A new analysis of the SPARCL trial has shown that in patients with recent stroke or transient ischemic attack (TIA), the total number of vascular events prevented with atorvastatin was more than twice the number of first events prevented.
“From a patient perspective, the total events are more relevant. Patients are generally living through the first events, and total events give us the overall picture of how these patients are going to fare over the next several years,” lead author Michael Szarek, PhD, SUNY Downstate Health Sciences University, New York City, told Medscape Medical News.
“There is increasing interest in looking at total events as well as first events in clinical trials in terms of a more accurate way to characterize disease burden,” he added.
The new analysis was published online in the Journal of the American College of Cardiology March 16, and will be released as part of the upcoming virtual American College of Cardiology 2020 Scientific Session/World Congress of Cardiology.
The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial compared atorvastatin with placebo in 4731 patients with recent stroke or transient ischemic attack and no known coronary heart disease. Primary results of the trial, published in the New England Journal of Medicine in 2006, showed that atorvastatin reduced the first occurrence of stroke and the first occurrence of a composite of vascular events.
The current analysis assessed the occurrence of all (first and subsequent) vascular events and the effect of atorvastatin to reduce these events by vascular territory (cerebrovascular, coronary, or peripheral).
Results showed that the placebo group had an estimated 41.2 first and 62.7 total vascular events per 100 participants over 6 years. There were 164 fewer first and 390 fewer total vascular events in the atorvastatin group (total events hazard ratio [HR], 0.68; 95% confidence interval, 0.60 – 0.77).
The total events reduction included 177 fewer cerebrovascular events, 170 fewer coronary events, and 43 fewer peripheral events. Over 6 years, an estimated 20 vascular events per 100 participants were avoided with atorvastatin treatment.
In terms of individual territories, there was a significant reduction in events in each one. “And while the absolute numbers of cerebrovascular and coronary events were reduced by a similar amount — 177 fewer cerebrovascular events and 170 fewer coronary events — the relative reductions were greater for coronary and peripheral events than for cerebrovascular events,” Szarek noted.
The relative reduction in cerebrovascular events was 24% compared with 46% for coronary events and 44% for peripheral events. “That’s because there were fewer coronary events and peripheral events overall than there were cerebrovascular events,” he explained.
“So our results show a greater benefit for coronary/peripheral events than cerebrovascular events even though these patients had [suffered] a cerebrovascular event and not a coronary event to enter the study. This shows that patients who have a stroke or TIA (most of which are ischemic events) are at a high risk of coronary events as well, and reducing their LDL is beneficial for coronary and peripheral event prevention as well as for future cerebrovascular event prevention,” Szarek commented.
“Our results reinforce the original data showing a reduction in first events with atorvastatin in this population. They are also in line with results of the Treating Stroke to Target (TST) study presented at the American Heart Association meeting last November,” he noted.
Risk/Benefit in Hemorrhagic Stroke Patients
This new analysis also gives more information about the risk and benefits of statins in patients with previous hemorrhagic stroke.
“Original results showed a small increase in risk of hemorrhagic stroke in the atorvastatin group, particularly in patients who had had a hemorrhagic stroke as their qualifying event,” Szarek said.
“Our results on total events show that there is an increase in total stroke events in the patients with hemorrhagic stroke as the qualifying event in the atorvastatin group, but despite this, the total vascular events overall — including coronary and peripheral events — are reduced to a similar extent as in the whole population.”
“There is still a remaining question about whether patients with a history of hemorrhagic stroke should be treated aggressively with statins, and the current advice is not to try and get LDL down as low as possible in this group. But these data give some additional information on assessing the risks and benefits of statin treatment in this situation,” he added.
However, there were only 93 patients with hemorrhagic stroke in this study, and only 41 total events in this group, so these numbers are small and caution is needed in their interpretation, Szarek cautioned.
Another interesting result in this analysis is that while total stroke was reduced only nonsignificantly (HR, 0.87; P = .09), total disabling strokes were significantly reduced (HR, 0.65; P = .007).
“So this suggests that aggressive LDL reduction after a stroke does reduce total numbers of disabling strokes in the future,” Szarek said.
The study was sponsored by Pfizer. Szarek reports the following disclosures: consultant/advisory board for CiVi and Esperion; data and safety monitoring board for Resverlogix and Baxter; steering committee for Sanofi and Regeneron.
American College of Cardiology 2020 Scientific Session/World Congress of Cardiology.
J Am Coll Cardiol. Published online March 16, 2020. Abstract