The document discusses diuretics for the treatment of hypertension. It summarizes that diuretics, especially chlorthalidone, are recommended as first-line treatment in major guidelines due to their efficacy in reducing blood pressure and preventing cardiovascular events like stroke, heart failure, and myocardial infarction. Chlorthalidone is preferred over hydrochlorothiazide as it has a longer duration of action, greater potency, and has shown stronger evidence of clinical benefits in reducing major cardiovascular outcomes in large trials and meta-analyses.

1. Diuretics in hypertension
Guidelines

2. Hypertension
Leading cause of global burden of disease

3. At what age should screening for
hypertension begin?
Blood pressure is one of the most important screenings because
high blood pressure usually has no symptoms so it cannot be
detected without being measured

4. Renal
failure
(>50%)
Heart
failure
(>50%)
Stroke
(35–40%)
Myocardial
Infarction
(20–25%)
Renal
failure
(>50%)
Heart
failure
(>50%)
Stroke
(35–40%)
Myocardial
Infarction
(20–25%)
Renal
failure
(>50%)
Heart
failure
(>50%)
Stroke
(35–40%)
Myocardial
Infarction
(20–25%)
Renal
failure
(>50%)
Heart
failure
(>50%)
Stroke
(35–40%)
Myocardial
Infarction
(20–25%)
Renal
failure
(>50%)
Heart
failure
(>50%)
Stroke
(35–40%)
Myocardial
Infarction
(20–25%)
Renal
failure
(>50%)
Heart
failure
(>50%)
Stroke
(35–40%)
Myocardial
Infarction
(20–25%)
Renal
failure
(>50%)
Heart
failure
(>50%)
Stroke
(35–40%)
Myocardial
Infarction
(20–25%)
Renal
failure
(>50%)
Heart
failure
(>50%)
Stroke
(35–40%)
Myocardial
Infarction
(20–25%)
Neal et al Lancet 2000;356:1955-64
Large number of clinical trials show that getting goal BP is
associated with dramatic reduction in
What are the benefits of
achieving goal BP?

5. What are the first line choices available for
management?

6. What are the first line choices available for
management?

7. What are the various agents
available in India?
Diuretics Dose
Hydrochlorothiazide 6.25-12.5 mg
Chlorthalidone 6.25-12.5 mg
Indapamide 1.5-2.5 mg
Amiloride 5-10 mg
Triamterene 50-100 mg
Shah SN et al. JAPI supplement. 2013 Feb; 61 17-23

8. Which international guidelines
discuss diuretics?
• Joint National Committee (JNC) VIII 2014
• European Society of Hypertension (ESH) 2013
• American Heart Association (AHA) 2015
• National Institute for Health and Care Excellence (NICE) 2011
• AHA 2011: Hypertension in elderly
• American Society of Hypertension (ASH)/ International society of
Hypertension (ISH) 2014
• Taiwan Society of Cardiology 2015
• Chinese Hypertension guidelines 2015
• Korean Society of Hypertension Guidelines 2013
• Japanese Society of Hypertension Guidelines 2014

9. Goal BP < 140/90
9
James PA et al. JAMA. 2014 Feb 5;311(5):507-20.
JNC VIII

11. Hypertension with CAD: AHA/ACC/ASH
Scientific Statement 2015, Mar 30
11
Pharmacological Treatment of Hypertension in the Management of
Ischemic Heart Disease
Rosendorff C et al. J Am Soc Hypertens.2015 Mar 30. pii: S1933-1711(15)00097-2.

12. If a diuretic is to be initiated or changed, offer a thiazide-
like diuretic, such as Chlorthalidone (12.5 mg–25.0 mg
once daily) in preference to a conventional thiazide
diuretic such as hydrochlorothiazide
NICE guidelines National Clinical Guideline Centre - 2011

13. Chlorthalidone differs from HCTZ by its longer duration of
action and greater potency
Circulation. 2011;123:2434-2506.

14. • Clinical outcome benefits (reduction of strokes and major
cardiovascular events) have been best established with chlorthalidone,
indapamide, and hydrochlorothiazide, although evidence for the first
two of these agents has been the strongest
• Chlorthalidone has more powerful effects on blood pressure than
hydrochlorothiazide (when the same doses are compared) and
has a longer duration of action
The Journal of Clinical Hypertension. 2014; 16(1) :14-26

15. • "Thiazide diuretics and thiazide-like diuretics (e.g. indapamide,
chlorthalidone, etc) remain essential in the treatment of
hypertension"
• "Chlorthalidone may be the preferred thiazide-type diuretic for
hypertension in patients at high risk of cardiovascular events"
• "Chlorthalidone is at least twice as potent as HCTZ and should
be considered as the initial therapy for patients with TRH
(treatment resistant hypertension)"
Chiang C-E, et al., Journal of the Chinese Medical Association (2014), http://dx.doi.org/10.1016/j.jcma.2014.11.005

16. • "All five classes of antihypertensive drugs, namely CCBs,
ACE-I, ARBs, thiazide diuretics and β-blockers, were
recommended as a possible choice for initial and maintenance
antihypertensive therapy"

17. • "Five classes of antihypertensive drugs, including ACE-I, β-
blockers, CCB, and diuretics, were equally recommended as a
firstline treatment"

18. • In hypertensive patients without compelling indications, the
antihypertensive drug to be first administered should be selected from
CCBs, ARBs, ACE-I and diuretics (Recommendation grade: A,
Evidence level: I)
• Diuretics are effective for salt-sensitive hypertension, including
hypertension in the elderly
• There is evidence on their preventive effects on stroke in the Japanese
• The use of low-dose thiazide diuretics and their analogs inhibits the
appearance of metabolic adverse effects.
The Japanese Society of Hypertension Committee for Guidelines for the Management of Hypertension. Hypertens Res 2014; 37: 253–392.

19. What is the difference between thiazide and
thiazide like diuretic?
Chlorthalidone: edge over HCTZ
• Structural differences
• PK-PD advantages
• Dual mode of action
• Effective BP control
• Large clinical trials
• Meta analysis
• Guidelines recommended
• Pleiotropic effects
• Expert opinion
• Better adverse effects profile
• Survival benefits

20. Chlorthalidone: edge over HCTZ

21. • Chlorthalidone versus thiazide diuretics: distinctly different
impacts on cellular and molecular mechanisms relevant to
pathogenesis of cardiovascular disease
– Reduces epinephrine-induced platelet aggregation
– Increases angiogenesis
Hypertension. 2010;56:335-337.

22. Why diuretics as a first line agent?
• Have been used since the late fifties
• One of the most important group of drugs used to reduce BP, due to
efficacy and cost-effectiveness profile
• Effective in reducing BP and preventing CVD
• Major impact on reducing the risk of
 Stroke
 Heart failure
 Myocardial infarction
 Death in the population
Current choice is chlorthalidone as it has edge over HCTZ

23. Thank you