Admission Rates, Time Trends, Risk Factors, and Outcomes of Ischemic and Hemorrhagic Stroke From German Nationwide Data

Discussion

We present nationwide data regarding the rates of hospitalized stroke in Germany from 2014 to 2019 along with subtype-specific demographics, clinical characteristics, complications, and outcomes. Overall, there were stable rates of stroke hospitalization during this time period with a small decline observed in recent years. Use of IV thrombolysis and mechanical thrombectomy progressively increased during this period along a parallel increase in the rate of hemorrhagic transformation. However, despite greater therapeutic intervention, in-hospital stroke mortality rates did not improve over this period, with hemorrhagic subtype and several comorbidities including CHF, LEAD, and cancer all predictive of a greater risk of death.

These national data show small decreases in rates of hospitalized stroke for both ischemic and hemorrhagic subtypes in Germany in 2018 and 2019. Our results are in keeping with reductions in stroke hospitalization and severity that have been observed in other developed countries including Israel,¹⁷ Norway,¹⁸ and the United Kingdom.¹⁹ These changes may reflect improved control of cardiovascular risk factors, the availability of high-equality evidence and guidelines on best practices in primary and secondary stroke prevention,^20,21 and more proactive implementation of stroke prevention clinics. Better hypertension control and improved antihypertensive use have also been reported in Germany during this time period.²² Reassuringly, in contrast to some previous population-based studies, we did not find an increasing stroke admission rate in younger age groups.^23,–,25 This discrepancy may relate to the more recent time period of this study because those studies that previously reported increases in “young stroke” were generally comparing the 1990s with the early 2000 period, after which this apparent increase appeared to plateau.^24,26 Although one may have expected greater reductions in hospitalization rates by the end of the period, improvements in diagnosis over time could have resulted in more accurate diagnoses in later years, thus affecting rates.

Few studies have looked at recent temporal trends in patient characteristics among acute stroke patients.²⁷ Overall, the number, median age, and risk factor profile among stroke patients remained stable between 2014 and 2019 in Germany. Ischemic stroke patients were more multimorbid with a greater prevalence of hypertension, atrial fibrillation, coronary heart disease, CKD, diabetes mellitus, dyslipidemia, and dementia compared with hemorrhagic stroke patients. A premorbid diagnosis of cancer was more prevalent in the latter group. These risk factor differences between the major stroke subtypes appear to be consistent over time and with prior literature.²⁸ Multimorbidity burden in stroke has important implications because it has been associated with an increasing risk of all-cause mortality, with mortality risk more than doubled for those with at least 5 morbidities compared with those with none.²⁹

For therapies and complications, there was nearly a three-fold increase in mechanical thrombectomy rates along with a smaller increase in IVT numbers during this time period. However, this was accompanied by increased hemorrhagic transformation. These changes align with the growing evidence during this period that thrombolytic therapy and mechanical thrombectomy among eligible patients were associated with less death and dependency despite a relative increase in symptomatic ICH in those treated with IVT.^5,30 Decompressive craniectomy rates remained stable for both ischemic and hemorrhagic stroke patients. The hemorrhagic stroke group experienced a greater number of poststroke complications with higher rates of bleeding and need for blood transfusion, AKI and requirement for RRT, sepsis, and cardiac arrest. They also had more complex care needs including requirement for mechanical ventilation, longer lengths of stay, and associated higher health care costs. These complications in the acute phase have been shown to worsen brain injury and have been linked to worse outcomes after hemorrhagic stroke.^31,32

In-hospital mortality rates were higher among patients with ICH compared with those with ischemic stroke. Despite recent improvements in evidence-based therapies³³ and postacute stroke management including stroke units³⁴ in the past decade, mortality rates did not improve for either subtype during the study time period. For ischemic stroke, these findings somewhat conflict with the improved short-term fatality rates observed in other population-based studies.^12,35 However, this discrepancy may be attributable to the relatively narrow time window of this study or to the crude trends that we present in comparison with some of the former studies. Because only aggregate data were available, we were unable to produce age-standardized rates, where improvement for ischemic stroke mortality has been previously described.¹² In contrast, the high mortality rates that we report after ICH are similarly well-described in other contemporary cohorts,^36,37 likely related to the lack of effective therapeutic options³¹ and the high complication rate as described above.³² There have been no successful phase 3 clinical trials for acute interventions in ICH to date. Therefore, admission to dedicated stroke or neurocritical care units with intensive prevention or early detection of complications has been proposed as the best approach to improve ICH outcomes.³⁸

Cancer, LEAD, and CHF were all strongly predictive of in-hospital mortality in both groups of patients. The association of cancer with poor survival after stroke has been well-described,³⁹ particularly in the setting of cryptogenic mechanisms, lung cancer, and systemic metastasis.⁴⁰ These factors are closely linked to hypercoagulability⁴¹ and correction of coagulopathy in the setting of cancer appears to be protective for stroke survival.⁴² Similarly, the presence of LEAD is known to increase the risk of secondary cardiovascular death and events,⁴³ including both ischemic and hemorrhagic stroke,⁴⁴ particularly if severe–that is, baseline ankle-brachial index (ABI) < 0.60 or history of amputation.⁴⁵ There is emerging evidence for the role of dual hemostatic blockade (aspirin and low-dose rivaroxaban) in such patients with polyvascular disease as it was associated with a lower risk of the composite outcome of cardiovascular death, stroke, or myocardial infarction in the COMPASS trial.⁴⁶ Stroke in patients with CHF has also previously been reported to be associated with worse outcomes and higher mortality,⁴⁷ underscoring the need for better prevention and treatment strategies in this vulnerable group.

This present study has many strengths resulting from the rigorous methodology applied to nationwide data, including consistency across cases. This is also a large and comprehensive sample of unselected participants who are also unbiased by insurance status, geographic location, or providing institution, and, therefore, the observed trends are high applicable to daily practice. High-quality, country-specific epidemiologic data such as these are an important way to monitor the global stroke burden.¹³

However, our study has several limitations. First, our analysis of administrative data may be subject to miscoding of ICD codes and despite rigorous abstraction processes, variation in reporting may still be present. Second, data acquisition was case-based rather than patient-based and, therefore, there could have led to a certain number of double-counted patients, for example, by hospital transfer. Third, hospital-based data has some inherent limitations including selection bias related to the indication for admission which is influenced by stroke severity and prognosis, and variable access to specialized stroke units and center-specific services. As such, hospitalization data may not reflect the full burden of stroke in the population. However, because Germany has a health care system with a very high admittance rate for transient ischemic attack and minor stroke, this national data set is very inclusive and representative of all cases of acute stroke. Fourth, because data were limited to ICD codes, no medication, laboratory or imaging data were available for analysis. For this reason, we were also unable to capture discharge disposition information (i.e., home, rehabilitation hospital, or nursing facility) which would have enhanced the richness of this report. Finally, we were unable to distinguish first from recurrent strokes because of the case-based nature of the data.

In conclusion, we have presented a nationwide, administrative data analysis of all patients hospitalized with acute stroke in Germany from 2014 to 2019. There were favorable trends toward improved rates of hospitalization in recent years although these were still accompanied by high in-hospital mortality rates, particularly for patients with ICH, who require research prioritization to identify novel therapeutic tools and optimal strategies to prevent and treat early complications. Our study also highlighted the impact of multimorbidity on short-term stroke survival and the need to personalize management strategies to these comorbidities.