Depending on aetiology, the natural risk for stroke recurrence during the first year after event has been described between 5% [2
] (stroke patients without high risk factors) and 20% [15
]. A secondary ischemic event has considerably more serious consequences leading to physical disability in more than 60% and death in more than 20% [25
]. In addition to the medical and personal impact of the recurrent stroke, the costs of recurrent events and rehospitalisation are enormous. Lifetime costs per first ever stroke case are more than 40.000 Euro in Germany [26
Growing evidence suggests that early diagnostic work-up with consequent initiation of multimodal preventive measures results in a major reduction of re-events. In patients with TIA, the “effect of urgent treatment of transient ischemic attack and minor stroke on early recurrent stroke” (EXPRESS) study was conducted as a population based sequential comparison [27
]. It demonstrated that urgent assessment of stroke aetiology and early start of secondary prevention was associated with reduced risk for recurrent stroke. The interventions comprised immediate start of poly-pharmaceutical risk factor control, antithrombotic therapy and interventional treatment for symptomatic carotid stenosis. However, patients were followed-up for only three months. Very similar effects were found in the SOS-TIA study with much lower recurrence rates as expected according to the ABCD [2
] score [17
Hence, it seems of crucial importance to start a secondary prevention program at an early stage after the cerebrovascular event. This is particularly important because shortly after the index event, patients are generally very motivated for participation in a structured support program.
In contrast to other diseases such as diabetes mellitus, coronary heart disease and COPD, stroke has not been selected for chronic disease management programs in Germany. Therefore, neither hospitals nor primary care physicians are able to offer intensive monitoring of cardiovascular risk factors to patients after stroke or TIA. Recommendations given in discharge letters frequently focus on medical treatments but not on recommendations regarding non-pharmacological treatments such as life style modifications including physical activities and dietary aspects. Family members are usually not involved in the treatment concepts. Since lifestyle is strongly influenced by the social network, patients frequently continue the unhealthy lifestyle. Smoking, poor diet coupled with physical inactivity and alcohol consumption are still leading causes of mortality [28
While the primary objective of INSPiRE-TMS is to investigate the effects of a structured multifactorial support program on the vascular re-event-free survival time, a number of completed or ongoing randomized studies examine effects of supported secondary prevention on differences in risk factor control, medication adherence or surrogate parameters. To our knowledge, none of them has been adequately powered to detect a difference in vascular recurrence free survival time [29
Some limitations of the study will need to be considered: First, there is a potential contamination effect in patients who are randomized to the control group. With the information given before randomization and during follow-up visits, these patients may be better informed about effective vascular prevention compared to the normal post-stroke population. This effect is frequently seen in prospective controlled trials. However, it seems unlikely that this contamination will lead to the same effect as the structured intervention program. Second, the information about life style parameters, adverse events and endpoint events will be self-reported. Thus, self-reported errors are to be expected in both groups and expectation bias by study personnel may occur in follow-up documentation. In order to control for these biases, follow-up assessment is planned to be done by study nurses blinded to the trial arm and not involved in the individual support program. The primary endpoints and serious adverse events will be documented in a written form by the patient prior to the follow-up-interview and will be adjudicated by a blinded Endpoint Committee. Third, the study is conducted in two European health systems and generalizability of the study results may therefore be questioned. However, the methods of intervention are standardized as far as possible in individual counseling and both the quality of risk factor control and rate of recurrent events will be described in detail in the control and intervention arms. This should allow a projection of the study results into other health systems.
In summary, the INSPiRE-TMS trial is designed to answer the question whether a structured support program for secondary prevention after a cerebrovascular event is effective in reducing new major vascular events. The results of the trial are expected for the year 2016.