Neurology -- Correspondence for Blanco et al., 69 (9) 904-910

Correspondence published:

Statin treatment withdrawal in ischemic stroke: A controlled randomized study: Luca Mascitelli, Francesca Pezzetta, San Vito al Tagliamento, Italy (1 November 2007)

Reply from the authors: José Castillo, Miguel Blanco and Antonio Dávalos (1 November 2007)

Statin treatment withdrawal in ischemic stroke: A controlled randomized study 1 November 2007

Luca Mascitelli,
Comando Brigata alpina Julia
8 Via S. Agostino, Udine 33100 Italy,
Francesca Pezzetta, San Vito al Tagliamento, Italy
Send Correspondence to journal:
Re: Statin treatment withdrawal in ischemic stroke: A controlled randomized study

lumasci{at}libero.it Luca Mascitelli, et al.

Blanco et al. studied a selected group of patients who were receiving statins before admission for acute hemispheric ischemic stroke and found that statin withdrawal for the first three days of hospitalization was associated with increased risk of death or dependency at 3 months. [1]
These findings indicate that the beneficial effects of statin drugs in stroke patients are independent of their cholesterol-lowering action.[1] Mounting evidence suggests that serum cholesterol is inversely and almost linearly related to stroke severity, and consequently post-stroke mortality is inversely related to cholesterol levels. [2]
The Stroke Prevention with Aggressive Reduction in Cholesterol (SPARCL) study shows that—-as compared to placebo—-the use of high-dose atorvastatin in accurately selected patients who had a stroke or TIA is associated with a non significant 13% risk reduction of nonfatal stroke during a 5-year follow-up, without improving survival. In addition, it also showed a 66% increase in the relative risk of hemorrhagic stroke among the patients receiving high-dose statin. [3]
It has been shown that low-density lipoprotein (LDL) cholesterol levels are inversely related to incident intracerebral hemorrhage. [4] Lower LDL cholesterol levels with or without statin treatment have also been shown to be strongly and independently related to a higher risk of symptomatic hemorrhagic transformation after ischemic stroke thrombolysis. [5]
It should be noted that thrombolysis was an exclusion criteria in the study by Blanco et al. Therefore, we believe that the usefulness of aggressive cholesterol-lowering therapy in the prevention of stroke is still unclear.
References
1. Blanco M, Nombela F, Castellanos M, et al. Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology 2007; 69: 904-910.
2. Olsen TS, Christensen RH, Kammersgaard LP, Andersen KK. Higher total serum cholesterol levels are associated with less severe strokes and lower all-cause mortality. Ten-year follow-up of ischemic strokes in the Copenhagen Stroke Study. Stroke 2007;38:2646-2651.
3. Amarenco P, Bogousslavsky J, Callahan A 3rd, et al.; Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549-559.
4.Sturgeon JD, Folsom AR, Longstreth WT Jr, Shahar E, Rosamond WD, Cushman M. Risk factors for intracerebral hemorrhage in a pooled prospective study. Stroke 2007;38:2718-2725.
5. Bang OY, Saver JL, Liebeskind DS, et al. Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis. Neurology 2007;68:737-742.
Disclosure: The authors report no conflicts of interest.

Reply from the authors 1 November 2007

José Castillo,
Department of Neurology, Hospital Clínico Universitario, University of Santiago de Compostela
Travesa da Choupana, s/n, 15706 Santiago de Compostela, Spain,
Miguel Blanco and Antonio Dávalos
Send Correspondence to journal:
Re: Reply from the authors

mecasti{at}usc.es José Castillo, et al.

We appreciate Drs. Mascitelli and Pezzetta’s comments on our article. In contrast to their statement on the benefit of statin treatment in acute stroke, our study suggests that the harmful effect of statin withdrawal was not related to the cholesterol levels on admission. This finding is in line with a potential rebound phenomenon mediated by oxidative stress, excitotoxicity and suppression of NO bioavailability, related to the pleiotropic effects of statins and not linked to the cholesterol levels. [6]
The association between hypocholesterolemia and higher post-stroke mortality is confounded by the lower frequency of small-vessel disease and smaller subcortical infarctions in patients with low cholesterol levels. [2] Although preliminary findings indicate a higher risk of symptomatic hemorrhagic transformation in stroke patients with low LDL-cholesterol levels treated with tPA, an independent relationship with prior statin treatment was not found. [5] Consequently, in our opinion, there is no reason to withdraw statins in the acute phase of stroke.
Methodologically, it does not seem correct to concatenate the probable mechanisms involved in the preventive effect of statins on vascular events with their effects on the acute phase, even less to question, with the data of our study, the results of the SPARCL study. [7]
References
6. Endres M, Laufs U. Discontinuation of statin treatment in stroke patients. Stroke 2006;37:2640-2643.
7. Amarenco P, Bogousslavsky J, Callahan A 3rd, et al. Stroke Prevention by Aggressive Reduction in Cholesterol Lewels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic stroke. N Eng J Med 2006;355:549-559.
Disclosure: Dr. José Castillo, Dr. José Vivancos, and Dr. Antonio Dávalos are scientific advisors to Pfizer. Dr. Antonio Dávalos is a member of the SPARCL Writing Committee. The rest of the authors report no conflicts of interest.