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Drug treatment in secondary prevention of stroke

Drug treatment in secondary prevention of stroke. Secondary stroke prevention Warlow C, et al. Lancet 2003;362:1211–24. Patients who have suffered a stroke or TIA remain at an increased risk of: A further stroke (about 5% per year, maybe 10% in the first year)

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Drug treatment in secondary prevention of stroke

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  1. Drug treatment in secondary prevention of stroke

  2. Secondary stroke prevention Warlow C, et al. Lancet 2003;362:1211–24 • Patients who have suffered a stroke or TIA remain at an increased risk of: • A further stroke (about 5% per year, maybe 10% in the first year) • MI (2–3% per year) Touze E et al. Stroke 2005;36:2748–55 • Stroke, MI or vascular death (about 7% per year) • Risks higher in the immediate period following a stroke/TIA: • Risk of further stroke may be 12% in first 30 days post stroke • Risk of stroke 10% in first 90 days post TIA • Even higher risks reported in some studies e.g. Coull AJ et al BMJ 2004;328:326–9 TIA = transient ischaemic attack MI = myocardial infarction

  3. Potential effects of secondary prevention Hankey GJ et al. Lancet 1999;354:1457–63 In a population of 1 million • There is a continuing pool of about 12,000 individuals who have had a previous TIA (n=3,000), stroke (n=8,000) or both (n=1,000) • Of these about 7% (800) will have a stroke each year (600 recurrent, 200 first strokes in TIA patients) • Effective secondary prevention strategies targeted at the 12,000 with prior stroke/TIA aim to avoid these 800 strokes Primary and secondary prevention important ‘It is estimated that 20,000 strokes a year could be avoided through preventive work on high blood pressure, irregular heartbeats, smoking cessation, and wider statin use’DH. National stroke strategy, Dec 2007

  4. Guidelines NICE • Stroke. Diagnosis and initial management of acute stroke and TIA, CG 68, July 2008 • Clopidogrel and MR dipyridamole in the prevention of occlusive vascular events, TA 90, May 2005 Royal College of Physicians (RCP) • National Clinical Guideline for stroke, 3rd edition, July 2008 Scottish Intercollegiate Guidelines Network (SIGN) • Management of patients with stroke or TIA, SIGN Guideline 108, Dec 2008 Clinical Knowledge Summaries (CKS) • Stroke and TIA, Feb 2008 Department of Health (DH) • National Stroke Strategy, Dec 2007 Other relevant NICE guidance • Management of hypertension in primary care, CG 34, June 2006 • Lipid modification, CG 67, May 2008 MR = modified-release

  5. Secondary prevention of strokeInterventions recommendedRoyal College of Physicians (RCP) July 2008 • Advice on lifestyle factors to all patients: • Stopping smoking • Regular exercise • Diet and achieving a satisfactory weight • Reducing the intake of salt • Avoiding excess alcohol • Blood pressure management • Antithrombotic treatment • Lipid-lowering agents • Carotid surgery (see NICE CG 68, July 2008)

  6. Antiplatelets for secondary prevention of strokeRCP. National Clinical Guideline for stroke. 3rd edition, July 2008NICE TA 90, May 2005 SIGN Guideline No. 108, Dec 2008 Which regimen? • MR dipyridamole and aspirin following an ischaemic stroke or a TIA NICE/RCP/SIGN How long for? • Continue for 2 years. Thereafter, or if MR dipyridamole not tolerated, revert to standard care (including long-term aspirin) NICE 2005, but… • RCP 2008andSIGN 2008do not restrict duration of combination treatment to 2 years What doses? • MR dipyridamole 200mg twice dailyNICE/RCP/SIGN • Aspirin • 50mg to 300mg daily RCP • 75mg daily SIGN • ‘low-dose aspirin (75mg/day) is tolerated by most people’ NICE

  7. What about people with tolerability issues?RCP. National Clinical Guideline for stroke. 3rd edition, July 2008NICE TA 90, May 2005 SIGN Guideline No. 108, Dec 2008 With MR dipyridamole • When using MR dipyridamole + aspirin, if MR dipyridamole not tolerated, revert to standard care (including long-term aspirin) NICE/RCP • Dose titration of dipyridamole may help to reduce the incidence of headache SIGN With aspirin • If proven hypersensitivity to aspirin or history of severe dyspepsia induced by low-dose aspirin, use clopidogrel alone (within licensed indication NICE) NICE/RCP/SIGN • Unable to make a recommendation for patients in whom aspirin contraindicated because of history of peptic ulcer. NICE • ‘Addition of a proton pump inhibitor should only be considered when there is dyspepsia or other significant risk of gastrointestinal bleeding associated with aspirin, to allow aspirin medication to continue’RCP

  8. RCP further recommendationsRCP. National Clinical Guideline for stroke. 3rd edition, July 2008 Recurrent stroke/TIA • Manage in the same way as those who have had a single event Intensifying treatment • ‘More intensive antiplatelet therapy or anticoagulation should only be given as part of a clinical trial or in exceptional circumstances’ Anticoagulation • Every patient with persistent or paroxysmal AF (unless contraindicated) • Don’t start unless haemorrhage excluded and not usually until at least 14 days after inset of disabling ischaemic stroke • Not for patients in sinus rhythm unless major cardiac source of embolism identified TIA = transient ischaemic attack AF = atrial fibrillation

  9. Antihypertensives for secondary prevention of strokeRCP. National Clinical Guideline for stroke. 3rd edition, July 2008NICE Hypertension CG 34, June 2006 SIGN Guideline No. 108, Dec 2008 • Check BP of all patients. Treatmentshould be‘in keeping’ with nationalguidelines. RCP i.e. see NICE hypertension guideline • Beta blockers should not usually be started 1st or 2nd line for preventing recurrent stroke, unless there are other specific clinical indications. RCP • Aim for 140/90 mmHg, unless diabetes. NICE. But RCP aim for 130/80 mmHg (higher if internal carotid artery stenosis) RCP • RCP agrees with NICE hypertension guideline 2006 except for target BP • Treat if BP >140/90 mmHg NICE • But SIGN slightly different: Consider allpatients for ACEI plus thiazide, regardless of BP unless CI. SIGN BP = blood pressure ACEI = ACE-inhibitor CI = contraindicated

  10. What does NICE recommend regarding lipid-lowering drugs?NICE, Lipid modification, CG 67, May 2008 • Offer statin therapy to everyone with established CVD • Do not delay to manage modifiable risk factors • Treat comorbidities and secondary causes of dyslipidaemia • Decision to treat should follow an informed discussion about risks and benefits • Initiate treatment with simvastatin 40mg • Offer people with ACS a higher intensity statin (see Lipid floor) • If simvastatin 40mg is contraindicated, offer a lower dose or alternative preparation (such as pravastatin) CVD = cardiovascular disease ACS = acute coronary syndrome

  11. What does NICE recommend? High doses of statins and targetsNICE CG 67: Lipid modification May 2008 • ‘Consider increasing to simvastatin 80mg or a drug of similar efficacy and acquisition cost if a total cholesterol of less than 4mmol/litre or an LDL cholesterol of less than 2mmol/litre is not attained’ • ‘Any decision to offer a higher intensity statin should take into account the patient's informed preference, comorbidities, multiple drug therapy, and the benefits and risks of treatment’ • NB A single cholesterol level reading may well under- or over-estimate a person’s true average cholesterol level by up to 14% LDL cholesterol = low density lipoprotein cholesterol

  12. Summary • Mortality, morbidity and disability are high after a stroke • Guidelines recommend trying to reduce the risk of recurrent stroke or other CV events by secondary prevention strategies: • Lifestyle advice (and programmes) • Antiplatelet treatment (low-dose aspirin plus MR dipyridamole) • BP lowering if hypertensive • Lipid-lowering

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