QUALITY USE OF
CARDIOVASCULAR MEDICATION
Dr Mark Abelson
Prescription Drugs and Drug Trials
• Drug development
- basic science research in a laboratory
- chemical patented (20 years)
- laboratory testing
- Phase 1 trials – tested for safety and efficacy in
animals
- Phase 2 trials – tested for safety in normal humans
- Phase 3 trials – show effective (better than placebo or
current standard treatment) and safe in many
thousands of patients around the world (double blind
• Drug launched (5 years patent remaining)
- post marketing surveillance
• $ +100 million
• Register with FDA / MCC (years)
“Alternative” Drugs
• Vitamins
• Minerals
• Cholesterol vaporises
• Tissue salts
NO RESEARCH
NO EVIDENCE OF EFFICACY
NO PRODUCTION CONTROL
NO REGISTRATION PROCESS
Trials done consistently show NO benefit eg. Folate, antioxidant vitamins
Conspiracy Theory
• Doctors and Universities – bribed / kick backs
from pharmaceutical companies?
• Lack of patient trust?
• Only want “natural” treatment ( death?)
Commonly Used Drugs
• Statins -reduce cholesterol
- Zocor, Simvastatin, Lipitor, Aspavor, Crestor, Prava, Lescol
– primary prevention (at risk but currently asymptomatic)
benefit in high risk persons
or
- secondary prevention (known with coronary artery disease)
30% reduction in future heart attack and stroke
• Aspirin - reduces blood stickiness
– primary (little benefit) or secondary prevention (25% )
• ACE-I / ARB – lower BP, improve heart failure
- Prexum, Coversyl, Lisinopril, Zetomax, Pharmapres, Enalapril,
Cozaar, Zartan, Diovan
Commonly Used Drugs
• Beta Blockers – reduce heart rate (angina) and
BP, heart failure
- Concor, Bilocor, Bisocor, Carloc, Dilatrend
• Calcium Channel blockers – reduce heart rate
and BP
- Verahexal, Calcicard, Ravamil, Amloc,
Norvasc, Zildem
New Comers
• Coralin – reduces heart rate without
decreasing BP and no BB side effects (lethargy,
impotence)
- angina and heart failure
• Dabigatran – thins blood like Warfarin but no
INR (blood) testing needed
- atrial fibrillation
Guideline recommendations for BP
goals
– <140/90mmHg for essential hypertension
– <130/80mmHg for hypertensive patients with
diabetes
• Most patients with hypertension will require
two or more antihypertensive agents to achieve
BP goal
*ESH/ESC: European Society of Hypertension/European Society of Cardiology
**JNC 7: Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, seventh report
Guidelines Committee. J Hypertens 2003; 21: 1011-53.
Chobanian AV, et al. JAMA 2003; 289: 2560-72.
Combination therapy needed to
achieve target SBP goals
Trial/SBP achieved
INVEST (136mmHg)
ALLHAT (138mmHg)
IDNT (138mmHg)
RENAAL (141mmHg)
UKPDS (144mmHg)
ABCD (132mmHg)
MDRD (132mmHg)
HOT (138mmHg)
AASK (128mmHg)
1
INVEST; data on file.
ALLHAT Collaborative Research Group. JAMA 2002; 288: 2981-97.
Brenner BM, et al. N Engl J Med 2001; 345: 861-9.
Lewis EJ, et al. N Engl J Med 2001; 345: 851-60.
Adapted from Bakris GL, et al. Am J Kidney Dis 2000; 36: 646-61.
2
3
Number of antihypertensive drugs
4
Hypertension: a risk factor for
cardiovascular morbidity and mortality
Biennial age-adjusted
rate per 1000
Coronary
50 artery disease
Stroke
Peripheral
Cardiac
arterial disease failure
Normal
Hypertensiv
e
40
30
20
10
0
MenWomen MenWomen MenWomen MenWomen
Risk ratio
2.0
2.2
3.8
2.5
2.0
3.7
4.0
3.0
Excess risk
22.7 11.6
9.1
3.8
4.9
5.3
10.4
4.2
Kannel WB. JAMA 1996; 275: 1571-6.
MRFIT: association of systolic BP and
diabetes with cardiovascular risk
CVD deaths
per 10,000 person-years
300
Non-diabetic
Diabetic
250
200
150
100
50
0
<120
120-139
Stamler J, et al. Diabetes Care 1993; 16: 434-44.
140-159
160-179
Systolic BP (mmHg)
180-199
200+
Early morning BP surge coincides with peak incidences of stroke and
myocardial infarction
Stroke (n=1,167)
Early morning
BP surge
50
160
45
140
40
35
120
30
100
25
80
20
60
15
40
20
0
McInnes G. J Am Soc Hypertens 2008;2:S16–22.
18.00
0.00
Time of day
06.00
12.00
10
5
0
MI (per hour)
Cerebrovascular events
(per 2 hours)
MI (n=2,999)
180