University of Groningen
Challenges in using cardiovascular medications in Sub-Saharan Africa
Berhe, Derbew Fikadu
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Berhe, D. F. (2017). Challenges in using cardiovascular medications in Sub-Saharan Africa. University of Groningen.
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General Discussion
and Future Perspective
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General discussion |
General discussion
The intention of this thesis was to increase the knowledge on cardio-vascular medication use in (Sub-Saharan) Africa, an area of increasing relevance to healthcare and healthcare policy, but with little available in-formation to date. The specific aims were to provide evidence on health-care professionals’ (HCPs’) medication knowledge, safety monitoring of cardiometabolic medicines, and hypertension treatment practices, from patient adherence and satisfaction with antihypertensive medication to treatment outcomes.
Selecting the right medication and informing a patient is greatly affected by knowledge and skills of the individual prescribing, and/or dispensing HCP. As the first contact point for patients, improving HCPs’ medication knowledge can help to optimize rational drug use, also help patients better understand why and how to take their medication in (Sub-Saharan) Africa. The first step for improvement of drug use is to understand current practices and identify the gaps. However, there is no comprehensive study that provides overview on medication knowledge of HCPs in (Sub-Saharan) Africa. In Chapter 2, we conducted a sys-tematic review on medication knowledge of HCPs in Africa. From the retrieved 64 papers, the overall HCPs’ medication knowledge appeared to be sub-optimal with few studies on cardiovascular disease (CVD) medications. Although, the message is not different for this population. About three-quarters of studies were on communicable disease medica-tions mainly antimalarial, antiretroviral medicamedica-tions for HIV, and dif-ferent types of vaccines. The studies had been performed in 12 African countries; however, 75% originated from four countries; Nigeria, Tan-zania, Kenya and Cameroon. The medication questions focused mainly on medication benefits with little emphasis on harms.
In conclusion, information on knowledge of HCPs of CVD medication is still lacking, in contrast to knowledge on communicable diseases (anti-malarial medications, antiretroviral agents for HIV, and different type of vaccines). The studies focusing on CVD were very few and suggest that the general sub-optimal medication knowledge also applies to this field. Further continued education is recommended across all included papers.
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| General Discussion and Future Perspective
One aspect of CVD medication knowledge is safety monitoring. The Sub-Saharan African (SSA) population may react differently to cardio-metabolic medications due to their genetic susceptibility to CVDs and different metabolic capacities (pharmacogenetics), interaction with infectious disease medications and diet habits. However, pharmacovig-ilance reports in the region focus primarily on medicines used for com-municable diseases [1, 2]. In Chapter 3, ADR reports for cardiomet-abolic medicines from SSA were compared with reports from the rest of the world (RoW). We used vigiPoint a method developed by WHO-UMC [3] that uses disproportionality analyses to compare reports on cardiometabolic drugs in SSA with two references; i.e a) ADR reports on cardiometabolic drugs outside SSA and b) ADR reports from SSA but for non-cardiometabolic medications. The number of potential ADRs reported for cardiometabolic medications in SSA, as in the RoW, has increased dramatically over the past decade; over three-quarter were received after 2007. In SSA, we found a cluster of disproportionally — significantly more often than in the RoW — reported ADRs, such as lip swelling, cough, angioedema, face oedema and swollen tongue that are most likely related to ACE-inhibitors, which were also among the medicines for which ADRs were most frequently reported. We thus identified a likely real population-based difference in ADR pattern. The relevant difference in ADR profile across populations suggests a need for monitoring the safety of cardiometabolic drugs considering the in-creasing prevalence of cardiometabolic disease in SSA and the role of ACE-inhibitors for treating these diseases [4].
In Chapter 5, we found most of patients on antihypertensive
med-ication did not have controlled BP, and treatment was not intensified for these with previously uncontrolled BP. Drugs were prescribed from ACE-inhibitors, diuretics, calcium channel blockers (CCBs), and beta blockers (BBs). Follow-up in a general hospital (compared to a spe-cialized hospital), longer treatment duration, age of patients, history of uncontrolled blood pressure (BP), and a treatment regimen containing diuretics were significant determinants for (not) achieving target BP. However, duration of therapy on antihypertensive medication was the only significant contributing factor for treatment intensification.
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General discussion |
The level of controlled BP and treatment intensification practice in our study was low. The findings suggest the need for in-depth under-standing and interventions of the identified determinants such as un-controlled BP on consecutive visits, older age, and type of hospital.
In chapter 6, we measured the medication adherence and patients’
treatment satisfaction using the validated questionnaires, respectively Morisky Medication adherence scale (MMAS) and Treatment Satisfac-tion QuesSatisfac-tionnaire for MedicaSatisfac-tion (TSQM) version 1.4 [5, 6]. We had translated and back translated both scales into to Tigrigna and Amharic languages. MMAS uses 8 questions and TSQM measures a patient’s satisfaction on four domains; i.e. effectiveness (TSQM 1–3); side effect (TSQM 4, 5–8); convenience (TSQM 9–11); and global satisfaction (TSQM 12–14).
More than three-quarter of ambulatory hypertensive patients had low or medium antihypertensive medication adherence. One in five patients experienced at least one ADE with a maximum of six ADEs per pa-tient. The most commonly reported ADEs were dyspeptic symptoms, headache, cough, fatigue/weakness, leg swelling, and palpitation/other cardiac problems. Global satisfaction was the lowest rated among all other TSQM domains. The highest mean score was for the ‘side effect’ domain. This score was high because most patients (80%) did not report any ADE and received a maximal score on this domain of 100%. Lower antihypertensive medication adherence score was associated with expe-riencing more ADEs and not being satisfied with treatment. Adherence was also negatively affected by treatment regimens containing calcium channel blockers, and taking medication over a year. The studies in this thesis add to the existing evidence on cardiometabolic use.
There is no universally accepted standard knowledge score; however, most educational institutes often use 60% as the pass mark. Studies in Norway, Netherlands, and in 15 European countries used a higher thresh hold (60–90% score). Comparison of these reports with our study should be made with cautious as the papers in our study covered much broader topics with a wide variety of medication knowledge questions, study designs and, different types of HCPs. Considering African spe-cific challenges — eg. low literacy rate in the general population — the
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| General Discussion and Future Perspective
overall medication knowledge score in our study is suboptimal. Nearly half of the studies originated from Nigeria implying little attention and research on HCPs’ medication knowledge in most of countries in Af-rica. Relatively medication harm aspect did not get much attention (in comparison to the medication benefit). CVD medication knowledge is severely understudied.
Currently pharmacovigilance is still in its infancy in SSA, but the large scale of medicines used to treat communicable diseases, eg. malaria, HIV, make it an important ‘playground’ for safety studies to identify hitherto unknown ADRs. Our study shows that also attention to safety of cardiometabolic medicines in SSA — that are often already widely used elsewhere — is valuable it is able to identify population-based dif-ferences in medication safety.
In the hypertension studies, we demonstrated low level of BP con-trols, low treatment intensification practice, poor medication adherence, and ADEs documentation. These findings, while extending the knowl-edge on hypertension management in an African setting paint an all too familiar picture of less than optimal control of the disease. Both HCP factors, knowledge and attitudes as reflected by the poor observed intensification of treatment, and patient factors, poor adherence con-tribute to this finding. Although, in our study adherence was not sig-nificantly associated with BP control, the extensive scientific knowledge [7–9], strongly supports efforts to improve adherence should be taken. Medicines that are not taken will not work!
Methodological issues and limitations
In this thesis, there are general and study specific limitations. Chapter 2 (the systematic review) covers a wide range of topics with different as-sessment methods of knowledge. The pooled estimates should be inter-preted with caution as studies were highly heterogeneous reporting a wide range of diseases that used varied measuring tools. An important issue limiting generalizability of the findings was that knowledge assess-ment tool developassess-ment was very poorly worked out in most papers. The
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Methodological issues and limitations |
review was limited in time to minimize heterogeneity of included stud-ies that may be affected by the advancements in medical sciences and especially access to information.
For chapter 3, the analytical method used (vigiPoint) to detect dif-ferential reporting rates of ADRs between SSA and RoW was univariate and could not see potentially influencing factors. However, the method is robust in identifying the well-known population based medication safety difference [10]. Lack of data on cardiometabolic drug utilization in SSA limits interpretation of the individual case safety reports (ICSR) data. The extent of medication use is an important factor for the number of reported ADRs, without this denominator (drug use) data the num-ber of spontaneously reported ADRs is inherently difficult to interpret. A further constraint is the well-known underreporting in spontaneous ADR systems that is ascribed to barriers in e.g. the pharmacovigilance system setup and HCPs awareness and attitudes towards ADR report-ing [11]. The lack of causality assessment was another limitation, but was beyond the scope of this study. This will require further work, and although the dataset seemed rather complete — not different in the SSA subset compared to RoW — it is unclear whether the data are suffi-ciently rich to allow a thorough review of causality.
Certain limitations challenge also the interpretation of the findings from chapter 5 and 6. We analyzed BP measurements as recorded in patients’ medical records which reflected actual clinical practice. The BP measure we used may be subject to recording and measurement error and has the same limitations as observational studies where medical records or database are used as data source. How prescribers considered interpersonal variability and avoid white-coat effect is also not known in Ethiopia. Furthermore, medical records may not have extensive patient information or not well-structured patient information — for example comorbidities may be underreported. We also did not study if medica-tion prescribed were in line with guideline recommendamedica-tions instead we focused on the actual impact of prescribing on BP.
Another limitation was the validity of the tool used to measure medica-tion adherence and treatment satisfacmedica-tion. We followed a standard step-wise translation procedure, but this did not include a cognitive validation.
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| General Discussion and Future Perspective
This means that it is not totally clear our Ethiopian patients fully com-prehended the questions asked. However, the tools were able to capture differences between study participants. Chapter 5 specific limitation was on reported adverse drug events (ADEs). Most of the patient-reported ADEs were typical for antihypertensive medication; however, a formal causality assessment was beyond the scope of this study. A common lim-itation for both chapters (5 and 6) was the issue of generalizability. These studies were performed in two tertiary and four secondary care hospitals in Ethiopia, the findings may thus not be applicable to other settings such as private practice, primary health care centers in Ethiopia.
In general, there is limited electronic database and poor recording practice in Ethiopia as with most countries in SSA healthcare setups. This may hamper healthcare service delivered, as the traditional paper work is often subjected to inconsistence, recording error, and also los-ing the whole document. That also makes difficult of linklos-ing healthcare services within or among institutes mainly with challenges of lost to follow-up for patients moved to other places.
Conclusion
In this thesis, we demonstrated that HCPs’ medication knowledge is suboptimal and that very little can be said on knowledge of cardio-vascular medications. With respect to performing pharmacovigilance activities in SSA, these are appropriately focusing on medicines used for communicable diseases. However, monitoring other types of medi-cations may pay off as well, as our study showed that population-based differential ADR profiles may be identified. Hypertension treatment practices in Ethiopia do not result in patients reaching treatment goals, and solutions to address this will have to face HCPs and patients, to improve treatment performance (treatment intensification) respectively adherence to medication.
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Implication for practice |
Implication for practice
The implication for HCPs medication knowledge (Chapter 2) is clear; the need for further training, especially continuous education, not only for medical, but also other HCPs. Chapter 3 finding signals the need to intensify cardiometabolic medication safety monitoring practices in light of increasing prevalence of CVDs burden in SSA.
Hypertension treatment practices and medication adherence im-provement strategies may include patient education and counseling, involving patients in decision making, training HCPs on patient coun-seling and ADE management [12]. Increasing the role of nurses and pharmacists in patient counseling may be a solution, as suggested else-where: “team based care for hypertension’’ [13].
Implication for (scientific) research
Research will need to focus on further studies of baseline HCP knowl-edge on cardiovascular medications, developing, testing and using generic questionnaires and design appropriate training programs focused at different HCP. These dedicated training programs should start in our view pre-graduation and be continued throughout a HCPs career. Repeated evaluation of validated knowledge questionnaires will then be able to refine and select the most effective training programs. For example, new communication tools to inform HCPs of benefits and risks of medication e.g. drug facts box may be developed and tested [14]. Strengthening drug information centers can address med-ication use challenges for HCPs, and also to patients. Further research is needed how to establish drug information centers which efficiently communicate to HCPs and the general public using different commu-nication tools.
Further research should focus on treatment outcomes, utilizing more robust outcomes; i.e. repeated measurements of BP and clinical outcomes. These studies should address the identified barriers to reach treatment goals and adherence. Studies may range from identifying
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| General Discussion and Future Perspective
medication specific knowledge gaps, designing effective and affordable communication tools to studies testing e.g. the ‘polypill’ that contains multiple agents targeting multiple CVD risk factors at once.
References
(1) Aagaard L, Strandell J, Melskens L, Petersen PS, Hansen EH. Global patterns of adverse drug reactions over a decade. Drug Saf 2012; 35:1171–82
(2) Ampadu HH, Hoekman J, de Bruin ML, Pal SN, Olsson S, Sartori D, et al. Adverse Drug Reaction Reporting in Africa and a Comparison of Individual Case Safety Report Char-acteristics Between Africa and the Rest of the World: Analyses of Spontaneous Reports in VigiBase®. Drug Saf 2016; 39:335–45.
(3) Pinpointing key features of case series in pharmacovigilance—a novel method. Drug Saf 2013; 36: 912–3.
(4) Dalal S, Beunza JJ, Volmink J, et al. Non-communicable diseases in sub-Saharan Africa: what we know now. Int J Epidemiol 2011; 40:885–901.
(5) Atkinson MJ, Sinha A, Hass SL, et al. Validation of a general measure of treatment sat-isfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes 2004; 2: 12. (6) Morisky DE, Ang A, Krousel‐Wood M, Ward HJ. Predictive validity of a medication
adherence measure in an outpatient setting. J Clin Hypertens 2008; 10:348–54.
(7) Chowdhury R, Khan H, Heydon E, et al. Adherence to cardiovascular therapy: a meta- analysis of prevalence and clinical consequences. Eur Heart J 2013; 34:2940–8.
(8) Grassi G, Seravalle G, Mancia G. Cardiovascular consequences of poor compliance to antihypertensive therapy. Blood Press 2011; 20:196–203.
(9) Corrao G, Parodi A, Nicotra F, et al. Better compliance to antihypertensive medications reduces cardiovascular risk. J Hypertens 2011; 29:610–18.
(10) Juhlin K, Star K, Norén GN. A method for data-driven exploration to pinpoint key fea-tures in medical data and facilitate expert review. Pharmacoepidemiol Drug Saf 2017 16. doi: 10.1002/pds.4285
(11) Biagi C, Montanaro N, Buccellato E, et al. Underreporting in pharmacovigilance: an intervention for Italian GPs (Emilia-Romagna region). Eur J Clin Pharmacol 2013; 692:237–244.
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References |
(13) Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Manage-ment of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood Press 2013; 22):193–278.
(14) Schwartz LM, Woloshin S, Welch HG. Using a Drug Facts Box to Communicate Drug Benefits and Harms. Ann Intern Med 2009; 150:516–27.
