Effects of Golden Hour Thrombolysis:A Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke (PHANTOM-S) Substudy

Importance  The effectiveness of intravenous thrombolysis in acute ischemic stroke is time dependent. The effects are likely to be highest if the time from symptom onset to treatment is within 60 minutes, termed the golden hour.

Objective  To determine the achievable rate of golden hour thrombolysis in prehospital care and its effect on outcome.

Design, Setting, and Participants  The prospective controlled Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke study was conducted in Berlin, Germany, within an established infrastructure for stroke care. Weeks were randomized according to the availability of a specialized ambulance (stroke emergency mobile unit (STEMO) from May 1, 2011, through January 31, 2013. We included 6182 consecutive adult patients for whom a stroke dispatch (44.1% male; mean [SD] age, 73.9 [15.0] years) or regular care (45.0% male; mean [SD] age, 74.2 [14.9] years) were included.

Interventions  The STEMO was deployed when the dispatchers suspected an acute stroke during emergency calls. If STEMO was not available (during control weeks, when the unit was already in operation, or during maintenance), patients received conventional care. The STEMO is equipped with a computed tomographic scanner plus a point-of-care laboratory and telemedicine connection. The unit is staffed with a neurologist trained in emergency medicine, a paramedic, and a technician. Thrombolysis was started in STEMO if a stroke was confirmed and no contraindication was found.

Main Outcomes and Measures  Rates of golden hour thrombolysis, 7- and 90-day mortality, secondary intracerebral hemorrhage, and discharge home.

Results  Thrombolysis rates in ischemic stroke were 200 of 614 patients (32.6%) when STEMO was deployed and 330 of 1497 patients (22.0%) when conventional care was administered (P < .001). Among all patients who received thrombolysis, the proportion of golden hour thrombolysis was 6-fold higher after STEMO deployment (62 of 200 patients [31.0%] vs 16 of 330 [4.9%]; P < .01). Compared with patients with a longer time from symptom onset to treatment, patients who received golden hour thrombolysis had no higher risks for 7- or 90-day mortality (adjusted odds ratios, 0.38 [95% CI, 0.09-1.70]; P = .21 and 0.69 [95% CI, 0.32-1.53]; P = .36) and were more likely to be discharged home (adjusted odds ratio, 1.93 [95% CI, 1.09-3.41]; P = .02).

Conclusions and Relevance  The use of STEMO increases the percentage of patients receiving thrombolysis within the golden hour. Golden hour thrombolysis entails no risk to the patients’ safety and is associated with better short-term outcomes.

Thrombolysis for acute deep vein thrombosis.

Standard treatment for deep vein thrombosis aims to reduce immediate complications. Use of thrombolysis or clot dissolving drugs could reduce the long-term complications of post-thrombotic syndrome (PTS) (pain, swelling, skin discolouration, or venous ulceration) in the affected leg. This is the second update of a review first published in 2004.
OBJECTIVES: To assess the effects of thrombolytic therapy and anticoagulation versus anticoagulation in the management of people with acute deep vein thrombosis (DVT) of the lower limb as determined by the effects on pulmonary embolism, recurrent venous thromboembolism, major bleeding, post-thrombotic complications, venous patency and venous function. SEARCH
METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched April 2013) and CENTRAL (2013, Issue 4).
SELECTION CRITERIA: Randomised controlled trials (RCTs) examining thrombolysis and anticoagulation versus anticoagulation for acute DVT were considered.
DATA COLLECTION AND ANALYSIS: In the previous review of 2010, one review author (LW) selected trials, extracted data and assessed study quality, with checking at all stages by the other review author (MPA). If necessary, we sought additional information from trialists. For this update (2013), LW and CB selected trials, extracted data independently, and sought advice from MPA where necessary. All studies, existing and new, required full risk of bias assessment in line with current Cochrane procedures. Two of LW, CB and MA independently assessed risk of bias with discussion with the third author where necessary.
MAIN RESULTS: Seventeen studies with 1103 participants were included. Complete clot lysis occurred significantly more often in the treatment group in early follow up (risk ratio (RR) 4.91; 95% confidence interval (CI) 1.66 to 14.53, P = 0.004) and at intermediate follow up (RR 2.37; 95% CI 1.48 to 3.80, P = 0.0004). A similar effect was seen for any degree of improvement in venous patency. Significantly less PTS occurred in those receiving thrombolysis, (RR 0.64; 95% CI 0.52 to 0.79, P < 0.0001). Leg ulceration was reduced although the data were limited by small numbers (RR 0.48; 95% CI 0.12 to 1.88, P = 0.29). Those receiving thrombolysis had significantly more bleeding complications (RR 2.23; 95% CI 1.41 to 3.52, P = 0.0006). Three strokes occurred in the treatment group, all in trials conducted pre-1990, and none in the control group. There was no significant effect on mortality detected at either early or intermediate follow up. Data on the occurrence of pulmonary embolism (PE) and recurrent DVT were inconclusive. Systemic thrombolysis is now not commonly used and catheter-directed thrombolysis (CDT) is the more favoured means of administration. This has been studied in iliofemoral DVT, and results from two trials are consistent with those from trials of systemic thrombolysis in DVT at other levels of occlusion.
AUTHORS’ CONCLUSIONS: Thrombolysis increases the patency of veins and reduces the incidence of PTS following proximal DVT by a third. Strict eligibility criteria are necessary to reduce the risk of bleeding complications and this limits the applicability of this treatment. In those who are treated there is a small increased risk of bleeding. In recent years CDT is the most studied route of administration, and results appear to be similar to systemic administration.

More Information on Thrombolysis Benefits for Ischemic Stroke.

Two studies using large databases provide details on timing and outcomes.

Clinical trials of thrombolysis for acute ischemic stroke typically have included fewer than 1000 patients. Two new studies involved larger datasets, allowing investigators to analyze important clinical issues in greater detail.

Saver and colleagues analyzed data from the national Get With The Guidelines–Stroke (GWTG-Stroke) database on 58,353 patients (median age, 72; 50.3% women) treated with tissue plasminogen activator (TPA) within 4.5 hours of symptom onset over a 9-year period. The median time from symptom onset to TPA administration was 144 minutes. Factors associated with earlier treatment included greater stroke severity, arrival by ambulance, and arrival during regular hours. Intracranial hemorrhage occurred in 4.9% of patients; 38.6% were discharged home. Earlier treatment, measured in 15-minute increments, was associated significantly with reduced mortality (odds ratio, 0.96), reduced intracranial hemorrhage (OR, 0.96), increased chance of independent ambulation at discharge (OR, 1.04), and increased rate of discharge to home (OR, 1.03).

The IST-3 collaborative group examined the effects of thrombolysis on 18-month quality-of-life and functional outcomes. Among more than 2300 patients from 10 countries who were randomized to usual care or thrombolysis within 6 hours of stroke, the adjusted odds of being alive and independent at 18 months were 28% greater with thrombolysis. Survival at 18 months did not differ. On a scale measuring mobility, self care, activity, pain, and anxiety, patient or caregiver reports of wellbeing improved significantly more between 6 and 18 months after stroke, and were better at 18 months, in the thrombolysis group, although anxiety was not lower.


The data from the large GWTG-Stroke database emphasize the importance of timely intervention for acute ischemic stroke. Currently, fewer than one third of patients are treated with thrombolysis with a door-to-needle time of <60 minutes (Stroke 2011; 42:2983). The Target: Stroke initiative of the American Heart Association/American Stroke Association aims to improve this rate to 50% in the next few years. Accelerating the pace of treatment will have multiple important benefits, including lower mortality and improved functional outcomes.

The study from the IST-3 investigators shows long-term benefits for functional status with prior thrombolytic therapy. Although multiple factors can affect health status 18 months after stroke (such as cardiac issues and infectious complications), the persisting improvements in functional status with prior thrombolytic therapy are reassuring.

Thrombolysis (different doses, routes of administration and agents) for acute ischaemic stroke..

BACKGROUND: Stroke is a leading cause of death and disability world wide. Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is licensed for treatment of acute ischaemic stroke in the early hours after symptom onset. It has been shown in randomised controlled trials (RCTs) and the 2009 Cochrane review of thrombolysis for acute ischaemic stroke to reduce dependency but at the increased risk of intracranial haemorrhage. Methods to reduce the risk of haemorrhage while retaining or enhancing the benefit could increase the use of thrombolytic treatment. While most available information comes from RCTs of intravenous rt-PA at 0.9 mg/kg, it is possible that other doses, drugs and other routes of administration might increase benefit and reduce the hazard.

OBJECTIVES: To assess the risks and benefits of different thrombolytic agents, doses and routes of administration for the treatment of acute ischaemic stroke. SEARCH
METHODS: We searched the Cochrane Stroke Group Trials Register (May 2012), MEDLINE (1966 to May 2012) and EMBASE (1980 to May 2012). We handsearched journals and conference proceedings, searched ongoing trials registers and contacted pharmaceutical companies and researchers.
SELECTION CRITERIA: Unconfounded randomised and quasi-randomised trials of different doses of a thrombolytic agent, or different agents, or the same agent given by different routes, in people with confirmed acute ischaemic stroke.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and quality, and extracted the data using a structured proforma. We cross-checked and resolved discrepancies by discussion to reach consensus. We obtained translations and additional information from study authors where required.
MAIN RESULTS: We included 20 trials involving 2527 patients. Concealment of allocation was poorly described. Different doses (of tissue plasminogen activator, urokinase, desmoteplase or tenecteplase) were compared in 13 trials (N = 1433 patients). Different agents (tissue plasminogen activator versus urokinase, tissue-cultured urokinase versus conventional urokinase, tenecteplase versus tissue plasminogen activator) were compared in five trials (N = 875 patients). Five trials (N = 485) compared different routes of administration. As some trials compared different agents and different doses, some patients contributed to two analyses. There was an approximately three-fold increase in fatal intracranial haemorrhages in patients allocated to higher than to lower doses of the same thrombolytic drug (odds ratio (OR) 2.71, 95% confidence interval (CI) 1.22 to 6.04). There was no difference in the number of patients who were dead or dependent at the end of follow-up between those allocated higher or lower doses of thrombolytic drug (OR 0.86, 95% CI 0.62 to 1.19). Higher versus lower doses of desmoteplase were associated with more deaths at the end of follow-up (OR 3.21, 95% CI 1.23 to 8.39). There was no evidence of any benefit for intra-arterial over intravenous treatment.
AUTHORS’ CONCLUSIONS: These limited data suggest that higher doses of thrombolytic agents may lead to higher rates of bleeding. However, the evidence is inadequate to conclude whether lower doses of thrombolytic agents are more effective than higher doses, or whether one agent is better than another, or which route of administration is the best, for acute ischaemic stroke. At present, intravenous rt-PA at 0.9mg/kg as licensed in many countries appears to represent best practice and other drugs, doses or routes of administration should only be used in randomised controlled trials.


According to this Cochrane meta-analysis, we still do not know which is the best thrombolytic agent nor he best dose nor the route of administration. We just have know that treating ischemic strokes with thrombolysis gives patients better quality of life and functional capacity up to 18 months later, according to new findings from the IST-3 study, published in the Lancet Neurology.

Source: Cochrane database


When It Comes to Stroke Treatment, Just 15 Minutes Can Make a Difference.

In patients with acute ischemic stroke, even small reductions in the time to thrombolytic therapy are associated with improved outcomes, according to a study in JAMA.

Using a national stroke registry, U.S. researchers examined outcomes among some 58,000 patients, at nearly 1400 hospitals, who received intravenous tissue plasminogen activator (tPA) within 4.5 hours after symptom onset. They found that with each 15-minute decrease in time to tPA therapy, patients were significantly less likely to die in the hospital or experience intracranial hemorrhage (odds ratio for each, 0.96). In addition, each 15-minute reduction was significantly associated with a greater likelihood to walk independently at discharge (OR, 1.04) and to be discharged home (OR, 1.03).

“These findings support intensive efforts to accelerate hospital presentation and thrombolytic treatment in patients with stroke,” the researchers conclude.

Source: JAMA