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Nunes Vicente Passos Morgado, Manuel Augusto
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- Pharmacist intervention program to enhance hypertension control: a randomised controlled trialPublication . Morgado, Manuel; Rolo, Sandra; Castelo-Branco, MiguelObjective Studies have demonstrated that hypertension remains inadequately managed throughout the world, with lack of adherence to BP-lowering medication being a major factor. The aim of the present study was to evaluate if a pharmaceutical care program could improve antihypertensive medication adherence and blood pressure control. Setting This study was conducted in a secondary care hypertension/dyslipidemia outpatient clinic in the university teaching hospital of Cova da Beira Hospital Centre, Covilha˜, located in the Eastern Central Region of Portugal. Method This report evaluates the pharmacist’s interventions during a prospective randomised controlled trial, from July 2009 to June 2010. Patients with diagnosis of essential hypertension attending the clinic for routine follow-up were randomly allocated either to a control group (no pharmaceutical care) or to an intervention group (quarterly follow-up by a hospital pharmacist during a 9- month period). The pharmacist interventions, aimed to increase medication adherence and blood pressure control, involved educational interventions and counselling tips directed to the patient. Main outcome measure Systolic blood pressure, diastolic blood pressure and blood pressure control (according to JNC 7 guidelines) assessed at the baseline visit and at the end of pharmaceutical care were the main outcome measures. Blood pressure measurements were performed by blinded nurses. Medication adherence was also evaluated, using a validated questionnaire at baseline and at the end of investigation. Results A total of 197 hypertensive patients were randomly assigned to the study (99 in the control group and 98 in the intervention group). Although there were no significant differences (P[0.05) in both groups concerning mean age, gender, body mass index, and antihypertensive pharmacotherapy, blood pressure control was higher in the intervention group (P = 0.005) at the end of the study. Significant lower systolic blood pressure (-6.8 mmHg, P = 0.006) and diastolic blood pressure (-2.9 mmHg, P = 0.020) levels were observed in the intervention group. Medication adherence was also significantly higher in the intervention group at the end of the study (74.5% vs. 57.6%, P = 0.012).Conclusion Pharmacist intervention can significantly improve medication adherence and blood pressure control in patients treated with antihypertensive agents.
- SGLT2i and GLP1RA effects in patients followed in a hospital diabetology consultationPublication . Lopes, António Cabral; Lourenço, Olga; Morgado, Manuel Augusto Nunes Vicente PassosAbstract Background: We aimed to investigate the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) in patients with type 2 diabetes mellitus (T2DM) in clinical practice. Research design and methods: A total of 340 patients were included. Data on age, gender, antidiabetic medications, and bioanalytical parameters were collected at baseline and one year later. Were analyzed estimated glomerular filtration rate (eGFR), blood sodium and potassium levels, blood pressure, weight, cardiovascular risk, and glycated hemoglobin (HbA1c). Results: Patients treated with SGLT2i exhibited a significant improvement in eGFR at the endpoint compared to baseline (p = 0.006). Both treatment groups experienced reductions in systolic blood pressure at the endpoint; especially patients treated with SGLT2i (p = 0.0002). GLP1RA treatment resulted in a statistically significant weight reduction from baseline to endpoint (p < 0.0001), with a higher percentage of patients achieving ≥ 5% weight loss compared to the non-GLP1RA group (33.6% vs. 19.8%). Both SGLT2i and GLP1RA treatments significantly reduced cardiovascular risk scores (p = 0.004 and p = 0.002, respectively). Additionally, both treatments were associated with a significant reduction in HbA1c levels at the endpoint (p = 0.010 and p = 0.002, respectively). Conclusions: Our findings suggest that SGLT2i and GLP1RA offer beneficial effects in patients with T2DM.
- Desenvolvimento e avaliação de estratégias para aumentar a adesão à terapêutica farmacológica anti-hipertensora: estudo da intervenção do farmacêutico hospitalar no controlo da pressão arterialPublication . Morgado, Manuel Augusto Nunes Vicente Passos; Sousa, Miguel Castelo Branco Craveiro de; Verde Lusquiños, José IgnacioIntrodução: A hipertensão arterial (HTA) é uma doença com elevada prevalência na população adulta, constituindo um importante problema de saúde pública devido às complicações cardiovasculares graves que origina. Apesar do vasto leque de opções terapêuticas disponíveis com eficácia comprovada em ensaios clínicos controlados e aleatorizados, a proporção de hipertensos cuja tensão arterial (TA) se encontra controlada é, ainda, muito baixa, tornando primordial a criação de linhas de investigação e o desenvolvimento de estratégias de intervenção nesta área. Objectivos: Numa primeira fase, determinar a percentagem de doentes hipertensos, da zona de influência do Centro Hospitalar Cova da Beira, E.P.E. (CHCB), com a TA controlada e estudar os factores preditores de TA não controlada. Numa segunda fase, desenvolver, implementar e avaliar uma intervenção farmacêutica hospitalar que permita aumentar o controlo eficaz da HTA. População e Métodos: Para o desenvolvimento da primeira parte do projecto, realizou-se um estudo observacional transversal em doentes adultos com diagnóstico de HTA que acorreram, de Julho a Setembro de 2009, à consulta de hipertensão / dislipidémia de do CHCB. Foi realizada uma entrevista estruturada tendo em vista a recolha de dados sobre: características sócio-demográficas, adesão à medicação anti-hipertensora, conhecimentos sobre a HTA e presença de reacções adversas medicamentosas (RAMs). Os dados antropométricos, fisiológicos e clínicos para a realização do estudo foram prospectivamente obtidos através dos processos clínicos. Para a definição de controlo da HTA, foram seguidos os critérios da Direcção-Geral da Saúde e do “Seventh report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure”(JNC 7). A determinação das variáveis independentes com influência significativa no controlo da TA foi efectuada por regressão logística. Para o desenvolvimento da segunda parte do projecto, realizou-se um ensaio clínico, controlado e aleatorizado tendo em vista o estudo do efeito da intervenção do farmacêutico hospitalar na adesão à terapêutica anti-hipertensora e no controlo da TA. Este ensaio decorreu de Julho de 2009 a Junho de 2010, tendo participado os mesmos doentes com diagnóstico de HTA que foram incluídos no estudo realizado na primeira fase do projecto. Resultados: Foram incluídos no estudo um total de 197 doentes hipertensos, os quais satisfizeram os critérios de inclusão e consentiram participar. Apenas 33,0% dos doentes tinham a TA controlada, sendo a taxa de adesão à terapêutica anti-hipertensora de 48,2%. A análise de regressão logística revelou a existência de três covariáveis com influência significativa no controlo da TA: adesão à medicação (OR = 4,8; IC 95%: 2,4-9,5; P < 0,001), estado marital (OR = 5,3; IC 95%: 1,7-16,4; P < 0,004) e diabetes (OR = 4,4; IC 95%: 1,4-13,5; P < 0,011). A mesma análise revelou, ainda, que as seguintes variáveis independentes influenciam significativamente a adesão à terapêutica: conhecimento dos valores alvo de TA (OR = 3,7; IC 95%: 1,9-7,4; P < 0,001), reacções adversas atribuídas à medicação antihipertensora (OR = 3,7; IC 95%: 1,6-8,3; P < 0,002), monitorização regular da TA (OR = 2,5; IC 95%: 1,2-5,2; P < 0,015), conhecimento da indicação dos medicamentos (OR = 2,4; IC 95%: 1,1-5,2; P < 0,021) e conhecimento dos riscos da HTA (OR = 2,1; IC 95%: 1,1-4,2; P < 0,026). Embora no início do ensaio clínico não existissem diferenças significativas em ambos os grupos do estudo (controlo e intervenção) no que respeita a todos os parâmetros relevantes analisados, no final da intervenção farmacêutica, a percentagem de doentes com a TA controlada era significativamente maior no grupo de intervenção (OR = 2,2; IC 95%: 1,3-4,0; P = 0,005). Foram, igualmente, observados, no final do estudo, valores significativamente mais baixos de TA sistólica (-6,8 mm Hg, P = 0,006) e de TA diastólica (-2,9 mm Hg, P = 0,020) no grupo de intervenção. No final do ensaio clínico observou-se, ainda, que a adesão à medicação era mais elevada no grupo de intervenção (74,5% vs 57,6%, P = 0,012). Conclusões: Uma percentagem significativa de doentes hipertensos a quem foram prescritos medicamentos anti-hipertensores não apresenta a TA controlada, sendo a taxa de adesão a estes medicamentos muito inferior à que seria desejável. A baixa adesão à terapêutica, o desconhecimento, por parte do doente, dos valores alvo de TA, dos riscos da HTA não controlada e das indicações dos medicamentos, bem como a ocorrência de RAMs e a falta de monitorização regular da TA devem ser estudados como possíveis causas de TA não controlada e devem ser considerados em qualquer intervenção que tenha como objectivo aumentar o controlo da TA. A intervenção farmacêutica pode modificar os factores que influenciam a adesão à terapêutica e aumentá-la significativamente, conduzindo, deste modo, a um aumento do controlo da TA em doentes tratados com anti-hipertensores. A inclusão do farmacêutico hospitalar na equipa multidisciplinar de saúde, responsável pelo tratamento dos doentes com HTA, constitui uma estratégia vantajosa para combater este importante problema de saúde pública.
- Clinical and Pharmacotherapeutic Profile of Patients with Type 2 Diabetes Mellitus Admitted to a Hospital Emergency DepartmentPublication . Lopes, António Cabral; Lourenço, Olga; Roque, Maria de Fátima dos Santos Marques; Morgado, Manuel Augusto Nunes Vicente PassosType 2 diabetes mellitus (T2DM) is closely associated with other pathologies, which may require complex therapeutic approaches. We aim to characterize the clinical and pharmacological profile of T2DM patients admitted to an emergency department. Patients aged ≥65 years and who were already using at least one antidiabetic drug were included in this analysis. Blood glycemia, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hemoglobin were analyzed for each patient, as well as personal pathological history, diagnosis(s) at admission, and antidiabetic drugs used before. Outcome variables were analyzed using Pearson’s Chi-Square, Fisher’s exact test, and linear regression test. In total, 420 patients were randomly selected (48.6% male and 51.4% female). Patients with family support showed a lower incidence of high glycemia at admission (p = 0.016). Higher blood creatinine levels were associated with higher blood glycemia (p = 0.005), and hyperuricemia (HU) (p = 0.001), as well as HU, was associated with a higher incidence of acute cardiovascular diseases (ACD) (p = 0.007). Hemoglobin levels are lower with age (p = 0.0001), creatinine (p = 0.009), and female gender (p = 0.03). The lower the AST/ALT ratio, the higher the glycemia at admission (p < 0.0001). Obese patients with (p = 0.021) or without (p = 0.027) concomitant dyslipidemia had a higher incidence of ACD. Insulin (p = 0.003) and glucagon-like peptide-1 agonists (GLP1 RA) (p = 0.023) were associated with a higher incidence of decompensated heart failure, while sulfonylureas (p = 0.009), metformin-associated with dipeptidyl peptidase-4 inhibitors (DPP4i) (p = 0.029) or to a sulfonylurea (p = 0.003) with a lower incidence. Metformin, in monotherapy or associated with DPP4i, was associated with a lower incidence of acute kidney injury (p = 0.017) or acute chronic kidney injury (p = 0.014). SGLT2i monotherapy (p = 0.0003), associated with metformin (p = 0.026) or with DPP4i (p = 0.007), as well as insulin and sulfonylurea association (p = 0.026), were associated with hydroelectrolytic disorders, unlike GLP1 RA (p = 0.017), DPP4i associated with insulin (p = 0.034) or with a GLP1 RA (p = 0.003). Insulin was mainly used by autonomous and institutionalized patients (p = 0.0008), while metformin (p = 0.003) and GLP1 RA (p < 0.0001) were used by autonomous patients. Sulfonylureas were mostly used by male patients (p = 0.027), while SGLT2 (p = 0.0004) and GLP1 RA (p < 0.0001) were mostly used by patients within the age group 65-85 years. Sulfonylureas (p = 0.008), insulin associated with metformin (p = 0.040) or with a sulfonylurea (p = 0.048), as well as DPP4i and sulfonylurea association (p = 0.031), were associated with higher blood glycemia. T2DM patients are characterized by great heterogeneity from a clinical point of view presenting with several associated comorbidities, so the pharmacotherapeutic approach must consider all aspects that may affect disease progression.
- Predictors of uncontrolled hypertension and antihypertensive medication nonadherencePublication . Morgado, Manuel; Rolo, Sandra; Macedo, Ana Filipa; Pereira, Luísa; Castelo-Branco, MiguelBackground: Although hypertension is, in most cases, a controllable major risk factor in the development of cardiovascular disease, studies have demonstrated that hypertension remains poorly controlled in Portugal. Our aim was to evaluate the covariates associated with poor blood pressure (BP) control in a Portuguese hypertensive population. Patients and Results: We conducted a cross-sectional survey in a hospital hypertension outpatient clinic, located in the Eastern Central Region of Portugal. Patients attending the clinic from July to September 2009 were asked to participate in a structured interview including medication adherence and knowledge about hypertension. Eligible participants were all adults aged 18 or over with an established diagnosis of arterial hypertension and had been on antihypertensive drug treatment for at least 6 months. Exclusion criteria were dementia, pregnancy, and breastfeeding. Detailed clinical information was prospectively obtained from medical records. A total of 197 patients meeting the inclusion criteria and consenting to participate completed the interview. Of these, only 33.0% had their BP controlled according to the JNC 7 guidelines. Logistic regression analysis revealed three independent predictors of poor BP control: living alone (OR = 5.3, P = 0.004), medication nonadherence (OR = 4.8, P < 0.001), and diabetes (OR = 4.4, P = 0.011). Predictors of medication nonadherence were: unawareness of target BP values (OR = 3.7, P < 0.001), a report of drug side effects (OR = 3.7, P = 0.002), lack of BP monitoring (OR = 2.5, P = 0.015) and unawareness of medication indications (OR = 2.4, P = 0.021), and of hypertension risks (OR = 2.1, P = 0.026). Conclusions: Poor medication adherence, lack of information about hypertension, and side effects should be considered as possible underlying causes of uncontrolled BP and must be addressed in any intervention aimed to improve BP control.
- Association of statin therapy with blood pressure control in hypertensive hypercholesterolemic outpatients in clinical practicePublication . Morgado, Manuel; Rolo, Sandra; Macedo, Ana Filipa; Castelo-Branco, MiguelBackground: Some clinical evidence revealed that statins, apart from lowering cholesterol levels, also have an antihypertensive effect. Our aim was to evaluate the existence of a possible association of statin therapy with blood pressure (BP) control in clinical practice. Materials and Methods: Patients attending a hypertension/ dyslipidemia clinic were prospectively evaluated. Those patients with a diagnosis of stage 1 hypertension and hypercholesterolemia who consented to participate were included in the study, either in the statin group (when taking a statin) or in the control group (when not taking a statin). Exclusion criteria included dementia, pregnancy, or breastfeeding, and history or evidence of stage 2 hypertension. Detailed clinical information was prospectively obtained from medical records. A total of 110 hypertensive patients were assigned to the study (82 in the statin group and 28 in the control group). Results: Although there were no signifcant differences (P > 0.05) in both groups concerning gender, body mass index, antihypertensive pharmacotherapy, and serum levels of high-density lipoprotein cholesterol and triglycerides, a higher BP control was observed in the statin group (P = 0.002). Signifcantly lower systolic BP (−6.7 mmHg, P = 0.020) and diastolic BP (−6.4 mmHg, P = 0.002) levels were reported in the statin group. Serum levels of low-density lipoprotein were also signifcantly lower in the statin group (P < 0.001). Conclusions: This observational study detected an association of statin therapy with BP control in hypertensive hypercholesterolemic patients in clinical practice. These fndings raise the possibility that statin therapy may be useful for BP control in the studied population.
- Pharmacist interventions to enhance blood pressure control and adherence to antihypertensive therapy: Review and meta-analysisPublication . Morgado, Manuel; Morgado, Sandra; Mendes, Liliana; Pereira, L.; Castelo-Branco, MiguelPurpose. Pharmacist interventions to enhance blood pressure (BP) control and adherence to antihypertensive therapy in adults with essential hypertension were reviewed. Methods. A literature search was conducted to identify relevant articles describing pharmacist interventions intended to improve adherence to antihypertensive medications. Studies were included if they described a pharmacist intervention to improve medication adherence and analyzed adherence to therapy and BP control as outcomes. A fixed-effects model was used to combine data from randomized controlled trials. Results. A total of 15 studies were identified, testing 16 different interventions and containing data on 3280 enrolled patients. Although 87.5% of the interventions resulted in significant improvements in treatment outcomes, only 43.8% of the interventions were associated with significant increases in medication adherence. All interventions that increased antihypertensive medication adherence also significantly reduced BP. Almost all the interventions that were effective in increasing adherence to medication were complex, including combinations of different strategies. Meta-analysis of 2619 patients in 8 studies found that pharmacist interventions significantly reduced systolic blood pressure (SBP) (p < 0.001) and diastolic blood pressure (DBP) (p = 0.002) and that the meta-analytic differences in SBP and DBP changes from baseline to endpoint in intervention and control groups were –4.9 ± 0.9 mm Hg (p < 0.001) and –2.6 ± 0.9 mm Hg (p < 0.001), respectively. Conclusion. A literature review and meta-analysis showed that pharmacist interventions can significantly improve medication adherence, SBP, DBP, and BP control in patients with essential hypertension. Interventions were complex and multifaceted and included medication management in all analyzed studies.
- PDE4 and PDE5 regulate cyclic nucleotides relaxing effects in human umbilical arteriesPublication . Verde, Ignacio; Silva, António José Santos; Cairrão, Elisa; Morgado, Manuel; Álvarez, EzequielCyclic nucleotides (cAMP and cGMP) are the main second messengers linked to vasodilatation. They are synthesized by cyclases and degraded by different types of phosphodiesterases (PDE). The effect of PDE inhibition and cyclases stimulation on 5-hydroxytryptamine (5-HT; 1 microM) and histamine (10 microM) contracted arteries was analysed. Stimulation of guanylate cyclase or adenylate cyclase relaxed the histamine- and 5-HT-induced contractions indicating that intracellular increase of cyclic nucleotides leads to vasodilatation of the human umbilical artery. We investigated the role of different PDE families in the regulation of this effect. The presence of the different PDE types in human umbilical artery smooth muscle was analysed by RT-PCR and the expression of PDE1B, PDE3A, PDE3B, PDE4C, PDE4D and PDE5A was detected. The unspecific PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX; 50 microM) relaxed histamine-contracted human umbilical artery on 47.4+/-7.2%. This effect seems to be due to PDE4 and PDE5 inhibition because among the selective PDE inhibitors used only the PDE4 inhibitor (rolipram; 1 microM) and the PDE5 inhibitors (dipyridamole and T0156; 3 microM and 1 microM respectively) induced significant relaxation (39.0+/-8.7, 30.4+/-6.0 and 36.3+/-2.8 respectively). IBMX, dipyridamole and T0156 produced similar relaxation on 5-HT-induced contraction. After forskolin, the addition of IBMX or rolipram increased the effect of the adenylate cyclase stimulator and almost completely relaxed the human umbilical artery contracted by histamine (92.5+/-4.9 and 90.9+/-4.7 respectively), suggesting a main role of PDE4. The data obtained with 5-HT contracted arteries confirmed this, because only rolipram and IBMX significantly increased the forskolin vasodilator effect. The administration of dipyridamole and T0156 after sodium nitroprusside (SNP) induced a significant increase of the SNP relaxant effect on histamine-contracted arteries, but PDE1 and PDE3 inhibition did not increase the effect of the guanylate cyclase stimulator. Similar effects were obtained in 5-HT contracted arteries, the SNP induced relaxation was increased by the PDE5 inhibition, but not by PDE1 or PDE3 inhibition. In summary, our results demonstrate that: 1) the increase of cAMP and/or cGMP levels induces relaxation of the human umbilical vascular smooth muscle; 2) four families of PDE are expressed in this smooth muscle: PDE1, PDE3, PDE4 and PDE5; 3) between these families, PDE4 and PDE5 are the key enzymes involved in the regulation of the relaxation associated to cAMP and cGMP, respectively.
- Efficacy of Aliskiren/Hydrochlorothiazide Combination for the Treatment of Hypertension: A Meta-Analytical ApproachPublication . Morgado, Manuel; Rolo, Sandra; Castelo-Branco, MiguelBackground: Single-pill combinations of aliskiren/hydrochlorothiazide have recently been approved by the European Medicines Agency for the treatment of hypertension. Objective: This study aimed to assess the antihypertensive efficacy of aliskiren/hydrochlorothiazide combination in reducing systolic and diastolic blood pressure in hypertensive patients. Methods: A search in International Pharmaceutical Abstracts, MEDLINE, The Cochrane Library and ISI Web of Knowledge was performed from 2000 to November 2009, to identify randomized, double-blind, clinical trials using aliskiren/hydrochlorothiazide for the treatment of hypertension. Studies were included if they evaluated the antihypertensive efficacy of aliskiren/hydrochlorothiazide in patients with mild or moderate essential hypertension and age 18 years. The meta-analytical approach calculated the weighted average reductions of systolic and diastolic blood pressure for each daily dosage combination. Results: We included 5 clinical trials testing several combinations of aliskiren/hydrochlorothiazide and containing data on 5448 patients. In all studies blood pressure was assessed at inclusion (baseline) and after 8 weeks of therapy. Blood pressure reductions and control rates were significantly (p < 0.05) higher with the aliskiren/hydrochlorothiazide combinations than with placebo and the same doses of aliskiren or hydrochlorothiazide alone. The weighted mean reductions (mm Hg) from baseline of systolic and diastolic blood pressure for each aliskiren/hydrochlorothiazide combination were: -15.8/- 10.3 (150/25 mg); -15.9/-11.8 (300/12.5 mg); -16.9/-11.6 (300/25 mg). Blood pressure control rates (%) for the above combinations were, at least, respectively: 43.8, 50.1 and 51.9. Conclusions: Aliskiren/hydrochlorothiazide provided clinically significant additional blood pressure reductions and improved blood pressure control rates over aliskiren or hydrochlorothiazide monotherapy.
- Blood pressure control and antihypertensive pharmacotherapy patterns in a hypertensive population of Eastern Central Region of PortugalPublication . Morgado, Manuel; Rolo, Sandra; Pereira, L.; Castelo-Branco, MiguelBACKGROUND: Interventions to improve blood pressure control in hypertension have had limited success in clinical practice despite evidence of cardiovascular disease prevention in randomised controlled trials. The objectives of this study were to evaluate blood pressure control and antihypertensive pharmacotherapy patterns in a population of Eastern Central Region of Portugal, attending a hospital outpatient clinic (ambulatory setting) for routine follow-up. METHODS: Medical data of all patients that attended at least two medical appointments of hypertension / dyslipidemia in a university hospital over a one and a half year period (from January 2008 to June 2009) were retrospectively analysed. Demographic variables, clinical data and blood pressure values of hypertensive patients included in the study, as well as prescribing metrics were examined on a descriptive basis and expressed as the mean +/- SD, frequency and percentages. Student's test and Mann-Whitney rank sum test were used to compare continuous variables and chi-square test and Fisher exact probability test were used to test for differences between categorical variables. RESULTS: In all, 37% of hypertensive patients (n=76) had their blood pressure controlled according to international guidelines. About 45.5% of patients with a target blood pressure <140/90 mmHg (n=156) were controlled, whereas in patients with diabetes or chronic kidney disease (n=49) the corresponding figure was only 10.2% (P<0.001). Among patients initiating hypertension / dyslipidemia consultation within the study period 32.1% had stage 2 hypertension in the first appointment, but this figure decreased to 3.6% in the last consultation (P=0.012). Thiazide-type diuretics were the most prescribed antihypertensive drugs (67%) followed by angiotensin receptor blockers (60%) and beta-blockers (43%). About 95.9% patients with comorbid diabetes were treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. CONCLUSIONS: Clinically important blood pressure decreases can be achieved soon after hypertension medical appointment initiation. However, many hypertensive patients prescribed with antihypertensive therapy fail to achieve blood pressure control in clinical practice, this control being worse among patients with diabetes or chronic kidney disease. As pharmacotherapy patterns seem to coincide with international guidelines, further research is needed to identify the causes of poor blood pressure control.