Addressing Gender Disparities in Secondary Heart Disease Prevention

Secondary prevention of heart disease and cardiovascular disease principally involves mitigating risk among individuals considered to be at high risk for serious adverse events that include stroke, heart attack, and sudden cardiac death.^1,2 Typically, this involves drug therapy and counseling.² In addition, research shows that women have higher rates of 30-day mortality from CVD and more often die because of their heart disease or following a heart attack compared with men.^3-5

Research presented at the 2024 European Society of Cardiology Congress explored gender-based outcomes disparities in cardiology care through the lens of secondary prevention of myocardial infarction, with research implications that extend to equitable health care policy and cardiology care of women and men.

Scotland

Investigators from the University of Aberdeen looked at long-term outcomes between 31,287 men (median [IQR] age, 64 [56-72] years and 15,776 women (median age, 69 [60-75] years) treated between 2010 and 2016, using 4 care models to estimate outcomes that were unadjusted (Model A) or that adjusted for age (Model B); year of admission, social deprivation, ST-elevation myocardial infarction (STEMI), and comorbidities (Model C); and Model C plus medications. The median follow-up was 8.4 (6.8-10.2) years.⁶

Non-STEMI (NSTEMI)—when there is a lack of oxygen to the heart⁷—was more common in women vs men (50.48% vs 46.62%) and STEMI—a heart attack due to a major artery blockage⁸—was more common in men (28.68% vs 23.29%) (both P < .001); however, treatment and follow-up medication differences were quite evident. Percutaneous coronary intervention and secondary prevention rates were far higher in the men (55.85% vs 42.27% and 66.26% vs 54.41%, respectively), and more men vs women received medications during follow-up treatment:

• Antiplatelet agents: 90.65% vs 86.73%
• Lipid-lowering agents: 90.07% vs 85.12%
• Angiotensin converting enzyme (ACE) inhibitors: 76.39% vs 66.38%

Under Models A, B, and C, the women had 41%, 14%, and 6% higher rates of in-hospital mortality, and under Models A and B, they had higher rates of all-cause mortality (38% and 7%, respectively), cardiovascular-related mortality (27% under Model A only), incident cardiovascular events (15% and 5%), and recurrent myocardial infarction (14% and 6%). However, after accounting for all confounders, the women were found to have 8% lower risks of all-cause mortality and major adverse cardiovascular events and an 18% lower risk of cardiovascular mortality.

The authors note that the results seen among women before adjustment, that they had “worse crude outcomes,” could be an indication of undertreatment and they call for “urgent identification” of the root causes of these disparate outcomes to ensure health equity.

Research presented at ERS 2024 explored gender-based outcomes disparities in cardiology care through the lens of secondary prevention of myocardial infarction, with research implications that extend to equitable health care policy. | Image Credit: Довидович Михаил-stock.adobe.com

Switzerland

Despite treatment guidelines calling for equivalent preventive measures for women and men, research from AMIS Plus, National Registry of Acute Myocardial Infarction in Switzerland,⁹ shows this often is not the case and that sex-related discrepancy in pharmacotherapy as secondary prevention is a persistent issue. Their retrospective analysis—comprising univariate and multivariate logistic regression analyses—covered 2003 to 2022 and evaluation of prescription rates of aspirin, P2Y12 inhibitors (antiplatelet medications), lipid-lowering agents, beta blockers, and angiotensin receptor blockers (ARBs)—what the investigators termed optimal medical therapy (OMT) at hospital discharge.¹⁰

The patient population was 75% men (n = 25,913; mean [SD] age, 66 [13] years) and 25% women (n = 8699; mean age, 71 [13] years) who received care at 69 Swiss hospitals. STEMI and NSTEMI were seen in 56% and 44%, respectively, of both groups. The most common medical history in both groups was hypertension, current smoker, and diabetes.

More women than men had a Charlson Comorbidity Index score higher than 1 (25% vs 21%), but baseline PCI and coronary artery bypass graft rates were higher among the men (89% vs 78% and 3.5% vs 2.6%) and fewer women (51% vs 60%) were prescribed OMT across all age groups—despite increasing prescribing rates of each medication over the study, except beta-blockers, and overall OMT from 36% to 60%.

OMT prescribing disparities were potentially influenced by younger age (odds ratio [OR], 0.99; 95% CI, 0.98-0.99; P < .001) and female sex (OR, 0.90; 95% CI, 0.85-0.95, P < .001), while PCI in women was shown to greatly influence OMT prescription (OR, 4.85; 95% CI, 4.49-5.24; P < .001).

These authors note that the overall OMT increase notwithstanding, that prescribing disparities still remain when considering age and female sex remains a great concern and that targeted interventions must be developed to ensure equity in secondary prevention care.

Israel

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are prescribed as primary and secondary prevention for cardiovascular disease.¹¹ In the secondary prevention setting, they are known to help lower levels of bad cholesterol (low-density lipoprotein cholesterol [LDL-C]) and thereby reduce the risk of atherosclerotic cardiovascular disease. However, gender-based prescription disparities, based on patient biological characteristics, continue to be seen but to remain poorly understood. A team from the Prevention Cardiology Clinic in Rabin Medical Center retrospectively analyzed data on prescriptions for evolocumab or alirocumab, classifying their findings by gender and measuring results via change in LDL-C at 3 and 12 months.¹²

They included 103 women (mean age, 70.0 [9.2] years) and 143 men (mean age, 65.48 [1.0] years) in their study. For both groups, secondary prevention was the most common indication for a PCSK9 prescription (48% in men and 26% in women), but primary prevention prescriptions were more than twice as common in the women vs the men (39.4% vs 16.3%; P < .001) despite baseline LDL-C being significantly higher in the former (138.9 vs. 117.3 mg/dL; P < .001). At baseline, more women also had a body mass index above 30 kg/m2 (32.7% vs 17.4%; P = .003) and hypertension 66.7% vs 57.5%; P < .001), but fewer had undergone coronary revascularization (47.1% vs 61%; P < .001).

More men also experienced greater declines in their LDL-C goals at 3 months and 12 months compared with the women when adherent to their treatment regimen:

• Below 70 mg/dL:
  • 3 months: 73.7% vs 57.4% (P ≤ .01)
  • 12 months: 76.1% vs 62.2% (P ≤ .05)
• Below 55 mg/dL:
  • 3 months: 57.1% vs 38.6% (P ≤ .01)
  • 12 months: 60.1% vs 39.8% (P ≤ .01)

Further, at 12 months, overall LDL-C was 46.8 mg/dL in the men vs 61.9 mg/dL in the women (P = .001). These differences were seen despite overall high treatment adherence rates at 3 months (91.8%) and 12 months (79.7%).

The authors explain that the high overall adherence rates may be due to these patients being evaluated through a dedicated prevention clinic, but that women remain less likely to achieve their treatment goals vs men due to the observed prescription disparities. These discrepancies need to be properly addressed, they underscored.

References

1. Marine JE, Russo AM. Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy. UpToDate. Updated February 2, 2023. Accessed September 8, 2024. https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy#:~:text=Secondary%20prevention%20of%20SCD%20refers,resuscitated%20from%20sudden%20cardiac%20arrest

2. Roadmap for secondary prevention of cardiovascular disease. World Heart Federation. Accessed September 8, 2024. https://world-heart-federation.org/cvd-roadmaps/whf-global-roadmaps/secondary-prevention/#:~:text=Definition,events%20or%20known%20cardiovascular%20disease

3. Mosca L, Barrett-Connor E, Wenger NK. Sex/gender differences in cardiovascular disease prevention what a difference a decade makes. Circulation. 2011;124(19):2145-2154. doi:10.1161/CIRCULATIONAHA.110.968792

4. Heart disease in women is not like heart disease in men. Columbia University Irving Medical Center. February 28, 2022. Accessed September 8, 2024. https://www.columbiadoctors.org/news/heart-disease-women-not-heart-disease-men#:~:text=More%20women%20than%20men%20die,their%20conditions%20are%20often%20misdiagnosed.&text=%E2%80%9CHeart%20disease%20is%20the%20No,College%20of%20Physicians%20and%20Surgeons

5. Women found to be at higher risk for heart failure and heart attack death than men. News release. American Heart Association. November 30, 2020. Accessed September 8, 2024. https://newsroom.heart.org/news/women-found-to-be-at-higher-risk-for-heart-failure-and-heart-attack-death-than-men#:~:text=Research%20Highlights%3A,time%20of%20their%20heart%20attacks

6. Pana TA, Mamas MA, Dawson DK, Myint PK. Sex differences in secondary prevention and outcomes post-myocardial infarction in Scotland. Presented at: ESC Congress; August 30-September 2, 2024; London, England.

7. NSTEMI: non-ST-elevation myocardial infarction (heart attack). Cleveland Clinic. Updated December 28, 2021. Accessed September 8, 2024. https://my.clevelandclinic.org/health/diseases/22233-nstemi-heart-attack

8. What is a STEMI? ECG Medical Training. June 24, 2015. Accessed September 8, 2024. https://www.ecgmedicaltraining.com/what-is-a-stemi/

9. AMIS Plus - National Registry of Acute Myocardial Infarction in Switzerland. Accessed September 8, 2024. https://amis-plus.ch/

10. Berther L, Radovanovic D, Roffi M. Sex-differences in prescription patterns of secondary prevention pharmacotherapy in patients with acute myocardial infarction: a 20-year perspective. Presented at: ESC Congress; August 30-September 2, 2024; London, England.

11. Kelley-Hedgepeth A. Are statins enough? when to consider PCSK9 inhibitors. Harvard Medical School. June 8, 2020. Accessed September 8, 2024. https://www.health.harvard.edu/blog/are-statins-enough-when-to-consider-pcsk9-inhibitors-2020060819986#:~:text=They%20are%20widely%20prescribed%20for,in%20patients%20with%20established%20CVD)

12. Hodeda L, Birati EY, Rotholz A. Gender differences in the treatment with PCSK9 monoclonal antibodies real world experience from a dedicated prevention clinic. Presented at: ESC Congress; August 30-September 2, 2024; London, England.