Many Stroke Patients Stop Statins or Never Start, With Dire Consequences

Better understanding of the benefits of statins for stroke prevention beyond the cardiology community may be key, one expert says.

Many Stroke Patients Stop Statins or Never Start, With Dire Consequences

Two new studies published this week shed some light on the use of statin therapy in the setting of acute ischemic stroke, with one study showing that stroke patients who stop taking the LDL cholesterol-lowering medication are at risk for adverse outcomes.

Individuals who discontinued statin therapy in the first 6 months after being discharged from the hospital following an ischemic stroke had a 42% greater risk of recurrent stroke when compared with individuals who adhered to therapy, according to one analysis. Among patients who were maintained on statin therapy but at a reduced dose, there was no signal of increased risk compared with individuals who were maintained on the originally prescribed dose.

Senior investigator Bruce Ovbiagele, MD (Medical University of South Carolina, Charleston), said the risk of recurrent stroke is highest in the first year and these patients should not be discontinuing their medication.

Given these results and the fact that most statin side effects are dose-dependent, if patients have side effects, consider reducing the dose or switching to another type of statin, rather than completely discontinuing statin treatment altogether,” he told TCTMD.

The second study showed that some patients don’t even have the opportunity to stop treatment since they are never prescribed statins in the first place. In an analysis of the REGARDS study, less than half of patients with ischemic stroke were prescribed a statin at discharge, a treatment gap that varied across the country and by other measures.

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

Nearly 1 in 5 Stroke Patients Stop Statins After Six Months

In the United States, high-dose statin therapy is a class I recommendation for all patients who have had an ischemic stroke or TIA due to atherosclerosis and all stroke/TIA patients who have comorbid atherosclerotic cardiovascular disease. The recommendation for high-dose statin therapy is based largely on the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.

In the first study, which was led by Meng Lee, MD (Chang Gung University College of Medicine, Taiwan), investigators used data from the Taiwan National Health Insurance Research Database to identify 45,151 ischemic stroke patients prescribed statins within 90 days of the event. Among the cohort, 18.5% had stopped their statin between 3 and 6 months, 7.0% were on a reduced statin dose, and the rest remained on the originally prescribed drug and dose.   

In addition to the higher risk of recurrent stroke, those who discontinued statin therapy had a 37% higher risk of all-cause mortality and a 19% higher risk of any hospitalization when compared with patients who were maintained on therapy. For those on the reduced dose, there was no increased risk of recurrent stroke nor any other signal of harm.

To TCTMD, Ovbiagele said the findings suggest that even at the reduced statin dose, these individuals had some degree of protection compared with individuals who stopped treatment entirely.

“The only study that has specifically looked at the effect of statins to prevent recurrent vascular events after stroke was the SPARCL trial and it utilized a high-dose statin, so we really don't know for sure whether lower-dose statins could be just as effective for preventing vascular events after a stroke as a high-dose statin,” he said.

Given that the benefits of statins extend beyond lowering LDL cholesterol, even a reduced dose is much better than not being on a statin at all, added Ovbiagele.

Jeffrey Anderson, MD (Intermountain Medical Center Heart Institute, Salt Lake City, UT), who was not involved in the study, said the data provides compelling evidence about how stroke risk increases once patients stop statins. In the trial, the 1-year risk of recurrent ischemic or hemorrhagic stroke increased from 4.4% among patients maintained on statins to 6.2% for those who stopped treatment.

“This isn’t like treating a urinary infection or bronchitis with an antibiotic,” he said. “You have to stay on these drugs. If you stop, you lose the benefit.” 

Also commenting for TCTMD, Robert Rosenson, MD (Icahn School of Medicine at Mount Sinai, New York, NY), said statins have been consistently shown to reduce stroke events even in individuals with coronary heart disease. The observed 40% increased risk of recurrent stroke seen in the Taiwanese analysis is in line with the risk of recurrent MI among patients who stop statin therapy.

The results suggests there is “a need for renewed education and campaigns for high-intensity statins,” particularly since nearly 1 in 5 patients stopped their medication in the first 6 months, said Rosenson.

US Data Suggests Disparities in Statin Utilization

In the REGARDS analysis, which was led Karen Albright, MD (Birmingham VA Medical Center, AL), the researchers studied discharge medication for participants hospitalized for an ischemic stroke. The analysis, which was restricted only to patients who were not statin users at the time of admission and had no history of atrial fibrillation, showed that only 48.7% of patients were prescribed a statin upon leaving hospital.

“These are unselected hospitals,” Albright told TCTMD. “A lot of the data we have to date are from hospitals committed to quality-improvement programs such as ‘Get With The Guidelines.’ They’re reporting a higher proportion of patients who are being prescribed a statin. . . In these unselected hospitals in the United States, we have room for improvement. Less than half is not great.” 

The treatment gap, however, varied by US region, by sex, and amongst black and white individuals. For example, the researchers looked specifically at statin prescription rates amongst hospitals located in the so-called “stroke belt,” which includes Alabama, Arkansas, Georgia, Indiana, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, and Virginia. These 11 states have previously been identified by the National Heart, Lung, and Blood Institute as having a 10% higher risk of death from stroke than the US average.

“There have been past reports suggesting that older Americans might not be prescribed a statin,” said Albright. “Our data showed that’s not true outside the stroke belt although it is true within it. There have also been reports that blacks are less likely to be prescribed a statin, but we didn’t see that in the stroke belt. In fact, we saw [blacks] were more likely to be prescribed a statin outside it.”

In the stroke belt, participants aged 65 years and older were 47% less likely to be discharged on a statin compared with younger stroke patients. Outside the stroke belt, black stroke patients were 42% more likely to be prescribed a statin than whites. Additionally, men in the stroke belt were 31% less likely to receive a statin at discharge compared with women, whereas outside the stroke belt, the converse was true.             

Albright said that with different hospital models, not just neurologists are taking care of stroke patients and given the vast amount of medical information available to internists, cardiologists, and other healthcare providers, some of the recommendations for treatment can be lost amongst competing guidelines and clinical studies.

Improvements in Prescribing Seen Later

To TCTMD, Anderson said physicians charged with developing the American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines widened their lens in 2013 to focus on reducing the risk of all forms of atherosclerotic cardiovascular disease, including the risk of stroke.

Anderson, who chaired the task force responsible for reviewing the 2013 ACC/AHA guidelines, said the treatment gap in the present study might not be quite as dire as the data suggest. For example, while less than 50% were prescribed statins in 2006 to 2010, more than 75% of stroke patients were prescribed the treatment at discharge in 2011 and 2012.

“That’s a lot of progress,” he said. “Having said that, there certainly still is a treatment gap and we’ve looked at our own data here, unpublished, and there’s a bigger treatment gap for stroke prevention than for coronary artery disease prevention. It’s newer and there isn’t as much evidence. I think we have a longer way to go with statins [in stroke] than we do with coronary heart disease.”   

For Rosenson, the US data from REGARDS raises the question as to whether clinicians are thinking about statins only as LDL cholesterol-lowering agents. Outside of lowering cholesterol, statins exert pleiotropic effects, such as reducing inflammation, decreasing oxidative stress, improving endothelial function, and inhibiting the thrombogenic response.

“It’s surprising that the use of high-intensity statins has not been well implemented in patients who have a manifestation of atherosclerosis that leads to a disabling disorder,” said Rosenson. “It’s unclear as to why there is a lack of understanding, or appreciation, and a lack of implantation about these data. We do know that the processes that occur in the coronary arteries also occur in the carotid arteries and cerebral circulation.”

Speaking specifically to the variations in prescribing seen across the country, these data highlight the need for not just national guidelines and treatment standards, but also adequate medical coverage.

“This is why we have had the [Affordable Care Act],” he said. “It’s not just for insurance coverage. It’s to ensure that patients are getting the right therapy.”

Sources
  • Lee M, Saver JL, Wu Y-L, et al. Utilization of statins beyond the initial period after stroke and 1-year risk of recurrent stroke. J Am Heart Assoc. 2017;6:e005658.

  • Albright KC, Howard VJ, Howard G, et al. Age and sex disparities in discharge statin prescribing in the Stroke Belt: evidence from the Reasons for Geographic and Racial Differences in Stroke study. J Am Heart Assoc. 2017;6:e005523.

Disclosures
  • Albright, Ovbiagele, and Lee report no relevant conflicts of interest.

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