A Case for Those Treating Heart Attacks

21. December 2015

When it comes to heart disease, women are second-class patients, and, when it comes to secondary prevention, they receive appropriate treatment less often than men. The reason may seem banal: they are less frequently treated for heart disease.

In a retrospective cohort study, Canadian researchers led by Dr Kate Smolina from the University of British Columbia investigated the records of 12,261 patients admitted with an acute myocardial infarction (AMI) between 2007 and 2009 and at least one year’s subsequent survival.

In particular, younger women (ages 20 to 54) were prescribed appropriate pharmacotherapy with beta-blockers, ACE inhibitors/ARBs, and statins significantly less frequently than men. There was barely any different in therapy adherence: both sexes complied between 42 and 50 per cent of the time. One year after discharge, only about a third of all AMI survivors were receiving optimal therapy, which suggests that further improvements in the therapeutic management of post-AMI patients are required to improve adherence.

The study data fails to identify the causes behind the different starts of treatment for the sexes. ‘There are two possible reasons why women take fewer cardiovascular medications than men in an outpatient setting,’ explains Dr Smolina. ‘It is either a consequence of physicians’ prescribing behaviour, or patients not taking their prescribed medication, or both.’ Nonetheless, the researchers believe more focus is needed in treating young women after a heart attack. ‘‘It is important for both physicians and patients to move away from the traditional thinking that heart disease is a man’s disease,’ Smolina said. ‘Heart disease in young women has only recently received research attention, so it is possible that physicians and patients still have the incorrect perception that these heart medications pose risks to younger women.’

Young, female and receiving less-than-optimal care

The recently published study is not the first to show that young women receive key heart medications less frequently. The differences already begin with the primary prevention and continue in the care received in hospital [Paywall] and also [Paywall] in secondary prevention. However, there are gendered differences in more than just the use of medication: in women with STEMI, it takes significantly, for example, for perfusion therapy (fibrinolysis or primary PCI) to be offered. It is no wonder, then, that female AMI patients continue to have a higher inpatient mortality rate than male AMI patients. An invasive diagnostic procedure in the form of a coronary angiography are less frequently performed on female patients with suspected acute myocardial infarction, although this goes hand in hand with a lower 5-year mortality rate. In addition, it is important for cardiac rehabilitation to take gender-specific needs into account. For example, women more frequently suffer with depressive symptoms, anxiety, and feelings of resignation after MI.

But the problem of gender-specific care already begins with the differential [Paywall] influence of risk factors. Elevated triglyceride levels (≥ 150 mg/dL), diabetes, and smoking, for example, have significantly more harmful effects on women than on men, while high HDL cholesterol levels are more protective. There are also important differences to consider when it comes to diagnosis: although both men and women typically complain of chest pain when suffering with an acute coronary syndrome, women often present a more multifaceted symptomatology, includes, for example, nausea, dizziness, fatigue, back pain, or sweating. The broad spectrum of complaints makes MI difficult to diagnose and often leads to the misdiagnosis and delayed hospital admissions of women.

Gender-specific risks and side effects plus opportunities

That women are not just female versions of men is also reflected in the treatment of cardiovascular diseases. For example, it is known that the sexes respond differently to certain drugs: Class 3 anti-arrhythmic agents (potassium channel blockers) more frequently result in side effects such as malignant arrhythmias in women. In addition, women experience bleeding complications more frequently than men, which plays a role in choosing the anticoagulant. But not everything is worse for women: there are also certain forms of therapy that provide women better results. For example, approach women with heart failure and left bundle branch block fare better than men on cardiac resynchronization therapy (CRT), and even largely independent of its duration, while men only show [Paywall] a high response rate at a QRS duration ≥ 150 ms. This also affects mortality rates: women with heart failure and LBBB benefit more from CRT implantation than men. It is therefore very unfortunate that CRT systems are nevertheless still more frequently used in men than in women.

But not only do women’s hearts respond differently than men’s, there also gendered differences with regard to pharmacokinetics. The causes behind the different metabolism of active substances include:

  • usually lower body weight and higher body fat percentage, which leads to a different distribution of drugs in the body
  • different expression of the cytochrome P450 enzyme family
  • lower activity of the ABC transporter P-glycoprotein (MDR1)
  • usually poorer kidney function, especially for small, older women

For this reason, it may be necessary to adjust the dose, for example, for cardiac glycosides and anti-clotting medications beyond mere adjustment for body weight. Even though dose tritration is indicated for beta-blockers at the start of therapy, women are commonly overdosed with them compared to men due to different levels of bioavailability.

Gender medicine ≠ gynaecology

The goal of gender medicine is not just to provide women with better healthcare, but also to ensure attention is paid to specificities of diseases in men and women, to explore the underlying causes of the gendered differences, and ensure that preventive and therapeutic measures are adequately tailored to each gender’s needs.

‘We believe that it is important to take a differentiated view of men and women and understand the problems of their diseases as gender-specific issues,’ says Professor Vera Regitz-Zagrosek, director of the Institute of Gender in Medicine (GIM) at the Charité Hospital in Berlin. ‘Gender medicine is not gynaecology: it just wants both genders to be considered equally.’

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