascular physiology that are balanced by auto-regulatory mechanisms to maintain homeostasis. However, in obstructive sleep apnea (OSA), the normal physiologic balance is upset, leading to hypoxia and sympathetic activation. OSA can range from mild to severe, and, therefore, its associations and their severity may depend on the severity of the sleep apnea. A potentially modifiable systemic risk factor, OSA has recently been increasingly associated with glaucoma, is independent of IOP. Through hypoxia-mediated damage to blood vessels and their compensatory mechanisms, OSA may alter blood flow to the optic nerve head and, in combination with other predisposing factors, lead to decreased ocular perfusion pressure. This in turn may directly affect the optic nerve or it may indirectly increase its susceptibility to other insults. The purpose of this review is to shed light on the association between OSA and glaucoma. © 2012 The Authors. Journal compilation © 2012 Royal Australian and New Zealand College of Ophthalmologists.

Dragon score for predicting success of thrombolysis pub in neurology

Objective: To develop a functional outcome prediction score, based on immediate pretreatment parameters, in ischemic stroke patients receiving IV alteplase.

Methods: The derivation cohort consists of 1,319 ischemic stroke patients treated with IV alteplase at the Helsinki University Central Hospital, Helsinki, Finland. We evaluated the predictive value of parameters associated with the 3-month outcome and developed the score according to the magnitude of logistic regression coefficients. We assessed accuracy of the model with bootstrapping. External validation was performed in a cohort of 330 patients treated at the University Hospital Basel, Basel, Switzerland. We assessed the score performance with area under the receiver operating characteristic curve (AUC-ROC).

Results: The DRAGON score (0–10 points) consists of (hyper)Dense cerebral artery sign/early infarct signs on admission CT scan (both = 2, either = 1, none = 0), prestroke modified Rankin Scale (mRS) score >1 (yes = 1), Age (≥80 years = 2, 65–79 years = 1, <65 years = 0), Glucose level at baseline (>8 mmol/L [>144 mg/dL] = 1), Onset-to-treatment time (>90 minutes = 1), and baseline National Institutes of Health Stroke Scale score (>15 = 3, 10–15 = 2, 5–9 = 1, 0–4 = 0). AUC-ROC was 0.84 (0.80–0.87) in the derivation cohort and 0.80 (0.74–0.86) in the validation cohort. Proportions of patients with good outcome (mRS score 0–2) were 96%, 88%, 74%, and 0% for 0–1, 2, 3, and 8–10 points, respectively. Proportions of patients with miserable outcome (mRS score 5–6) were 0%, 2%, 5%, 70%, and 100% for 0–1, 2, 3, 8, and 9–10 points, respectively. External validation showed similar results.

Conclusions: The DRAGON score is valid at our site and was reliable externally. It can support clinical decision-making, especially when invasive add-on strategies are considered. The score was not studied in patients with basilar artery occlusion. Further external validation is warranted.

Risk of warfarin association with bleeding with antibiotics

Baillergeon J. et al.  Am J Med 2012; 125:183-9.

 

Antibiotic (class)          odds ratio of bleeding (univariate/multivariate)

 

Azole antifungals             6.49/4.57

macrolides                      2.09/1.86

quinolones                      2.20/1.69

cotrimoxazole                 3.06/2.70

penicillins                       1.89/1.92

cephalosporins                2.85/2.45

 

Use of other meds

 

SSRI                               1.45/1.34

SNRI                               1.34/1.17

corticosteroid                   2.58/2.30

antiplatelet                       1.57/1.43

CYP2CP                          1.11/1.07

 

 

sICH after alteplase, on v. not on warfarin

Seet RCS et al.  Stroke 2011; 42:2333-2335

Authors highlight increased risk of alteplase in warfarin patients treated at a single site, irrespective of htn or stroke etiolgy, or INR . 

NNT and NNH with t-pa by time administered

Lansberg et al. Stroke 2009  meta-analysis of 6 stroke trials of t-pa.

Time to treat      NNT            NNH   (NNT= number needed to treat or number needed to harm)

0-90 minutes       3.6                65
90-180 minutes   4.3                38
180-270 min       5.9                30
270-360 min       19.3              14

Debates on Intracranial artery disease (ICAD) at ISC 2012, and imaging

Lessons from Sampris-- Wingspan stent trial was stopped due to more deaths in stent group.  However, issues that were brought out include that sites had inexperienced interventionalists with an average enrollment of 2 per site, total enrollment fairly small, plus criteria for enrollment was not (necessarily) ideal since we don't know who best candidates are.  One comment was that randomized trials if done too early (as here) retard innovation.

 

An  important finding of Sammpris ties in with the theme of the year, which is that medical management has improved. 2 year mortality of ICD declined from 20 percent in earlier trials to about 12 % in Sammpris.  The putative hero is aggressive 2011 medical management, with all it entails for tighter blood pressure control, tighter LDL-c reduction, attention to so called minor risk factors including metabolic syndrome, HDL, CRP and others.

 

One woman commented on her own "no metal " experience with angioplasty and made a case for a clinical trial with "no metal."  The main risk of failure was not seen in her series of series. (Thanh Nguyen).  Thereupon a discussion ensued about whether or not brain arteries are like coronary arteries where we already have learned so much.  Brain arteries have no external lamina are smaller caliber and more prone to perforation. 

 

Tom Brott opined that future trials of ICAD will need to compare procedures with new "best medical."

 

IMAGING

 

Debate again, is over what is best imaging protocol for stroke.  Data was presented that CT-P does NOT improve 90 day modified Rankin scores over regular noncontrast CT as a stratifier.  CT-P does add to time to catheter.  Time to order is a major delay point.  Whatever is used should be comfortable at facility. 

 

Purpose of extra procedures (advanced MRI or CT) is to exclude futile procedures and cases likely to hemorrhage (do no harm) as well as tell anatomy of occlusion to guide procedure. D-P mismatch, as last year, is not key, core infarct size is much more important (can tell best on MRI diffusion studies or possibly CBV). Exceptions are malignant pattern (see DEFUSE trial)  Evaluation of collateral flow is gaining prominence. One speaker commented that they still intervene on the ten percent that imaging says are futile. 

 

 

Dissection and i-v alteplase treatment

Quereshi et al.  Arch Neurol 2011; 68: 1536-42

Authors reviewed database finding about 1 % of 48,000 stroke patients had an underlying dissection. Alteplase was less effective in this stroke type in lowering disability, but the rates of hemorrhage were similar to other stroke types, and the lower outcome was not due to alteplase therapy.

Cognitive and Neurologic Outcomes after CABG

Selnes, Gottesman, ....McKhann.  NEJM 2012; 366: 250-7  Review article

Bullet points  STROKE
1.  1.6 % rate overall, but rate may increase 10x if radiographic/clinically silent CVA's included

2.  Mechanism of micro/macroemboli with cross clamping needs to be modified to include hypotension and inflammatory response.  Caplan et al , proposed the combination of hypotension and microemboli leads to more injury because microemboli aren't washed out as readily.

3.  risk factors for neurologic morbidity: age, DM, HTN, history of stroke  Others:  PREOPERATIVE FACTORS (and odds ratio) :  athero of ascending aorta (2.0), h/o of TIA/CVA (2.1); h/o of subcortical disease (4.1), carotid stenosis (5.3); PVD (2); DM (1.2 or 2.8);HTN (1.8 or 1.3);  high pulse pressure (1.1);prior cardiac surgery (1.4); smoking history (1.6).     OPERATIVE FACTORS:  Hypotension (8.4); manipulation of aorta (1.8); bypass time > 2 hours (1.4).    POSTOP FACTORS: AD (.8 to 2.6). (article gives references for each risk factor).

4.  PREVENTION:  Use of individualized factors, and use of preop or postop ASA which are both controversial.  Use of eipaortic ultrasound to guide decision to cross clamp.  Use of carotid screening preop.  Avoiding combined carotid/coronary procedures.  All of these ideas have limited data.  Operative monitoring with TCD or near infraredspectroscopy has been used. 

COGNITIVE DECLINE

Factors include:
1.  preop cognitive abilities/disabilities
2,  

Recovery after spinal cord infarcts; long term outcomes in 115 patients

Neurolgy 2012;;78: 114-121  Robertson, Brown, Wijdicks, and Rabinstein.  Mayo Clinic

Authors debunk myths of spinal cord infarcts.  Retrospective study of patients show many improved over time.  Among their findings

1.  Gradual improvement was common after hospital dismissal. More than half walked aided or unaided eventually.

2. One third of those catheterised at dismissal did not require catheter long term

3. MRI's were frequently normal initially and even occassionally on followup MRI

4.  ASIA A/B predicted a poor outcome, but not invariably.  Other predictors of poor outcome included absent Babinski sign, sensory level, longitudinally extensive MRI, and lesions in highest thoracic level.  NON RISK FACTORS included age, mechanism, gender were not predictive of a poor functonal outcome

5.  There was a fairly high early mortality, around 26 % that was associated with HTN, DM, smoking, PVD, severity of impairment, and age (ie traditional risk factors mostly).

6.  Pain especially back pain was a common initial finding and a common longterm problem of survivors.

Lacune subtypes and risk factors

Authors divided lacunes into very small (<3 mm) and small (3-7 mm) and larger (8-20 mm).  The hypothesized mechanism for very small lacunes and small lacunes was lipohyalinosis and larger lacunes was microatheroma. 

Risk factors for small lacunes (lipohyalinosis) in 1548 patients analyzed included age, African American race, HTN, diabetes, ever smoking.   HBA1C could be substituted for DM. 

Very small lacunes had similar risk factors as small lacunes.  Diabetes was key risk factor here.

8-20 mm lacunes (microatheroma) were associated with ever smoking, age, and LDL levels.

Conclusion is that diabetes leads to disorder of systemic microcirculation leading to very small lacunes.  LDL and smoking lead to microatheroma