Electrocardiographic risk factors for sudden death : a study with 245 cases of sudden death during a two-year follow-up after 24-hour electrocardiography in 6693 patients

The present study was designed to assess the relation between parameters derived from twelve lead and twenty four hour electrocardiography and the occurrence of sudden death. More specifically, the aim was to study the risk implications of QTc interval duration (a parameter of the total duration of depolarization and repolarization of the myocardium) in the 12 lead electrocardiogram and that of high QTc interval variability, low heart rate variability, and frequent ventricular arrhythmias in the 24 hour electrocardiogram. A further objective of the study was to determine the prognostic value of all electrocardiographic parameters taken together with other clinical data. The epidemiology and etiology of sudden death is described in chapter two. Emphasis is placed on to those mechanisms which are detectable by electrocardiographic methods. In this chapter, the specific aims of the study are formulated. The methodological aspects of the study are presented in chapter three. General aspects of the nested case-referent study design are introduced and a description of the study population, the observed incidence of sudden death, and baseline characteristics are given. In chapter four the risk implications for sudden death of QTc prolongation in the twelve lead electrocardiogram are analysed and compared with the literature. In chapter five the risk implications of parameters concerning QTc and RR interval duration and variability as derived from 24 hour electrocardiography are studied. Detailed information on the computer-aided study analysis of the 24 hour electrocardiograms is supplied in the appendices of this chapter. In chapter six a prognostic model taking into account all electrocardiographic parameters in addition to routine clinical characteristics is developed. Chapter seven provides a general discussion of the findings of this study and their implications. Finally, an english and dutch summary are supplie

Secondary prevention after cerebral ischaemia of presumed arterial origin: is aspirin still the touchstone?

Patients who have had a transient ischaemic attack or nondisabling ischaemic stroke of presumed arterial origin have an annual risk of death from all vascular causes, non-fatal stroke, or non-fatal myocardial infarction that ranges between 4% and 11% without treatment. In the secondary prevention of these vascular complications the use of aspirin has been the standard treatment for the past two decades. Discussions about the dose of aspirin have dominated the issue for some time, although there is no convincing evidence for any difference in effectiveness in the dose range of 30-1300 mg/day. A far greater problem is the limited degree of protection offered by aspirin: the accumulative evidence from trials with aspirin alone and only for cerebrovascular disease of presumed arterial origin as qualifying event indicates that a dose of aspirin of at least 30 mg/day prevents only 13% of serious vascular complications

Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke

Objective: To study the early time course of major bleeding and its subtypes in patients with cerebral ischemia on dual and single antiplatelet therapy. Methods: We performed a post hoc analysis on individual patient data from 6 randomized clinical trials (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events [CAPRIE], Second European Stroke Prevention Study [ESPS-2], Management of Atherothrombosis With Clopidogrel in High Risk Patients [MATCH], Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA], European/Australasian Stroke Prevention in Reversible Ischaemia Trial [ESPRIT], and Prevention Regimen for Effectively Avoiding Second Strokes [PRoFESS]) including 45,195 patients with a TIA or noncardioembolic ischemic stroke. We studied incidence rates of bleeding per antiplatelet regimen stratified by time from randomization (≤30, 31–90, 91–180, 181–365, >365 days). We calculated incidence rates per trial and pooled estimates with random-effects meta-analysis. We performed Poisson regression to assess differences between time periods with adjustment for age and sex. Results: The incidence of major bleeding on aspirin plus clopidogrel and aspirin plus -dipyridamole was highest in the first 30 days, 5.8 and 4.9 per 100 person-years, respectively, and was significantly higher than at 31 to 90 days (rate ratio 1.98, 95% confidence interval 1.16–3.40 for aspirin plus clopidogrel; rate ratio 1.94, 95% confidence interval 1.24–3.03 for aspirin plus dipyridamole). Incidence rates on aspirin and clopidogrel monotherapy were 2.8 and 2.5 per 100 person-years, respectively, in the first 30 days, with no significant change over time. The time course was similar for gastrointestinal bleeds. There was no early excess of intracranial hemorrhage in patients on either dual or single antiplatelet therapy. Conclusion: Dual antiplatelet therapy is associated with high early risks of major and gastrointestinal bleeding that decline after the first month in trial cohorts

Quality of life after infrainguinal bypass grafting surgery

AbstractPurpose: The purpose of this study was to compare quality of life in patients with and without various ischemic complications after infrainguinal bypass grafting surgery for occlusive vascular disease. Methods: A sample of patients (n = 746) randomized in the Dutch BOA study (n = 2645), a multicenter trial that compared the effectiveness of oral anticoagulant therapy with aspirin in the prevention of infrainguinal bypass graft occlusions, was entered in this study. On the basis of clinical outcomes of the trial, the patients were grouped as follows: patients with patent grafts (n = 409); patients with nontreated graft occlusions, subdivided into an asymptomatic group (n = 32) and a symptomatic group (n = 65); patients with subsequent revascularizations (n = 194); patients with amputations (n = 36); and patients with failed secondary revascularizations followed by secondary amputation (n = 38). In case an outcome event occurred, the patients were regrouped accordingly. Every half year, the patients completed a Short Form–36 and a EuroQol questionnaire. A multilevel model was used for repeated measure analysis. Results:The mean follow-up time was 21 months. The quality of life in patients with nontreated asymptomatic occlusions was roughly similar to the quality of life in patients with patent grafts. Patients with symptomatic nontreated occlusions had the lowest outcome with regard to pain as compared with the other groups. Furthermore, physical and social functioning was lower for these patients than for patients with patent grafts. Revascularizations, successful or not, negatively affected pain, social functioning, and physical and emotional role. After successful revascularization, some improvement was observed in pain, physical and social functioning, and general and mental health as compared with the group with nontreated symptomatic occlusions. Amputation deteriorated physical functioning strikingly, especially after failed secondary revascularization. These patients also had the lowest scores of all the groups in the dimensions of social functioning, physical and emotional role, and mental health. EuroQol score showed deterioration of quality of life after all events, except for asymptomatic occlusions. The same patterns emerged if we stratified our analysis according to the indication for the initial operation: claudication or limb salvage. Quality of life was constant over time in all the groups in the observed period. Conclusion: Quality of life in patients with asymptomatic occluded grafts is similar to quality of life in patients with patent grafts. Revascularization of symptomatic occluded grafts improves quality of life to a certain extent. Amputation, in particular after failed secondary revascularization, seemed to be the lowest possible outcome. The results of the Short Form-36 and EuroQol measurements were in line with the clinical expectations. The association of disease severity with scores on the instruments supports the construct validity of these outcome measures for an objective assessment of quality of life in controlled studies. (J Vasc Surg 1999;29:913-9.

Cost-effectiveness of oral anticoagulants versus aspirin in patients after infrainguinal bypass grafting surgery

AbstractPurpose: Several antithrombotic therapies are available for the treatment of patients with peripheral vascular diseases. It is unknown how quality of life and costs of treatment are influenced by different therapies. This study assessed the cost-effectiveness of oral anticoagulants versus aspirin in patients after infrainguinal bypass grafting surgery. Methods: Clinical outcome events and event-free survival were collected from 2650 patients in 77 centers who participated in the Dutch Bypass Oral anticoagulants or Aspirin trial. Approximately half the patients had critical ischemia; 60% received vein grafts, and 20% had femorocrural bypass grafts. A model that was primarily driven by clinical outcome events was used as a means of determining quality of life (EuroQol EQ-5D) and costs for each patient. The main outcome measure was the incremental health care costs in relation to the additional number of quality-adjusted life years and the additional number of event-free years. Results: The mean costs during the 21 months of follow-up were ϵ 6875 per patient in the oral anticoagulants group versus ϵ 7072 in the aspirin group (difference, 197; 95% CI, –746 to 343). The event-free survival was 1.10 years in the group treated with oral anticoagulants versus 1.09 years in the group treated with aspirin (difference, 0.01; 95% CI, –0.07 to 0.08), whereas the corresponding quality-adjusted life years were 1.06 and 1.05, respectively (difference, 0.01; 95% CI, –0.03 to 0.06). Conclusion: Health care costs, event-free survival, and quality-adjusted life years in patients after infrainguinal bypass surgery were not different in patients treated with aspirin and patients treated with oral anticoagulants. The extra costs of monitoring patients treated with oral anticoagulants were limited and play no role in the decision for treatment. (J Vasc Surg 2001;34:254-62.

Cost-benefit of outcome adjudication in nine randomised stroke trials

Background: Central adjudication of outcomes is common for randomised trials and should control for differential misclassification. However, few studies have estimated the cost of the adjudication process.Methods: We estimated the cost of adjudicating the primary outcome in nine randomised stroke trials (25,436 participants). The costs included adjudicators’ time, direct payments to adjudicators, and co-ordinating centre costs (e.g. uploading cranial scans and general set-up costs). The number of events corrected after adjudication was our measure of benefit. We calculated cost per corrected event for each trial and in total.Results: The primary outcome in all nine trials was either stroke or a composite that included stroke. In total, the adjudication process associated with this primary outcome cost in excess of £100,000 for a third of the trials (3/9). Mean cost per event corrected by adjudication was £2295.10 (standard deviation: £1482.42).Conclusions: Central adjudication is a time-consuming and potentially costly process. These costs need to be considered when designing a trial and should be evaluated alongside the potential benefits adjudication brings to determine whether they outweigh this expense

Extent of hypoattenuation on CT angiography source images in Basilar Artery occlusion: prognostic value in the Basilar Artery International Cooperation Study

<p><b>Background and Purpose:</b> The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) quantifies the extent of early ischemic changes in the posterior circulation with a 10-point grading system. We hypothesized that pc-ASPECTS applied to CT angiography source images predicts functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS).</p> <p><b>Methods:</b> BASICS was a prospective, observational registry of consecutive patients with acute symptomatic basilar artery occlusion. Functional outcome was assessed at 1 month. We applied pc-ASPECTS to CT angiography source images of patients with CT angiography for confirmation of basilar artery occlusion. We calculated unadjusted and adjusted risk ratios (RRs) of pc-ASPECTS dichotomized at ≥8 versus <8. Primary outcome measure was favorable outcome (modified Rankin Scale scores 0–3). Secondary outcome measures were mortality and functional independence (modified Rankin Scale scores 0–2).</p> <p><b>Results:</b> Of 158 patients included, 78 patients had a CT angiography source images pc-ASPECTS ≥8. Patients with a pc-ASPECTS ≥8 more often had a favorable outcome than patients with a pc-ASPECTS <8 (crude RR, 1.7; 95% CI, 0.98–3.0). After adjustment for age, baseline National Institutes of Health Stroke Scale score, and thrombolysis, pc-ASPECTS ≥8 was not related to favorable outcome (RR, 1.3; 95% CI, 0.8–2.2), but it was related to reduced mortality (RR, 0.7; 95% CI, 0.5–0.98) and functional independence (RR, 2.0; 95% CI, 1.1–3.8). In post hoc analysis, pc-ASPECTS dichotomized at ≥6 versus <6 predicted a favorable outcome (adjusted RR, 3.1; 95% CI, 1.2–7.5).</p> <p><b>Conclusions:</b> pc-ASPECTS on CT angiography source images independently predicted death and functional independence at 1 month in the CT angiography subgroup of patients in the BASICS registry.</p&gt

Carotid stenting: is there an operator effect? A pooled analysis from the carotid stenting trialists' collaboration.

BACKGROUND AND PURPOSE: Randomized clinical trials show higher 30-day risk of stroke or death after carotid artery stenting compared with surgery. We examined whether operator experience is associated with 30-day risk of stroke or death in the Carotid Stenting Trialists' Collaboration database. METHODS: The Carotid Stenting Trialists' Collaboration is a pooled individual patient database including all patients recruited in 3 randomized trials of stenting versus endarterectomy for symptomatic carotid stenosis (Endarterectomy Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Angioplasty versus Carotid Endarterectomy trial, and International Carotid Stenting Study). Lifetime carotid artery stenting experience, lifetime experience in stenting procedures excluding the carotid, and annual number of procedures performed within the trial (in-trial volume), divided into tertiles, were used to measure operator experience. The outcome event was the occurrence of any stroke or death within 30 days of the procedure. The analysis was done per protocol. RESULTS: Among 1546 patients who underwent carotid artery stenting, 120 (7.8%) had a stroke or death within 30 days of the procedure. The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience (P=0.8) or operator lifetime stenting experience excluding the carotid (P=0.7). In contrast, the 30-day risk of stroke or death was significantly higher in patients treated by operators with low (mean ≤3.2 procedures/y; risk 10.1%; adjusted risk ratio=2.30 [1.36-3.87]) and intermediate annual in-trial volumes (3.2-5.6 procedures/y; 8.4%; adjusted risk ratio=1.93 [1.14-3.27]) compared with patients treated by high annual in-trial volume operators (>5.6 procedures/y; 5.1%). CONCLUSIONS: Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year

Balancing Benefits and Risks of Long-Term Antiplatelet Therapy in Noncardioembolic Transient Ischemic Attack or Stroke

Lifelong treatment with antiplatelet drugs is recommended following a transient ischemic attack or ischemic stroke. Bleeding complications may offset the benefit of antiplatelet drugs in patients at increased risk of bleeding and low risk of recurrent ischemic events. We aimed to investigate the net benefit of antiplatelet treatment according to an individuals’ bleeding risk. METHODS: We pooled individual patient data from 6 randomized clinical trials (CAPRIE [Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events], ESPS-2 [European Stroke Prevention Study-2], MATCH [Management of Atherothrombosis With Clopidogrel in High-Risk Patients], CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance], ESPRIT [European/Australasian Stroke Prevention in Reversible Ischemia Trial], and PRoFESS [Prevention Regimen for Effectively Avoiding Second Strokes]) investigating antiplatelet therapy in the subacute or chronic phase after noncardioembolic transient ischemic attack or stroke. Patients were stratified into quintiles according to their predicted risk of major bleeding with the S(2)TOP-BLEED score. The annual risk of major bleeding and recurrent ischemic events was assessed per quintile for 4 scenarios: (1) aspirin monotherapy, (2) aspirin-clopidogrel versus aspirin or clopidogrel monotherapy, (3) aspirin-dipyridamole versus clopidogrel, and (4) aspirin versus clopidogrel. Net benefit was calculated for the second, third, and fourth scenario. RESULTS: Thirty seven thousand eighty-seven patients were included in the analyses. Both risk of major bleeding and recurrent ischemic events increased over quintiles of predicted bleeding risk, but risk of ischemic events was consistently higher (eg, from 0.7%/y (bottom quintile) to 3.2%/y (top quintile) for major bleeding on aspirin and from 2.5%/y to 10.2%/y for risk of ischemic events on aspirin). Treatment with aspirin-clopidogrel led to more major bleedings (0.9%–1.7% per year), than reduction in ischemic events (ranging from 0.4% to 0.9/1.0% per year) across all quintiles. There was no clear preference for either aspirin-dipyridamole or clopidogrel according to baseline bleeding risk. CONCLUSIONS: Among patients with a transient ischemic attack or ischemic stroke included in clinical trials of antiplatelet therapy, the risk of recurrent ischemic events and of major bleeding increase in parallel. Antiplatelet treatment cannot be individualized solely based on bleeding risk assessment

Assessment of collateral status by dynamic ct angiography in acute mca stroke: Timing of acquisition and relationship with final infarct volume

BACKGROUND AND PURPOSE: Dynamic CTA is a promising technique for visualization of collateral filling in patients with acute ischemic stroke. Our aim was to describe collateral filling with dynamic CTA and assess the relationship with infarct volume at follow-up. MATERIALS AND METHODS: We selected patients with acute ischemic stroke due to proximal MCA occlusion. Patients underwent NCCT, single-phase CTA, and whole-brain CT perfusion/dynamic CTA within 9 hours after stroke onset. For each patient, a detailed assessment of the extent and velocity of arterial filling was obtained. Poor radiologic outcome was defined as an infarct volume of\70 mL. The association between collateral score and follow-up infarct volume was analyzed with Poisson regression. RESULTS: Sixty-one patients with a mean age of 67 years were included. For all patients combined, the interval that contained the peak of arterial filling in both hemispheres was between 11 and 21 seconds after ICA contrast entry. Poor collateral status as assessed with dynamic CTA was more strongly associated with infarct volume of 70 mL (risk ratio, 1.9; 95% CI, 1.3-2.9) than with single-phase CTA (risk ratio, 1.4; 95% CI, 0.8-2.5). Four subgroups (good-versus-poor and fast-versus-sl