Reading of the Week: Prevention Works – the New JAMA Psychiatry Paper on MIs & Mortality in Patients with Schizophrenia

From the Editor

Statistically, people with major mental illness have a life expectancy that is decades shorter than those without. Not only is that gap significant, but it may be growing. In a 2013 paper, drawing on Danish data, Nielsen et al. showed that the expansion of life expectancy seen in the general population over the past 30 years hasn’t been enjoyed by those with schizophrenia.

Why the gap? And what can be done? A major new paper in JAMA Psychiatry considers the treatment of myocardial infarction. Like Nielsen et al., Aalborg University’s Pirathiv Kugathasan and his co-authors use Danish national databases. They focus on the use (or lack of use) of cardioprotective medications, like statins, after MI. Interestingly, they find that when people with schizophrenia have cardioprotective medications, they can match the outcomes of those without mental illness.

Is heart health the way to address the gap?

In this week’s Reading, we consider the Kugathasan et al. paper, as well as the accompanying editorial. Then we consider the big question: what can be done?

DG

Cardiac Care and Outcomes

“Association of Secondary Preventive Cardiovascular Treatment After Myocardial Infarction With Mortality Among Patients With Schizophrenia”
Pirathiv Kugathasan, Henriette Thisted Horsdal, Jørgen Aagaard, Svend Eggert Jensen, Thomas Munk Laursen, René Ernst Nielsen

JAMA Psychiatry, 24 October 2018  Online First

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2707998

Cardiovascular disease, including ischemic heart disease and stroke, is the leading cause of death worldwide. Deaths from cardiovascular disease have decreased during the past decades, especially in Western Europe, North America, and Japan. This decrease in cardiovascular death is believed to be a result of multiple factors, including improvement in lifestyle behavior (eg, smoking cessation, physical activity, and balanced diet), implementation of interventional cardiologic procedures (eg, coronary artery bypass grafting and percutaneous coronary intervention [PCI]), and increases in prophylactic cardiovascular treatment (antithrombotics, β-blockers, angiotensin-converting enzyme inhibitors [ACEIs], and statins).

Patients with schizophrenia have an excess cardiac mortality, which contributes to a shortened life expectancy of 15 to 20 years compared with the general population. Studies on survival after ischemic heart disease have reported worse outcomes in patients with schizophrenia compared with people without mental illness. The causes of the differences in outcome are unclear, although earlier findings suggest deficits in quality of medical care and fewer cardiac interventions performed in patients with schizophrenia compared with the general population. Recent studies indicate that patients with schizophrenia who receive cardiac revascularization procedures have poorer outcome after ischemic heart disease, and a recent Danish population-based study found that patients with severe mental illness (SMI) are less likely to receive recommended, long-term, secondary preventive medications after PCI; this finding is further supported by a study that found no differences in short-term mortality but an increased long-term mortality rate after ischemic heart disease in patients with schizophrenia compared with the general population.

Taking recommended cardioprotective medication after myocardial infarction (MI) reduces hospital admissions, health care costs, and all-cause mortality in patients without psychiatric conditions. Studies on the prescription rate of cardioprotective medication in patients with SMI have been limited, and no studies have examined the association of prophylactic cardiac treatment exposure with mortality rates after MI in patients with schizophrenia compared with the rates in the general population. In the current study, we investigated the association of secondary preventive cardiovascular treatment with all-cause mortality after MI in patients with schizophrenia compared with those without schizophrenia using the Danish nationwide health care registries.

Pirathiv Kugathasan

So beings a new paper by Kugathasan et al.

Here’s what they did:

• Drawing on various national databases, the authors did “a retrospective cohort study included all individuals admitted with first-time MI in Denmark from January 1, 1995, to December 31, 2015.”
• They compared those with schizophrenia with the general population.
• The databases included the National Patient Registry (covering admissions and diagnoses, as well as prescriptions) and the Danish Causes of Death Register (containing data on age of death and underlying cause of death).
• They considered whether these individuals were treated with one of five therapeutic drug groups: antiplatelets, vitamin K antagonists, β-blockers, ACEIs, and statins.
• “The primary study outcome was time to all-cause mortality using time of medication exposure as a time-dependent covariate.”
• Various statistical analyses were done. “The primary analysis was a Cox proportional hazards regression model that evaluated all-cause mortality using drug exposure as defined previously as a time-varying covariate.”

Here’s what they found:

• The cohort included 105 018 patients with MI. 684 patients of this group were diagnosed with schizophrenia (0.7%).
• Demographically, those with schizophrenia tended to be male (70.6%) and had a mean age in their late 50s (57.3 years) – similar to the general population.
• “A total of 307 patients with schizophrenia (44.9%) and 27 752 patients from the general population (26.6%) died after index (P < .001). Causes of death were equally distributed between groups, with 66.2% of all deaths being defined as cardiovascular deaths. Patients diagnosed with schizophrenia who did not receive cardioprotective treatment had the highest mortality rate (HR, 8.78) compared with the general population treated, with treated patients diagnosed with schizophrenia having an increased HR of 1.97…”
• “In the adjusted model, we found that patients diagnosed with schizophrenia did not have an increased HR for all-cause mortality compared with patients from the general population who received triple therapy as cardioprotective treatment (adjusted HRs: 1.86 vs 6.65 for dual therapy and 4.38 vs 13.10 for no treatment).”

In this large, nationwide, retrospective cohort study of 105 018 patients with MI with a total follow-up of 796 435 person-years, we found that when patients with schizophrenia were exposed to cardioprotective treatment, the mortality rate was high compared with patients not exposed, using treatment-exposed patients from the general population as reference. By comparing the associations between different cardiac therapy strategies and mortality rates, we found that patients with schizophrenia who received any combination of triple therapy had the lowest mortality rates.

A few thoughts:

1. This is a good study.

2. The paper adds nicely to the literature. As the authors note: “The current study was the first, to our knowledge, to investigate the association between exposure to cardioprotective medication after MI and mortality rates among patients with schizophrenia compared with the general population.”

3. The numbers are striking. The study finds a high mortality rate during the follow-up period among patients with schizophrenia – 45% of patients with schizophrenia, compared with only 27% of other patients. Two-thirds of deaths in both groups were because of cardiovascular disease. (!)

4. People with schizophrenia who were untreated were nearly nine times more likely to die compared to the general population who was treated. With some treatment, people with schizophrenia fared better, with double the odds of dying over the general population who were treated.

5. But triple therapy bestowed on them the same benefits as the general population. In other words, with aggressive treatment, people with schizophrenia rivalled those without mental illness in outcomes. (!) The lead author noted in an interview: “Cardioprotective medication after myocardial infarction should be carefully managed to improve prognosis.”

6. The paper has limitations. It assumes that people prescribed cardioprotective medications took them. And though the authors attempted to address confounding factors, we don’t know about lifestyle factors (such as diet habits, physical activity, and smoking status).

7. The paper appears with an accompanying editorial written by Emory University’s Dr. Benjamin G. Druss, “Can Better Cardiovascular Care Close the Mortality Gap for People With Schizophrenia?”

Benjamin G. Druss

He opens:

People with schizophrenia die a mean of 15 years younger than the general population,a gap that has not improved over time and may be worsening. Over the past decade, this statistic has become a catalyst for efforts to improve the physical health and longevity of populations with schizophrenia and other serious mental illnesses across the globe.Given the extensive body of literature documenting the problem of excess mortality in schizophrenia, surprisingly little is known about the mechanisms that underlie it. The causes of mortality listed on death certificates for people with schizophrenia are similar to those seen in their communities. In developing countries, people with serious mental illnesses most commonly die of infectious diseases.In developed countries, deaths among individuals with schizophrenia are most likely to be because of cardiovascular disease, reflecting its high base prevalence and mortality burden in the broader population.But knowing these immediate causes of death provides only limited actionable information.

Dr. Druss goes on to summarize the finding of the study, then concludes (on a somewhat sour note):

It is striking that the study found substantial gaps in quality and lifespan for people with schizophrenia in Denmark, a country with one of the lowest rates of income inequality and most comprehensive insurance programs in the world. Denmark’s health laws provide universal access to publicly financed health care, with most psychiatric and medical care provided through salaried clinicians and limited cost sharing with patients. The country has been a global leader in quality improvement, with an increasing focus on measuring and improving care across sectors.The study findings suggest that these benefits alone are not sufficient to ensure the health and longevity of people with schizophrenia.

The editorial can be found here: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2707995.

8. How do people in Canada do with major mental illness? In a 2017 CMAJ paper, Gatov et al. found: “Mortality rates among people with schizophrenia were 3 times higher than among those without schizophrenia.” Co-author Paul Kurdyak commented: “Our study shows that individuals with schizophrenia are not benefiting from public health and health care interventions to the same degree as individuals without schizophrenia…” The paper can be found here: http://www.cmaj.ca/content/189/37/E1177.

9. As I noted in a past Reading, internist Dhruv Khullar recently wrote on this topic for The New York Times, “The Largest Health Disparity We Don’t Talk About.” He cited several examples in the United States of programs tailored to the needs of those with both psychiatric and physical problems. For example, from Maryland: “The weight loss program was devised for patients with serious mental illness, who often struggle with memory, attention and learning issues. The patients were taught material in small chunks with frequent repetition; role-played the selection of healthy foods; and got help organizing their homes to enable a healthier lifestyle.” Unlike the usual care – where patients didn’t actually lose weight – those in the weight loss program lost 7.5 pounds and 40% lost 5% of their total body weight. His essay can be found here: https://www.nytimes.com/2018/05/30/upshot/mental-illness-health-disparity-longevity.html. The NEJM paper on weight loss: https://www.nejm.org/doi/full/10.1056/NEJMoa1214530.

10. For those in Greater Toronto Area, there will be a conference on this topic this month, organized by CAMH and UHN. https://www.camh.ca/en/driving-change/about-camh/events/supporting-medical-care-for-people-living-with-mental-illness

Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.