Discussion
The primary findings of this nationwide study were as follows. Patients with schizophrenia presented approximately 10 years earlier with AMI, but had an increased absolute risk for MACE (all-cause mortality, reinfarction, stroke or heart failure), all-cause death and heart failure, within 5 years, compared with patients without schizophrenia. After adjustments for multiple confounders, patients with schizophrenia had a more than doubled risk of MACE and mortality after AMI, compared with patients without schizophrenia.
We found large outcome differences in relation to schizophrenia; after adjustments for age and sex, we found that patients with schizophrenia had an increased risk of the composite endpoint MACE and all individual endpoints. After further adjustment for comorbidities and treatment the HR remained more than double for MACE and mortality and almost one and a half times higher for heart failure. In a comparable study conducted in Denmark1 investigating MACE following acute coronary syndrome in patients with schizophrenia, the researchers found an increased risk of MACE and all-cause mortality, and additionally an increased risk of stroke. Nonetheless, MACE was comprised fewer variables and the adjustment models were different in the Danish study. In a systematic review13 of mortality in 37 studies found the standard mortality rate in schizophrenia to be 2.58, which corresponds with the increased risk found in our study. A large scale meta-analysis by Correll et al6 investigating cardiovascular disease in patients with severe mental illness likewise corroborates the association between increased risk of heart failure and schizophrenia seen in our study.
As previously discussed, the increased risks can be attributed to multiple mechanisms, among these an increased prevalence of various comorbidities in the population with schizophrenia. Interestingly, in our study we only found increases in baseline prevalences of smoking, diabetes, heart failure, COPD and previous bleeding and a lower prevalence of hypertension. Furthermore, patients with schizophrenia more frequently demonstrated sinus rhythm and pathological Q waves on ECGs, which is in line with previous work.14 15 The latter may not only be indicative of prior recognised MI but also of unrecognised MI or missed STEMI, which is further supported by the fact that patients with schizophrenia in our study more frequently presented with atypical AMI symptoms (ie, dyspnoea) rather than typical (ie, chest pain).
Results regarding comorbidities in AMI patients with schizophrenia varies as some studies show an increased prevalence of hypertension and hyperlipidaemia,16 17 and other studies show lower prevalences of hypertension and hyperlipidaemia.1 18 The variation may perhaps be attributed to dissimilarity in population size and inclusion criteria or under-diagnosis of somatic comorbidities.19 An alternative reason can be the lower awareness of comorbidities found in patients with schizophrenia20 which may impede care and consequently contribute to the increased MACE presented in this study. Yet another factor which could contribute is physician bias in deprioritising patients with schizophrenia during a myocardial infarction. However, in this study we found a homogeneity in system and patient delay between the populations and a longer LOS in patients with schizophrenia following myocardial infarction, ruling out these variables as contributing factors to the increased MACE. Finally, we found patients with schizophrenia to more often present with cardiac arrest, worse ventricular function during hospitalisation and they less often underwent coronary angiography, PCI and CABG during hospitalisation. Adjustment for these variables only slightly attenuated the association between schizophrenia and poor outcome, indicating that other factors remain highly influential.
Following the AMI, there were additional dissimilarities as patients with schizophrenia were less likely to receive any of the recommended guideline medications during discharge: aspirin, P2Y12 inhibitors, ACE-inhibitors/ARBs, beta blockers and statins. This was further confirmed after adjusted multiple logistic analysis which showed ACE-inhibitors/ARBs and statins to be prescribed less frequently. These results are in accordance with a study by Mitchell et al21 investigating prescription of medication in severe mental illness, where they presented evidence for lower than expected rates of prescription of ACE-inhibitors/ARBs, beta blockers and statins for patients with schizophrenia. A Danish study by Kugathasan et al22 investigating the association between secondary preventive treatment after AMI and mortality found scarcer redeemed prescription of guideline recommended medications in a population with schizophrenia, and concluded cardioprotective treatment following AMI to be fundamental in decreasing cardiovascular mortality in this group, underlining the importance of ensuring patients receive guideline recommended medications following AMI.
Clinical implication
This study found an increase of MACE at 5 years and evidence of fewer guideline recommended prescriptions following AMI. The mechanisms to why these patients experience worse outcome are many, but some may be modifiable. Improved guideline recommended treatment is essential and should not be overlooked in patients with schizophrenia. More importantly, primary preventive strategies should be introduced in early stages of these patients’ lives and the authors of this study suggest a multidisciplinary approach with improved collaboration between psychiatrists, cardiologists and other involved disciplines in order to combat the poor outcome seen in this high-risk patient population.
Limitations
First, we included patients over a period of 18 years, in which both the treatment options and guideline recommendations have changed. We accounted for the possibility of time bias by adjusting for year of AMI in a sensitivity analysis, which did not alter the results. Second, the patients with schizophrenia in our study were almost 10 years younger; whether this is attributable to patient selection, that is, older patients with schizophrenia are perhaps more conservatively managed and not treated in coronary care units or catheterisation labs, thus causing an under-representation in the SWEDEHEART registry, or a reflection of a greatly accelerated atherosclerotic cardiovascular disease process will have to be furtherly investigated in future studies. Finally, this was a register-based observational study with known inherent limitations such as risk of selection bias and confounding by indication, making causal conclusions uncertain, as well as potential underdiagnosis and misclassification of ICD-codes resulting in an underestimated prevalence. The 30-day blanking period of MI applied to avoid misclassification of reinfarctions could further contribute to this limitation, however, not blanking the period could have incorrectly inflated reinfarction rates.