Probability Of Reperfusion Research Articles

Time to angiographic reperfusion in acute ischemic stroke: decision analysis.

Our objective was to use decision analytic modeling to compare 2 treatment strategies of intravenous recombinant tissue-type plasminogen activator (r-tPA) alone versus combined intravenous r-tPA/endovascular therapy in a subgroup of patients with large vessel (internal carotid artery terminus, M1, and M2) occlusion based on varying times to angiographic reperfusion and varying rates of reperfusion. We developed a decision model using Interventional Management of Stroke (IMS) III trial data and comprehensive literature review. We performed 1-way sensitivity analyses for time to reperfusion and 2-way sensitivity for time to reperfusion and rate of reperfusion success. We also performed probabilistic sensitivity analyses to address uncertainty in total time to reperfusion for the endovascular approach. In the base case, endovascular approach yielded a higher expected utility (6.38 quality-adjusted life years) than the intravenous-only arm (5.42 quality-adjusted life years). One-way sensitivity analyses demonstrated superiority of endovascular treatment to intravenous-only arm unless time to reperfusion exceeded 347 minutes. Two-way sensitivity analysis demonstrated that endovascular treatment was preferred when probability of reperfusion is high and time to reperfusion is small. Probabilistic sensitivity results demonstrated an average gain for endovascular therapy of 0.76 quality-adjusted life years (SD 0.82) compared with the intravenous-only approach. In our post hoc model with its underlying limitations, endovascular therapy after intravenous r-tPA is the preferred treatment as compared with intravenous r-tPA alone. However, if time to reperfusion exceeds 347 minutes, intravenous r-tPA alone is the recommended strategy. This warrants validation in a randomized, prospective trial among patients with large vessel occlusions.

Reperfusion Half-Life

We hypothesized that the probability of reperfusion can be modeled by an exponential decay (ie, half-life) function and that this reperfusion half-life is decreased by thrombolytic treatment. Serial perfusion MRI scans were evaluated for evidence of reperfusion in intravenous tissue plasminogen activator-treated (n=45) and untreated (n=103) patients. The cumulative probability of reperfusion for each group was fit with exponential decay functions. The resulting reperfusion half-life (ie, the time it takes half the sample to reperfuse) was calculated. In untreated patients, a monoexponential decay function fit the data well (R(2)=0.95) with a half-life of 29.1 hours. In tissue plasminogen activator-treated patients, the data were best fit with a biexponential decay function (R(2)=0.99) that had a fast and a slow component. The fast component is attributable to tissue plasminogen activator therapy and has a half-life of 0.71 hours, whereas the slow component was similar to that of the untreated group. Approximately 3.5 hours after the start of treatment, the effect of tissue plasminogen activator on the probability of reperfusion was negligible. The probability of reperfusion can be well described by the reperfusion half-life. Determination of the fast component reperfusion half-life may be an approach to compare the relative potency of different thrombolytic agents.

STEMI management: trials, registries, and the real world

Primary angioplasty (P-PCI) is the preferred treatment of patients with ST-segment elevation myocardial infarction (STEMI) in both American and European guidelines. The reason for this preference is the evidence that the mechanical approach improves coronary patency, TIMIflow rates and ultimately the overall survival. Nevertheless, P-PCI has its own drawbacks: it needs skill and must be delivered in a timely fashion (two contrasting requirements, in that skill is linked to activity volume which, in turn, decreases along with catheterization laboratories proliferation); not to mention the costs. So far, in no single study has P-PCI been shown to reduce mortality, a goal whose achievement has been suggested only in an overview of small trials. Moreover, the advantage fades when P-PCI is compared with contemporary lytic regimens [1]. Therefore, it may be asked whether this apparent small advantage of P-PCI may be generalized to the real world. Indeed, it has been recognized for a long time that trials show what can be accomplished under careful observation and certain restricted conditions. The same results may not invariably or necessarily be observed when the treatment passes into general use. The above considerations have stimulated the establishment of registries, which are supposed to monitor treatment quality by providers. The overview of Italian registries (BLITZ-1, MISTRAL, VENERE, GESTIMA and PRIMA) shows that there is no difference in mortality between P-PCI and thrombolysis (7.0 vs 6.8%, P = NS). Registries show interesting data, worth discussing in the scientific community, but usually are flawed by the voluntary nature of data entry and, often, by the lack of an audit process. As a result, outcomes in registries are in between those observed in trials and those taking place in the real world. Balzi et al. [2] should be congratulated for their excellent work, describing in detail the way STEMI patients are managed in the Florence health district (years 2000–2001). Not only they have collected all relevant clinical data, but they have also cross-checked the registry patients with patients showing a discharge ICD9-CM 410 code in the same area. Data pertaining to those patients discharged with a 410 code who had not been entered in the registry, were submitted to an audit process before final entry. The most interesting finding of the study is the low reperfusion rate (with either P-PCI or thrombolysis): 54.4% overall, 71% among patients less than 65 years old, 60% for those 65–74 years old, 43% in the 75–84 age range and 31% for those patients 85 or more years old. It is not clear what was the reason for such a low reperfusion yield. The Florence health district is a busy area, well equipped in transportation facilities, with a short distance from spoke to hub hospitals, and with a good catheter laboratory available on a 24-h basis. Multivariable analysis identified age and co-morbidities as important constraints upon reperfusion, but also the type of hospital was strongly associated with the probability of reperfusion. Being admitted to the hospital where P-PCI was available increased 5-fold the probability of reperfusion. It may be concluded that the perception of the importance of reperfusion is different in spoke versus hub hospitals, particularly for those higher-risk patients with advanced age and co-morbidity. G. Melandri (&) F. Semprini S. Nanni D. Calabrese F. Vagnarelli A. Branzi Dipartimento Cardio-Toraco-Vascolare, Istituto di Cardiologia, Policlinico S.Orsola, via Massarenti 9, 40138 Bologna, Italy e-mail: giovanni.melandri@aosp.bo.it

Early thrombolysis inhibits peri-infarct depolarizations in embolic MCA occlusion.

Rats submitted to middle cerebral artery (MCA) clot embolism were treated with tissue plasminogen activator (TPA) 1.5 and 3.5 h post-occlusion. Reperfusion patterns were monitored by measuring cortical laser-Doppler flow; the direct current potential was measured to detect peri-infarct depolarizations (PID), a known mechanism of ischemic injury. TPA treatment induced reperfusion in 58% of treated animals that was delayed by 41 +/- 7 min (mean +/- s.e.m.) from treatment onset. The probability of reperfusion did not differ significantly between the two treatment groups. TPA treatment led to a 3-fold reduced frequency of PID if administered early or if successful reperfusion was observed (each p < 0.001). Early thrombolysis inhibits, but does not block, PID as an important mechanism of ischemic injury in embolic stroke.