Kamal, Ayeesha Kamran

Khan, Maria

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eCommons@AKUSection of Neurology Department of MedicineJune 2010High dose atorvastatin after stroke or transientischaemic attack (SPARCL)--does every strokepatient in Pakistan deserve a statinMaria KhanAga Khan UniversityAyeesha Kamran KamalAga Khan UniversityFollow this and additional works at: http://ecommons.aku.edu/pakistan_fhs_mc_med_neurolPart of the Neurology CommonsRecommended CitationKhan, M., Kamal, A. (2010). High dose atorvastatin after stroke or transient ischaemic attack (SPARCL)--does every stroke patient inPakistan deserve a statin. Journal of the Pakistan Medical Association, 60(6), 505-6.Available at: http://ecommons.aku.edu/pakistan_fhs_mc_med_neurol/24Vol. 60, No. 6, June 2010 505Evidence Based MedicineHigh dose Atorvastatin after stroke or Transient IschaemicAttack (SPARCL) — Does every stroke patient in Pakistan deserve a statin?Maria Khan, Ayeesha Kamran KamalStroke Service and Vascular Fellowship Program, Aga Khan University Hospital, Karachi, Pakistan.Why is this study important? It was well established from previous studies thattherapy with 3-hydroxy-3-methylglutaryl coenzyme Areductase inhibitors (statins) reduces the risk of strokeamong patients with coronary heart disease and those atincreased risk for cardiovascular disease. But prior to thisstudy no data existed regarding the benefits of statins inpatients with history of stroke or transient ischemic attacks.The aim of Stroke Prevention by AggressiveReduction in Cholesterol Levels (SPARCL) trial was todetermine the impact of 80 mg of Atorvastatin per day onstroke prevention in patients with history of stroke or TIAwithin the past six months and with no known history ofcoronary artery disease. Who were the participants?Patients were eligible if they had a stroke or TIA oneto six months before randomization. Haemorrhagic strokeswere also included if the physicians felt that these patientswere at risk of ischaemic events. Patients withcardioembolic strokes, subarachnoid haemorrhage,LDL<100 and modified Rankin score greater than 3 wereexcluded. A patient with a Modified Rankin Score of 3 is apatient with Moderate disability; requiring some help, butable to walk without assistanceThese patients were selected from twenty sevencountries across five continents. Majority of the patientswere from Europe. The contribution from the Middle Eastwas limited to just 61 patients from Israel. There were noSouth Asian patients in this landmark trial.What was the intervention?A total of 6670 patients were screened, 4731 weredeemed eligible and were randomly assigned to double-blind therapy with either 80 mg of Atorvastatin per day orplacebo. 2365 were randomized to active arm and 2366 tothe placebo arm. Follow-up visits were scheduled one, three, and sixmonths after enrollment and every six months thereafter.Patients were followed up for a median of 4.9 years.Efficacy and safety analyses were both on intention totreat basis.The two groups were well matched in terms of age,gender, blood pressure, entry event, other risk factors andconcomitant medication use. They were also well matchedwith respect to their baseline lipid values.What was the outcome?The mean values for LDL, total cholesterol andtriglycerides were significantly lower in the Atorvastatinarm compared to the placebo arm. Hence treatment wasadhered to. LDL cholesterol was 72.9±0.5 mg per deciliterin the Atorvastatin group, as compared with 128.5±0.5 mgper deciliter in the placebo group (P<0.001); totalcholesterol, 147.2±0.6 as compared with 208.4±0.6 mg perdeciliter (P<0.001); and triglycerides, 111.5±1.3 ascompared with 145.0±1.3 mg per deciliter, respectively(P<0.001). ); high-density lipoprotein (HDL) cholesterolwas 52.1±0.3 in the active arm as compared with 51.0±0.3mg per deciliter in the placebo arm (P = 0.006).A primary end point (any nonfatal or fatal stroke)occurred in 265 patients in the Atorvastatin group and 311in the placebo group (unadjusted P = 0.05). Afterprespecified adjustment for baseline factors, Atorvastatinwas associated with a 16.0 percent relative reduction in therisk of nonfatal or fatal stroke (hazard ratio, 0.84; 95 percentconfidence interval, 0.71 to 0.99; P = 0.03).Analysis of secondary end points showed reductionsin the combined risk of stroke and TIA. The risk ofcardiovascular events, including major coronary events andrevascularization procedures, was reduced substantially.There was however, no significant difference betweentreatment groups in overall mortality.There were significant differences in the treatmenteffects based on the type of stroke. The risk was decreasedfor ischaemic and unclassified strokes but it was increasedfor haemorrhagic strokes with a hazard ratio of 1.66 (95%CI 1.08-2.55).Persistent elevation of alanine or aspartateaminotransferase (>3 times the upper limit of the normalgroup on two consecutive occasions) was more frequent inthe atorvastatin group (51 patients, or 2.2%) than in theplacebo group (11 patients or 0.5%). There were no cases ofliver failure. Safety analysis revealed no significant differences inthe two arms in terms of serious adverse events.What were the author's conclusions?The authors concluded that aggressive lowering ofcholesterol in patients with history of prior stroke or TIAsignificantly decreases the risk of recurrent non fatal stroke,major cardiovascular events and need for revascularization.On the basis of this data, 46 patients (95 percentconfidence interval, 24 to 243) would need to be treated forfive years to prevent one stroke, 29 patients (95 percentconfidence interval, 18 to 75) to prevent one majorcardiovascular event, and 32 patients (95 percentconfidence interval, 22 to 59) to avoid one revascularizationprocedure.So how important are statins in Pakistanistroke patients?After Diabetes and Hypertension, the third importantmodifiable risk factor for stroke is dyslipidaemia. This trialclearly shows that aggressive lowering of cholesterol inpatients 1-6 months from their stroke or TIA, reduces therisk of recurrent strokes and other cardiovascular events aswell. Until this study, most of us did not consider a stroke ora TIA an independent vascular indication for statinadministration. It is important for us to consider the cost,risk and benefits of statin therapy in every South Asianpatient with ischaemic stroke - at the very least. Although the study was not powered to detect impactin various stroke subtypes, there was an increase in the riskof haemorrhages overall. This effect may be magnified inSouth Asian setting as there is a relatively higher proportionof patients (30 % vs. 17%) who present with intracerebralhaemorrhage. Additionally, the liver enzymes must becarefully monitored in areas where Hepatitis is endemic.The potential risk of recurrent haemorrhage should beconsidered when one is deciding whether to administer astatin to patients who have had a haemorrhagic stroke andthe enzymes must be monitored judiciously. Although the numbers needed to treat for preventionare significant, this does not undermine the importance ofthe intervention. It does however, put statin therapy lowerdown in the priority list where cost is a major limitation totreatment. We should encourage local, cheaper genericstatins to assuage some of the cost issues with therapy. Recommended Reading: 1. SPARCL Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, et al.High dose Atorvastatin after stroke or transient ischemic attack. N Engl J Med2006; 355: 549-59.506 J Pak Med Assoc

High dose atorvastatin after stroke or transient ischaemic attack (SPARCL)--does every stroke patient in Pakistan deserve a statin

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