Effects of European Society of Cardiology guidelines on medication profiles after hospitalization for heart failure in 22,476 Dutch patients: from 2001 until 2015.

Prescriber adherence to guideline-recommended medication in patients with heart failure (HF) in clinical practice is suboptimal. We analyzed how evolving guideline recommendations influenced medication profiles after a first HF hospitalization. We extracted medication profiles from the Dutch PHARMO Database Network for 22,476 patients with a diagnosis of HF at hospital discharge between 2001 and 2015. The percentage of patients prescribed the combination of a beta-blocker (BB) and an angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) increased from 24 to approximately 45% within this 15-year period. The percentage of patients who also used a mineralocorticoid-receptor antagonist (MRA) reached approximately 20%. The probability of being prescribed these combinations decreased with increasing age. As a consequence of the policy change in the ESC guideline 2001, the use of BB increased from less than 40% in 2001 to about 70% by 2015. The percentage of patients prescribed an ACEI and/or an ARB, an MRA, or a diuretic was about stable, at respectively 63%, 37%, and 82%. Although the 2012 ESC guideline also advised MRA in the New York Heart Association (NYHA) class II, there was no increase in MRA prescriptions. Compliance with the ESC guidelines varied for the individual recommendations. Remarkably, there was no significant increase in MRA prescriptions. At the same time, developments were demonstrated, which were not instigated by the guidelines, like the shift from ACEI to ARB. Although the exact HF classification of our patients was unknown, given a relatively stable case mix, our data provide insight into "real-world" pharmacological management.

Non-cardiovascular medication and readmission for heart failure: an observational cohort study.

Background Among heart failure (HF) patients, hospital readmissions are a major concern. The medication taken by a patient may provide information on comorbidities and conditions and may be used as an indicator to identify populations at an increased risk of HF readmission. Aim This study explored the use of non-cardiovascular medication at hospital discharge from the first HF admission in search of indicators of high risk of readmission for HF. Method The study included 22,476 HF patients from the Dutch PHARMO Database Network at their first HF hospitalization. The data was divided into training and validation sets. A Cox regression model with demographics, date of first HF hospital admission and non-cardiovascular medication present at discharge, adjusted for cardiovascular medication, was developed in the training set and subsequently implemented in the validation set. Results The study included 22,476 patients, mean age 76.7 years (range 18-104) and median follow-up time 2.5 years (range 0-15.7 years). During the study period 6,725 (29.9%) patients were readmitted for HF, with a median time-to-readmission of 7 months (range 0-14.3 years). Non-cardiovascular medication associated with a high risk of readmission for HF were identified as indicators of high risk, with no implied causal relationship. Patients prescribed antigout medications presented a 25% increased risk of readmission (HR 1.25, 95%CI 1.09-1.45, P = 0.002). Patients using insulin had an 18% higher risk of readmission versus patients not using insulin (HR 1.18, 95%CI 1.06-1.32, P = 0.002), but not versus patients treated with other blood-glucose-lowering drugs. No association between the risk of readmission and NSAIDs use was observed. Conclusion The results suggest that diabetes is responsible for the higher HF-readmission risk observed in patients prescribed insulin. The observed risk in users of antigout medication should be further investigated. The absence of an association with the use of NSAIDs should be interpreted with caution.

Adherence to Statin Therapy and Attainment of LDL Cholesterol Targets in an Outpatient Population of Type 2 Diabetes Patients: Analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT).

Objective: To assess adherence to statin therapy and its association with sociodemographic data, medical characteristics, LDLc levels, and LDLc target attainment in real-world T2D patients treated in secondary care. Research Design and Methods: Cross-sectional analyses were performed on baseline data of 393 patients in the DIAbetes and LifEstyle Cohort Twente (DIALECT). The medication possession ratio (MPR), calculated with pharmacy dispensing data, was used to determine adherence to statins for an intended period of 24 months. Statins were included in the analyses if they were used for at least six consecutive months with at least three dispenses. Adherence was defined as an MPR ≥80%. Associations with adherence were assessed using descriptive statistics and binary logistic regression. Results: Overall, 80% of the patients had a statin prescription and of those, 89% were adherent. The proportion of patients who reached LDLc targets of ≤2.5 mmol/L and <1.8 mmol/L differed significantly between the adherent, nonadherent and non-statin group (90% vs. 74% vs. 46%; p < 0.01 and 56% vs. 26% vs. 6%; p < 0.01, respectively). Serum LDLc levels were lower in the adherent versus the nonadherent and non-statin group (1.76 ± 0.60 vs. 2.23 ± 0.90 vs. 2.71 ± 0.67 mmol/L; p < 0.01). Higher HbA1c levels were independently associated with nonadherence (OR: 1.05, 95% CI 1.01-1.08; p < 0.01). Mediation adherence (OR: 2.88, 95% CI 1.04-7.97; p = 0.041) and lower BMI (OR: 0.88, 95% CI 0.81-0.96; p < 0.01) were independently associated with attaining the LDLc target of ≤2.5 mmol/L. Conclusion: In patients with T2D treated in secondary care, statin adherence was relatively high and was associated with significantly lower LDLc levels. It is important to identify nonadherence as it appeared an important determinant of failure to reach LDLc targets. The finding that many patients who failed to attain LDLc targets did not receive statin treatment offers an opportunity to improve diabetes care.

Heart failure medication after a first hospital admission and risk of heart failure readmission, focus on beta-blockers and renin-angiotensin-aldosterone system medication: A retrospective cohort study in linked databases.

BACKGROUND: This study assessed the association between heart failure (HF) medication (angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin-receptor blockers (ARB), beta-blockers (BB), mineralocorticoid-receptor antagonists (MRA) and diuretics) and HF readmissions in a real-world unselected group of patients after a first hospital admission for HF. Furthermore we analysed readmission rates for ACEI versus ARB and for carvedilol versus ß1-selective BB and we investigated the effect of HF medication in relation to time since discharge. METHODS AND FINDINGS: Medication at discharge was determined with dispensing data from the Dutch PHARMO Database Network including 22,476 patients with HF between 2001 and 2015. After adjustment for age, gender, number of medications and year of admission no associations were found for users versus non-users of ACEI/ARB (hazard ratio, HR = 1.01; 95%CI 0.96-1.06), BB (HR = 1.00; 95%CI 0.95-1.05) and readmissions. The risk of readmission for patients prescribed MRA (HR = 1.11; 95%CI 1.05-1.16) or diuretics (HR = 1.17; 95%CI 1.09-1.25) was higher than for non-users. The HR for ARB relative to ACEI was 1.04 (95%CI 0.97-1.12) and for carvedilol relative to ß1-selective BB 1.33 (95%CI 1.20-1.46). Post-hoc analyses showed a protective effect shortly after discharge for most medications. For example one month post discharge the HR for ACEI/ARB was 0.77 (95%CI 0.69-0.86). Although we did try to adjust for confounding by indication, probably residual confounding is still present. CONCLUSIONS: Patients who were prescribed carvedilol have a higher or at least a similar risk of HF readmission compared to ß1-selective BB. This study showed that all groups of HF medication -some more pronounced than others- were more effective immediately following discharge.

Decrease in Switches to 'Unsafe' Proton Pump Inhibitors After Communications About Interactions with Clopidogrel.

BACKGROUND: In 2009 and 2010 medicines regulatory agencies published official safety statements regarding the concomitant use of proton pump inhibitors and clopidogrel. We wanted to investigate a change in prescription behaviour in prevalent gastroprotective drug users (2008-2011). METHODS: Data on drug use were retrieved from the Out-patient Pharmacy Database of the PHARMO Database Network. We used interrupted time series analyses (ITS) to estimate the impact of each safety statement on the number of gastroprotective drug switches around the start of clopidogrel and during clopidogrel use. RESULTS: After the first statement (June 2009), significantly fewer patients switched from another proton pump inhibitor to (es)omeprazole (-14.9%; 95% CI -22.6 to -7.3) at the moment they started clopidogrel compared to the period prior to this statement. After the adjusted statement in February 2010, the switch percentage to (es)omeprazole decreased further (-4.5%; 95% CI -8.1 to -0.9). We observed a temporary increase in switches from proton pump inhibitors to histamine 2-receptor antagonists after the first statement; the decrease in the reverse switch was statistically significant (-23.0%; 95% CI -43.1 to -2.9). CONCLUSIONS: With ITS, we were able to demonstrate a decrease in switches from other proton pump inhibitors to (es)omeprazole and an increase of the reverse switch to almost 100%. We observed a partial and temporary switch to histamine 2-receptor antagonists. This effect of safety statements was shown for gastroprotective drug switches around the start of clopidogrel treatment.

Prescription behavior for gastroprotective drugs in new users as a result of communications regarding clopidogrel - proton pump inhibitor interaction.

Safety concerns of the concomitant use of clopidogrel and proton pump inhibitors (PPIs) were published in 2009 and 2010 by the medicines regulatory agencies, including a direct healthcare professional communication. We examined the association between various safety statements and prescription behavior for gastroprotective drugs in naïve patients in the Netherlands during the years 2008-2011. Data from the PHARMO Database Network were analyzed with interrupted time series analyses to estimate the impact of each communication on drug prescriptions. Dispensings were used as a proxy variable for prescription behavior. After the early communication in January 2009, 15.5% (95% CI 7.8, 23.4) more patients started concomitantly with (es)omeprazole and 13.8% (95% CI 6.5, 21.2) less with other PPIs. Directly after the first statement in June 2009, we found a steep increase in histamine 2-receptor antagonists (H2RA) peaking at 25%, placing those patients at risk for gastrointestinal events. This effect for H2RA faded away after a few months. In February 2010, when the official advice via an adjusted statement was to avoid (es)omeprazole, we found a decrease of 11.9% (95% CI 5.7, 18.2) for (es)omeprazole and an increase of +16.0% (95% CI 10.3, 21.7) for other PPIs. Still 22.6% (95% CI 19.5, 25.7) of patients started on (es)omeprazole in February 2010, placing them at risk for cardiovascular events. Advices of regulatory authorities were followed, however, reluctantly and not fully, probably partly because of the existing scientific doubt about the interaction.

Effects of short-term addition of NSAID to diuretics and/or RAAS-inhibitors on blood pressure and renal function.

BACKGROUND: The combined post-operative use of diuretics and/or renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of nonsteroidal anti-inflammatory drug (NSAID) associated renal failure because of a drug-drug interaction. OBJECTIVE: The aim of this study was to investigate the effect of the short-term (<4 days) post-operative combined use of NSAIDs with diuretics and/or RAAS inhibitors on renal function and blood pressure. SETTING: One teaching hospital in the Netherlands. METHOD: The study-design was a prospective, observational cohort-study. Based on postoperative treatment with NSAIDs, the intervention-group was compared to a control-group (no NSAIDs treatment). MAIN OUTCOME MEASURE: Systolic blood pressure and renal function expressed by the estimated glomular filtration rate (eGFR) calculated with the modification of renal desease formula. RESULTS: 97 patients were included in the intervention-group, 53 patients in the control-group. Patient characteristics were comparable except for one variable: 'combined use of a diuretic with a RAAS inhibitor' which was higher in the control-group (62 vs. 43 %, p = 0.046). Odds ratio for clinically relevant increase in systolic blood pressure was 0.66 (CI95 % 0.3-1.5). Odds ratio for clinical relevant decrease in renal function was 2.44 (CI95 % 1.1-5.2). On day 4 eGFR of 3 patients in the intervention- and 1 in the control-group was <50 ml/min/1.73 m(2). CONCLUSION: Odds ratios showed no significant difference of a clinically relevant increase in systolic blood pressure but showed a higher risk for a clinically relevant decrease in renal function in the intervention group. However this decrease resulted in a relevant impaired renal function (<50 ml/min/1.73 m(2)) in only 3 patients in the interventiongroup and 1 patient in the control-group. In the post-operative patient, without preexisting impaired renal function, concurrent diuretics and/or renin-angiotensinaldosterone system inhibitor therapy can be combined with short-term NSAID treatment.