Ongoing Sex Disparity in Post-Acute MI Statin Therapy

Patrice Wendling

April 18, 2018

A new study shows guideline-recommended high-intensity statins continue to be underused in women after a myocardial infarction (MI).

Among more than 88,000 US adults with an acute MI in 2014 and 2015, 56% of men and 47% of women filled a prescription for high-intensity statins after hospital discharge.

"In any single subgroup examined, the sex difference was still there to the disadvantage to women," lead study author Sanne AE Peters, PhD, University of Oxford, United Kingdom, told | Medscape Cardiology.

The study was published online April 16 in the Journal of the American College of Cardiology.

Peters said research has consistently shown that despite evidence of similar benefit, women are less likely than men to receive statin therapy for the secondary prevention of cardiovascular disease (CVD) and that the intensity is lower when they are prescribed a statin. The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guidelines offer no specific recommendation for the sexes but advocate high-intensity statin therapy for all patients aged 75 years and younger with established CVD.

She noted that several initiatives directed at women's heart health have also been launched, including the Go Red for Women campaign, and that there are no fewer than three AHA guidelines for the prevention of CVD in women.

To examine contemporary trends in statin prescribing, the investigators examined data from 16,898 US adults (age < 65 years; 26% women) with an MI and commercial health insurance in the MarketScan database and 71,358 Medicare beneficiaries (age ≥ 66 years; 49% women) with an MI.

The intensity of each statin was defined in accordance with the 2013 ACC/AHA cholesterol guideline and for the main analysis included atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg.

A high-intensity statin prescription was filled by 61% of men and 50% of women with no history of statin therapy, 39% of men and 30% of women with prior low-/moderate-intensity statin use, and 92% of men and 90% of women with prior high-intensity statin use.

After adjustment for demographic characteristics, comorbidities, and healthcare use, the women-to-men risk ratio (RR) for filling a high-intensity statin prescription after discharge was 0.91 (95% CI, 0.90 - 0.92) in the total population.    

Notably, the sex difference was larger among the youngest and oldest patients and in those without a history of diabetes, coronary heart disease, or heart failure. The finding in the two extreme age groups is particularly concerning because the oldest are at the highest risk and younger women have recently been shown to have the slowest rate of decline in CVD rates in the United States, the authors note.

The investigators also looked at sex differences in high-intensity statin use over time, using a second analysis of patients who met the same inclusion criteria but were hospitalized with an MI from January 2007 to June 30, 2015.

Over this period, the percentage of patients who filled a postdischarge high-intensity statin prescription increased from 27% to 60% among men and from 22% to 50% among women.

Even though high-intensity statins were prescribed significantly more, particularly after 2011, the gender gap remained stable, Peters said.

Women were 6% less likely to fill a high-intensity statin than men in 2007 (RR, 0.94; 95% CI, 0.91 - 0.97) and 9% less likely in 2015 (RR, 0.91; 95% CI, 0.89 - 0.93).

"Despite a lot of things going on, like the Go Red campaign and similar initiatives, we didn't see any changes from 2007 to 2015, suggesting that there may be more structural things going on or that it takes even longer for a sex difference to reduce and ultimately disappear," she said.

Information was not available on the severity of the MI or on treatment provided in the hospital, which could explain the treatment decisions made, Peters said. Patient refusal may also be a factor, as some studies suggest women are more likely to experience side effects from statins and to discontinue statin therapy, though the evidence around this is not that strong. 

Another explanation is that "healthcare providers perceive women to be at lower risk of recurrent MI, despite the fact that they are at an elevated risk at least as high as men's risk," she said.

Nebulous Targets?

Toniya Singh, MD, a noninterventional cardiologist at St Louis Heart and Vascular, Missouri, and member of the ACC Women in Cardiology Leadership Council, told | Medscape Cardiology, "Even though we've worked much harder in getting more people to realize women are just as much at risk, they don't reach that threshold in many practitioners' mind."

At the same time, she said teratogenicity with statin therapy is an obstacle for younger women and that it can be a bit harder overall to get women on high-intensity statins because of concerns about myalgia.

Singh suggested that the shift from specific cholesterol targets in the 2013 ACC/AHA cholesterol guidelines also may be a factor.

"People had problems with taking those numbers away, and I think that also may have played a role in these numbers maybe not looking as robust because there wasn't as much of a push to getting a certain number," she said. "The guidelines said to aim for the best possible number you can get to with as much therapy as the patient can tolerate. So that introduces a lot of wiggle room, so to speak."

The tide may be turning, however, in the wake of recent protein convertase subtilisin/kexin type 9 inhibitor trials, such as FOURIER and ODYSSEY Outcomes, showing that patients with atherosclerotic CVD or post-acute coronary syndrome can safely achieve low-density lipoprotein (LDL) cholesterol levels below 20 mg/dL and reap cardiovascular and even mortality benefits.

"I think that is probably one of the things that will push people harder to get LDL down and not to be satisfied if you're at 70 and say 'Good enough,' and hopefully that effect will help both men and women," Singh said.

To | Medscape Cardiology, Gina Lundberg, MD, clinical director of the Emory Women's Heart Center, Atlanta, Georgia, and an AHA spokesperson, agreed that the recommendation to get cholesterol as low as possible is "kind of nebulous" and said that having hard targets was easier for people to follow, particularly in women's care, where patients see obstetrician/gynecologists, family and internal medicine practitioners, and nurse practitioners.

"Not that many women are seeing cardiologists before age 60 or before an event, so the information has to filter through a lot of disciplines," she said.

Going forward, Lundberg said a key to change lies in education for both patients and practitioners. She noted that even though the guidelines moved away from the ratio of LDL to high-density lipoprotein cholesterol years ago, she still encounters patients who use it to gauge their CVD risk and statin use, while others are swayed by what she described as "a huge force" against statins on the Internet.

With statin prices around $4 a month or even free at some drug stores and "too many trials that prove statins are good for women for primary prevention and extremely good in secondary prevention, these shouldn't be the reasons why women aren't on statins," Lundberg added.

Annabelle Santos Volgman, MD, and colleagues from Rush University in Chicago, Illinois, suggest in a related editorial that the possibility of provider bias, based on the erroneous ongoing perception of women with acute MI being at lower risk for recurrence, "would be disappointing considering the extensive efforts to educate providers and public to the contrary."

They suggest that any provider bias can be explained by the pathophysiologic differences between women and men in ischemic heart disease (IHD). Women presenting with acute coronary syndrome are less likely to have flow-limiting coronary artery disease than men and more likely to present with nonobstructive IHD.

"Without flow-limiting coronary lesions on angiography, providers may not recognize nonobstructive IHD as warranting a high-intensity statin prescription," Volgman and coauthors write.

Peters is supported by a UK Medical Research Council Skills Development fellowship. The editorialists, Singh, and Lundberg report no relevant financial relationships.

J Am Coll Cardiol. Published April 16, 2018. Abstract, Editorial

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