Atorvastatin Reduces First and Subsequent Vascular Events Across Vascular Territories in the SPARCL Trial

Literature - Szarek M, Amarenco P, Callahan A et al. - J Am Coll Cardiol. 2020. doi: 10.1016/j.jacc.2020.03.015

Introduction and methods

Patients with a history of symptomatic ischemic cerebrovascular disease are at continued risk for subsequent events. Studies that focus only on first events do not reflect the total burden of a disease. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial showed that treatment with atorvastatin reduced first occurrence of stroke and first occurrence of a composite outcome of vascular events in patients with recent stroke or transient ischemic attack and no known coronary heart disease, compared to placebo [1]. This post-hoc analysis of the SPARCL trial evaluated the occurrence of total (first and subsequent) vascular events and determined the effect of atorvastatin in reducing these events. In addition, the effect of atorvastatin in reducing events was examined by vascular territory (cerebrovascular, coronary, or peripheral).

The SPARCL trial included patients (≥18 years of age) who had a stroke or transient ischemic attack 1-6 months prior to randomization, LDL-c levels of 100-190 mg/dL (2.6-4.9 mmol/L), and no known coronary heart disease. A total of 4,731 patients were randomized in a 1:1 ratio to receive either atorvastatin (80 mg daily) or matching placebo. The primary analysis of this post-hoc study included first and total vascular events (first and subsequent events). Median follow-up was 4.9 (4.4, 5.5) years.

Main results

• There were 1,212 first events and 2,046 total vascular events. 470 Of the 1,104 participants with a nonfatal first event experienced more than one vascular event (9.9% of the total study population).
• The estimated number of vascular events over six years in the placebo group was 41.2 for first events and 62.7 for total events per 100 patients. Treatment with atorvastatin reduced first vascular events by 27% (HR 0.73, 95%CI 0.66-0.82, p<0.001) and total vascular events by 32% (HR 0.68, 95%CI 0.60-0.77, p<0.001).
• Total cerebrovascular events were reduced with atorvastatin treatment by 24% (HR 0.76, 95%CI 0.66-0.88, p<0.001), total coronary events by 46% (HR 0.54, 95%CI 0.42-0.70, p<0.001), and total peripheral events by 44% (HR 0.56, 95%CI 0.35-0.89, p=0.014).
• Above a LDL-c level of 100 mg/dL at month 3, there was a weak relationship between LDL-c and vascular events (>90% of patients in the placebo group had LDL-c≥100 mg/dL at month 3, compared to <10% in the atorvastatin group). In contrast, there was a strong relationship between LDL-C and risk of vascular events below 100 mg/dL, with lower LDL-c levels translating to lower risk.
• A subgroup analysis in patients with diabetes showed that there were 328 vascular events among 399 patients with diabetes. This corresponds to an estimated 98.7 events per 100 participants over six years. Atorvastatin treatment reduced this risk by 50% (HR 0.50, 95%CI 0.40-0.64).

Conclusion

References

Find this article online at J Am Coll Cardiol.