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Treatment Of Hypertension
In Diabetes
BY
Dr. Khaled Helmy
Al Mahmora Chest Hospital
Hypertension
&
Diabetes
Hypertension
Diabetes
 Hypertension affecting 20–60% of patients with diabetes.
 In type 2 diabetes, hypertension is often present as part
of the metabolic syndrome while in type 1 diabetes,
hypertension may reflect the onset of diabetic nephropathy.
 Hypertension substantially increases the risk of both
macrovascular and microvascular complications.
 Hypertensive diabetic patients are also at increased
risk for diabetes-specific complications including
retinopathy and nephropathy.
 In recent years, adequate data from well-designed
randomized clinical trials have demonstrated the
effectiveness of aggressive treatment of hypertension
in reducing both types of diabetes complications.
Hypertension
Diabetes
 Diabetes increases the risk of coronary events
twofold in men and fourfold in women after menopause.
 People with both diabetes and hypertension
have approximately twice the risk of cardiovascular
disease as non-diabetic people with hypertension
 In the U.K. Prospective Diabetes Study (UKPDS)
epidemiological study, each 10-mmHg decrease in
mean systolic blood pressure was associated with
reductions in risk of 12% for any complication related
to diabetes, 15% for deaths related to diabetes, 11%
for myocardial infarction, and 13% for microvascular
complications.
Normotensive Hypertension
 In recent years, adequate data from well-designed
randomized clinical trials have demonstrated that
structural changes in vessels start 5 years before
BP elevated .
 patients who still have normal BP but have the
high risk to develop high Bp(Patient at risk) are
classified as normotensive hypertension and of
course one of them is diabetic patients and they
should be managed as soon as possible .
Strategy for management of
Hypertensive Diabetic pts
 Proper blood sugar control .
 Achieve target level of BP control for
diabetic patients
 Early Detection of both diabetes and
hypertension complications & manage them
as well as delay their progression
 Improve patients quality of life .
Target levels of blood pressure
in patients with Diabetes
 The UKPDS and the Hypertension Optimal Treatment
(HOT) trial
both demonstrated improved outcomes ,
especially in preventing stroke, in patients assigned to
lower blood pressure targets.
 A target blood pressure goal of <130/80 mmHg is
reasonable if it can be safely achieved <125/75 mmHg
(in proteinuria >0.5-1g/d)
 It is very clear that many people will require more than
one drug to achieve the recommended target.
Non-drug management of
Hypertension
 Moderate sodium restriction ,reduce salt intake from 200mmol
(4600 mg) to 100mmol (2300 mg) daily 5 mm fall in DBP.
 Weight reduction (Loss of 1 kg weight decrease mean
arterial pressure of about 1 mm Hg.
 Moderately intense physical activity: 30-45 mins of brisk
walking most days of the week has been shown to reduce BP.
 Stop smoking  decease micro, macrovasular Compilications
 Role of very low calorie diets ?
 Pharmacologic agents that induce weight loss?
Drug therapy of
Hypertension in Diabetes
 There is strong evidence that pharmacological
therapy of hypertension in patients with diabetes
is effective in producing substantial decreases in
cardiovascular and micro vascular diseases.
 It must be noted that many patients required more
than one drug to achieve the specified target
levels of blood pressure control.
 The UKPDS-Hypertension in Diabetes Study showed
no significant difference in outcomes for treatment
based on an ACE inhibitor compared with a ß-blocker.
Drug therapy of
Hypertension in Diabetes,cont
 ACE inhibitors and ß-blockers appear to be superior
to DCCBs therefore, DCCBs appear to be appropriate
agents in addition to but not instead of ACE inhibitors
, and ß-blockers .
 The UKPDS-Hypertension in Diabetes Study showed
no significant difference in outcomes for treatment
based on an ACE inhibitor compared with a ß-blocker.
 There are no long-term studies of the effect of
ß -blockers, loop diuretics, or centrally acting
adrenergic blockers on long-term complications
of diabetes
Role of ACEIs & ARBs in Diabetes
 A variety of trials have demonstrated that ACEIs / ARBs
therapy should be considered the standard therapy to
retard worsening albuminuria and subsequent renal disease.
 In Addition to their proper BP control, ACE inhibitors can
retard the progression of microalbuminuria and can lower
the percentage of patient who progress to end-stage
renal disease and death.
 All patients with asymptomatic or symptomatic heart failure
due to left ventricular systolic dysfunction should receive
an ACE inhibitor. Approximately 50% of patients post-MI
have significant left ventricular dysfunction and could benefits
from ACE inhibitor therapy.
Role of ACEIs & ARBs in Diabetes,cont
 A meta-analysis of 20 published and two unpublished
trials was carried out to determine whether ACE inhibitors
could slow the progression of renal disease of varying
degree showed that treatment of chronic renal insufficiency
with ACE inhibitors delayed the progression of disease
compared with placebo.
 ACE inhibitors have a favorable effect on cardiovascular
outcomes , this cardiovascular effect may be mediated by
mechanisms other than blood pressure reduction.
Role of ACEIs & ARBs in Diabetes ,cont
 There are numerous studies documenting the effectiveness
Of ACE inhibitors and ARBs in retarding the development
and progression of diabetic complications :
 EUCLID Study (Lisinopril vs placebo)
Type1 Diabetic retinopathy
 CALM study (Lisinopril vs Candestran & combination)
BP & Microalbuminurea
 RENAAL study(Losartan vs placebo)
Type 1 Diabetic nephropathy
 HOPE study (Ramiplil vs placebo)
Reduction of MI,stroke ,CV death
All- cause death in high risk pts esp DM.
 IDNT study (Irbesartan vs amlodipine vs placebo)
 MARVAL study (Valsartan) Type 2 Diabetic nephropathy
Irbesartan & Valsartan delay nephropathy
amlodipine no better than placebo
ACEIs Vs ARBs
ACEIs Vs ARBs
Angiotensinogen
Renin
Blockade
Other Substrates?
Renin
Angiotensin I
Bradykinin & other substrates
ACE
inhibitors
ACE
Angiotensin II
Angiotensin II receptor antagonists
?
AT2
Actions?
AT1
Psychological actions
blocking the
Renin-Angiotensin
system
ACEIs Vs ARBs
 Evidence for beneficial outcomes (especially renal) with
ARBs is growing but varying opinion on their optimal role.
 Unfortunately, several ARB outcome trials have avoided
a head-to-head comparison with ACEIs.
 Losartan was not superior to captopril in patients with
heart failure( ELITE II) , captopril reduced CV-death in post-MI
patients more than losartan( OPTIMAAL) However, both of
these studies found that less patients discontinued losartan
due to adverse effects
 ARBs are an alternative in patients who develop ACEI
induced cough but are more expensive than most ACEIs
 ACEI-ARB combinations show some promise for renal
outcomes( CALM, COOPERATE), however they are expensive.
Approach to Combination Therapy
The ABCD Approach
A = ACEI or ARB
B = -blocker
C = CCB
D = diuretic low-dose
 If initial drug is A or B  adding drug C or D
provides a synergistic effect.
 If initial drug is C or D  adding drug A or B
provides a synergistic effect; (C+diuretic, also option).
•Verapamil or diltiazem with a β-blocker negative effects on heart
(e.g. ↓ heart rate and ↓ cardiac output)
•CCBS and α-blockers potential for excessive hypotension;
increased risk of falls, etc.
Drug therapy in
Hypertension with Diabetes
Monotherapy
1st potion ACEIs
nd
OR 2 option ARBs
+
Combination
 Thiazide like diuretic (low dose→HCT 12.5-25mg od)
 B blocker (cardioselective-e.g. atenolol, metoprolol)
 Long acting calcium channel blockers (amlodipine)
Summary
 Non-pharmacological measures (particularlyweight loss
and reduction in salt intake) should be encouraged in all
patients with diabetes, independently of the existing
blood pressure.
 The goal blood pressure to aim at during behavioural
or pharmacological therapy is below 130/80 mmHg.
 To reach this goal, most often combination therapy
will be required.
 It is recommended that all effective and well tolerated
antihypertensive agents are used, generally in combination.
Summary,cont
In diabetic patients with high blood pressure, who
may sometimes achieve blood pressure goal
by monotherapy, the first drug to be tested should
be a blocker of the renin–angiotensinsystem
(ACE & ARBS)
 The finding of microalbuminuria in type
1 or 2 diabetics is an indication for antihypertensive
treatment, especially by a blocker of the
renin–angiotensin system, irrespective of the blood
pressure values(normotesive Hypertension).
Summary,cont
 DCCBs (compared with ACE inhibitors, ARBs,
ß-blockers, or diuretics) should be used as
second-line drugs for patients who cannot tolerate
the other preferred classes or who require additional
agents to achieve the target blood pressure.
 Other classes, including Alph -blockers, may be
used under specific indications such as symptoms
of BPH.
 Achievement of the target blood pressure goal with
a regimen that does not produce burdensome
side effects and is at reasonable cost to the patient
is probably more important than the specific drug strategy.
Thank you