Factors associated with non-adherence to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in older patients with peripheral arterial disease.

Introduction: As in other chronic conditions, medication adherence is important in the treatment of peripheral arterial disease (PAD). Our study aimed at a) analysing non-adherence to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in groups of older ACEI and ARB users with PAD, and b) identifying characteristics associated with non-adherence. Methods: We focused on the implementation phase of adherence (i.e., after treatment initiation and before possible discontinuation of treatment). The study cohort included ACEI/ARB users aged ≥65 years in whom PAD was newly diagnosed during 2012. Non-adherence was defined as Proportion of Days Covered (PDC) < 80%. Results: Among 7,080 ACEI/ARB users (6,578 ACEI and 502 ARB users), there was no significant difference in the overall proportion of non-adherent patients between ACEI and ARB users (13.9% and 15.3%, respectively). There were differences in factors associated with non-adherence between the groups of persistent and non-persistent (i.e., discontinued treatment at some point during follow-up) ACEI and ARB users. Increasing age, dementia and bronchial asthma were associated with non-adherence in persistent ACEI users. General practitioner as index prescriber was associated with adherence in the groups of non-persistent ACEI users and persistent ARB users. Conclusion: Identified factors associated with non-adherence may help in determining the groups of patients who require increased attention.

Reinitiation and Subsequent Discontinuation of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers among New and Prevalent Users Aged 65 Years or More with Peripheral Arterial Disease.

Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) are recommended in the treatment of arterial hypertension in patients with peripheral arterial disease (PAD). The aims of our study were: (a) to analyse the extent of reinitiation and subsequent discontinuation in older hypertensive PAD patients non-persistent with ACEIs/ARBs; (b) to determine patient and medication factors associated with reinitiation and subsequent discontinuation; and (c) to compare these factors between prevalent and new users. The analysis of reinitiation was performed on a sample of 1642 non-persistent patients aged ≥65 years with PAD newly diagnosed in 2012. Patients reinitiating ACEIs/ARBs were used for the analysis of subsequent discontinuation identified according to the treatment gap period of at least 6 months without any prescription of ACEI/ARB. In the group of non-persistent patients, 875 (53.3%) patients reinitiated ACEIs/ARBs during a follow-up (24.8 months on average). Within this group, subsequent discontinuation was identified in 414 (47.3%) patients. Being a new user was associated with subsequent discontinuation, but not with reinitiation. Myocardial infarction during non-persistence and after reinitiation was associated with reinitiation and lower likelihood of subsequent discontinuation, respectively. Being a prevalent or a new user is associated with the use of medication also after initial discontinuation.

Prevention and treatment of cancer associated venous thromboembolism - interdisciplinary consensus.

The increasing volume of the data and experience with direct oral anticoagulants (DOACS) in the primary and secondary prevention of venous thromboembolism in oncologic patients (CAVTE) has recently lead to changes in several international guidelines. We reflect these changes within the conditions in Slovak republic. In the primary prevention of CAVTE we recognise oncosurgical patients and nonsurgical patients: hospitalised and out patients. Low molecular weight heparins are still dominant in the primary prevention of CAVTE. Regarding the treatment and the secondary prevention of CAVTE, we recommend always to consider the possibility to use DOACs as they proved to be non inferior to LMWH. However, LMWH should be prefered over DOACs as well as over warfarin (VKA) in all patients who are in a clinically unstable condition with the high risk of bleeding and/or interaction with the systemic treatment. Primarily in the patients with intraluminal tumours of the upper part of the gastrointestinal tract and genitourinary tumours with the high risk of bleeding. As for the lack of data, LMWH are still preferd also in patients with primary tumours and metastatic disease of the central nervous system and in hemato oncology.

Gender Differences in Non-Persistence with Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers among Older Hypertensive Patients with Peripheral Arterial Disease.

The beneficial effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in hypertensive patients with peripheral arterial disease (PAD) depends on long-term persistence. The aims of our study were to analyse gender differences in non-persistence with ACEIs/ARBs, and to identify the characteristics associated with the likelihood of non-persistence. Our study cohort included 7080 hypertensive patients (4005 women and 3075 men) aged ≥65 years, treated with ACEIs/ARBs, in whom PAD was diagnosed between 1 January and 31 December 2012. Non-persistence was identified according to a treatment gap of 6 months without ACEI/ARB prescriptions. The characteristics associated with non-persistence were identified using the Cox regression model. At the end of the 5-year follow-up, 23.2% of the whole study cohort, 22.3% of men, and 23.9% of women were non-persistent with ACEIs/ARBs, with no significant gender differences in persistence. While a number of characteristics were associated with non-persistence, only three characteristics had consistent, statistically significant associations in both genders: being a new ACEI/ARB user increased the likelihood of non-persistence, and general practitioner as index prescriber and increasing the overall number of medications decreased the likelihood of non-persistence. Information on the differences in characteristics that are associated with non-persistence between genders may help to better identify patients for whom special attention should be paid to improve their persistence.

Adherence to Antiplatelet Medications among Persistent and Non-Persistent Older Patients with Peripheral Arterial Disease.

Secondary prevention of peripheral arterial disease (PAD) includes administration of antiplatelet agents, and adherence to medication is a requirement for an effective treatment. The aim of this study was to analyse adherence measured using the proportion of days covered (PDC) index separately in persistent and non-persistent patients, and to identify patient- and medication-related characteristics associated with non-adherence in these patient groups. The study cohort of 9178 patients aged ≥ 65 years in whom PAD was diagnosed in 1/-12/2012 included 6146 persistent and 3032 non-persistent patients. Non-adherence was identified as PDC < 80%. Characteristics associated with non-adherence were determined using the binary logistic regression model. In the group of persistent patients, 15.3% of subjects were identified as non-adherent, while among non-persistent patients, 26.9% of subjects were non-adherent to antiplatelet medication. Administration of dual antiplatelet therapy (aspirin and clopidogrel) and a general practitioner as index prescriber were associated with adherence in both patient groups. Our study revealed a relatively high proportion of adherent patients not only in the group of persistent patients but also in the group of non-persistent patients before discontinuation. These results indicate that most non-persistent PAD patients discontinue antiplatelet treatment rapidly after a certain period of adherence.

Reinitiation and Subsequent Discontinuation of Antiplatelet Treatment in Nonpersistent Older Patients with Peripheral Arterial Disease.

The successful treatment of peripheral arterial disease (PAD) depends on adequate adherence to medications including antiplatelet agents. The aims of this study were (a) to identify the proportion of nonpersistent patients who reinitiated antiplatelet therapy and how many of them discontinued therapy after reinitiation, and (b) to identify patient- and medication-related characteristics associated with the likelihood of reinitiation and discontinuation among reinitiators. The analysis of reinitiation was conducted on 3032 nonpersistent users of antiplatelet agents aged ≥65 years, with PAD newly diagnosed in 2012. Discontinuation (i.e., a treatment gap of ≥6 months without antiplatelet medication prescription) was analysed in 2006 reinitiating patients. To identify factors associated with the likelihood of reinitiation and discontinuation, Cox regression with time-dependent covariates was used. Reinitiation was recorded in 2006 (66.2%) of 3032 patients who had discontinued antiplatelet medication. Among these 2006 reinitiators, 1078 (53.7%) patients discontinued antiplatelet therapy again. Ischemic stroke and myocardial infarction during nonpersistence and bronchial asthma/chronic obstructive pulmonary disease were associated with an increased likelihood of reinitiation. University education was associated with discontinuation among reinitiators. Factors associated with the probability of reinitiation and discontinuation in reinitiators make it possible to identify older PAD patients in whom "stop-starting" behaviour may be expected.

Non-Persistence With Antiplatelet Medications Among Older Patients With Peripheral Arterial Disease.

Introduction: Antiplatelet therapy needs to be administered life-long in patients with peripheral arterial disease (PAD). Our study was aimed at 1) the analysis of non-persistence with antiplatelet medication in older PAD patients and 2) identification of patient- and medication-related characteristics associated with non-persistence. Methods: The study data was retrieved from the database of the General Health Insurance Company. The study cohort of 9,178 patients aged ≥ 65 years and treated with antiplatelet medications was selected from 21,433 patients in whom PAD was newly diagnosed between 01/2012 and 12/2012. Patients with a 6 months treatment gap without antiplatelet medication prescription were classified as non-persistent. Characteristics associated with non-persistence were identified using the Cox regression. Results: At the end of the 5 years follow-up, 3,032 (33.0%) patients were non-persistent. Age, history of ischemic stroke or myocardial infarction, clopidogrel or combination of aspirin with clopidogrel used at the index date, higher co-payment, general practitioner as index prescriber and higher overall number of medications were associated with persistence, whereas female sex, atrial fibrillation, anxiety disorders, bronchial asthma/chronic obstructive pulmonary disease, being a new antiplatelet medication user (therapy initiated in association with PAD diagnosis), and use of anticoagulants or antiarrhythmic agents were associated with non-persistence. Conclusion: In patients with an increased probability of non-persistence, an increased attention should be paid to improvement of persistence.

Baroreflex sensitivity and carotid intima-media thickness in risk stratification of prehypertensives and hypertensives.

BACKGROUNDː The aim of the study was to evaluate the clinical significance of baroreflex sensitivity (BRS) and carotid intima media thickness (IMT) in risk stratification of hypertensives and subjects with high normal blood pressure (SHNBP). METHODSː A total of 20 patients (61±13 years of age, 10 female/10 male) with essential, treated hypertension and 20 subjects (59±8 years of age, 10 female/10 male) with high normal blood pressure were enrolled. The interrelationship between BRS expressed in ms/mmHg (BRS) and IMT of common carotid artery (CCA) in hypertensives and subjects with high normal blood pressure (SHNBP, prehypertensives) was evaluated. BRS was determined by the sequence and spectral method: a five-minute non-invasive beat-to-beat recording of blood pressure (BP) and R-R interval with use of Collin CBM-7000 monitor, controlled breathing at a frequency of 0.1 Hz. Duplex ultrasonographic examination of the carotid wall and IMT of both CCA and carotid bulb were performed in all patients. RESULTSː Essential hypertension was associated with decreased BRS (r =-0.53, P<0.001). We found out that there was no significant difference between BRS and IMT CCA values in mild treated hypertensives and those in SHNBP. This finding was independent of age-dependent decrease of BRS. SHNBP and hypertensives with critical value BRS≤5 ms/mmHg have significantly increased IMT CCA. CONCLUSIONSː Decreased BRS is an early sign of autonomic dysfunction even in prehypertensive period. SHNBP and hypertensives with BRS≤5ms/mmHg have significantly increased IMT CCA. The principal result of this study showed that BRS and carotid IMT in relatively low-risk hypertensives and SHNBP could identify subjects at higher cardiovascular risk.

Effect of Low Dose Atorvastatin Therapy on Baroreflex Sensitivity in Hypertensives.

INTRODUCTION: Impaired baroreflex function is associated with a shift in autonomic balance towards sympathetic dominance, which may play important role in the development of arterial hypertension and consequent target organ damage. AIM: To determine the effect of treatment on the cardiovascular autonomic modulation expressed by baroreflex sensitivity (BRS) in hypertensives. METHODS: A total of one hundred fourteen hypertensive patients (58 male/56 female, 65 ± 13 years of age, BMI 30 ± 3.4 kg/m(2)) were enrolled. Control group of 20 subjects with normal blood pressure (BP) (ten male/ten female, 59 ± 8 years of age, body mass index 28.3 ± 2.5 kg/m(2)) without any treatment was also studied. BRS and BRSf were determined by the sequence and spectral method: a 5-min on-invasive beat-to-beat recording of blood pressure and R-R interval with use of Collin CBM-7000 monitor, controlled breathing at a frequency of 0.1 Hz. RESULTS: Significant negative correlation between spontaneous BRS and BP was present in hypertensives (r = -0.52, p < 0.001). All cohort of hypertensive patients had significantly lower BRS than subjects with normal blood pressure (p < 0.05). The greatest decline in BRS values was in hypertensive patients with metabolic syndrome, who had BRS values <5 ms/mmHg. Hypertensives with hypercholesterolaemia on low dose statin therapy (atrovastatin 20 mg) had higher BRS/BRSf values than statin free patients (p < 0.05). Only BRSf not BRS was significantly increased in hypertensives with beta-blockers. CONCLUSION: An inverse correlation between blood pressure and BRS is present in hypertensives. BRS and BRSf is higher in low dose statin-treated patients with essential hypertension.

Effect of short term aerobic exercise on fasting and postprandial lipoprotein subfractions in healthy sedentary men.

BACKGROUND: Our goal was to investigate the effect of short term exercise on fasting and postprandial lipoprotein profile. METHODS: Healthy sedentary men exercised 20 min for four days. The intensity of exercise was modulated to maintain 75-80 % of a calculated HRmax. Before and after the exercise program, fasting and postprandial (4 h after standard meal) concentrations of lipoprotein subfractions were measured by an electrophoresis in polyacrylamide gel and total concentrations of TAG, LDL and HDL by enzymatic colorimetric method. After 2 days of rest, fasting and postprandial concentrations of lipoprotein fractions and subfractions were measured to determine a persistency of a changes in the lipoprotein profile. RESULTS: 4 days of physical exercise led to statistically significant decrease of concentration of triacylglycerol in fasting (76.29 ± 20.07, 53.92 ± 10.90, p < 0.05) and postprandial state (139.06 ± 23.72, 96.55 ± 25.21, p < 0.05) VLDL in fasting (21.88 ± 3.87, 18.00 ± 3.93, p < 0.05) and postprandial state (23.88 ± 3.52, 19.25 ± 3.62, p < 0.05), total cholesterol in fasting (162.26 ± 23.38, 148.91 ± 17.72, p < 0.05) and postprandial state (163.73 ± 23.02, 150.08 ± 18.11, p < 0.05). Atherogenic medium LDL decreased also in fasting (9.89 ± 3.27, 6.22 ± 2.55, p < 0.001) and postprandial state (8.88 ± 6.51, 6.88 ± 5.57, p < 0.001). However decrease of large IDL (25.38 ± 3.54, 23.88 ± 3.91, p < 0.05) and large LDL particles (42.89 ± 11.40, 38.67 ± 9.30) was observed only in postprandial state. Total HDL concentration remained unchanged but we observed statistically significant decrease of small HDL particles in fasting (6.11 ± 2.89, 4.22, p < 0.05) and postprandial state (6.44 ± 3.21, 4.56 ± 1.33, p < 0.05). Concentration of these particles are associated with progression of atherosclerosis. All changes of fasting and postprandial lipoprotein profile disappeared after 2 days of rest. CONCLUSION: Just 4 daily settings of 20 min of physical exercise can lead to significant positive changes of fasting and postprandial lipoprotein profile.