Statins Overlooked for Secondary Stroke Prevention

Patrice Wendling

August 08, 2017

PUZI, TAIWAN and BIRMINGHAM, VA — Two new studies highlight the need to look beyond the cholesterol-lowering effects of statins to their benefits in secondary stroke prevention.

In the first study[1], stopping statins within 6 months of an ischemic stroke was associated with a 42% increase in the adjusted risk of any recurrent stroke in the first year.

Switching to a lower statin dose did not increase the risk of recurrent stroke or other hard events. Still, nearly one in five patients in the Taiwanese study stopped their prescribed statin in the first 6 months.

In the second study[2], less than half of patients with an ischemic stroke were discharged on a statin from US hospitals inside the so-called "Stroke Belt."

"You should definitely remain on these drugs, especially for at least the first year when we know the risk of stroke recurrence is highest," senior investigator of the first study, Dr Bruce Ovbiagele (Medical University of South Carolina, Charleston), said.

The SPARCL trial convincingly demonstrated that high-dose atorvastatin prevents recurrent stroke, and US guidelines recommend initiating statins in patients with clinical atherosclerotic disease including stroke. But often there's fragmentation of care between neurologists and the physiologist when the patient goes on to rehabilitation and primary care, Ovbiagele observed.

"So what happens many times is that the person's dose is reduced or if they have side effects, they are taken off completely, when what our study seems to suggest is consider lowering it or switching to something else, but certainly do not take them off completely because that is going to expose them to potentially higher risk," he said.

The two studies were published August 2, 2017 in the Journal of the American Heart Association.

Stopping Statins

In the first analysis, the investigators, led by Dr Meng Lee (Chang Gung University College of Medicine, Taiwan), used data from the Taiwan National Health Insurance Research Database to identify 45,151 ischemic stroke patients prescribed moderate- or high-intensity statins within 90 days of discharge. Statin intensity was defined based on 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guidelines.

Between 3 and 6 months, 18.5% of patients stopped their statin, 7% were on reduced statins, and the rest remained on their initial statin therapy. During the 1-year follow-up, there were 2120 recurrent strokes.

In multivariate analysis, stopping statins was associated with a 42% higher 1-year adjusted risk of recurrent ischemic or hemorrhagic stroke (6.2% vs 4.4%; hazard ratio [HR] 1.42, 95% CI 1.28–1.57) but also higher relative risks of all-cause mortality (HR 1.37, 95% CI 1.11–1.70), all major events (HR 1.38, 95% CI 1.26–1.51), and any hospitalization (HR 1.19, 95% CI 1.14–1.24).

However, no significant associations with intracerebral hemorrhage and MI were identified.

Reduced statin therapy was not associated with additional risks of any recurrent stroke (HR 0.94, 95% CI 0.78–1.12), intracerebral hemorrhage (HR 0.65, 95% CI 0.34–1.23), all-cause mortality (HR 0.97, 95% CI 0.66–1.42), MI (HR 0.96, 95% CI 0.68–1.35), or all major events (HR 0.94, 95% CI 0.80–1.10).

Community Perspective

Several trials have shown that even small amounts of statins are protective, but this study adds "a community perspective of a wider-scale use of statins" and "shows convincingly that too many people are having their statins discontinued, and the risk of recurrent stroke is quite high among those where it is discontinued," former AHA president and current American Association of Neurology president Dr Ralph Sacco (University of Miami, FL) told | Medscape Cardiology.

"So to me, the take-home message for primary-care physicians as well as cardiologists and neurologists is that we need to probably continue lifelong therapy with statins because of ischemic stroke."

That said, Sacco emphasized that statins alone are not enough.

"A recurrent stroke is probably the most feared outcome among stroke survivors, so we need to do everything we can: blood-pressure control, diabetes control, statin use, lifestyle modification, antiplatelets, and anticoagulation if they have atrial fibrillation (AF)," he said.

Of note, the study excluded patients with AF, end-stage renal disease, or those not prescribed antiplatelet therapy within 90 days or between 3 and 6 months postdischarge.

Subgroup analyses based on propensity score-matching data found no interaction between most baseline characteristics and statin utilization status over follow-up, except for a detrimental effect of statin discontinuation mostly in patients with minor stroke severity.

"From a patient's perspective, because they've got away with a more minor event, they may lose the sense of urgency regarding taking a statin," Sacco said. "From a physician's perspective, this is the group that we need to focus on more intensively to reduce the risk of a more major stroke."

Limitations of the study are the lack of LDL-cholesterol values over time, some patients may have received statins without filing a medication claim, and the database lacked information on whether a recurrent stroke was related to a medical procedure or occurred during hospitalization for a non–stroke-related event.

"Additional prospective studies should be carried out to clarify the underlying mechanisms, such as LDL-cholesterol rebound and/or inflammation, linking statin discontinuation to higher risk of recurrent stroke," the investigators concluded.

Skipping Statins

The second study, led by Dr Karen Albright (Birmingham VA Medical Center, AL) analyzed discharge medications among 323 participants (45.8% male, 49% black) with no known history of AF hospitalized for ischemic stroke between 2003 and 2013 in the prospective REGARDS study.

None of the participants were using statins at the time of admission, and 55.7% lived in the Stroke Belt states of Alabama, Arkansas, Georgia, Indiana, Kentucky, Louisiana, Mississippi, North and South Carolina, Tennessee, and Virginia.

In all, 48.7% of stroke survivors were prescribed a statin at discharge. These patients were more likely to have dyslipidemia than those not prescribed a statin (92.1% vs 82.3%; P=0.008), while resident training was the only factor that distinguished hospitals more likely to prescribe than not (53.7% vs 38.5%; P=0.006).

"This is important because as we know both from stroke and cardiac studies, what happens in the hospital is a big predictor of what happens in the community," commented Ovbiagele, who was not involved with the study.

There was a trend for statin prescribing to increase over time from about 23% in 2004 to a high of 77.8% in 2012. The increase may be partially attributed to publication of the SPARCL trial in 2006, as the first increase in statin prescribing began in 2007 and prescription rates in those with dyslipidemia also increased after 2006, the authors note.

Multivariate results found that among Stroke Belt residents, participants 65 years and older were 47% less likely to be discharged on a statin than those younger than 65 years (relative risk [RR] 0.53, 95% CI 0.38–0.75). This association was not identified in non–Stroke Belt residents.

Men living in the Stroke Belt were also 31% less likely than their female counterparts to be discharged on statins (RR 0.69, 95% CI 0.50–0.94); whereas men living outside the Stroke Belt were more likely to receive a statin at discharge (RR 1.38, 95% CI 0.99–1.92).

Finally, in contrast to prior Get With the Guidelines-Stroke studies, there was no significant difference among Stroke Belt residents in discharge statin prescribing between blacks and whites.

"Particular attention to the Stroke Belt residency is essential, given that between 2% to 15% of the excess stroke mortality traditionally attributed to race is actually attributable to geography," the authors write.

"The REGARDS data give you a much rawer sense of what is happening in the Stroke Belt potentially with hospitals that are not necessarily with the kind of systems of care that the Get With the Guidelines hospitals have, so it's very, very instructive, I thought," Ovbiagele said.

The first study was funded by grants from the Ministry of Science and Technology and Change Gung Memorial Hospital, both in Taiwan. Its authors report no financial relationships, nor does Sacco. Albright reported no financial relationships; disclosures for the coauthors are listed in the paper.

Follow Patrice Wendling on Twitter: @pwendl. For more from | Medscape Cardiology, follow us on Twitter and Facebook.


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