Vol 16, No 2 (2019)

Aim. To evaluate patients’ (pts.) compliance with Ventavis inhaled treatment. Secondary aim: to study pts. characteristics; reason for low compliance; changes in 6-minute walking distance (6MWD) test and dyspnea score; changes in the parameters of pulmonary hemodynamics; pulmonary function changes; quality of life (QOL) according to compliance with Ventavis use; to assess frequency, severity and other characteristics of AE. Materials and methods. Prospective, multicenter, single cohort non-interventional IV phase study IVENT (NCT01971450). The study lasted 12 month. Pts. evaluation was scheduled as follows: initial visit done at baseline (pts. inclusion) - iV, 6 (follow-up visit 1) - V1, and 12 (follow-up visit 2, final) month - V2 thereafter. Evaluation of basic demographic and functional characteristics using needed armamentarium was planned at these time points. Treatment compliance was analyzed at 1 (6 month) and 2 (12 month) follow-up visits (ITT population). Results. As many as 82 pts. averages (mean±SD) 47.6±14.2 years with mean PH syndrome duration 3.2±5.7 years were included. Substantial number of pts. presented with severe disorders in anamnesis, i.e. pulmonary embolism, heart defect, arterial hypertension, heart failure in 35.4; 14.6; 36.6 and 70.7% of pts., respectively. PH syndrome verification methods varied with right heart catheterization (RHC) being the most prevalent one in 45.1% of pts., following by echocardiography (EchoCG) in 30.5%. At the iV EchoCG was performed in all the pts; and at the final visit in 82.9%; RHC - in 62.2% and 7.3%, respectively. Study population mean 6MWD estimated to be 257.7±109.6 m at the time of inclusion with Borg index score 6.4±4.2. All 82 pts. were being treated with iloprost inhaled [average daily dose 8.0±7.9 (95% CI 6.2-9.7) mcg] at the iV. 53 and 29 pts. of ITT population formed ‘sufficient-compliant’ (SC) and ‘low-compliant’ (LC) subgroups (sbgr.), respectively. Patients’ compliance of inhaled treatment with Ventavis in the overall population was shown to be 82.3±27.7% at the V1 and 81.8±28.4% at the V2; in SC sbgr. - 96.9±5.4 and 96.6±5.8%, respectively; in LC sbgr. - 49.1±29.1 and 46.4±29.9%, respectively. AE, lack of the drug or drug ineffectiveness, patient preferences not to receive the drug were demonstrated to be the main reasons for treatment discontinuation in both sbgr. At 6 month mean daily dose of iloprost was 7.7±5.5 mcg; at 12 month 7.2±4.9 mcg. At the iV 63.4% of pts. was receiving inhalations 6 times in a days at month 6 and 12 - 58.5% and 48.8%, respectively. Mean number of inhalations per day was estimated to be 5.9±1.3 at the iV and 6.1±1.3 at V1 and V2. Ventavis treatment interruptions were registered in 37.8% of pts. at the end of observation period (22.6% SC sbgr.; 65.5% LC sbgr.). Premature discontinuation of the drug treatment was noted in 8.5% of pts. at V1 and 20.7% at the V2. Dose correction took place in 4.9% and 1.2% of pts. at V1 and final visit, accordingly. SC sbgr. of pts. at baseline was characterized by 6MWD of 266.9±114.23 vs. 240.5±100.2 m in LC one. At 12 month 6MWD had increased up to 307.1±115.4 vs. 263.5±107.4 m in SC and LC sbgr., respectively. Baseline Borg dyspnea score in SC sbgr. was 6.1±3.8 vs. 6.9±4.9 in LC pts. At the end of the study, Borg dyspnea score for SC and LC pts. estimated to be 6.3±3.6 and 7.7±5.7, respectively. Thus, in SC sbgr. was achieved positive changes in 6MWD with persistent dyspnea, but in LC sbgr. dyspnea severity had increased. In ITT population systolic PAP (SPAP) measured by EchoCG was slightly decreased from 83.2±27.9 to 76.6±29.7 mmHg at the final visit; in SC sbgr. - from 82.5±24.1 to 76.5±26.7 mmHg; in LC sbgr. - from 84.5±34.5 to 76.8±35.7 mmHg. Due to the fact RHC data is available only for several pts., it is impossible to analyze changes in hemodynamic variables. Patients’ QoL according to SF-12 questioner showed positive changes from mean score 30.8±7.7 to 35.1±9.3 in SC pts. at the end of observation. QoL in LC sbgr. did not change substantially. Same trend could be revealed when evaluating psychological component: 41.7±10.6 and 46.3±10.9 in SC sbgr.; 40.6±11.4 and 40.2±11.7 in LC sbgr. During the study 64 AE in 24.4% of pts. were registered, 37 AE in 17.1% of pts. judged to be drug-related. Iloprost dose was remaining unchanged in 13.4% of pts., whereas in 2.4% of pts. dose decreased; in 8.5% of pts. drug intake was discontinued. At the end of the study, 35 AE in 15.9% of pts. successfully resolved. The most frequent AE became cough (9.8%), dysphonia (3.7%), headache (6.1%), dizziness (4.9%), syncope (3.7%), asthenia (2.4%), edema (2.4%). Overall 24 serious AE (SAE) had occurred in 20.7 of pts. 17 (out of 24) SAE in 11 (37.9%) pts. emerged in LC sbgr. None of the SAE were considered to be drug-related. Iloprost dose remained unchanged in 6.1% of pts. (8 SAE cases), treatment paused in 1.2% of pts., and treatment was discontinued in a single case. 13 SAE in 11 (13.4%) pts. were fatal, 4 SAE in 4 (4.9%) pts. had resolved, 3 SAE in 2 (2.4%) pts. was resolving, 4 SAE in 2 (2.4%) pts. were continuing at the end of observation. In 8 cases in 6 (7.3%) pts. dose correction measures were not undertaken; in 6 SAE cases in 5 (6.1%) pts. there is no information available. Conclusion. In general population studied, it’s been demonstrated sufficient PH patients’ compliance of Ventavis inhaled treatment.

This review is devoted to the problem of drug-induced hypertension (H). It summarizes the literature data on drugs and substances that can increase blood pressure, discusses the mechanisms of their hypertensive action. Many classes of drugs such as steroids, nonsteroidal anti-inflammatory drugs, sympathomimetics, immunosuppressants, oral contraceptives, antidepressants, erythropoietin, etc. can cause episodic or persistent increase in blood pressure, cause uncontrolled hypertension, reduce the effectiveness of antihypertensive drugs. The development of drug-induced hypertension is realized through a number of pathophysiological mechanisms: sodium retention with subsequent increase in the volume of circulating blood, activation of the sympathetic nervous system, direct effect on the smooth muscles of arterioles, there are other, not fully studied mechanisms. Drug-induced H may also be the result of pharmacokinetic or pharmacodynamic drug interactions. To suspect the presence of drug-induced hypertension, in the first place, should be in persons with newly diagnosed hypertension, as well as in patients who previously had a well-controlled hypertension (stable target blood pressure - BP levels) when they have episodes of unexplained increase in BP without a clear relationship with physical or psycho-emotional stress. It is very important to have a properly collected history with a focus on a thorough assessment of the medicines taken by the patient, especially newly prescribed, as well as those purchased at the pharmacy independently, including over-the-counter, this will avoid unnecessary and/or expensive studies and unnecessary prescriptions of additional antihypertensive drugs. The article presents these measures for the prevention and correction of drug-induced H. The appointment of new drugs by a doctor to patients receiving antihypertensive therapy should necessarily take into account their impact on the risk of drug-induced hypertension. Prescribing drugs that cause an increase in BP levels should either be avoided or, if alternative treatment regimens are not possible, strict control of the patient's BP level (including the method of home monitoring of BP) and, if necessary, the correction of antihypertensive therapy. When canceling a drug that causes drug-induced hypertension, BP returns to its original level, which is proof of the iatrogenic cause of hypertension.

Aim. To study the relationship of orthostatic hypotensive reactions (OHR), detected using active (AOT) and passive orthostatic tests (POT) with the state of cognitive functions in patients with arterial hypertension (AH) in older age groups. Materials and methods. 75 patients with hypertension I-III stage were examined (67±5 years). Patients received regular antihypertensive therapy, excluding medication on the day of the study. The study of the OHR was carried out using a 5-minute AOT and 5-minute POT with a minute-by-minute measurement of blood pressure on the shoulder using the oscillometric method and continuous non-invasive measurement of systolic (SBP) and diastolic (DBP) blood pressure in the finger artery by a photocompensation method (Task Force Monitor, CNSystems, Austria). The presence or absence of classical orthostatic hypotension (COH) and initial orthostatic hypotension (IOH) was assessed according to the criteria of the European Society of Cardiology (ESC-2018). The study of cognitive functions was carried out using a brief study of the mental state (Mini-Mental State Examination - MMSE), the clock drawing test and the Münstenberg test. The analysis was performed using Statistica 6.0. Data from sets with normal distribution were compared using student's t-test, Mann-Whitney test was used when comparing data with a distribution different from the normal one. To compare the groups on qualitative characteristics used Fisher's exact test. Results. In 23 (31%) patients, different types of OHR were identified, of them, 9 (12%) had isolated IOH, 14 (19%) had COH, among which 7 patients had a combination of COH+IOH). The revealed COH was neurogenic in all patients. The test result for drawing clocks in patients with OHR was significantly worse compared with patients without OHR (7.5±1.5 vs 8.4±0.8, p<0.05 at a rate of 10 points). The results of the Munsterberg test showed a decrease in the level of attention and concentration in patients with OHR (21.4±2.2 vs 22.5±1.2 respectively, p<0.05). The MMSE test did not reveal significant differences in individuals with OHR (26.1±2.28 vs 27.8±0.8 points, p>0.05). A decrease in cognitive functions was observed in patients with COH compared with patients without OHR (Munsterberg test: 21.2±2.6 vs 22.5±1.2, p<0.05; clock drawing test: 7.3±1.5 vs 8.4±0.8, p<0.05; MMSE test: 26.3±2.3 vs 26.9±1.2, p>0.05 respectively). In patients with IOH, this pattern was not observed (patients with IOH and without OHR: Munsterberg test: 21.9±1.27 vs 22.5±1.2, p>0.05; clock drawing test: 7.7±1.7 vs 8.4±0.8, p>0.05; MMSE test: 25.7±2.3 vs 26.9±1.2, p>0.05 respectively). Conclusion. OHR was detected in 31% of patients with AH in older age groups. The most pronounced decrease in cognitive functions was observed in patients with hypertension with COH.