These drugs may harm more than help after a stroke linked to a degenerative brain condition.
The drugs known as statins do many good things. They are the most powerful cholesterol-lowering agents discovered so far. They help prevent heart attacks in people who have had one, as well as in those at high risk for one. They lessen the risk of having an ischemic (clot-caused) stroke, the most common kind of stroke in the United States. Use of statins has been linked to stronger bones, better brain health in old age, and other noncardiovascular benefits.
But statins aren’t miracle drugs. Some people who take one have a heart attack or stroke anyway. Like any drug, they can cause unwanted side effects. And a report in Archives of Neurology adds a note of caution about statin use in one group of people — those who have had a hemorrhagic (bleeding) stroke in an outer lobe of the brain.
Types of bleeding stroke
As the name implies, a deep intracerebral hemorrhage occurs deep in the brain. It is usually caused by high blood pressure. A lobar intracerebral hemorrhage occurs in one of the outer lobes. It is often caused by a degenerative condition called cerebral amyloid angiopathy, in which a protein builds up inside arteries in the brain.
Modeling benefits and risks
In the early 2000s, the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial tested whether statins were helpful after a stroke. More than 4,700 stroke survivors participated. Half took 80 milligrams of atorvastatin (Lipitor) a day for five years; the other half took a placebo. Those taking Lipitor had fewer heart attacks, ischemic strokes, or other cardiovascular “events.” But volunteers in the Lipitor group also experienced more hemorrhagic strokes than the control group.
A team led by Dr. Steven M. Greenberg, professor of neurology at Harvard-affiliated Massachusetts General Hospital (MGH), used the data from SPARCL to model the benefits and risks of statin therapy among survivors of a hemorrhagic stroke. The team calculated something called quality-adjusted life years. These are an estimate of the quantity and the quality of life yet to come.
The researchers looked at two types of hemorrhagic stroke — deep intracerebral hemorrhage and lobar intracerebral hemorrhage. These happen in different parts of the brain. Deep intracerebral hemorrhage is usually caused by high blood pressure, and doesn’t tend to recur. Lobar intracerebral hemorrhage is usually caused by a degenerative condition called cerebral amyloid angiopathy. In this condition, a protein called amyloid builds up in the walls of arteries in the brain. People who have had one lobar intracerebral hemorrhage tend to have another.
Among SPARCL participants with a deep intracerebral hemorrhage, the model showed that taking the statin didn’t help or harm. For those who’d had a lobar intracerebral hemorrhage, though, taking a statin subtracted about 2.2 quality-adjusted life years (Archives of Neurology, January 2011).
Things you do for one part of your body may have unintended consequences elsewhere. Statins, for example, block an enzyme called hydroxymethylglutaryl–coenzyme A (HMG-CoA) reductase. In the liver, this enzyme helps make cholesterol; blocking it lowers cholesterol levels. But the enzyme is found in other parts of the body, and a statin doesn’t circulate only to the liver. The repercussions of blocking HMG-CoA reductase outside of the liver are only now being discovered, through work like that from the MGH team.
Keep in mind that this is just one study based on data from one clinical trial. “We don’t know whether there would have been an increase in hemorrhagic stroke in SPARCL had a different statin been used, or a different dose of atorvastatin, or the study population had been different,” cautioned Dr. Greenberg, who heads the hemorrhagic stroke research program at MGH. He would like to see his team’s finding replicated before making recommendations about statin use by stroke survivors.
Dr. Larry B. Goldstein, director of the Duke Stroke Center, has a slightly less cautious take on the findings. In an editorial that accompanied the MGH paper, he argued that until there are data to the contrary, “the use of statins in patients with hemorrhagic stroke should be guided by the maxim of nonmaleficence — Primum non nocere,” meaning “First, do no harm.”
Should you take a statin if you have had a hemorrhagic stroke? Your chances of having a heart attack may be so high that the benefits of taking one outweigh the small and unproven risk of a second stroke. On the flip side, it’s possible that a statin isn’t right for you. If life is a balancing act, living with cardiovascular disease is even more so. Talk with your doctor to find out where you stand.