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Cumulative Gains in Stroke Prevention With Optimal Control of Each Additional Risk Factor

ARTICLE IN BRIEF

The risk of recurrent stroke was reduced by only 2 percent in patients who had optimal control of a single risk factor; 22 percent if they had optimal control of two risk factors; 38 percent with control of three; and 65 percent with optimal control of all four.

SEATTLE—For each of four risk factors that is optimally controlled, stroke patients gain a stepwise, additional reduction in the risk of a second stroke or major cardiovascular event, according to a secondary analysis of data from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study described here at the AAN meeting.

The risk of recurrent stroke was reduced by only 2 percent in patients who had optimal control of a single risk factor, the study found, compared to 22 percent if they had optimal control of two risk factors, 38 percent with control of three, and 65 percent with optimal control of all four.

The risk of a major cardiovascular event likewise dropped in stepwise fashion for each additional risk factor optimally controlled, reaching a 75 percent reduction with optimal control of all four.

The post-hoc analysis of data from the 4,731 patients enrolled in SPARCL followed for an average of 4.98 years after a stroke or transient ischemic attack and no known coronary heart disease, examined outcomes relative to control of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and blood pressure.

“The take-home message is to treat patients to target on all four risk factors,” said the study's lead author, Pierre Amarenco, MD, professor and chairman of the department of neurology and Stroke Center at the Bichat University Hospital and Denis Diderot University and Medical School in Paris, at the meeting.

TAKE-HOME MESSAGE

A neurologist who specializes in the treatment of stroke said the study's findings offered an important message for clinicians who have, until now, often focused on controlling LDL to the exclusion of other fats.

“There has been so much emphasis on LDL that we tend to focus our therapy on that,” said James C. Grotta, MD, a professor and chair of neurology at the University of Texas Medical School in Houston and stroke program director at Memorial Herman-Texas Medical Center. “I'm guilty of that too. They've found it's equally important to lower HDL and triglyceride for stroke prevention.”

While SPARCL was originally designed to test the benefits of 80 mg of atorvastatin, Dr. Amarenco said that neurologists may need to look toward other fat-lowering agents to reach targets for HDL and triglycerides.

“Lowering LDL is important, but there may still be a benefit to considering HDL-raising agents like niacin,” he said.

The implications of the study gained urgency with new findings from a national survey, also reported here, showing that only half of patients who have had a prior stroke achieved optimal control of their blood pressure, and that less than half had optimal control of LDL. The analyses, presented in two posters from researchers at the University of California-Los Angeles (UCLA), used data from the 2005-2006 National Health and Nutrition Examination Survey.

“Doctors are not aggressive enough in trying to reduce these biomarkers to guideline-recommended levels,” said a co-author of those papers, Bruce Ovbiagele, MD, associate professor of neurology at UCLA and director of its stroke prevention program.

“Because we get so much bang for our buck out of statins, we tend to fixate on them,” he said. “Statins do a wonderful job in reducing LDL, but they only boost HDL by about 10 percent and reduce triglycerides by about 20 percent. For HDL, the best agent we have is extended release niacin.”

Dr. Ovbiagele encouraged neurologists to establish a routine for assuring that all stroke patients are uniformly assessed for medication needs.

“It's advisable to have a systematic algorithm in place, either in the inpatient or outpatient setting,” he said. “Doctors are well meaning, but with competing interests, patients tend to fall through the cracks. We've found that a systematic program really helps to make sure that no patient leaves the hospital without these meds. Before they go home, the nurse goes through a checklist and makes sure the patient was put on a statin, a blood pressure medication, or whatever else was indicated. It makes it just easier to make sure the patient is getting uniform care.”

STROKE PREVENTION STRATEGIES

While agreeing that it is vital for neurologists to be sure their stroke patients leave the hospital with prescriptions for all indicated medications and an explanation of drug benefits, Dr. Amarenco said that these efforts are not enough. The problem, he said, is that “as soon as the hospital door is closed, they forget most of what you said. If we don't take care of the patient after the hospital, we miss our goal.”

At his hospital in Paris, he said, “we now have a stroke prevention clinic with four nurse practitioners. They educate patients in three sessions, one per week, one on blood pressure, one on lipids, one on diet control and smoking habits. Thereafter they have an appointment at four months, eight months, and 12 months. This kind of strategy is necessary to help the patient get to the 75 percent relative risk reduction at five years.”

The SPARCL investigators defined optimal treatment levels as an LDL below 70, HDL above 50, triglycerides less than 150, and blood pressure less than 120/80. While prior studies have shown the value of achieving each target individually, he said, he didn't know “whether combing these approaches would reduce the risk of stroke further.”

Figure

DR. PIERRE AMARENCO: “The take-home message is to treat patients to target on all four risk factors,” including of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and blood pressure.

As a post hoc analysis, the paper's results should be considered hypothesis-generating until further data is gathered, Dr. Amarenco emphasized. But he pointed to similar results seen in a study of coronary atherosclerosis published in March in the Journal of the American College of Cardiology. That paper, whose senior author was Cleveland Clinic cardiologist Steven Nissen, MD, found that patients who had both a low level of LDL (no more than 70 mg/dl) and a systolic blood pressure of no greater than 120 mm Hg had significantly less progression of coronary atheroma on intravascular ultrasound.

Similar coronary results were reported in a 2004 paper in the Journal of Human Hypertension, in which Greek investigators found that the combination of a statin with an ACE inhibitor “reduced cardiovascular events more than a statin alone and considerably more than an ACE inhibitor alone.”

REFERENCES

• Chhatriwalla AK, Nicholls SJ, Nissen SE, et al. Low levels of low-density lipoprotein cholesterol and blood pressure and progression of coronary atherosclerosis. J Am Coll Cardiol 2009; 53(13):1110–1115.
    • Athyros VG, Mikhailidis DP, Elisaf M, et al., for the GREACE Study Collaborative Group. Effect of statins and ACE inhibitors alone and in combination on clinical outcome in patients with coronary heart disease. J Hum Hypertens 2004;18:781–788.