Stroke and cholesterol

• primary prevention - reduction in risk of first stroke with lipid lowering treatment
  • a meta-analysis of statin trials, including the Heart Protection Study (HPS), revealed that for an average reduction of about 1.0 mmol/l in LDL cholesterol there was a 21% reduction in stroke risk (95% CI 0.73 to 0.85) (1)
  • a more recent meta-analysis showed a 17% proportional reduction in the incidence of first stroke of any type (rate ratio 0.83, 95% CI 0.78 to 0.88) per mmol/l lower LDL cholesterol
    • the reduction in incidence was a result of a 19% reduction in ischaemic strokes (0.81, 95% CI 0.74 to 0.89) and no apparent difference in haemorrhagic stroke
  • therefore there is evidence from clinical statin therapy trials for stroke primary prevention via statin treatment. This applies to people with established CVD, those with hypertension, diabetes, and others who are at high total risk of developing CVD (3)
    • the TNT study has examined the use of high dose versus low dose statin therapy and stroke risk in patients with CHD (4):
      • a prespecified secondary endpoint analysis was undertaken comparing the two atorvastatin doses and risk of stroke:
        
        • the study found that among patients with established coronary disease, treating to an LDL-cholesterol substantially below 100 mg/dl with 80 mg/day atorvastatin reduces both stroke and cerebrovascular events by an additional 20% to 25% compared with the 10 mg/day dose
          • cerebrovascular events
            • 3.9% (atorvastatin 80mg per day); 5% (atorvastatin 10mg per day)
            • RRR 23% (95% CI 7 to 35); NNT 89 (57 to 593)
        • an increase in hemorrhagic stroke was not seen at low LDL-C levels. However there was a 6 fold increase in consecutive abnormal LFTs (1.2% v 0.2%)
• secondary prevention - use of statin treatment following a stroke
  
  
  • the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial revealed evidence that, in patients with recent stroke or TIA and without known coronary heart disease, 80 mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events, despite a small increase in the incidence of hemorrhagic stroke (5)

Notes:

• a meta-analysis involving 121,000 patients examined the use of statin therapy in stroke prevention (6):
  • only one trial reported on statin therapy for secondary prevention (5) and was included in the meta-analysis
  • pooled RR of statin therapy for all-cause mortality (n=116,080) was 0.88 (95% CI, 0.83-0.93). Each unit increase in low-density lipoprotein (LDL) resulted in a 0.3% increased RR of death (P=.02)
  • the authors concluded that statin therapy provided high levels of protection for all-cause mortality and nonhemorrhagic strokes.
  • reinforces the need to consider prolonged statin treatment in patients at high risk of major vascular events, but caution remains for patients at risk of bleeds - although in this meta-analysis groups did not differ for haemorrhagic strokes (eleven trials reported hemorrhagic stroke incidence (total n=54,334, RR 0.94, 95% CI, 0.68-1.30)

Reference:

• (1) Amarenco P, Labreuche J, Lavallee P, et al. Statins in stroke prevention and carotid atherosclerosis. Systematic review and up-to-date, meta-analysis. Stroke 2004;35:2902-9.
• (2) Cholesterol Treatment Trialists? Collaboration. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis for date from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-78.
• (3) JBS2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005; 91 (Supp 5).
• (4) Waters DD et al. Effects of high-dose atorvastatin on cerebrovascular events in patients with stable coronary disease in the TNT (treating to new targets) study. J Am Coll Cardiol. 2006 Nov 7;48(9):1793-9.
• (5) N Engl J Med. 2006 Aug 10;355(6):549-59
• (6) O'Regan C et al. Statin therapy in stroke prevention: a meta-analysis involving 121,000 patients. Am J Med. 2008 Jan;121(1):24-3