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Therapeutics

Atorvastatin reduced stroke and CV events after recent stroke or TIA in patients with no known coronary heart disease

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ACP J Club. 2007 Jan-Feb;146:7. doi:10.7326/ACPJC-2007-146-1-007


Clinical Impact Ratings

GIM/FP/GP: 5 stars

Geriatrics: 5 stars

Neurology: 6 stars


Source Citation

The SPARCL Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549-59. [PubMed ID: 16899775]


Abstract

Question

In patients with no known coronary heart disease (CHD) and recent stroke or transient ischemic attack (TIA), is atorvastatin more effective than placebo for reducing stroke?

Methods

Design: Randomized placebo-controlled trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels [SPARCL] trial).

Allocation: {Concealed}†.*

Blinding: Blinded (clinicians, patients, data safety and monitoring committee, {data collectors, outcome assessors, and data analysts}†).*

Follow-up period: Median 4.9 years (range 4.0 to 6.6 y).

Setting: 205 centers in 27 countries.

Patients: 4731 patients > 18 years of age (mean age 63 y, 60% men) who had ischemic or hemorrhagic stroke or TIA 1 to 6 months before randomization, were ambulatory, had a modified Rankin score ≤ 3, and a low-density lipoprotein (LDL) cholesterol level 100 to 190 mg/dL (2.6 to 4.9 mmol/L). 69% of enrolled patients had had previous stroke. Exclusion criteria included atrial fibrillation, embolism from other cardiac sources, and subarachnoid hemorrhage.

Intervention: Atorvastatin, 80 mg/d (n = 2365), or placebo (n = 2366).

Outcomes: Fatal or nonfatal stroke. Secondary outcomes included all-cause death and 7 composite endpoints: stroke or TIA; cardiac death, nonfatal myocardial infarction, or resuscitation after cardiac arrest (major coronary event); stroke plus any major coronary event (major cardiovascular [CV] event); major coronary event or unstable angina (acute coronary event); acute coronary event plus coronary revascularization, unstable angina, or angina or ischemia requiring hospitalization (any coronary event); coronary, carotid, or peripheral revascularization; and any previous composite endpoint plus peripheral vascular disease (any CV event).

Patient follow-up: 96% (intention-to-treat analysis).

Main results

Atorvastatin reduced fatal or nonfatal stroke and all 7 secondary composite endpoints more than did placebo (Table). Groups did not differ for all-cause death (9.1% vs 8.9%; hazard ratio 1.0, 95% CI 0.8 to 1.2).

Conclusion

In patients with no known coronary heart disease and recent stroke or transient ischemic attack, atorvastatin reduced stroke and coronary and cardiovascular events.

*See Glossary.

Source of funding: Pfizer.

For correspondence: Dr. K.M.A. Welch, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA. E-mail michael.welch@rosalindfranklin.edu.


Table. Atorvastatin vs placebo in patients with no known coronary heart disease and recent stroke or transient ischemic attack (TIA) at median 4.9 years‡

Outcomes Atorvastatin Placebo RRR (95% CI) NNT (CI)
Fatal or nonfatal stroke 11% 13% 15% (0.9 to 28) 51 (28 to 817)
Composite endpoint of stroke or TIA 16% 20% 21% (11 to 31) 24 (17 to 46)
Major coronary event§ 3.4% 5.1% 34% (13 to 50) 58 (40 to 156)
Major CV event|| 14% 17% 19% (7.3 to 29) 32 (21 to 80)
Acute coronary event¶ 4.3% 6.4% 34% (16 to 49) 46 (32 to 101)
Any coronary event** 5.2% 8.6% 41% (26 to 53) 29 (22 to 45)
Revascularization 4.0% 6.9% 44% (27 to 56) 33 (26 to 54)
Any CV event†† 22% 29% 23% (15 to 30) 16 (12 to 24)

‡CV = cardiovascular. Other abbreviations defined in Glossary; RRR, NNT, and CI calculated from control event rates and adjusted hazard ratios in article.
§Cardiac death, nonfatal myocardial infarction, or resuscitation after cardiac arrest.
||Stroke plus any major coronary event.
¶Major coronary event or unstable angina.
**Acute coronary event plus coronary revascularization, unstable angina, or angina or ischemia requiring hospitalization.
††Any previous composite endpoint plus peripheral vascular disease.


Commentary

The SPARCL trial was the first to evaluate the effects of statins on patients with cerebrovascular disease but without known CHD. Patients who received atorvastatin, when compared with those who received placebo, had a 2.2% absolute risk reduction (ARR) in stroke and a 3.5% ARR in vascular events (stroke or major cardiac event) after 5 years. To put these numbers in perspective, this magnitude of ARR is similar to that of antiplatelet therapy (1).

Before SPARCL, the only available data on statins in patients with cerebrovascular disease were from a subgroup analysis of the Heart Protection Study (HPS) (2). HPS did not show a reduction in recurrent stroke rates, although there was a 5.1% ARR in vascular events over 5 years. SPARCL and HPS differ in 2 important ways. First, SPARCL enrolled patients much sooner after a cerebrovascular event than did HPS. Because recurrent stroke rates are highest in the first year, statins given sooner after a stroke may have a greater effect on reducing these rates. Second, patients in SPARCL received a larger dose of a more potent statin than did patients in HPS. Accordingly, the mean LDL reduction was greater in SPARCL than in HPS (56 vs 39 mg/dL).

One caveat is that patients taking statins in both SPARCL and HPS had a higher absolute risk for hemorrhagic stroke by 0.6% to 0.9% over the duration of their studies.

SPARCL showed that statins modestly reduced risk for both stroke and vascular events in patients with recent stroke without known CHD. Along with antithrombotic and antihypertensive therapy, statins should be given to most patients with a recent cerebrovascular event to prevent further vascular events.

Eric Cheng, MD, MS
Veterans Affairs Greater Los Angeles Healthcare System and University of California, Los Angeles
Los Angeles, California, USA


References

1. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71-86. [PubMed ID: 11786451]

2. Collins R, Armitage J, Parish S, Sleight P, Peto R. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet. 2004;363:757-67. [PubMed ID: 15016485]