Uncontrolled Hypertension Management.pptx

Triple Combination in Hypertension Management

1. Triple Combination is the era in Uncontrolled Hypertension Management: Why is it so ?

2. WHO Report : September 2023

3. Major complications of uncontrolled / difficult to manage BP 3 Increase in BP increases risk for kidney disease progression

4. BP Control Rates are Suboptimal Despite the clear benefits of reducing BP to target level, rate of BP control are suboptimal in most countries BP control rates are particularly poor in low-income Countries BP control rate are <30% in several Asia-Pacific Countries

5. Get The Pressure Down!! Awareness, Diagnosis & Best antihypertensive which prevent complications will save lives ! Of Deaths from Stroke 51% Of Deaths from Coronary Heart Disease 45% Deaths due to HT 7.5 million Total global deaths 13% http://www.who.int/gho/ncd/risk_factors/blood_pressure_prevalence_text/en/

6. Diseases Attributable to Hypertension Hypertension Heart failure Stroke Coronary heart disease Myocardial infarction Left ventricular hypertrophy Aortic aneurysm Retinopathy Peripheral vascular disease Hypertensive encephalopathy Chronic kidney failure Cerebral hemorrhage http://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/high-blood-pressure/art-20045868. All Vascular

7. CV mortality risk SBP/DBP (mm Hg) 1 2 3 4 5 6 7 8 115/75 135/85 155/95 175/105 CV Mortality Risk Doubles With Each 20/10 mm Hg BP Increment* Assadi F. Prehypertension : Int J Prev Med. 2014 Mar;5( Suppl 1):S4-9.

8. Reasons for Not A chieving BP Control Poor adherence and persistence with therapy. Physicians’ reluctance to switch to an alternative treatment and/or increase doses if BP remains uncontrolled. Selected antihypertensive drug does not target the mechanism causing the patient’s hypertension. http://www.mayoclinic.org/diseases-conditions/high-blood-pressure/basics/treatment/con-20019580 accessed on 9-oct-2015

9. Need for Combination Therapy Clinical Evidences

10. Combination Therapy: A Practical Necessity Required in ~ 75% of hypertensives to achieve target BP Greater efficacy Faster achievement of target BP Higher response rates May make therapy effective in broader population Additive antihypertensive effects through complimentary pharmacologic mechanisms In some cases, improved side effect profile Gradman AH, Basile JN, Carter BL, et al. J Clin Hypertens (Greenwich). 2011;13:146–154.

11. Combination Therapy is More Effective Than High Dose Monotherapy Incremental SBP reduction ratio of observed to expected additive effects Wald DS, et al. Am J Med 2009;122:290-300

12. Higher BP Control Rates Are Achieved With Single Pill Combinations 12 Change in proportion of patients achieving BP goals relative to monotherapy (%) Patients receiving a single pill combination are more likely to achieve BP goals than those receiving free combinations or monotherapy Gu Q, et al. Circulation 2012;126:2105-14 *p<0.05 vs monotherapy **p<0.01 vs. monotherapy Regional guidelines on combination therapy| March 2013

13. Single Pill Combinations are R ecommended by Guidelines Single pill combinations (SPCs) or fixed-dose combinations have numerous advantages over multiple drug combination therapy Current hypertension guidelines generally recommend SPCs over multiple drug treatment with their individual components Gupta AK, et al. Hypertension 2010;55:399-407 Bangalore S, et al. Am J Med 2007;120:713-9 Dusig R. VHRM 2010;6:321-5 Mancia G, et al. J Hypertens 2009;27:2121-58

14. Comparison of Monotherapy and Free and Single Pill Combinations Monotherapy Free combination Single pill combination Convenience ✔ ✗ ✔✔ a Adherence − − ✔ Efficacy ✗ ✔ ✔ Tolerability ✗ ✔ ✔ b Flexibility ✔✔ ✔✔ ✔ c a Switching and dose titration less likely to be required than for monotherapy b Single pill may be better tolerated as doses tend to be lower than in free combinations c Flexibility with single pill combinations is increasing as the range of doses increases Xinhuan Wana et al., Asian Journal of Pharmaceutical Sciences Volume 9, Issue 1, February 2014, 1–7

15. TRIPLE COMBINATION THERAPY – ESH 2023 New guidelines

16. 16 Cilnidipine has multiple approaches in reno-protection J Hypertens. 2010 May; 28(5): 1034–1043. Hypertens Res. 2012 Nov;35(11):1058-62. doi : 10.1038/hr.2012.96.

17. Change in pulse rate (PR) after Amlodipine and Cilnidipine treatment compared to the pretreatment value Change in urinary protein/creatinine ratio during the 6-month treatment period in the Amlodipine and Cilnidipine group Cilnidipine significantly reduces HR and UACR, Amlodipine increases Zaman ZA et al. Int J Basic Clin Pharmacol . 2013 Apr;2(2):160-164

18. 18 Mega-Trial of Cilnidipine proves it reduces HR by 9.7 bpm, effective in morning hypertension ACHIEVE-One study These effects of cilnidipine are new features not known in conventional L‐type Ca channel blockers Cilnidipine reduces HR better when it is higher than 85bpm Generally, morning hypertension involves increased sympathetic activity, and the renin‐angiotensin system (RAS). Cilnidipine reduced MSBP and MPR even in patients who had already been administrated β‐blockers or RAS inhibitors (including ARBs and ACE inhibitors). These additive BP‐ and PR‐lowering effects of cilnidipine may be a reflection of dual L‐and N‐type Ca channel–blocking actions differing from β‐adrenergic receptor blocking and RAS‐inhibiting actions “High-rate morning hypertension” characterized by high MSBP and MPR. Cilnidipine is the optimal CCB in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034443/

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20. J Clin Pharmacol. 1998;38(6):477–491. J Clin Pharmacol. 1995;35(11):1060–1066. Am J Cardiol. 1995;76(8):595–597.

21. 21 ESC/ ESH HYPERTENSION GUIDELINE RECOMMENDS DUAL COMBINATION THERAPY AS A INITIAL THERAPY First look at the new 2018 European Guidelines for the treatment ofhigh blood pressure. 2018 ESC and ESH joint guidelines for themanagement of arterial hypertension. Available from URL:ht tp:/ /www.eshonline.org/esh-annual-meeting/

22. 22 TRIPLE DRUG COMBINATION About 24% to 32% of patients with HTN will require more than two drugs to achieve their BP target. A rational combination in this setting would be an RAAS inhibitor, a CCB, and a diuretic.

23. 23 Single- pill triple combinations of different classes of drugs with complementary mechanisms of action help to treat patients to goal with improved efficacy and better adherence to treatment Triple drug fixed dose combination of Telmisartan, Amlodipine and hydrochlorothiazide was found to be effective and safe option for the optimal management of hypertension .

24. 24 TRIPLE DRUG COMBINATION Triple fixed- dose drug combinations should be reserved only for patients with uncontrolled BP with 2 agents, poor adherence in complex therapeutic regimens or on inappropriate free- drug combinations. Triple therapy may help overcome clinical inertia by prescribing more potent antihypertensive formulations in one pill. Beyond the choice between different triple fixed- dose combinations it is important to evaluate at shortterm whether BP is controlled within target and whether the administered fixed- dose treatment is associated with good compliance

25. 25 Curr Vasc Pharmacol. 2017;16(1):61- 65.

26. 26 How to build up appropriate triple drug combinations. Curr Vasc Pharmacol. 2017;16(1):61- 65.

27. 27 CHANGING TRENDS IN PHARMACOTHERAPY FOR HYPERTENSION IN INDIA 47 53 10 20 30 40 50 60 70 Mono Combo Malhotra et al. Eur J Clin Pharm. 2001;57:535 49 51 10 20 30 40 50 60 70 Mono Combo Sreedharan et al. Int J Clin Pharm Ther. 2011;49:277 27 73 10 20 30 40 50 60 70 Mono Combo Gupta R, et al. 2018. Unpublished.

28. 29 Summary Within a population of 30% affected by hypertension, 72% of the patients remain uncontrolled in India The reasons for uncontrolled hypertension are varied including ignorance, mis-diagnosis / underdiagnosis, and undertreatment, patient adherence is also a key factor Guidelines recommend triple combinations for uncontrolled hypertension to improve outcomes and patient adherence Cilnidipine a novel CCB , well established in India in hypertension management also offers reno-protective benefits in uncontrolled hypertensives who are at high risk for CKD Also, sympatholytic activities of cilnidipine make it the choice of CCB in youngsters as well for HTN control and reduction of HR Hypertension is a multi-dimensional disease, which has moved beyond just control of numbers , the major focus is on end-organ protection in the long term Wise choice of molecules can help patients with the best outcomes in their hypertensive journey and improve adherence as well

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