1. Most patients require combination antihypertensive therapy to achieve blood pressure targets, as monotherapy typically only lowers blood pressure by 9/6 mmHg on average. 2. Preferred combinations include ACE inhibitors or ARBs with diuretics, or ACE inhibitors or ARBs with calcium channel blockers. 3. Combination therapy should be initiated routinely for patients who need over a 20/10 mmHg reduction in blood pressure to reach targets.

1. RATIONAL COMBINATION THERAPIES
FOR MANAGING HYPERTENSION
A MOHAMED KASIM

2. DEFINITION: Hypertension may be defined as that level blood pressure
at which then institution of therapy reduces blood pressure related
morbidity and mortality.
Current clinical criteria for defining generally based on the average of
two or more seated blood pressure readings during each of tow or
more outpatient visits.
In children and adolescents it is defined as systolic/ diastolic pressure
consistently more than 95th percentile for age, sex and height.

3. • JNC 7 (reclassified) classification of blood pressure:
Classification SBP DBP
Normal less than 120 less than 80
Prehypertension 120-139 80-89
Stage-1 HTN 140-159 90-99
Stage-2 HTN more than 160 more than 100

4. CAUSES :
1- Primary or idiopathic cause
2- Secondary cause:
Renal- Parenchymal disesase, Renal cysts, Renal tumors, obstructive
uropathy
Renovascular- Arteriosclerotic Fibromuscular dysplasia
Adrenal- Primary aldosteronism, Cushings, Pheochromocytoma,
Aortic coarctation
Obstructive sleep apnea
Pre-eclampsia/Eclampsia

5. Neurogenic – Psychogenis, diencephalic syndrome, polyneuritis, Acute
increased ICT, spinal cord section
Endocrine causes- Hypothyroidism, Hyperthyroidism, Hypercalcemia,
Acromegaly
Drug Induced- High dose oestrogens, Adrenal Steroids, cyclosporine,
decongestants, Tricyclic antidepressants, NSAIDS, cocaine

6. Classifications of Anti- Hypertensives:
1- ACE inhibitors
2- Angiotensin(AT1 receptor) Blockers
3- Calcium channel blockers
4- Diuretics
5- Beta blockers
6- Alpha blockers
7- Beta + alpha blockers
8- Central sympatholytics
9- Vasdodilators

7. INTODUCTION:
1- The goal of antihypertensive therapy is to abolish the risk associated
with blood pressure elevation without affecting their quality of life.
2-Drug selection is based on the efficacy of lowering the blood pressure
and also in reducing the cardiovascular end points.

8. • COMBINATION THERAPY A PRACTICAL NECESSITY:
BP is primarily determined by 3 factors renal sodium excretion and
resultant plasma and total body volume, cardiac performance and vascular
tone.
Both sympathetic nervous system and RAAS are intimately involved in
adjusting these parameters.
In addition genetic makeup, diet and environmental factors influence BP in
individual patients.
In recent meta analysis of law and colleagues of 354 randomized double
blind trials the mean reduction is 9.1/5.5 mmhg. But there was a little
difference between a diuretic, beta blocker, ACE inhibitor and ARB or CCB
In ALLHAT only 26% achieved BP control with single drug and in HOT trial
33% achieved control with monotherapy, 45% required 2 drugs 22%
needed three or more drugs.

9. In LIFE study trial in which goal was to reduce BP less than 140/90 was
pursued in LVH patients and in patients with BP more than 175/80.
More than 90 % required combination therapies.
The aggregate available data from all these studies suggests that 75%
of patients required combination therapies to achieve contemporary
BP targets.

10. • COMBINATION THERAPY: THEORETIC CONSIDERATIONS.
1- Efficacy
2- Tolerability
3- Adherence
4- Cost

11. PATIENT SELECTION: INITIAL THERAPY:
1) Should treatment be started with monotherapy or a combination?
2) If two drugs are initiated, should they be administered as single
entities or an single pill combinations.
By beginning with combination therapy, counter regulatory responses
will be reduced, thus there will be a increase in percentage of
responders.
In VALUE trial , post analysis indicated that subjects who reached target
BP within 6months of entering the protocol demonstrated substantially
better outcomes throughout the 5yr duration of the study.

12. Current guidelines suggest that two be used for initial therapy if there
is a 20/10mmhg elevation in BP above goal.
In meta-analysis of weir the magnitude of in terms of time-specific
achievement of BP was greater in Stage-1 compared to Stage-2
subgroup.
Among patients in Stage 1 72% achieved JNC-7 target with valsartan
monotherapy , whereas 92% were achieved in those who received
initial combination therapy – Valsartan with HCTZ.

13. • PREFERRED COMBINATIONS:
1- ACE inhibitor/Diuretics
2- ARB/Diuretics
3- ACE inhibitor/CCB
4- ARB/CCB

14. •ACCEPTED COMBINATIONS:
1- Beta-Blockers/Diuretics
2- CCB(DHP)/Beta- Blockers
3- CCB/Diuretics
4- Renin inhibitor/Diuretics
5- Renin inhibitor/ARB
6- Thiazide diuretics/K sparing diuretics

15. •LESS EFFECTIVE
1- ACE inhibitor/ARB
2- ACE inhibitor/Beta- blockers
3- ARB/Beta- blockers
4- CCB(DHP)/Beta- blockers
5- Centrally acting agents/Beta- Blockers

16. •SUMMARY:
1- Use combination therapy to routine achieve BP targets.
2- Use only preferred or acceptable two- drug combinations.
3- Initiate combination therapy routinely in patients who require
20/10mmhg BP reduction to achieve target BP.
4- Initiate combination therapy in Stage-1 patients especially when the
second agent will improve the side- effect profile of initial therapy.

17. THANK YOU