|Year : 2017 | Volume
| Issue : 1 | Page : 22-27
Management of hypertension: Insights into prescribing behavior with focus on angiotensin receptor blockers
S Ramakrishnan1, Shahu Ingole2, Arindam Dey2, Rishi Jain2
1 Department of Cardiology, AIIMS, New Delhi, India
2 Emcure Pharmaceuticals Limited, Pune, Maharashtra, India
|Date of Web Publication||17-Jul-2017|
Emcure Pharmaceuticals Limited, Survey No. 255/2, Rajiv Gandhi IT Park, Hinjawadi, Phase 2, Pune - 411 057, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Angiotensin receptor blockers (ARBs) are emerging as an attractive first choice antihypertensive as recommended by various guidelines. However, choice among the first-line antihypertensive classes and among ARBs differs between practicing physicians. Aims: This survey aimed to understand the usage preferences of ARBs and its place in for treating hypertension (HTN) among physicians from various clinical settings in India. Methods: A cross-sectional survey was conducted with a prevalidated survey questionnaire consisting of 25 questions for HTN management. Practicing general physicians and cardiologists were approached for seeking their perception, opinions, and prescribing behavior. Results: Responses of 594 physicians and cardiologists were received. As opined by 90.1% of physicians, newly diagnosed HTN represented more than 10% of their overall patient load. As a monotherapy, 59.9% of the physicians preferred ARB as the first choice in newly diagnosed HTN patients, followed by calcium channel blocker (12.3%) and angiotensin-converting-enzyme inhibitor (8.1%). Of all ARBs, telmisartan is preferred by 73% of physicians. Most physicians prefer telmisartan among all ARBs for 24 h blood pressure (BP) control, including morning BP surge (76.4%) and for prevention of cardiovascular morbidity and mortality (78.8%) followed by olmesartan and losartan. Predominantly, majority of physicians (89.1%) agreed for the beneficial role of telmisartan in preventing onset of microalbuminuria and nephropathy. Conclusion: Indian physicians prefer ARBs as the first choice in most hypertensive patients, which shows agreement with the guideline recommendations followed globally. Telmisartan has emerged as the most preferred ARB among all, for most of the HTN patients including those with comorbidities.
Keywords: Angiotensin receptor blockers, hypertension, telmisartan
|How to cite this article:|
Ramakrishnan S, Ingole S, Dey A, Jain R. Management of hypertension: Insights into prescribing behavior with focus on angiotensin receptor blockers. J Pract Cardiovasc Sci 2017;3:22-7
|How to cite this URL:|
Ramakrishnan S, Ingole S, Dey A, Jain R. Management of hypertension: Insights into prescribing behavior with focus on angiotensin receptor blockers. J Pract Cardiovasc Sci [serial online] 2017 [cited 2020 Mar 30];3:22-7. Available from: http://www.j-pcs.org/text.asp?2017/3/1/22/210868
| Introduction|| |
Hypertension (HTN) is a disease of complex etiology, affecting an estimated 1.39 billion people worldwide by 2010; almost 31.1% of the world's adults had HTN – 28.5% (27.3%–29.7%) in high-income countries and 31.5% (30.2%–32.9%) in low- and middle-income countries. The burden of HTN in India is soaring with reported prevalence from epidemiological studies in urban and rural population to be in the range of 25%–30%. A systematic review and meta-analysis reported an overall prevalence of HTN in India to be 29.8%, affecting 33% urban and 25% rural Indians. HTN is a major modifiable risk factor for premature cardiovascular (CV) disease and stroke globally. Effective control of blood pressure (BP) can bring down the disastrous consequences of HTN to a greater extent. A recent meta-analyses showed that every 10 mmHg decrease in systolic BP significantly reduced the risk of major CV disease (CVD) events (relative risk 0.80, 95% confidence interval [CI] 0.77–0.83), coronary heart disease (0.83, 0.78–0.88), stroke (0.73, 0.68–0.77), and heart failure (0.72, 0.67–0.78), which eventually led to a significant 13% reduction in all-cause mortality (0.87, 0.84–0.91) in population-based studies.
Several guidelines published in 2013 have critically appraised evidence-based practices and advised an individualized approach to drug treatment of HTN.,, All these guidelines recommend achieving optimum BP control for an overall reduction in CV risk. The Eighth Joint National Committee (JNC-8) supports treating hypertensive persons aged 60 years or older to a BP goal of <150/90 mmHg and hypertensive persons 30 through 59 years of age to a BP goal of <140/90 mmHg. While the JNC-8 has the similar treatment recommendations for patients with or without diabetes, most of the other bodies suggest that only angiotensin-converting-enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) should be the first-line treatment for patients with diabetes. In the case of patients with a history of chronic kidney diseases (CKDs), ACEIs or ARBs are recommended to be the first line. Nonetheless, the selection of the most suitable antihypertensive monotherapy or combination therapy depends on careful evaluation of an individual patient and appropriate consideration of drug pharmacology.
Thus, ARBs are emerging as an attractive first choice antihypertensive along with ACEIs, calcium channel blockers (CCBs), and diuretics as recommended by various guidelines. However, choice among the first-line antihypertensive classes and among ARBs differs between practicing physicians. Furthermore, there is no clear consensus on which ARB to be preferred in HTN with various comorbidities. In addition, real-life data on physicians' inclination relative to global recommendations, clinical effectiveness, and drug tolerability of ARBs are scarce. This survey aimed to understand the usage preferences of ARBs and its place in combination therapy for treating HTN among physicians from various clinical settings in India.
| Methods|| |
A cross-sectional survey was conducted for 3 months from May 2016 to July 2016 in the outpatient departments (OPDs) of physicians across various cities in India. Physicians were selected based on those seeing the patients of HTN and having a clinical experience of at least 2 years and willing to provide their views on HTN management so as to address all the questions of survey questionnaire. The survey questionnaire consisting of 25 questions was prepared and validated in a small group of physicians. The salient features of the questionnaire included information regarding patient pool of newly diagnosed with HTN, preferred therapy for newly diagnosed stage one, stage two HTN, elderly and those with different comorbidities, and preferred ARB in these patients. Practicing general physicians and cardiologists were approached for seeking their perception, opinions, and prescribing behavior. The physicians were explained about the purpose of the study; if interested and willing, they were requested to complete the validated questionnaire which was collected back and analyzed. As this was a cross-sectional survey of practitioners and patients were not approached and patient data were not taken, Ethics Committee approval was not taken.
The number of responses to each question was categorized and percentages for all the responses were calculated. Missing data was not considered for calculating percentages. Data were expressed in n (%).
| Results|| |
A total of 594 physicians and cardiologists who were managing a considerable percentage of newly diagnosed as well as uncontrolled hypertensive patients in routine clinical practice were surveyed. As opined by 90.1% of physicians, among all the hypertensive patients being treated in a month, newly diagnosed HTN represented more than 10% of their overall patient load [Table 1]. Among these newly diagnosed patients, around 20%–40% of patients had stage two HTN as opined by 41.8% of physicians. Furthermore, as observed by 32.3% and 25.8% of physicians, a large pool of their OPD patients (20%–40% and 40%–60%, respectively) remained uncontrolled on monotherapy.
As a monotherapy, 59.9% of the physicians preferred ARB as the first choice in newly diagnosed HTN patients, followed by CCB (12.3%) and ACEI (8.1%). Diuretics (3.2%) and beta-blockers (BBs) (3.5%) were not preferred as the initial choice for treatment [Figure 1]. ARBs were preferred predominantly for treating >50% of the newly diagnosed patients by 33.2% of physicians, while 35.7% of physicians used ARBs in 20%–40% of their newly diagnosed patients. When asked about the criteria followed by physicians for prescribing ARB in newly diagnosed patients, it was observed that most of the physicians (68%) preferred using ARB as an initial choice rather than using it only if patients become intolerant to ACEIs.
|Figure 1: Preferred antihypertensive in newly diagnosed patients. ACEI: Angiotensin.converting.enzyme inhibitor, ARB: Angiotensin receptor blocker, CCB: Calcium channel blocker.|
Click here to view
Of all the ARBs, telmisartan was preferred by almost 73% of physicians; 34.8% of physicians preferred to use in more than 50% of their patients, and 38.2% of physicians preferring it in 20%–40% of the patients. Most physicians prefer telmisartan among all ARBs for 24 h BP control including morning BP surge (76.4%) and for prevention of CV morbidity and mortality (78.8%) followed by olmesartan and losartan [Figure 2]. Majority physicians (83.3%) agreed that telmisartan has an additional beneficial role in diabetes mellitus (DM) owing to its pleiotropic effects on peroxisome proliferator-activated receptor-gamma (PPAR-gamma) receptors, and 87.2% of physicians confirmed that they initiate telmisartan as first-line agent for HTN patients with DM. Predominantly, majority of physicians (89.1%) agreed for the beneficial role of telmisartan in preventing onset of microalbuminuria and nephropathy.
|Figure 2: Choice of ARB for 24 h BP control and cardiovascular events. BP: Blood pressure, CV: Cardiovascular, ARB: Angiotensin receptor blocker.|
Click here to view
Combination of ARB and CCB was preferred in HTN patients if the patient was diabetic (52.7%), elderly (42.6%), and had nephropathy (42.9%) [Figure 3]. In patients who were uncontrolled on monotherapy, a combination of ARB with CCB and diuretics was preferred by 37.7% and 32.3% of physicians, respectively [Figure 4].
|Figure 3: Preferred combination drug therapy for hypertension. HTN: Hypertension, A: Angiotensin receptor blocker, D: Diuretics, C: Calcium channel blocker.|
Click here to view
|Figure 4: Preferred combination in uncontrolled hypertensive patients receiving monotherapy. ARB: Angiotensin receptor blocker, CCB: Calcium channel blocker, ACEI: Angiotensin.converting.enzyme inhibitor.|
Click here to view
Chlorthalidone was the preferred diuretic for combination therapy followed by hydrochlorothiazide (65.2% and 21%, respectively). Telmisartan with hydrochlorothiazide was the preferred combination in newly diagnosed stage one and stage two HTN (71% and 44.6%, respectively). An equal number of physicians surveyed asserted to favor this combination of telmisartan with hydrochlorothiazide in stage one HTN with DM and stage one HTN with nephropathy (53.2% and 54.2%, respectively). A total of 76.4% of physicians confirmed to start this combination in uncontrolled HTN patients who are on monotherapy. Most of the physicians (38.6%) reported that they need to start triple-drug combination in almost 10%–20% of their patients, whereas 22.6% of physicians start triple-drug combinations in <10% of their patients. For uncontrolled HTN on dual therapy, triple-drug combination of ARB, CCB, and diuretics is the most preferred choice reported by 81% of physicians.
Among all the antihypertensive groups, ARBs were reported to have better safety profile and better patient compliance with highest incidence of adverse effects being observed with BBs by 31.6% of physicians and highest discontinuation rate being observed with ACEIs by 26.9% of physicians. With telmisartan use, only 27.3% and 31.6% of physicians reported adverse event rates of <1% and <2%, respectively. Furthermore, 33.5% and 27.4% of physicians reported discontinuation rates of <1% and <2%, respectively [Figure 5].
|Figure 5: Adverse events and discontinuation rates with telmisartan use.|
Click here to view
| Discussion|| |
Uncontrolled HTN is a major public health problem with potential to make a considerable impact on the morbidity and mortality associated with CVD and stroke. A recent study from Western India reported poor BP control with only about 37.4% of patients having BP values <140/90 mmHg. Understanding the preferences of physicians for managing HTN with available classes of pharmacological agents is important, especially in the light of recent recommendations by the JNC-8 and other clinical practice guidelines.
This cross-sectional survey provides useful information on physicians' preferences for the clinical management of patients with HTN. Our study findings demonstrate that ARBs are the most preferred agents for monotherapy in newly diagnosed HTN, especially telmisartan topping the list, being prescribed by almost 73% of the practitioners. Consistent with our study results, a recent survey from Western, Eastern, and South India reported ARBs being prescribed by 70.6% of the physicians. Surprisingly, diuretics are not considered as initial therapy for most patients, being prescribed by a very small group (3.2%) of physicians – contrary to the recommendations by both JNC-7 and JNC-8 panel. A study from North India reported the highest prescription rates of ACEIs (59%), followed by ARBs (52%), CCBs (29%), diuretics (27%), and BBs (14%). The results are unlike the current study as far as preference of ARBs over ACEIs, BBs, and diuretics is concerned. As against initial recommendations of using ARB in ACEI intolerant patients, our survey results have clearly pointed out that most of the physicians prefer ARB as initial choice rather than using it in ACEI intolerant patients.
Telmisartan was preferred for 24 h BP control including morning BP surge and prevention of CV morbidity and mortality by almost two-thirds of the physicians (76% and 79%). With longest plasma elimination half-life of approximately 24 h as well as the highest affinity for the angiotensin II type 1 receptor, telmisartan provides long-lasting antihypertensive effects compared with other ARBs. Telmisartan has the highest volume of distribution being the most lipophilic ARBs, which facilitates greater tissue/organ penetration. Consequently, telmisartan has been recommended as a preferred ARB treatment option with a number of clinical advantages, such as long-lasting BP control and CV protection. The renin–angiotensin–aldosterone system plays an important role in the pathophysiology of HTN and is closely related with cardio- and cerebrovascular events and CKD. Evaluating each ARB is important in the pharmacotherapy of HTN. Selection of a particular drug among the class of drug depends on various factors including patient profile, age, associated comorbidity, cost of therapy, and side effects. Telmisartan, a long-acting ARB, is indicated for the treatment of HTN and for CV risk reduction and has a preferential pharmacodynamic profile compared with several other ARBs. The ONTARGET study demonstrated that telmisartan has ability to reduce CV morbidity in patients who manifest atherothrombotic CVD. Telmisartan treatment in the TRANSCEND trial was associated with a significant reduction in the number of myocardial infarction events in HTN patients compared with normotensive individuals. In addition, telmisartan provides better BP lowering to ACEIs in the entire 24 h period – early morning, late morning, daytime as well as nighttime.
Majority of the surveyed physicians (87.2%) supported the use of telmisartan in HTN patients owing to its pleiotropic effects on PPAR-gamma receptor. This property of telmisartan was reported to provide additional advantages in HTN patients with insulin resistance and glucose intolerance. According to a meta-analysis of eight trials, telmisartan proved superiority in reducing fasting plasma glucose and increasing adiponectin levels compared to other ARBs. The group agreed for the beneficial role of telmisartan in preventing onset of microalbuminuria and nephropathy, which has been recognized as an important therapeutic option for type 2 DM. A retrospective study from India found ARBs (losartan and telmisartan) to be more effective in delaying the progression of diabetic nephropathy with added renoprotection when compared to ACEI (ramipril). There is ample evidence supporting the use of ARBs in diabetic patients; a real-world study findings supported the practice of using ARBs as a first-line therapy from the perspective of stroke prevention in patients with HTN and diabetes.
The unique characteristics also make telmisartan as the preferred ARB choice in combination therapy of BP lowering agents, especially with CCB in elderly, diabetic, and patients with nephropathy. Telmisartan with hydrochlorothiazide was the preferred combination in newly diagnosed stage one and stage two HTN as well as in patients with DM and nephropathy. For uncontrolled HTN on dual therapy, triple-drug combination of ARB, CCB, and diuretics is the most preferred choice. Triple-drug fixed-dose combination therapy of telmisartan, amlodipine, and hydrochlorothiazide was found to be an effective, safe, and convenient treatment approach in achieving the desired BP goal according to the JNC-8 with increased likelihood of patient adherence and compliance.
With telmisartan use, most of the physicians reported adverse event and discontinuation rates of <1% in their clinical practice. Evidence from pooled analysis of clinical trials show statistically significantly fewer discontinuations due to adverse events with telmisartan, which is similar to our study findings. Several studies have shown that treatment with ARBs (in particular telmisartan) is well tolerated in patients who are intolerant of ACEIs., Due to their superior tolerability, ARBs are usually associated with a higher rate of adherence than ACEIs. In a large cohort of patients in Italy, the discontinuation rates of the initial monotherapy were lower for ARBs compared with ACEIs (hazard ratio, 0.92; 95% CI, 0.90–0.94).
Once detected, improved management with adequate BP control can prevent thousands of premature deaths due to strokes and heart attacks every year. To achieve the optimum BP goals, ARBs or ACEIs are recommended by various guidelines as the most effective agents, both as monotherapy or in combination therapies with either diuretics or CCBs. The results of current survey are in full accordance to the recommendations made by the JNC-8 with more preference being given to ARB in all age groups except for diuretics, which are still under prescribed. Although HTN guidelines do not recommend any specific ARB to be used in HTN patients with different comorbidities, real-life clinical practice experience of Indian physicians depicted in this study suggests that telmisartan is the most preferred ARB for all subsets of HTN patients and outscores other ARBs in terms of pleiotropic benefits.
The major limitation of this survey is that it was physicians' opinion and practices with subjective responses; the actual prescription patterns were not tracked and analyzed based on BP cutoff values recommended by the JNC-8.
| Conclusion|| |
Indian physicians prefer ARBs as the first choice in most hypertensive patients, which shows agreement with the guideline recommendations followed globally. Telmisartan has emerged as the most preferred ARB among all, for most of the HTN patients including those with comorbidities. ARB with CCB is the favorable option for dual antihypertensive therapy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, et al.
Global disparities of hypertension prevalence and control: A systematic analysis of population-based studies from 90 countries. Circulation 2016;134:441-50.
Gupta R. Convergence in urban-rural prevalence of hypertension in India. J Hum Hypertens 2016;30:79-82.
Anchala R, Kannuri NK, Pant H, Khan H, Franco OH, Di Angelantonio E, et al.
Hypertension in India: A systematic review and meta-analysis of prevalence, awareness, and control of hypertension. J Hypertens 2014;32:1170-7.
Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, et al.
Blood pressure lowering for prevention of cardiovascular disease and death: A systematic review and meta-analysis. Lancet 2016;387:957-67.
Go AS, Bauman MA, Coleman King SM, Fonarow GC, Lawrence W, Williams KA, et al.
An effective approach to high blood pressure control: A science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension 2014;63:878-85.
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.
Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, et al.
2013 ESH/ESC Guidelines for the management of arterial hypertension: The task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013;31:1281-357.
Kovell LC, Ahmed HM, Misra S, Whelton SP, Prokopowicz GP, Blumenthal RS, et al.
US Hypertension Management Guidelines: A review of the recent past and recommendations for the future. J Am Heart Assoc 2015;4. pii: E002315.
Mallat SG. What is a preferred angiotensin II receptor blocker-based combination therapy for blood pressure control in hypertensive patients with diabetic and non-diabetic renal impairment? Cardiovasc Diabetol 2012;11:32.
Choudhary R, Sharma SM, Kumari V, Gautam D. Awareness, treatment adherence and risk predictors of uncontrolled hypertension at a tertiary care teaching hospital in Western India. Indian Heart J 2016;68 Suppl 2:S251-2.
Bharatia R, Chitale M, Saxena GN, Kumar RG, Chikkalingaiah, Trailokya A, et al.
Management practices in Indian patients with uncontrolled hypertension. J Assoc Physicians India 2016;64:14-21.
Dhanaraj E, Raval A, Yadav R, Bhansali A, Tiwari P. Prescription Pattern of Antihypertensive agents in T2DM patients visiting tertiary care centre in North India. Int J Hypertens 2012;2012:520915.
Burnier M. Telmisartan: A different angiotensin II receptor blocker protecting a different population? J Int Med Res 2009;37:1662-79.
Kakuta H, Sudoh K, Sasamata M, Yamagishi S. Telmisartan has the strongest binding affinity to angiotensin II type 1 receptor: Comparison with other angiotensin II type 1 receptor blockers. Int J Clin Pharmacol Res 2005;25:41-6.
Unger T, Paulis L, Sica DA. Therapeutic perspectives in hypertension: Novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches. Eur Heart J 2011;32:2739-47.
Dézsi CA. The different therapeutic choices with ARBs. Which one to give? When? Why? Am J Cardiovasc Drugs 2016;16:255-66.
Verdecchia P, Angeli F, Gentile G, Mazzotta G, Reboldi G. Telmisartan for the reduction of cardiovascular morbidity and mortality. Expert Rev Clin Pharmacol 2011;4:151-61.
Foulquier S, Böhm M, Schmieder R, Sleight P, Teo K, Yusuf S, et al.
Impact of telmisartan on cardiovascular outcome in hypertensive patients at high risk: A Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular disease subanalysis. J Hypertens 2014;32:1334-41.
Williams B, Lacourcière Y, Schumacher H, Gosse P, Neutel JM. Antihypertensive efficacy of telmisartan vs. ramipril over the 24-h dosing period, including the critical early morning hours: A pooled analysis of the PRISMA I and II randomized trials. J Hum Hypertens 2009;23:610-9.
Jugdutt BI. Clinical effectiveness of telmisartan alone or in combination therapy for controlling blood pressure and vascular risk in the elderly. Clin Interv Aging 2010;5:403-16.
Suksomboon N, Poolsup N, Prasit T. Systematic review of the effect of telmisartan on insulin sensitivity in hypertensive patients with insulin resistance or diabetes. J Clin Pharm Ther 2012;37:319-27.
Cao Z, Cooper ME. Efficacy of renin-angiotensin system (RAS) blockers on cardiovascular and renal outcomes in patients with type 2 diabetes. Acta Diabetol 2012;49:243-54.
Pathak JV, Dass EE. A retrospective study of the effects of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in diabetic nephropathy. Indian J Pharmacol 2015;47:148-52.
] [Full text]
Pai PY, Muo CH, Sung FC, Ho HC, Lee YT. Angiotensin receptor blockers (ARB) outperform angiotensin-converting enzyme (ACE) inhibitors on ischemic stroke prevention in patients with hypertension and diabetes – A real-world population study in Taiwan. Int J Cardiol 2016;215:114-9.
Balraj MS, Faruqui AA. Efficacy and safety of triple drug fixed-dose combination of telmisartan, amlodipine and hydrochlorothiazide in the management of hypertension. Int J Res Med Sci 2015;3:1858-62.
Mancia G, Schumacher H. Incidence of adverse events with telmisartan compared with ACE inhibitors: Evidence from a pooled analysis of clinical trials. Patient Prefer Adherence 2012;6:1-9.
Telmisartan Randomised AssessmeNt Study in ACE iNtolerant Subjects with Cardiovascular Disease (TRANSCEND) Investigators, Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, et al
. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: A randomised controlled trial. Lancet 2008;372:1174-83.
Bangalore S, Kumar S, Messerli FH. Angiotensin-converting enzyme inhibitor associated cough: Deceptive information from the Physicians' Desk Reference. Am J Med 2010;123:1016-30.
Corrao G, Zambon A, Parodi A, Poluzzi E, Baldi I, Merlino L, et al.
Discontinuation of and changes in drug therapy for hypertension among newly-treated patients: A population-based study in Italy. J Hypertens 2008;26:819-24.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]