2. Hypertension
• Worldwide hypertension remains the most common
modifiable risk factor for cardiovascular disease,
affecting 25-30% of adults, rising to 70-80% in the
elderly.
• Despite significant improvements in the treatment
of hypertension over the last 30 years, high blood
pressure is still a significant cause of mortality
(responsible for approximately 6% of deaths world
wide )
3. Relationship between HTN and CVD
• The relationship between blood pressure and
cardiovascular events is continuous, with each
20 mmHg increment in systolic blood pressure
or 10 mmHg increment in diastolic blood
pressure associated with at least a doubling of
risk of death from stroke, ischaemic heart
disease or other vascular causes.
4. HTN and CVD
• Clinical trial suggests that by lowering blood
pressure to agreed target levels the incidences
of cardiovascular and Cerbovascular events
are significantly reduced
• Pooled results of many trial suggest that an
overall reduction in SBP by only 2mmHg
reduces the risk of cardiovascular events by 7-
10%
5. Target BP :Far beyond Reach
• Despite advances in Pharmacotherapy, 45-
80% of Patients fail to achieve internationally
agreed target
• Recent Data shows that control rates are
about 25% I western Europe
• In BP-Care survey in nine central and eastern
European countries , on average 27% of
treated patients achieved the recommended
target of <140 /90mmhg
7. Target BP :Far beyond Reach
• Taking into account that both treated and
untreated patients were included in the
Western European data , it was estimated that
only about 17% of the hypertensive
population in Europe are well controlled
• Data from US National Health and Nutrition
Examination survey ( NHANES ) showed that
52to 62% of treated patients were
uncontrolled
8. Uncontrolled HTN and its
consequences
Consequences of uncontrolled blood pressure
in treated patients is serious
Such patients have 57% greater risk of all
cause mortality and 74% greater risk of
Cardiovascular mortality when compared to
patients of controlled BP
9. Risk of all-cause and cardiovascular mortality in
different patient
groups in the NHANES III survey in US adults
10. Uncontrolled HTN and its
consequences
• The relationship between blood pressure and
cardiovascular events is continuous, with each
20 mmHg increment in systolic blood pressure
or 10 mmHg increment in diastolic blood
pressure associated with at least a doubling of
risk of death from stroke, ischaemic heart
disease or other vascular causes.
11.
12. High Blood pressure and Its
consequences
• Uncontrolled HTN has important
consequences for increasing risk of
• CVD
• Kidney disease
• Micro vascular disease
• Dementia
• Alzheimer’s Disease
• Parkinson Disease
13. Reason for Poor control of BP
• Physicians may be reluctant to take appropriate
action possibly due to
• Concern about the potential increased risk of
side effect
• The perceived complexity of the treatment
regimen or treatment cost
• Mis diagnosis , in Particular the problem of
hypertension
• Non –adherence with treatment is also one of
the reason
14. Reason for Poor control of BP
• Multifactorial aetiology of hypertension
• Due to Involvement of a number of complex
physiological responses in regulation of blood
pressure , monotherapy is effective only in
25% of the patients
• Simply up titrating the dose of treatment is
unlikely to significantly improve response .
15. Reason for Poor control
• The complexity of underlying causes of
hypertension is a further important cause of
poor blood pressure control
• A retrospective study of patients with newly
diagnosed hypertension suggested that
excessive reliance on monotherapy was the
most important factor contributing to poor
control , with 40% of patients remaining on
monotherapy at the end of the study
16. Reason for Poor control of BP
• The limited efficacy of individuals therapies in
controlling blood pressure and the time taken
new treatments sequentially may lead to loss
of motivation from both patient and
Physicians
17. The Increasing Importance of
Combination Therapy
• Combination therapy is now considered to be
critically important for improved blood
pressure control
18. Advantage of Combination Therapy
• Complementary mode of actions for optimal blood
pressure lowering effect
• Inhibits the counter regulatory responses that occur
when physiological system is blocked by single agent
• Effective in patients with moderate /severe
hypertension ( 160/100mmHg) who account for
some 10-15% of hypertensive populations and are at
substantially greater risk of future CVD risk
19. Advantage of Combination Therapy
• Decreases blood pressure variability when
compared with Monotherapy .
• Such variability is strong predictor of storke
and another good reason for using
combination therapy
20. Advantage of Combination Therapy
• All Large prospective clinical trials like
• ALLHAT
• Life
• ASCOT –BPLA
Endorses
Combination Therapy
ALLHAT ( Antihypertensive and lipid lowering
treatment to prevent Heart attack trial )
21. Advantage of Combination Therapy
• Nearly 80% of patients in ASCOT-BPLA were
two or more medications at the end of the
study
• Meta analysis of 42 trials in nearly 11000
hypertensive patients showed that combining
two different anti-hypertensive classes
provides approximately 5 times additional
reduction in blood pressure compared with
doubling the dose of single drug
22.
23. Advantage of Combination Therapy
• Another Meta analysis of 119 randomized
double-blind placebo controlled trials of major
classes of antihypertensive monotherapies
showed that, an average first and second
drugs given alone lower blood pressure by
only 7.0/4.6mmHg, whereas when they are
given together blood pressure reduction was
14.6/8.6mmHg
24. Guidelines Recommendations
• Emphasize the need of combination therapy
• Highlight the necessity of using multiple
therapies with complimentary mode of Action
to achieve blood pressure targets
25. Recommendations for Combination
Therapy
• The JNC 7 guidelines states that most
hypertensive patients will require 2 or more
drugs to achieve blood pressure control
• The 2007 ESH/ESC hypertension guidelines
emphasize the need for treatment with
multiple antihypertensive agents to attain
blood pressure goals .
26. ESH /ESC 2013 Recommendations
• The recent ESH / ESC guidelines strengthens
this approach with the statement that in
“ In vast majority hypertensive patients ,
effective blood pressure control can only be
achieved by combination Therapy of at least 2
anti-hypertensives drugs ( from different
classes )
27. Possible combinations
• The ESH/ESC guidelines recommend different combinations that
have been found to be effective and well tolerated in randomized
trial
28. Acceptable combinations of Anti-
hypertensive drug classes
• Acceptable dual combinations based on outcomes ,anti-
hypertensive efficacy and tolerability, as recommended
by international guidelines
• These combinations are of drug with complimentary
modes of action which allow patient to meet blood
pressure targets
29.
30. Problems of Combination therapy
• Increased pill burden leading to poor
compliance
• Patients with HTN have many co-existing
morbidities which also require multiple drugs .
The resulting therapeutic complexities lead to
poor compliance and increased Risk of CVD
• Notably , one study demonstrated a 35%
reduction in compliance with a four times a dy
regimen when compared with a once daily
dose
31. Increased PILL burden
• The increased pill burden is significant
contributory factor to poor compliance
• Data from a retrospective US study of
compliance with anti-hypertensive and Lipid
lowering therapy show that taking fewer other
medications for co-morbidities is associated
with higher likelihood of compliance
32.
33. Consequences of Poor compliance
with therapy
• Non compliance with therapy is associated with
• Excess Morbidity and Mortality
• Less Likely to achieve blood pressure Goals
• Study of 840 patients from 13 US managed care
organization showed that poorly complaint
individual were 45% less likely to achieve blood
pressure target of <140/90 mmHg
34.
35. Consequences of Improved
Compliance
• Improved compliance with anti-hypertensive
medications has been shown to have
significant beneficial effects on cardiovascular
outcomes and to decrease risk of
hospitalizations
• Good compliance with therapy has been
associated with significant 38% reduction in
Cardiovascular events
36.
37. Need of an Hour
• Compliance with therapy can be improved by
simplification of drug regimens, both reducing
frequency of dosing and overall pill burden
• Most importantly Compliance are improved
with
FIXED DOSE COMBINATION
38. FDC
• FDC of anti-hypertensives drug in a single
once daily tab are an important strategy
• To reduce pill burden
• Improves level of compliance with therapy
• Causes significant reductions in CVD events
• Endorsed by various Meta analysis of cohort
studies
39.
40. Reappraisal of ESH /ESC guidelines
• A Reappraisal of ESH /ESC guidelines 2007
strongly recommends the use of fixed dose
combination therapy Stating :
• “ Whenever possible , use of fixed dose
combinations should be preferred because
simplification of treatment carries advantages
for compliance with treatment”
41. Benefits of FDC
• A recent study compared compliance with therapy
over 12 month in 14,449 patients receiving FDC or
free combinations of the same anti-hypertensive
drugs
• Patients receiving FDC anti-hypertensive therapies
showed a 22.5% increased rate of compliance and
43.4% increased rate of persistence with therapy
when compared with those patients on free
combinations of anti-hypertensive
42. Summary
• Combination therapy with two anti-
hypertensive’s drugs with complimentary
mode of action is required for most
hypertensive's patients in order of achieve
internationally agreed Blood Pressure targets
• A number of evidence based combinations are
available to physicians and guidelines
encourage the early use of combination
therapy
43. Summary
• Guidelines recommends various drugs and
emphasize the importance of FDC .
• Combining complimentary treatments in a single
tablet recognizes the need to treat the multiple
cause of hypertension while maximizing compliance
with therapy .
• Evidence shows that such an approach will improve
blood pressure control and minimize adverse effect
to reduce the risk of cardiac and cerbrovascular
events
