Hypertension and Diabetes are life style disease and are the major burden of global Health due to complications. India currently has 40.9 million diabetic patients and it is expected to rise to is expected to rise to 69.9 million by 2025 unless urgent and effective preventive steps are taken.¹ One and half billion people will suffer from hypertension² and 300 million will suffer from diabetes by 2025.³ Prevalence of hypertension is 60% in type 2 DM.⁴ Patients with T2DM has two fold higher chances of suffering from hypertension in comparison to age match subjects without diabetes.⁵ Hypertension has been shown as a major risk factor not only for the development of diabetes but also for the development of micro and macro vascular complications like neuropathy, nephropathy, retinopathy, coronary artery disease, stroke, Peripheral Vascular Disease (PVD) in diabetic patients. The benefits of Blood Pressure (BP) control in diabetic patients exceed the benefits of tight glycemic control and vital to the prevent and retard progression of both microvascular and macrovascular complications of hyperglycemias.⁶ Therefore, all of the hypertension management guidelines, that is, eighth report of Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure-2013 (JNC-8),⁷ American Diabetes association (ADA) 2014⁸ and European Society of Hypertension (ESH 2013)⁹ focused aggressively on Blood Pressure (BP) control in diabetic patient to below 140/80-90 mmHg. JNC 8 recommended target of diastolic BP <90 mmHg and ESC 2013 recommended <85 mmHg. But ADA recommended target of DBP <80 mmHg. There are limited data from India regarding physician’s choices of anti-hypertensive therapies for a patient with diabetes in single- and multiple-drug based regimens. Therefore, we undertook this study to evaluate treatment patterns in diabetic patients with hypertension; those are being followed at our institute. Our objectives were:

1. To evaluate the utilization of ACEI or Angiotensin Receptor Blockers (ARBs) and other preferred anti-hypertensive therapies based on the JNC VIII guidelines as agents to treat diabetic hypertension,
2. To compare utilization of different types of antihypertensive therapies in other comorbid conditions
3. To assess BP control in this population.
4. To assess awareness about hypertension in the study group.

This study was conducted on diabetic patients who had hypertension as well attending Medicine department August 2014 to December 2014. Prescribing Pattern of Antihypertensive drugs was analysed on all diabetic patients reporting to medicine OPD at our institute was screened. Around n=446 patients were recruited on the basis of inclusion and exclusion criteria.

Patients with advance renal failure (serum creatinine >3.5 mg %) and patients with malignant hypertension were excluded. Patients were diagnosed hypertensive if they had at least 2 visits with diagnosis of hypertension or they had prescription of antihypertensive drug with one recording of elevated BP or they had elevated BP on two visits. Elevated BP was defined as systolic BP >139 mmHg and Diastolic BP (DBP) >89 mmHg.⁷ Patients were diagnosed as diabetic if they had two visits with diagnosed of diabetes or they had prescription of antidiabetic drugs or insulin or raised glycosylated haemoglobin. Patients were diagnosed with CAD if they had symptoms suggestive of CAD with ECG evidence or echocardiographic evidence or positive treadmill test or evidence in coronary arteriography. Data of antihypertensive drugs was recorded and grouped according to class of drug.

Antihypertensive drugs were grouped in to seven groups - Calcium channel blockers, beta blockers, diuretics, Alfa blockers, Angiotensin Convertase Enzyme Inhibitors (ACEI), Angiotensin Receptor Blockers (ARB), centrally acting drugs. Data for antihypertensive drugs was recorded in form of need of monotherapy, two drugs or three drugs therapy. Data for non-pharmacological therapy was also recorded like salt restriction, loss of weight or exercise.

There were 224 patients in this study. Our study group comprised of n=122 males and n = 101 females. Gender ratio of study group was 1.18:1(males: females). Demographic data of patients has been described in Table 1. Around (46.18%) were on monotherapy and remaining patients were on combination antihypertensive drugs. There was total n=398 antihypertensive drug exposures Table 2. Patient needed mean antihypertensive drug of 1.88.

Number of drugs - Monotherapy was needed in 46.18% (n =103) patients and dual therapy was required in 32.73% (n=74) patients. Thirty-Nine patients (17.48%) were on triple drug therapy and n=8 (8.07%) were on quadruple drug therapy.

Type of drug - Angiotensin receptor blockers found to be most commonly prescribed drugs. Angiotensin inhibitors (angiotensin receptor blockers and ACE inhibitors) were utilized in 71% patients. These were followed by calcium channel blockers, diuretics, and beta blockers Table 2.

Table 1: Showing epidemiology data.

Table 2: Showing utilization of various drugs.

Combination Utilization pattern - Angiotensin receptor blocker with diuretics was the most commonly used dual drug combination strategy in our study. It was followed by combination of beta blocker with calcium channel blocker, calcium channel blocker with angiotensin receptor blocker, ACE inhibitor with diuretic and ACE inhibitor with beta blocker. Combination utilization pattern has been shown. Combination of Beta blocker with calcium channel blocker and diuretic was most commonly (51.28%) used in patients on triple drug combination. Combination of ARB, diuretic with CCB was used in 33.3% and combination of Alfa blocker, BB and diuretic was used in 10.24%. Combination of ACEI, CCB with diuretic was used in 5.12% patients. Combination of ACEI/ARB, diuretic with centrally acting drugs was used in 15.9% patients. Majority patients (50%) on quadruple therapy were on combination of Alfa blocker, diuretic, ACE inhibitor and central agonist. Combination of Alfa blocker, diuretic, central agonist with CCB or ARB was used in remaining 50% patients.

Awareness about hypertension - About 81.2% patients were aware about the disease. Only 52% patients knew about systolic and diastolic pressure. There was awareness in 38.56% patients about target blood pressure. Control of hypertension - Hypertension control was achieved in (37.66%) patients. BP control was taken as office BP recording of <140/90 mmHg. Sixteen patients with diabetic nephropathy had office BP recording of <140/90 mmHg. 

Our study tried to find utilization of various antihypertensive drugs in diabetic hypertensive patients and awareness about hypertension. A prescription-based study is an effective way to assess and evaluate prescribing altitude of physicians.¹⁰ Majority of patients in our study were on multidrug regimens. Only 46% patients were on single drug therapy. It is consistent with other studies.^11,12

Berlowitz et al.¹³ have shown worse BP control in patients with diabetes and less intensive anti-hypertensive medication therapy. ARB was the most common drug prescribed in 44.39% patients either alone or in combination. ACEI/ARB were used in 158 (71%) patients either alone or in combination. Most of the patients (76.6%) on single drug were receiving either ACEI or ARB. There is suggestion that ARBs should be a regular component of combination treatment and preferred drug in patients on monotherapy in diabetics.¹⁴ It has been described that initial monotherapy ACE inhibitors may be superior to dihydropyridine CCB in reducing cardiovascular events.^15,16 Calcium channel blockers were used in 37.66% patients either in combination or as monotherapy. JNC 8 also recommends calcium channel blockers as first line drug in diabetic hypertensive patient.⁷ CCBs ranked second followed by diuretics when considering overall utilization pattern of various anti-hypertensive drugs but Johnson et al found thiazide was second most frequently prescribed drug followed by CCBs and beta blocker. CCBs ranked second followed by diuretics when considering overall utilization pattern of various anti-hypertensive drugs in Indian study.¹⁷ Diuretics were used in 34% patients either as single or combination therapy. Diuretic use ranked third after CCBs and these were more commonly used as part of multidrug regimen. Dhanraj et al. described same pattern in their study on diabetic hypertensives.¹⁸ Beta Blockers were used in 26% patients. Usage of BB was significantly higher in patients with CAD in our study. BB has protective effect in CAD and other studies ^19,20 also found higher use of BB in patients with CAD.

ARB/ACEI with diuretic was the most commonly used combination therapy. It is consistent with other study. Patients with nephropathy needed higher no of antihypertensive drugs. Use of ACEI/ARB was higher in patients with nephropathy than without nephropathy. Shah et al.¹⁷ also found similar pattern in their patients. Use of ACEI and ARB has been recommended by ADA⁹ also. Blood pressure control was achieved in 37.66% patients. Our control rates are better than other studies ^19-22 with control rate of 25-32%. This may be due to difference in sample size. Patients with nephropathy had lesser percentage of patients with control of hypertension than patients without nephropathy. Shah et al¹⁷ also described similar pattern. Awareness about hypertension was found in 81% patients. Asfaq et al. also found awareness in 80% patients attending tertiary care hospital.²²

Our study showed that majority of diabetic hypertensive patients needed multiple drug therapy to control hypertension. Most of the patients were on ARBs/ACE inhibitors. This was according to recommendation by ADA or JNC8. Patients with diabetes had lesser chance of control of hypertension. Hypertension control was achieved in 37% patients. We found awareness rate of 81% in our study group. Still there is room for better control of hypertension and optimization of antihypertensive therapy.

1. Sicree, R., J. Shaw, and P. Zimmet. "Diabetes and Impaired Glucose Tolerance." Diabetes Atlas, edited by D. Gan, 3rd ed., International Diabetes Federation, 2006, pp. 15–103.
2. Kearney, P. M., et al. "Global Burden of Hypertension: Analysis of Worldwide Data." The Lancet, vol. 365, no. 9455, 2005, pp. 217–23.
3. Wild, S., et al. "Global Prevalence of Diabetes: Estimates for the Year 2000 and Projections for 2030." Diabetes Care, vol. 27, no. 5, 2004, pp. 1047–53.
4. National Institutes of Health. Diabetes in America. 2nd ed., NIH Publication, 1995, pp. 95–1468.
5. Miller, G. J., et al. "Incidence of Hypertension and Non-Insulin Dependent Diabetes Mellitus and Associated Risk Factors in a Rapidly Developing Caribbean Community: The St James Survey, Trinidad." Journal of Epidemiology & Community Health, vol. 50, no. 5, 1996, pp. 497–504.
6. UK Prospective Diabetes Study (UKPDS) Group. "Tight Blood Pressure Control and Risk of Macrovascular and Microvascular Complications in Type 2 Diabetes." BMJ, vol. 317, no. 7160, 1998, pp. 703–13.
7. James, P. A., et al. "2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults." JAMA, vol. 311, no. 17, 2014, pp. 1809–20.
8. Mancia, G., et al. "2013 ESH/ESC Guidelines for the Management of Arterial Hypertension." European Heart Journal, vol. 34, no. 28, 2013, pp. 2159–219.
9. American Diabetes Association. "Standards of Medical Care in Diabetes—2014." Diabetes Care, vol. 37, suppl. 1, 2014, pp. S14–80.
10. Yuen, Y. H., et al. "Drug Utilization in a Hospital General Medical Outpatient Clinic." Journal of Clinical Pharmacy and Therapeutics, vol. 23, 1998, pp. 287–94.
11. Bakris, G. L., et al. "Preserving Renal Function in Adults with Hypertension and Diabetes." American Journal of Kidney Diseases, vol. 36, no. 3, 2000, pp. 646–61.
12. The ALLHAT Collaborative Research Group. "Major Outcomes in High-Risk Hypertensive Patients." JAMA, vol. 288, no. 23, 2002, pp. 2981–97.
13. Berlowitz, D. R., et al. "Hypertension Management in Patients with Diabetes." Diabetes Care, vol. 26, no. 2, 2003, pp. 355–59.
14. Mancia, G., et al. "Guidelines for the Management of Arterial Hypertension." European Heart Journal, vol. 28, no. 12, 2007, pp. 1462–536.
15. Nather, A., et al. "Epidemiology of Diabetic Foot Problems." Journal of Diabetes and Its Complications, vol. 22, no. 2, 2008, pp. 77–82.
16. Reiber, G. E. "The Epidemiology of Diabetic Foot Problems." Diabetic Medicine, vol. 13, suppl. 1, 1996, pp. S6–11.
17. Shah, J., et al. "Study of Utilization Pattern of Antihypertensive Drugs in Hypertensive Diabetic Patients." International Journal of Medical Science and Public Health, vol. 2, 2013, pp. 175–80.
18. Dhanaraj, E., et al. "Prescription Pattern of Antihypertensive Agents in T2DM Patients." International Journal of Hypertension, vol. 2012, 2012, Article ID 520915.
19. Yusuf, S., et al. "Effects of Ramipril on Cardiovascular Events in High-Risk Patients." New England Journal of Medicine, vol. 342, no. 3, 2000, pp. 145–53.
20. Sweileh, W. M., et al. "Patterns of Antihypertensive Therapy in Diabetic Patients." Saudi Journal of Kidney Diseases and Transplantation, vol. 21, 2010, pp. 652–59.
21. Johnson, M., and H. Singh. "Patterns of Antihypertensive Therapies Among Patients with Diabetes." Journal of General Internal Medicine, vol. 20, no. 9, 2005, pp. 842–46.
22. Ashfaq, T., et al. "Awareness about Hypertension among Patients Attending Primary Health Care Centre." Journal of the Pakistan Medical Association, vol. 57, no. 8, 2007, pp. 396–99.