Guidelines: friend or foe?: Opportunities for improvement of cardiovascular pharmacotherapy based on evidence from real-world observational data

Guidelines play an important role in health care in the pharmacotherapeutic treatment of patients. They can originate from various sources, such as scientific specialist associations or national authorities. In the general introduction of this thesis we described the delicate balance for guidelines between friend and foe. Furthermore, we described the advantages and disadvantages of real-world data and real-world evidence. These two themes, guidelines and real-world evidence from real-world data, formed the starting point of this thesis. In Chapter 2 and 3 we investigated the association between prescription behaviour related to gastroprotective drugs and communications by regulatory authorities regarding the interaction between clopidogrel and proton pump inhibitors. Physicians and pharmacists had to choose the lesser of two evils: on the one hand choosing for gastroprotection with a less effective drug, and on the other hand, medicolegal aspects and the theoretical risk of diminished efficacy of clopidogrel. In Chapter 4 we reviewed the penetration of European guidelines for heart failure on the basis of the prescription of evidence-based medication in a large cohort of patients at discharge after a first hospital admission for heart failure. The setting was in the Netherlands between 2001 and 2015, a period in which major progress was made in the treatment of heart failure. Compliance with these guidelines varied for the individual recommendations. Remarkably, there was, for example, no significant increase in mineralocorticoid-receptor antagonist prescriptions. At the same time developments were demonstrated, which were not instigated by the guidelines, like the shift from angiotensin-converting-enzyme inhibitor to angiotensin-receptor blocker. Insight into the implementation of current guidelines can help to ameliorate the implementation of future guidelines. Patients discharged after a first hospitalisation for heart failure have a high risk of a readmission. We investigated the association between medication, prescribed at discharge, and the risk of a heart failure readmission. At first, in Chapter 5 the core heart failure medication was investigated: angiotensin-converting-enzyme inhibitors/angiotensin-receptor blockers, beta-blockers, mineralocorticoid-receptor antagonists and diuretics. In Chapter 6 the association between additional heart failure medication and non-heart failure cardiovascular medication, and readmission for heart failure was analysed. In Chapter 7 a hypothesis generating study is presented into the association between non-cardiovascular medication and readmissions for heart failure as the pharmacological treatment of non-cardiovascular comorbidities can influence the risk for readmission for heart failure. The association with readmission was in some cases in accordance with what is known already. However, also some unexpected observations were made. In the general discussion we tried to bring back the evidence from our two large cohorts, respectively 39,496 and 22,476 patients, to what it means for an individual patient. The role of the clinical pharmacist for cardiovascular patients is described as well