Is the Maximum Dose of 90 mg Alteplase Sufficient for Patients With Ischemic Stroke Weighing >100 kg?

Abstract

Background and Purpose— Intravenous alteplase for acute ischemic stroke has a maximum dose limit of 90 mg. Consequently, patients >100 kg body weight receive a lower per-kilogram dose compared with those ≤100 kg. We investigated if the lower per-kilogram dose is associated with poor early neurological improvement and worse outcome after thrombolysis. Methods— Of 27 910 patients registered in Safe Implementation of Treatment in Stroke–International Stroke Thrombolysis Register (SITS-ISTR; 2002 to 2009), 1190 (4.3%) weighed >100 kg. Major neurological improvement was used to estimate recanalization (National Institutes of Health Stroke Scale improvement ≥8 points or score of 0 at 24 hours). Outcome measures included symptomatic intracerebral hemorrhage (National Institutes of Health Stroke Scale deterioration ≥4 points within 24 hours and Type 2 parenchymal hemorrhage), functional independence (modified Rankin Scale 0 to 2), and mortality at 3 months. Results— Patients >100 kg received a lower per-kilogram alteplase dose (0.82 versus 0.90, P <0.001), were younger (62 versus 70 years, P <0.001), had a lower baseline National Institutes of Health Stroke Scale (10 versus 12, P <0.001), but more frequently had cardiovascular risk factors. Major neurological improvement at 24 hours occurred in 27.7% in both groups. Symptomatic intracerebral hemorrhage occurred in 2.6% versus 1.7% ( P =0.03) in >100 kg versus ≤100 kg. Functional independence was 59.7% versus 53.6% ( P <0.001) and mortality was 14.4% versus 15.1% ( P =0.54). After adjustment for baseline characteristics, there was no significant difference for major neurological improvement or functional independence between >100 kg and ≤100 kg, but >100-kg patients had a higher odds ratio for symptomatic intracerebral hemorrhage (OR, 1.6; 95% CI, 1.06 to 2.41; P =0.02) and mortality (OR, 1.37; 95% CI, 1.08 to 1.74; P =0.01). Conclusions— Our results support the current upper dose limit. There was a higher incidence of symptomatic intracerebral hemorrhage in patients >100 kg despite the lower per-kilogram recombinant tissue plasminogen activator dose. Major neurological improvement and functional independence were similar.

The Impact of Body Mass Index on the Thrombolytic Treatment of Acute Ischemic Stroke

“…Similarly, we found a significant difference concerning the relevant NIHSS score improvement, favoring the ≤ 100 kg group. This contradicts the findings by Diedler et al [5] , who found no significant difference for major neurological improvement or functional independence, despite a higher rate of symptomatic intracranial hemorrhage. It should be noted that outcome parameters differed slightly among these studies.…”

“…As shown in both previous studies on this topic, the male gender was significantly associated with weight >100 kg and patients were significantly younger [4,5] . Our patients >100 kg were also younger, even though statistical significance was marginally missed (p = 0.050).…”

“…Additionally, patients weighing >100 kg receive a lower relative dose of recombinant tissue plasminogen activator (rtPA) than the (western) standard of 0.9 mg rtPA per kilogram body weight, because the maximum dose of rtPA is limited to 90 mg [3] . This issue has been addressed only in a few studies, where no disadvantage for these patients was reported [4][5][6] . It is, however, an important topic, not only because the proportion of these patients is increasing but also because of the fact that in some areas (i.e.…”

Obesity paradox in stroke – Myth or reality? A systematic review

“…[38–43] The examined clinical endpoints were functional outcome, which was defined as favorable (mRS score 0 or 1), good (mRS 0–2) or poor (mRS 3–6). In addition, the following endpoints were measured: symptomatic and asymptomatic intracranial hemorrhages, discharge destination, and mortality.…”

“…[40] Diedler et al assessed data of 27’910 patients registered in Safe Implementation of Treatment in Stroke–International Stroke Thrombolysis Register (SITS-ISTR). [38] After adjustment for baseline characteristics, the odds ratio for favorable outcome was similar in patients ≤100 kg and >100 kg, but patients >100 kg (n = 1’190) had again a significantly higher risk for mortality (OR: 1.37, 95% CI 1.08–1.74). [38] Seet et al observed in their study on 169 patients that frequency of poor functional recovery and sICH were very similar among obese, overweight, and normal weight patients after IVT.…”