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Medical News & Perspectives
September 11, 2019

Cardiovascular Corner: Prescription Omega-3s, Stroke Rehab, and Statins After Age 75

JAMA. Published online September 11, 2019. doi:10.1001/jama.2019.14485

This Medical News series offers an occasional roundup of developments in cardiovascular medicine.

Omega-3 fatty acids, cardiac rehabilitation for stroke, and statin use in elderly individuals made the news in recent months.

Omega-3s and Triglycerides

Prescription omega-3 (ω-3) fatty acids at a dose of 4 g per day are safe and effective for reducing elevated triglyceride levels in most people, not just those with very high levels, according to a recent American Heart Association (AHA) science advisory. Before the drugs are prescribed, however, physicians should treat underlying causes, such as poorly controlled type 2 diabetes and hypothyroidism, and counsel patients on diet and lifestyle modifications.

The advisory, which appeared in Circulation, came 17 years after an AHA scientific statement recommended fish consumption and fish oil supplements totaling 2 to 4 g per day of ω-3 fatty acids among people with elevated triglyceride levels. Since then, the US Food and Drug Administration (FDA) has approved several prescription ω-3 fatty acids for people with very high levels at or above 500 ml/dL.

Only 1% to 2% of the population, however, has levels that high. Physicians often also prescribe the capsules for patients with elevated triglyceride levels of 200 to 499 mg/dL, known as hypertriglyceridemia, which affects 25% to 30% of the population.

The new advisory provides support for that off-label use and recommends against patients using fish oil dietary supplements, which the FDA doesn’t regulate to the same degree as it does prescription agents. The advisory panel reviewed 17 clinical trials of ω-3 fatty acid prescription agents and dietary supplements. The studies suggest that prescription doses reduce triglyceride levels by 20% to 30% among people with hypertriglyceridemia, regardless of statin use.

According to the advisory’s first author, Ann Skulas-Ray, PhD, a nutritional scientist at the University of Arizona, the panel delayed publication to include results from the recent Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT). That study found a 25% lower risk of major adverse cardiovascular events with 4 g per day of a prescription agent containing the ω-3 fatty acid eicosapentaenoic acid (EPA) among patients with high triglyceride levels who were taking statins.

However, concerns have been raised about the use of mineral oil as the placebo in the REDUCE-IT trial, which may increase cardiovascular disease risk by interrupting the absorption of statins and other medications. The ongoing Statin Residual Risk Reduction With Epanova in High Cardiovascular Risk Patients With Hypertriglyceridemia (STRENGTH) trial will also evaluate hard end points like heart attacks, but using a corn oil placebo and a prescription agent that contains both EPA and docosahexaenoic acid (DHA). The advisory panel found that prescription formulations containing DHA along with EPA raised low-density lipoprotein cholesterol but only among people with very high triglyceride levels.

Cardiovascular Rehabilitation for Strokes

Physical and occupational therapies for stroke survivors focus on functional recovery, with little or no emphasis on aerobic fitness. This means that even when stroke rehabilitation ends, many patients have limited endurance. Decreased physical activity and increased sedentary time often keep these patients from engaging in everyday life and increase their risk of an additional stroke or other cardiovascular diseases. Group-based aerobic programs for stroke survivors could help.

A recent meta-analysis published in the Journal of the American Heart Association suggests that such interventions improve stroke patients’ aerobic capacity. The analysis included 19 studies involving 485 stroke survivors that focused primarily on group aerobic exercise interventions. Patients attended the programs a few times a week over 8 to 12 weeks, a frequency and duration similar to that of cardiac rehabilitation. Because the study designs differed, control group comparisons weren’t included in the review.

In studies that included the 6-minute walk test, a common measure of endurance, participants walked an additional 53.3 m on average after completing the program, more than half the width of a city block. This meant that 58% of participants in the “limited community ambulator” category transitioned to “unlimited community ambulator” status after the program. Those in the latter group can typically walk on uneven terrain, shop, and navigate public venues.

As for what type of exercise worked best, mixed aerobic activity—a combination of walking, biking, and seated stepping, for example—had the most impact, followed by walking and then biking or seated stepping. Those with the least mobility and endurance impairments when they started the program saw the biggest gains. Importantly, the improvements occurred regardless of how much time had passed since the patient’s stroke.

Insurance plans currently do not cover cardiac rehab for stroke survivors. Until that changes, physicians should have knowledge of the structured-exercise community programs available to stroke survivors in their area and refer patients to these options. Patients can also exercise on their own (potentially with guidance from their physical therapist) or with a trainer. Cardiologists can provide advice on appropriate intensities.

The bottom line for stroke survivors: “A regular aerobic exercise program of at least 30 minutes 2 to 3 times a week for 8 to 12 weeks can provide endurance gains that can impact their daily lives, and these gains can be made regardless of how long it has been since their stroke,” said Elizabeth Regan, a PhD candidate in exercise science at the University of South Carolina and the study’s first author.

Statins After Age 75

Current US and European guidelines lack recommendations about discontinuing statins for primary prevention in elderly patients, and many physicians continue to prescribe the drugs in this age group despite possible adverse effects. A recent observational study suggests that stopping statins in old age could be unwise.

Elderly people with no history of cardiovascular disease who discontinued statins had a 33% increased risk of being hospitalized for a cardiovascular event in the study, published in the European Heart Journal. The risk of admission for heart problems was greater than for stroke: coronary events and cerebrovascular events increased 46% and 26%, respectively.

The study involved French national health care database records from 120 173 people who were 75 years old in 2012 to 2014. The individuals were taking statins for at least 2 years at the start of the study, and discontinuation was defined as 3 consecutive months without a prescription. The group was followed up for an average of 2.4 years. In that time, 14.3% discontinued statins and 4.5% were admitted for a cardiovascular event.

Joël Coste, MD, PhD, an epidemiologist at the Hôpital Cochin in Paris and the study’s senior author, emphasized that the findings don’t prove that stopping statins caused the heart attacks or strokes. Although his team controlled for factors including discontinuation of other heart drugs, previous hospital admissions, comorbidities, and frailty indicators, data on other factors, like smoking, obesity, baseline cholesterol levels, and the precise reasons for statin discontinuation, were not available.

A large, randomized clinical trial looking at statin outcomes among people aged 70 years or older is under way in Australia, but the results aren’t expected for a few years. Until then, the new study suggests “potential cardiovascular risk reduction associated with continuing statin therapy after the age of 75 years in persons already taking these drugs for primary prevention,” Coste said.

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