Combination Therapy in Hypertension with Diabetes: Preferential Consideration for CCB and ARBs

Published On 2021-01-04 07:15 GMT   |   Update On 2021-01-04 08:59 GMT

The last edition of the International Diabetes Federation (IDF) Atlas offered projections that continue to put India at the second slot in the prevalence of type 2 diabetes right up to 2045. And the numbers remain staggering —over 134 million Indians will be diabetics in the next 25 years. (1) Hypertension occurs twice as common in patients with diabetes than in comparison to patients without diabetes. (2) In the setting of such a tenacious association and its impending threatening consequences, it remains a clinician's priority to make a prudent choice to initiate management of hypertension in diabetes with appropriate initial combination therapy for optimising long term outcomes, including both - cardiovascular and renal endpoints.

Advertisement

Patients with both diabetes and hypertension together possess a significantly greater risk for premature microvascular and macrovascular complications. Aggressive control of blood pressure (BP) can help to decrease both, micro- and macrovascular complications. Multidrug regimens are frequently required in diabetic hypertensives. While achieving the target BP of <130/80 is the numerical objective to arrest and prevent the progression of macro- and microvascular complications in hypertension with diabetes. (1), it may be important to consider agents which improve cardiovascular and renal outcomes in these patients.

Advertisement
An important factor leading to poor BP control is the limited use of combination drug treatment, despite scientific evidence of its superior ability to control BP in patients with difficult-to-treat hypertension. In addition, combination treatment allows achieving BP control more easily (and more quickly) as compared with monotherapy (3) . More than 70% of adults treated for hypertension eventually require at least two antihypertensive agents for achieving blood pressure control (4)
Advertisement
When hypertensive patients do not achieve target blood pressure control, the options to try and achieve required treatment goals are to increase the dose of monotherapy (which increases the risk of side effects) or to use drug combinations with minimum side effects. In order to avoid complications, it is important to start treatment as soon as possible, achieve the goals in the shortest time possible and ensure treatment adherence (5) . The mechanisms which lead to blood pressure rise in a patient vary – monotherapy acts on one or at best two of these mechanisms, while the use of a combination of drugs allows for action on multiple different hypertensive mechanisms (6). By combining two drugs with different mechanisms of action, an antihypertensive effect of two to five times greater compared to monotherapy is possible (7). Increasing the dose of monotherapy reduces coronary events by 29% and cerebrovascular events by 40%, while combining two antihypertensive agents with a different mechanism of action reduces coronary events by 40% and cerebrovascular events by 54%, respectively (8). Thus, the use of combination therapy provides greater target organ protection than increasing the dose of monotherapy. Fixed-dose single pill combinations offer additional advantages, such as improved adherence by 24% and potentially reduced cost (9) - all these benefits are of much clinical and practical value for hypertensive patients with diabetes.
Advertisement
Combinations of antihypertensive drugs also have actions unrelated to their effect on blood pressure that can have an impact on the prognosis of patients (10) . As per the last European Society of Cardiology (ESC) guidelines recommendations for the management of hypertension, combination treatment is recommended for most hypertensive patients as initial therapy. Preferred combinations recommended comprise a RAS blocker (either an ACE inhibitor or an ARB) with a CCB or diuretic. (11)
Drugs that inhibit the renin angiotensin system have been effective in the prevention of cardiac and renal complications. Hypertension, specifically systolic hypertension, is inadequately controlled by monotherapy in most type 2 diabetic patients. Long-acting calcium channel blockers (CCBs) appear to be an appropriate candidate to lower systolic BP levels below 130 mm Hg (12).
Cilnidipine - L/N-type calcium channel blocker (CCB), has been reported to have more beneficial effects on proteinuria progression in hypertensive patients than amlodipine, an L-type CCB. The N-type calcium channel blockade that inhibits renal sympathetic nerve activity might reduce glomerular hypertension by facilitating vasodilation of the efferent arterioles (13). Cilnidipine is known to dilate both afferent and efferent arterioles by its effect on N-type calcium channels and thus reduces urinary albumin and protein excretion (14). In a study conducted on Indian Diabetic patients, cilnidipine use resulted in an additive effect in microalbuminuria reduction over and above the well- proven effect of ACE inhibitors (15). Telmisartan is reported to be effective in lowering blood pressure and improving metabolic parameters in Indian T2DM patients with or without complications (16)
Angiotensin Receptor Blockers in combination with newer generation calcium channel blockers like cilnidipine may offer specific clinical benefits, which in turn, could improve long term cardiovascular outcomes. Thus, cilnidipine – dual type (L- and N-type) calcium channel blocker and telmisartan – a well-established long-acting, often referred to as a 'metabolic sartan' seem to be a valuable single-pill combination for management of hypertension with diabetes as initial therapy for optimising long term renal, metabolic and cardiovascular outcomes in these patients.
The above article has been published under the MD brand Connect Initiative. For more information on Cilnidipine and telmisartan combination click here 
References
Adapted from
1 Ramya Kannan, India is home to 77 million diabeticsc, second highest in the world, November 2019, URL https://www.thehindu.com/sci-tech/health/india-has-second-largest-number-of-people-with-diabetes/article29975027.ece
2 Ganesh J, Viswanathan V. Management of diabetic hypertensives. Indian J Endocrinol Metab. 2011 Oct;15 Suppl 4(Suppl4):S374-9. doi: 10.4103/2230-8210.86982. PMID: 22145142; PMCID: PMC3230084.
3 Mancia G, Rea F, Corrao G, Grassi G. Two-Drug Combinations as First-Step Antihypertensive Treatment. Circ Res. 2019 Mar 29;124(7):1113-1123. doi: 10.1161/CIRCRESAHA.118.313294. PMID: 30920930.
4 Smith DK, Lennon RP, Carlsgaard PB. Managing Hypertension Using Combination Therapy. Am Fam Physician. 2020 Mar 15;101(6):341-349. PMID: 32163253.
5 Oparil S, Acelajado MC, Bakris GL, Berlowitz DR, Cífková R, Dominiczak AF, Grassi G, Jordan J, Poulter NR, Rodgers A, Whelton PK. Hypertension. Nat Rev Dis Primers. 2018;4:18014.https://doi.org/10.1038/nrdp.2018.14
6 Burnier M. Antihypertensive combination treatment: state of the art. Curr Hypertens Rep. 2015;17:51. https://doi.org/10.1007/s11906-015-0562-0
7 Wald DS, Law M, Morris JK, Bestwick JP, Wald NJ. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med. 2009;122:290–300. https://doi.org/10.1016/j.amjmed.2008.09.038
8 Rubio-Guerra AF, Castro-Serna D, Elizalde-Barrera CI, Ramos-Brizuela LM. Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and RAAS inhibitors. Integr Blood Press Control. 2009;2:55–62. https://doi.org/10.2147/IBPC.S6232
9 Bakris GL. Combined therapy with a calcium channel blocker and an angiotensin II type 1 receptor blocker. J Clin Hypertens. 2008;10(1 Suppl 1):27–32. PubMed PMID:18174781
10 Guerrero-García C, Rubio-Guerra AF. Combination therapy in the treatment of hypertension. Drugs Context. 2018 Jun 6;7:212531. doi: 10.7573/dic.212531. PMID: 29899755; PMCID: PMC5992964.
11 Williams B et al, 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018 Oct;36(10):1953-2041. doi:10.1097/HJH.0000000000001940. Erratum in: J Hypertens. 2019 Jan;37(1):226. PMID: 30234752.
12 Nosadini R, Tonolo G. Cardiovascular and renal protection in type 2 diabetes mellitus: the role of calcium channel blockers. J Am Soc Nephrol. 2002 Nov;13 Suppl 3:S216-23. doi: 10.1097/01.asn.0000034687.62568.9b. PMID: 12466317.
13 Soeki T, Kitani M, Kusunose K, Yagi S, Taketani Y, Koshiba K, Wakatsuki T, Orino S, Kawano K, Sata M. Renoprotective and antioxidant effects of cilnidipine in hypertensive patients. Hypertens Res. 2012 Nov;35(11):1058-62. doi: 10.1038/hr.2012.96. Epub 2012 Jul 5. PMID: 22763473.
14 Fujita T, Ando K, Nishimura H, Ideura T, Yasuda G, Isshiki M, et al. Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin-angiotensin inhibition in hypertensive patients with chronic renal disease. Kidney Int 2007;72:1543-9
15 Singh VK, Mishra A, Gupta KK, Misra R, Patel ML, Shilpa. Reduction of microalbuminuria in type-2 diabetes mellitus with angiotensin-converting enzyme inhibitor alone and with cilnidipine. Indian J Nephrol. 2015 Nov-Dec;25(6):334-9. doi: 10.4103/0971-4065.151764. PMID: 26664207; PMCID: PMC4663769
16 Gadge P, Gadge R, Paralkar N, Jain P, Tanna V. Effect of telmisartan on blood pressure in patients of type 2 diabetes with or without complications. Perspect Clin Res 2018;9:155-60.
Tags:    
Advertisement

Disclaimer: This site is primarily intended for healthcare professionals. Any content/information on this website does not replace the advice of medical and/or health professionals and should not be construed as medical/diagnostic advice/endorsement or prescription. Use of this site is subject to our terms of use, privacy policy, advertisement policy. © 2020 Minerva Medical Treatment Pvt Ltd

Our comments section is governed by our Comments Policy . By posting comments at Medical Dialogues you automatically agree with our Comments Policy , Terms And Conditions and Privacy Policy .

Similar News