This brief post mentions some of the landmark clinical trials regarding post-stroke secondary prevention. A summary of the data regarding the current state of stroke pharmacotherapy & treatment is presented. Perfect for the medical student on the stroke team/neurology.
Stroke Secondary Prevention Trials
- IST: (Intl. Stroke Trial) & CAST (Chinese Aspirin Stroke Trial): Aspirin reduces about 10 deaths/recurrent strokes per 1000 in short term (weeks) after stroke – start aspirin with 48hrs after stroke.
- CAPRIE: (Clop + Asp for Prev. of Recurrent Isch. Events): Long-term treatment (1 to 3 years) with Clopidogrel in Stroke, MI, or PAD was more effective than Aspirin. Clopidogrel is slightly superior to aspirin in high risk groups.
- CHARISMA: dual antiplatelet therapy (aspirin + clopi) in patients with ESTABLISHED CVS disease IS BENEFICIAL at reducing MI, stroke. Not beneficial in other patients.
- SPARCLE: supports the use of aggressive reduction in cholesterol levels for 2˚ stroke prevention
- PROGRESS: ACEi (Perindopril) reduces risk of ischaemic or haemorrhagic stroke in patients with established CVS disease, regardless of whether or not the stroke was haemorrhagic or ischaemic OR whether or not the patient was hypertensive. Reduces mortality by 30 %
- CURE: (Clopidogrel for Unstable Angina to prevent recurrence): Clopidogrel + Aspirin is superior to monotherapy by 20%
Q “Tell me about Stroke Trials”
Regarding stroke trials and secondary prevention, the IST and CAST trials show that Aspirin should be started with 48hrs after stroke as it reduces death and recurrent stroke in the short term. The CAPRIE trial showed that clopidogrel is superior to aspirin in the long term. CHARISMA furthermore indicates that dual antiplatelet therapy in the form of Aspirin + Clopidogrel is beneficial and may be superior to monotherapy, however dual antiplatelet therapy post-ischemic stroke has many differing studies and individual patient population and risk factors must be taken into account.
Regarding statin therapy, the SPARCLE trial showed that agreessive cholesterol reduction prevents secondary stroke, and should be initiated in all those following ischemic stroke.
Finally, regarding ACE inhibitors, the PROGRESS trial showed that in all types of stroke – both hemorrhagic and ischemic – ACEi’s reduce all-cause mortality by approximately 30% regardless of whether HTN is present or not. It is important to note however that dropping blood pressure too fast and too early following the cerebral insult has been linked to increased morbidity and mortality.
Currently, novel stroke trials are investigating the use of local tPa administration to the sit of ischemic insult via interventional radiology. While (tPa) alteplase has been the standard of care in ischemic stroke trials for the last many years – it has recently come into question regarding the true mortality benefit. Criteria now allow us to select patients more carefully and the true population who benefit from systemic thrombolytic therapy following ischemic stroke is likely quite modest – compared to what we have previously thought.