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Medication

(ref 229, 230)

Prompt treatment improves prognosis. Virtually all patients with stroke will need vascular risk factor control using medication.

Antihypertensives: Hypertension remains the most important risk factor for haemorrhage and infarction.

  • It should not generally be treated immediately after stroke. Only malignant hypertension is treated acutely.
  • Secondary prevention usually begins at about 2 weeks following stroke, aiming for a blood pressure <140/80 mmHg at all times.
  • After transient ischaemic attack, if there is no immediate access to specialist assessment, antihypertensive medication can be started at once.
  • The optimal first-line medication is a long-acting ACE inhibitor combined with a diuretic. However, it is likely that the most important action is to lower the blood pressure, with no definite evidence of a class-specific effect. (ref 231)
  • Lowering so-called ‘normal’ blood pressure after stroke may also be beneficial. (ref 231)

Antiplatelet treatment: Usually given to all those with ischaemic stroke both acutely and for secondary prevention. There is no definite evidence that giving aspirin (300 mg stat) acutely is detrimental to those with intracranial haemorrhage; (ref 232) however, most defer until the results of neuroimaging. There are three main strategies for antiplatelet use in secondary prevention:

  • aspirin alone (75 mg od)
  • aspirin combined with slow-release persantin (Asasantin Retard 200 mg bd)
  • clopidogrel (75 mg od)

Aspirin alone is first line, with clopidogrel usually reserved for those with aspirin intolerance and increasingly in those who have a further vascular event while on aspirin (so called aspirin failure). Combination aspirin with persantin may be of greater benefit than aspirin alone,(ref 233) but use of this combination first line is variable, some preferring to add persantin in the event of ‘aspirin failure’. Persantin alone is rarely used. Clopidogrel as monotherapy or combined with aspirin is being used increasingly in high-risk patients and those with concurrent ischaemic heart disease (ref 234) (BNF section 2.9)

Statins: Beneficial in secondary prevention whatever the level of blood cholesterol. Current practice is to start a statin in almost everyone following an ischaemic stroke  or TIA (ref 235)

Others: Warfarin is reserved for patients with atrial fibrillation and some other cardiac conditions.

Antiplatelet treatment and statins are not monitored beyond ensuring normalization of cholesterol levels, if raised. Treatment of hypertension needs long-term and sometimes intensive short-term monitoring and titration. Patients after stroke need medication in addition to lifestyle measures. Patients need to understand that this triple approach is additive and that the reduction in risk afforded is long term and not from day to day.

References

229 Gubitz G, Sandercock P. Stroke management. Clin Evidence 2002; 8: 169-183. (AI) This systematic review in people with ischaemic stroke found that giving aspirin (compared with placebo) within 48 hours of stroke onset significantly reduces death or dependency at six months and significantly increases the numbers making a complete recovery. Specialist stroke rehabilitation units significantly reduce death or dependency after a median follow-up of one year compared with usual non-specialist care.

230 Clinical Evidence Writers on Stroke Prevention. Stroke prevention. Clin Evidence 2002; 8: 184-208. (AI) Antiplatelet treatment reduces the risk of serious vascular events in people with previous stroke or transient ischaemic attack (TIA) compared with placebo or no antiplatelet treatment. Antihypertensive treatment reduced stroke among people with a previous stroke or TIA, whether they were hypertensive or not. Low-dose aspirin (75-100 mg) daily is as effective as higher doses in the prevention of serious vascular events.

231 PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033-1041. (BII) This blood-pressure-lowering regimen reduced the risk of stroke among both hypertensive and nonhypertensive individuals with a history of stroke or transient ischaemic attack.

232 Sandercock P, Gubitz G, Foley P, Counsell C. Antiplatelet therapy for acute ischaemic stroke (Cochrane Review). In: The Cochrane Library, Issue 2, 2003. Oxford: Update Software. (AI) Nine studies were analysed. Antiplatelet therapy with aspirin at 160-300 mg daily, started within 48 hours of onset of presumed ischaemic stroke, reduces the risk of early recurrent ischaemic stroke without a major risk of early haemorrhagic complications and improves long-term outcome.

233 Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high-risk patients. Br Med J 2002; 324: 71-86. (Erratum appears in Br Med J 2002; 324: 141.) (AII) Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with ischaemic stroke or previous stroke. Low-dose aspirin (75-100 mg) is an effective antiplatelet regimen for long-term use, but in acute settings an initial loading dose of at least 150 mg may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.

234 Hankey GJ, Sudlow CLM, Dunbabin DW. Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients (Cochrane Review). In: The Cochrane Library, Issue 2, 2003. Oxford: Update Software. (AI) Four studies were analysed. Thienopyridine derivatives are modestly but significantly more effective than aspirin in preventing serious vascular events in patients at high risk (and specifically in transient ischaemic attack/ischaemic stroke patients), but there is uncertainty about the size of the additional benefit.

235 Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002, 360: 7-22. (CII) Among the high-risk individuals studied, these antioxidant vitamins appeared to be safe. Although this regimen increased blood vitamin concentrations substantially, however, it did not produce any significant reductions in the five-year mortality from, or incidence of, any type of vascular disease, cancer or other major outcome.

Last edited: 26/1/2004


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