Download Erectile Dysfunction and Cardiovascular Disease

Erectile Dysfunction and
Cardiovascular Disease
ED and Cardiovascular Diseases
GU
CAD
Dysmetab
.
Atheroscl.
Malattie cardiovascolari e
disfunzione erettile
• Alterazione vascolare
• Aterosclerosi diffusa, ostruzione al
flusso ematico
• Produzione di EDRF
• Peptidi vasoattivi
• Sindrome dismetabolica
• Terapia farmacologica
• Psicologica
Malattie cardiovascolari e
disfunzione erettile
Effetto della terapia farmacologica
• Diuretici
• Beta-bloccanti
• Ca- antagonisti
Verapamil
Diltiazem
Amlodipina
• ACE-Inibitori
• ATII antagonisti
• Alfa-litici
Frequente
Frequente
Frequente
Frequente
Frequente
Frequente
Raro
Potenziamento erezione
Study Design
3 months
Run in
Sildenafil
Atenolol - do not know drug
Atenolol - do not know side effects
Atenolol - know side effects
Placebo
Sildenafil
Placebo
Sildenafil
Placebo
Report of ED
QOL Questionnaire
Silvestri et al. In Press Eur Heart J 2003
Beta-blockers and Report of ED
% of patients reporting ED
35
P<0.01
30
25
P<0.05
20
15
10
5
0
Blinded
Knew drug no SE
Comparisons vs pts blinded on treatment drug
Silvestri et al. In Press Eur Heart J 2003
Knew drug and SE
% of patiets reporting improvement
of ED
Effect of Sildenafil Citrate and Placebo
in Patients Reporting ED
100
90
80
70
60
50
Sildenafil Citrate
Blinded
Silvestri et al. In Press Eur Heart J 2003
Placebo
Knew drug
Knew SE
Incidence of Cardiovascular Disease in Patients
Referred for ED
Study Objective
 Evaluate cardiovascular risk and incidence of cardiovascular disease
in cardiac asymptomatic patients with ED
Study esign
 Indication of exercise ECG and eventually to coronary angiography to
50 cardiac asymptomatic patients with suspected vasculogenic ED
Pritzker MR. Circulation. 1999; 100 (suppl 1): I-711. Abstract 3751
Cardiovascular Disease in Patients with ED
 In 40 patients out of 50 (80%) there was presence of multiple risk factors for
CAD
 Family history
(n=32)
 cigarette smoking
(n=40)
 total cholesterol >200 mg/dl
(n=35)
 HDL-c <40 mg/dl
(n=18)
 Hypertension
(n=24)
 Sedentary life style
(n=38)
 diabetes
(n=10)
 Exercise ECG was positivein 28/50 pazients
 Coronary angiography was performed in 20 patients and showed
 proximal LAD or 3vd in 6 pts
 2 vd in 7
 Single vessel disease in 7 pts
Pritzker MR. Circulation. 1999; 100 (suppl 1): I-711. Abstract 3751
ED and Cardiovascular Disease
 Asymptomatic patients with vasculogenic ED have a high incidence of
CAD and high prevalence of CAD risk factors
 but only a minority undergoes cardiovascular screening
 Screening for cardiovascular disease in patients with vasculogenic ED
may help to identify patients at high risk of cardiovascular events
Pritzker MR. Circulation. 1999; 100 (suppl 1): I-711. Abstract 3751
Cardiac Contraindications to
Sexual Activity
• Acute Ischemic Syndromes
• Severe Heart Failure (NYHA IV)
• Severe malignant effort-induced tachyarrhythmia
ACC/AHA Clinical Statement
Myocardial Ischemia During Sexual
Activity in Patients with CAD
All Patients with myocardial
ischemia during sexual
activity had also
ischemia on Holter
ECG monitoring
22%
11%
67%
Silent Ischemia
Drory et al Am J Cardiol 1995
Angina
No Changes
Myocardial Ischemia During Sexual
Activity in Patients with CAD
beats/minute
• In 19 pts with CAD
during sexual activity
ß-blockers completely
abolished ECG
changes and
symptoms
140
120
100
80
60
40
20
0
No Therapy
Drory et al Am J Cardiol 1995
ß-blockers
Regulation of Smooth Muscle
Relaxation and Effect of Sildenafil
Neurons or
Endothelium
Nitric
Oxide
Sildenafil
Sildenafil Use and Myocardial Ischemia
in Patients with CAD
•
•
•
•
Exercise tolerance
Ischemic treashold
Effect of Sildenafil on Myocardial Ischemia
Effect of Sildenafil on Myocardial Ischemia
in patients with CAD on therapy
Use of Sildenafil in Patients with CAD
Using NItrates
• Chronic use of nitrats has no beneficial efect upon
cardiovasular mortality and morbidity and
therefore can be easily changed with other drugs
for the treatment of CAD in those patients
requiring Sildenafil
• Acute nitrate administration must be always
performed under medical supervision and the dose
must be adjusted according to the degree of
peripheral vasodilation
Effect of Sildenafil in Patients with CAD
treated with ß-blockers
16
14
12
10
No. 8
6
4
2
0
**
Positive ETT
Basal
Atenolol
Atenolol +S
Patrizi R. et al. It Heart J 2001
Atenolol +P
Effect of Sildenafil in Patients with CAD
treated with ß-blockers
700
600
**
sec.
500
400
300
200
100
0
Time to 1 mm
Resting
Atenolol
Patrizi R. et al. It Heart J 2001
Atenolol +S
Atenolol +P
Effects on Primary/Secondary End
Points
Placebo
Sildenafil
30
25
*
20
15
*
26.5
10
17.3
*
20.4
9.8
5
4.7
8.7
4.7
3.9
0
Time to
limiting angina
Time to
angina
*P<0.05
Fox KM et al Circulation 2001, abstract supplement
Time to 1 mm
ST-segment
depression
Exercise
duration
% change compared to baseline
Trimetazidine and Nitrates on
Total Ischemic Burden
TMZ
Nitrates
10
0
-10
-20
-30
-40
-50
Episodes
P=0.07 between treatments
Rosano et al Eur Heart J 2003 (abstr)
Minutes
Trimetazidine and Nitrates on Ischemic
Episodes During Sexual Activity
TMZ
0
-5
-10
-15
-20
-25
-30
-35
-40
-45
-50
Rosano et al Eur Heart J 2003 (abstr)
Nitrates
P<0.04
% change compered to baseline
Trimetazidine vs Nitrates on the Control
of Anginal Episodes
Episodes
No. of GTN
0
-10
-20
-30
-40
p<0.01 vs baseline
-50
-60
p<0.01 vs baseline
p<0.01 vs baseline
p=0.048 vs nistrates
p<0.01 vs baseline
p<0.04 vs nistrates
-70
Nitrates
Rosano et al Eur Heart J 2003 (abstr)
Trimetazidine
Trimetazidine plus Sildenafil vs Nitrates
Positive Exercise Tests
30
25
p<0.05
p<0.01
20
15
10
5
0
Baseline
Rosano et al Eur Heart J 2003 (abstr)
ISMN
Trimetazidine-Sildenafil
Trimetazidine plus Sildenafil vs Nitrates
Change compared to baseline (bpm;
mmHg)
Heart Rate and Blood Pressure
10
8
6
4
2
0
-2
-4
-6
-8
Heart Rate
SBP
ISMN
Rosano et al Eur Heart J 2003 (abstr)
TMZ-Sild
seconds
Trimetazidine plus Sildenafil or
Nitrates on Exercise Test Parameters
900
800
700
600
500
400
300
200
100
0
Time to 1 mm
Time to Angina
Baseline
Rosano et al Eur Heart J 2003 (abstr)
TMZ+S
Exercise Time
Nitrates
P<0.01 for all comparisons TMZ+S vs Baseline
P<0.05 for all comparisons TMZ+S vs Nitrates+P
Trimetazidine plus Sildenafil or
Nitrates on ST segment Depression
2,5
mm
2,0
P=0.048
1,5
1,0
0,5
0,0
ST depression
TMZ+S
Nitrates
Sildenafil: Mortality
Patient group
Cause of
death
Placebo
Viagra® (trials)
Viagra® (DSRU)
CVS*
CVS*
MI and IHD
Incidence/100
patient yrs
(95% CI)
0.3 (0.1 –1.0)
0.3 (0.1 –0.8)
0.26 (0.15–0.42)
*CVS = cardiovascular system
Reference: DSRU Study;
Viagra® Package Insert
Sildenafil
Age Standardised Mortality (MI and IHD)
• Sildenafil
– 0.3/100 patient years
(95% CI 0.2–0.4)
• British Heart Foundation
– 0.3/100 patient years
Conclusions




Sildenafil has positive effect on cardiac
haemodynamics and increase coronary blood flow
The effect of Sildenafil on blood pressure is
minimal
Sildenafil has a positive effect on exercise-induced
myocardial ischemia in patients with CAD
The use of sildenafil in patients with myocardial
ischemia well controlled by anti-anginal drugs is
safe