|Year : 2019 | Volume
| Issue : 1 | Page : 18-24
Pattern and appropriateness of antihypertensive prescriptions among hospitalized hypertensives in Nigeria
Adeseye A Akintunde1, Kamilu M Karaye2, Daniel Olusegun-Joseph3, SA Balarabe2, Oladimeji G Opadijo1
1 Department of Medicine, Ladoke Akintola University of Technology and LAUTECH Teaching Hospital, Ogbomoso, Nigeria
2 Department of Medicine, Bayero University and Aminu Kano University Teaching Hospital, Kano, Nigeria
3 Department of Medicine, Lagos University Teaching Hospital and University of Lagos, Lagos, Nigeria
|Date of Submission||24-Jul-2018|
|Date of Decision||24-Apr-2019|
|Date of Acceptance||12-Jun-2019|
|Date of Web Publication||22-Oct-2019|
Dr. Adeseye A Akintunde
Department of Medicine, Ladoke Akintola University of Technology and LAUTECH Teaching Hospital, P. O. Box 3238, Ogbomoso
Source of Support: None, Conflict of Interest: None
Introduction: Prescribers' compliance to relevant guidelines may be a reflection of the depth of thoroughness in therapy, awareness, and a pointer to pitfalls in reducing cardiovascular mortality. This study was aimed to study the pattern and appropriateness of antihypertensive prescriptions among hospitalized patients with hypertensive disorders in Nigeria.
Materials and Methods: This was a retrospective study. All medical admissions over a 1-year from January 1 to December 31, 2013, were reviewed from three teaching hospitals across Nigeria. Two hundred and eighty-eight hospitalized hypertensive patients were identified with complete records. The pattern of drugs prescription and their compliance with the Joint National Commission VII criteria was determined.
Results: The mean age was 57.6 ± 15.7 years. Associated comorbid conditions include heart failure, transient ischemic attack, and type 2 diabetes mellitus. Commonly prescribed drugs include angiotensin-converting enzyme inhibitors (ACE-I), diuretics, calcium channel blockers (CCBs), and angiotensin receptor blockers. The proportions of participants using these drugs were 57.3%, 34.0%, 26.4%, and 12.5%, respectively. Fifty-one (20.73%) were on a single medication, 108 (43.9%) were on two medication classes while 87 (35.37%) were on drugs from at least three classes of antihypertensive pharmacotherapy. Combination therapy is frequent among hospitalized hypertensive patients in this study. The common pattern of two-drug combination among study participants included ACE-I and diuretics. The most common three-drug combinations included ACE-I, CCBs, and diuretics.
Conclusion: Majority of study participants were on combination therapy and had multiple comorbid cardiovascular risk factors, target organ damage, and complications. Antihypertensive prescriptions across three tertiary centers in Nigeria appear to follow relevant clinical guidelines with minimal differences across the centers.
Keywords: Antihypertensive drugs, guidelines, Nigeria, pattern
|How to cite this article:|
Akintunde AA, Karaye KM, Olusegun-Joseph D, Balarabe S A, Opadijo OG. Pattern and appropriateness of antihypertensive prescriptions among hospitalized hypertensives in Nigeria. Nig J Cardiol 2019;16:18-24
|How to cite this URL:|
Akintunde AA, Karaye KM, Olusegun-Joseph D, Balarabe S A, Opadijo OG. Pattern and appropriateness of antihypertensive prescriptions among hospitalized hypertensives in Nigeria. Nig J Cardiol [serial online] 2019 [cited 2019 Nov 21];16:18-24. Available from: http://www.nigjcardiol.org/text.asp?2019/16/1/18/269648
| Introduction|| |
Hypertension and its complications are a major reason for medical admissions, even in developing countries due to a rapid epidemiologic transmission.,,, Many hypertensive patients present with target organ damage and other complications even at diagnosis. These complications include stroke, renal failure, hypertensive heart failure, peripheral arterial disease, and malignant hypertension., The major aim of treating hypertension is to reduce the total cardiovascular risk and mortality. This is achieved conventionally by antihypertensive therapy and treatment of other clustered cardiovascular risk factors. Various guidelines have recommended various blood pressure (BP) targets often based on dynamic body of evidence from clinical research and sometimes expert opinion.,,, The Joint National Council on detection, prevention, evaluation, and treatment of high BP Joint National Commission (JNC VIII) report seems conservative about setting too many different goals for many different comorbid conditions unlike previous reports, and it is at present generating controversies worldwide. The Joint National Council on detection, treatment, and prevention of hypertension seventh report (JNC VII) appears to be more generally acceptable. Nonetheless, the compliance of prescribers to acceptable internationally relevant guidelines may be a reflection of depth of thoroughness in therapy, awareness, and aggression in reducing cardiovascular risk and mortality based on the present evidence. Many factors may determine the choice of therapy in hypertension, especially in developing countries. They include cost, availability, prescribers' awareness, side effects, or drug interactions among others., We have earlier demonstrated the pattern of adherence to antihypertensive medications in one of the participating centers in this study. Practice guidelines often provide an informed guide in clinical decision-making and do not replace patient–doctor interaction. It could help ascertain relative similarity in the management of similar conditions and also could be a measure of quality of care. The adherence of clinicians especially internist to the relevant guidelines on the management of hypertension and its complications are not well studied among Africans. This study aimed to describe the pattern of antihypertensive medications and compliance to known international guidelines and other associated factors affecting pharmacotherapy in the management of patients with hypertension and its complications who were admitted to three tertiary centers in Nigeria.
| Materials and Methods|| |
This was a retrospective study carried out in three large teaching hospitals in North and Southern Nigeria. The centers were Ladoke Akintola University of Technology Teaching Hospital, Ogbomoso, Oyo State and Lagos University Teaching Hospital (LUTH), Idi Araba, Lagos State both in Southern Nigeria, and Aminu Kano University Teaching Hospital (AKTH), Kano, in Northern Nigeria. Ethical approval was obtained from all the centers.
All medical admissions over a 1-year period from January 1, to December 31, 2013, were reviewed. The admission, discharge, and mortality registers of the medical wards in these teaching hospitals were reviewed and used to identify cases of hypertension-related medical admissions. They included those with hypertensive disorders including stroke, renal failure, heart failure, and severe malignant hypertension. Admission, clinical, and biochemical parameters, admission outcome, numbers, dosage, and types of antihypertensive medications taken by patients were retrieved from the case notes of all patients. All clinical, biochemical, and related data were entered into a data sheet and eventually transferred to a statistical package. Other information obtained from the case records of patients included age, gender, occupation, height and weight, educational status, history of alcohol usage, smoking, and marital status. The systolic and diastolic BPs at admission were recorded. The presence of clinical conditions such as dyslipidemia, heart failure, stroke or transient ischemic attack (TIA), renal failure, peripheral arterial disease, hypertensive encephalopathy, and diabetes mellitus was determined. Other comorbid clinical conditions, such as chronic obstructive pulmonary disease, bronchial asthma, urinary tract infection, liver disease, anemia, thyroid disease, and neoplasms, were also noted. The result of relevant investigations such as electrocardiography, echocardiography, fasting or random blood sugar, electrolytes, urea and creatinine, and full blood count was also recorded.
The appropriateness of the drugs was validated based on conventional guidelines for antihypertensive pharmacotherapy. This may not totally reflect their drugs usage over time as it does not capture their adherence and compliance. Hypertension is defined as any subject with persistent BP >140 mmHg systolic and/or >90 mmHg diastolic BP or who has been prescribed antihypertensive medications before the index admission. Adults >18 years were included in the study, if their medical records were retrievable. The definition of other clinical conditions was ascertained by relevant clinical history and confirmation by managing consultants backed up by appropriate investigations. We have earlier demonstrated that majority (up to four-fifths of these patients had one or more comorbid conditions which were most likely cardiovascular with the most frequent being heart failure. Statistical analysis was done using the Statistical Package for Social Sciences 17.0 SPSS Inc., (Chicago Ill, USA). All means (standard deviations and proportions/ranges were used to describe patients' characteristics for quantitative and qualitative variables, respectively. Chi-square test, Fisher's exact probability, and Student's t-test were used to compare categorical and continuous variables. P < 0.05 was taken as statistically significant.
| Results|| |
The mean age of study participants was 57.6 ± 15.7 years. The mean age was similar between the three groups. The mean systolic and diastolic BPs were 150.2 ± 35.8 versus 93.0 ± 22.4 mmHg. Mean systolic BP was significantly higher among the participants from LAUTECH Teaching Hospital (LTH), Ogbomoso, Nigeria, than the two other centers, as shown in [Table 1]. Similarly, diastolic BP was significantly higher among participants from LTH center than the two other groups. Systolic and diastolic BPs were similar between the AKTH and LUTH centers. However, mean random blood sugar was similar between LUTH and AKTH but higher than LTH center. Mean packed cell volume, number of participants who took alcohol smoked cigarette, or had dyslipidemia were significantly different between the three groups as shown in [Table 1]. The proportion of patients who took alcohol, smoked cigarette, and who had dyslipidemia were 19.8%, 10.1%, and 17.0%, respectively.
The profile of target organ damage, complications, and associated comorbid conditions among study participants is shown in [Table 2]. Among complications and comorbid conditions in all the study participants, heart failure was the most common reported in 29.2% of participants. This was followed by a history of stroke or TIA, type 2 diabetes mellitus (T2DM), and renal failure which were reported in 25.7%, 21.2%, and 18.1%, respectively. When the centers were compared to one another, heart failure was the most common in LTH similar to what was reported from LUTH while stroke/TIA was the most common in AKTH followed by T2DM and then heart failure. Other comorbid conditions or complications identified among study participants included peripheral arterial disease, hypertensive encephalopathy, deep venous thrombosis, pneumonia, liver disease, anemia, neoplasms, and chronic pulmonary arterial disease. This is shown in [Table 2].
|Table 2: Profile of target organ damage, complications, and associated co-morbid conditions among study participants|
Click here to view
The mean number of drugs used in this study was 1.99 ± 0.98. There was more tendency toward multiple drugs in LTH than LUTH and AKTH as reflected in significant difference in the mean number of drugs/medications used in these centers. The pattern of drug use among the study participants is shown in [Table 3]. Among all of them, the commonly used drugs include angiotensin-converting enzyme inhibitors (ACE-I), followed by diuretics, calcium channel blockers (CCBs), and angiotensin receptor blockers (ARBs). The proportions of participants using these drugs were 57.3%, 34.0%, 26.4%, and 12.5%, respectively. This was the prevalent pattern in two of the study centers (AKTH and LUTH) but a bit different from LTH where diuretics were the most commonly prescribed medications (67.6%) followed by ACE-I (62.2%). This was closely followed by CCBs (55.4%). Drugs that were infrequently used include beta blockers and centrally acting agents.
|Table 3: Pattern of drugs use among study participants based on each center|
Click here to view
Most of the patients included in this review were on at least one medication even though their adherence was not evaluated. At least more than four-fifths of all participants in this study were on at least one medication by the time of admission. Pharmacotherapy in hypertension management is an important step to reduce the associated cardiovascular morbidity and mortality. Two hundred and forty-six of the study participants had records of drug use at admission. The others were not on any antihypertensive therapy despite being known patients with hypertension or were not even aware of the diagnosis at admission. Of the study participants, 51 (20.73%) were on a single medication, 108 (43.9%) were on two medication classes while 87 (35.37%) were on drugs from at least three classes of antihypertensive pharmacotherapy as shown in [Table 3].
[Table 4] shows the pattern of antihypertensive prescription among study participants among middle-aged compared to elderly patients. ACE-I, ARBs, CCB, and diuretics were more likely used among elderly hospitalized hypertensives especially among patients in LTH while the same applies for ACE-I and beta blockers in AKTH and for ACE-I and ARBs in LUTH. The elderly hospitalized hypertensive patients were more likely to be on multiple combination therapy in LTH and LUTH compared to AKTH as shown in [Table 4]. It is worthy of note that there is major similarity in the prescription pattern of antihypertensive for almost all the drug classes across the three centers for ACE-I, ARBs, CCB, diuretics, beta blockers, and methyldopa as shown in [Table 4] as there was no statistical significance between the prescription pattern in the three centers. For patients who were on a single antihypertensive drug, the most common antihypertensive prescription was ACE-I closely followed by diuretics. It is important to note that majority of those who had a single drug class of CE-I prescription were patients with additional T2DM or heart failure.
|Table 4: Prescription pattern of antihypertensive medications and relationship with age between the sites|
Click here to view
Combination therapy was frequent among hospitalized hypertensive patients in this study. The most common pattern of two-drug combination among study participants included ACE-I and diuretics. This was followed closely by combination of ACE-I and CCBs. Other options in two-drug combinations included ARB and CCB, Beta-blockers and diuretics and CCBs and diuretics. It appeared that diuretics formed the baseline for most prescriptions among study participants, except there were compelling indications to use another drug class. Other drugs classes were then often added including ACE-I, ARBs, beta blockers, and CCBs.
The most common three-drug combination often included ACE-I, CCBs, and diuretics. This was followed by the combination of ARB, CCBs and diuretics and then the combinations of ACE-I, CCBs and methyldopa. There were various options used for four-drug antihypertensive combination among study participants. The common prescription pattern included a combination of ACE-I, diuretics, CCBs, and diuretics. Another combination option was ARBs, diuretics, beta blockers, and CCBs. This is shown in [Table 5].
|Table 5: Common drugs combination used in the management of hypertension in this study|
Click here to view
| Discussion|| |
Hypertension is involved in many medically related admissions across Africa., The contribution of hypertension to medical morbidity and mortality is therefore enormous as it has been shown in other studies with stroke, anemia, T2DM, and renal failure. It is the most common associated comorbid condition among many medical admissions.,, Many national and international guidelines for the management of hypertension have been published. Most clinicians are often guided by their preference for any of the major guidelines available for the management of hypertension. Previously, diuretics were considered to be the first-line drugs, especially for blacks. However, guidelines by the JNC VII recommend both CCBs as well as ACE-I as first-line drugs in addition to diuretics. It therefore appears that prescribers in the management of hypertension and its related comorbid diseases appear to be in tune with current realities in the management and antihypertensive prescription in the three centers in Nigeria even though there were very minor insignificant differences in the prescription pattern in the three centers. In LTH, Ogbomoso, Nigeria, diuretics followed by ACE-I, followed by CCBs were the commonly prescribed medications while from AKTH Kano, ACE-I followed by CCBs, and then diuretics were the most commonly prescribed drugs in that order. From LUTH, ACE-I followed by diuretics were the most commonly prescribed drugs among patients admitted with hypertension-related diseases over the study period. Beta blockers were the third most common prescription drug among patients from LUTH. The prescription pattern reported in this study is similar to what has been reported from different centers across the world.,,
This brings to fore that prescribers in this environment are well aware of the current clinical guidelines on the management of hypertension and that the subtle difference might have been due to a combination of factors including patients personal factor, costs, comorbid conditions, and availability. Combination of antihypertensive medications was often used for effective long-term management and treat comorbid conditions. This study revealed that multiple combination therapies were more likely to be prescribed for chronic hypertensive diseases in this environment. The pattern of prescription may reflect on the monitoring, evaluation, and necessary modifications to the prescribing habits to achieve rational and cost-effective treatment. Those from LTH were more likely to be on more medications compared to those from LUTH and then AKTH. Most of our patients were on combination therapy, and this is also similar to what was reported from other centers.,, Most of the patients seen in teaching hospitals with hypertension are often high-risk patients with poor BP control and having many other comorbid factors hence requirement to use multiple drug combination. With combination therapy, control tends to be better, and this is also justified by the multifactorial etiopathogenesis of hypertension. There is also a significant reduction in side effect profile when using small doses of multiple drugs. Furthermore, hypertension in black people runs an aggressive course and control is achieved with multiple drug therapy rather than monotherapy.,
The trend toward the use of ACE-I in this study may not be unconnected with the fact that a significant proportion of patients in this study may have compelling indications according to standardized guidelines for the use of ACE-I/ARBs including diabetes mellitus and early stage of chronic kidney disease (CKD). This may account for the overwhelming majority use of ACE-I in this study. As shown in this study, a significant proportion of our patients had comorbid condition that warrant the use of ACE-inhibition, including diabetes mellitus, renal disease, stroke, and heart failure. Ajayi et al. showed that the use of antihypertensive drug regimen inclusive of ACE inhibition and CCBs may be associated with greater salutary effect on indices of diastolic function even in the presence of an equivalent effect on systolic function and BP. A meta-analysis to compare the renoprotective effect of combining ACE-I/ARBs and CCB in patients with hypertension and CKD showed no additional benefit beyond that which could be achieved with ACE-I/ARB monotherapy among whites.
There are considerable variations in the pattern of antihypertensive medication prescription in different countries. There is an increasing trend in the use of ACE-I and ARBs for hypertension both for single-dose medications and combination therapy among Nigerians as shown in this study. The use of ACE-I or ARB as compelling indications is important, especially among patients with T2DM, heart failure, or renal disease as comorbid factors. This is similar to what was reported from a study in Taiwan. The pattern of prescription is also in agreement with current international guidelines such as the JNC8 guidelines recommending both CCBs and ACEI as first-line drugs in addition to diuretics as combination options in the management of hypertension., Other researchers from other parts of the country from earlier studies has reported similar outcome in the outpatient hypertensive patients.,
| Conclusion|| |
Antihypertensive prescriptions across three tertiary centers in Nigeria appear to follow appropriate international acceptable and relevant guidelines with minimal differences across the centers. Majority of hypertensive patients admitted were on combination therapy and had multiple comorbid cardiovascular risk factors, target organ damage, and complications. Aggressive primary and secondary prevention will be necessary to prevent complications of hypertension among Africans. There is also a need for local guidelines on the management of hypertension to further improve the management of hypertension.
This study has some inherent limitations:First, it was a retrospective study, and it was not possible to associate causality directly. Second, the prescription pattern was majorly driven by the presence of long-term complications of hypertension as majority of patients already had complications during admission. The centers were also few and may not totally represent the general state all over the country as to the pattern prescription among hypertensive admitted into the medical unit. Again, the drugs being taken at admission were only taken into consideration.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Okunola OO, Akintunde AA, Akinwusi PO. Some emerging issues in medical admission pattern in the tropics. Niger J Clin Pract 2012;15:51-4. [Full text]
Akinwusi PO, Okunola OO, Opadijo OG, Akintunde AA, Ayodele OE, Adeniji AO. Hypertensive heart failure in Osogbo South Western Nigeria: Clinical presentation and outcome. Nigerian Med Pract 2009;56:53-6.
Kolo PM, Jibrin YB, Sanya EO, Alkali M, Peter Kio IB, Moronkola RK. Hypertension-related admissions and outcome in a tertiary hospital in Northeast Nigeria. Int J Hypertens 2012;2012:960546.
Arodiwe EB, Ike SO, Nwokediuko SC. Case fatality among hypertension-related admissions in Enugu, Nigeria. Niger J Clin Pract 2009;12:153-6.
] [Full text]
Bosu WK. The prevalence, awareness, and control of hypertension among workers in West Africa: A systematic review. Glob Health Action 2015;8:26227.
Ogah OS, Okpechi I, Chukwuonye II, Akinyemi JO, Onwubere BJ, Falase AO, et al.
Blood pressure, prevalence of hypertension and hypertension related complications in Nigerian Africans: A review. World J Cardiol 2012;4:327-40.
Guideline Sub-committee. World Health Organization –International Society of Hypertension (WHO/ISH) Guideline for the Management of Hypertension. J Hypertens 1999;17:151-85.
The sixth report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997;157:2413-46.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr., et al.
The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 report. JAMA 2003;289:2560-72.
James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al
. 2014 evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507-20.
Amira CO, Okubadejo NU. Antihypertensive pharmacotherapy in a developing economy: Pattern, acquisition costs and conformity to international guidelines in a tertiary-care setting. J Hum Hypertens 2006;20:894-7.
Milchak JL, Carter BL, James PA, Ardery G. Measuring adherence to practice guidelines for the management of hypertension: An evaluation of the literature. Hypertension 2004;44:602-8.
Akintunde AA, Akintunde TS. Antihypertensive medications adherence among Nigerian hypertensive subjects in a specialist clinic compared to a general outpatient clinic. Ann Med Health Sci Res 2015;5:173-8.
] [Full text]
Karaye KM, Akintunde AA, Olusegun-Joseph A, Balarabe SA, Okunowo BO, Opadijo OG, et al
. Mortality and co-morbidities among hospitalized hypertensives in Nigeria. Int Cardiovasc Forum J 2017;11:37-41.
Zanchetti A. Hypertension-related mortality and morbidity. J Hypertens 2015;33:1979-80.
Román O, Cuevas G, Badilla M, Valenzuela A, Cumsille F, Valverde L, et al.
Morbidity and mortality of treated essential arterial hypertension in a 26 years follow up. Rev Med Chil 2002;130:379-86.
Xu H, He Y, Xu L, Yan X, Dai H. Trends and patterns of five antihypertensive drug classes between 2007 and 2012 in China using hospital prescription data. Int J Clin Pharmacol Ther 2015;53:430-7.
Adigun AQ, Ishola DA, Akintomide AO, Ajayi AA. Shifting trends in the pharmacologic treatment of hypertension in a Nigerian tertiary hospital: A real-world evaluation of the efficacy, safety, rationality and pharmaco-economics of old and newer antihypertensive drugs. J Hum Hypertens 2003;17:277-85.
Olanrewaju TO, Aderibigbe A, Busari OA, Sanya EO. Antihypertensive drug utilization and conformity to guidelines in a Sub-Saharan African hypertensive population. Int J Clin Pharmacol Ther 2010;48:68-75.
Oyewo EA, Ajayi AA, Ladipo GO. A therapeutic audit in the management of hypertension in Nigerians. East Afr Med J 1989;66:458-67.
Lemogoum D, Seedat YK, Mabadeje AF, Mendis S, Bovet P, Onwubere B, et al.
Recommendations for prevention, diagnosis and management of hypertension and cardiovascular risk factors in Sub-Saharan Africa. J Hypertens 2003;21:1993-2000.
Akintunde AA. Epidemiology of conventional cardiovascular risk factors among hypertensive subjects with normal and impaired fasting glucose. S Afr Med J 2010;100:594-7.
McClellan W, Tuttle E, Issa A. Racial differences in the incidence of hypertensive end-stage renal disease (ESRD) are not entirely explained by differences in the prevalence of hypertension. Am J Kidney Dis 1988;12:285-90.
Marketou ME, Zacharis EA, Koukouraki S, Stathaki MI, Arfanakis DA, Kochiadakis GE, et al.
Effect of angiotensin-converting enzyme inhibitors on systemic inflammation and myocardial sympathetic innervation in normotensive patients with type 2 diabetes mellitus. J Hum Hypertens 2008;22:191-6.
Ajayi OE, Akintomide AO, Adigun AQ, Ajayi AA. Left ventricular diastolic function in Nigerian patients with essential hypertension: A retrospective study to compare angiotensin converting enzyme inhibitors, calcium channel blockade or their combination. Arch Drug Inf 2008;1:29-34.
Huang RS, Cheng YM, Zeng XX, Kim S, Fu P. Renoprotective effect of the combination of renin-angiotensin system inhibitor and calcium channel blocker in patients with hypertension and chronic kidney disease. Chin Med J (Engl) 2016;129:562-9.
Liu PH, Wang JD. Antihypertensive medication prescription patterns and time trends for newly-diagnosed uncomplicated hypertension patients in Taiwan. BMC Health Serv Res 2008;8:133.
Osibogun A, Okwor T. Anti-hypertensive prescription and cost patterns in an outpatient department of a teaching hospital in Lagos State Nigeria. J Prev Med Prev Med 2014;4:156-63.
Altaf M, Rasheed A, Mujtaba A, Mohammed S. Drug utilization evaluation of antihypertensives in geriatric patients in a tertiary care hospital. Int J Pharm Pharm Sci 2014;6:261-4.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]