Transcript Document

Highlights in ischaemic
cardiovascular disease
Doc dr Amra Džanković
Results from KYOTO HEART study
Designed to examine the effects of valsartan as an add-on to
conventional therapy on morbidity and mortality in uncontolled
hypertensive patients with one or more cardiovascular (CV) risk
factors
Valsartan (up to 160mg/daily) add-on treatment to improve blood
pressure (BP) control prevented more CV events than conventional
non-ARB treatment
.
Results from The KYOTO HEART
Study
There was significant (p<0.03) reductions in
the incidents of angina pectoris, stroke,
and new-onset diabetes. Adverse events
were low in both groups.
No benefit was seen in the reduction of MI
incidence, in which most cardiologists are
interested.
ARBs are efficacious and even superior to
other drug classes in stroke prevention, but
their efficacy with regard to coronary
events remains uncertain.
Results from the PROTECT Trial
The efficacy and safety of adenosine A1 receptor antagonist
rolofylline versus placebo on symptoms in 2033 patients who were
hospitalized with heart failure (HF) within 24 hours with signs of fluid
overload, impaired renal function and high serum levels of B-type
natriuretic peptide.
Rolofylline 30mg/day or placebo
Most subjects were reciving multiple HF medications within the 2 weeks
prior to study enrollment, including ACE inhibitor or ARB (75%), beta-blocker
(76%), aldosterone inhibitor (43%), and digoxin (28%).
There was no significant difference in the primary endpoint, wherein
40.6% of rolofylline subjects versus 36% of placebo subjects achieved
treatment success
Rolofylline appeared to incrase neurological complications , including
seizures (11 subjects vs no subjects on placebo), stroke (16 vs 3).
The ACTIVE program
It was designed to evaluate the effect of additional blood
pressure (BP) reduction with angiotensin receptor blocker
(ARB) on common complications of patients with AF,
including HF, stroke, and other embolic events.
On top of this extensive background therapy, irbesartan
provided an additional reduction in BP (6.8/4.5 mmHg).
The composite endpoint of stroke, MI, and vascular death
occurred with equal frequency in the irbesartan and placebo
groups.
Only one component of the primary endpoint, HF
hospitalization, occurred less frequently in the irbesartan
group.
BP lowering with multiple antyhipertensive agents may result in
an even greater clinical benefit.
GRACE Registry Study
PCI had become the most common strategy of
revascularization in emergent/serious cases but
was associated with more frequent repeat
revascularization in the 6 months after discharge.
CABG was associated with good survival in lowerrisk patients but resulted in more frequent
incidents of acute stroke.
PCI and CABG appear complementary, and both
types of revascularization improve 6-months
survival in comparsion with an initially
conservative medical strategy
Primary PCI versus fibrinolysis in
very elderly patients
Primary percutaneous intervention (PCI) was not found to
provide an advantage over fibrinolytic therapy for very elderly
patients with acute mycordial infarction.
Althgouh TRIANA lacked the statistical power to
demonstrate the superiority of PCI over fibrinolytic therapy,
the observed risk reduction was consistent with the benefit
that had been anticipated with primary PCI in the initial
design of the study.
Primary angioplasty should be considered the
treatment of choice even for very old patients with
STEMI.
In situations in which primary PCI is not avaliable, safety
findings from TRIANA indicate that fibrinolysis may be
considered as an alternative, with an acceptable rate of
intracerebral hemorrhage among old patients who are
carefully selected for fibrinolytic therapy.
Results from the AAA study
Showed no support for the routine use of
aspirin for the primary prevention of
vascular events in people with
asymptomatic atherosclerosis.
There was no difference between treatment
groups for either primary or secondary endpoints.
There was an incrase in major hemorrhages that
required hospitalization in the aspirin group (2% of
subjects in the aspirin group vs 1.2% of subjects in
the placebo group).
Gastrointestinal ulcers were also more frequent in
subjects who were taking aspirin.
Results from AAA Study
.
CURRENT-OASIS 7
The clopidrogel optimal loading dose, randomized
trial to determine optimal clopidrogel and aspirin
dosing in subjects with acute coronary syndrome
(ACS) within 24 hours of ischemic symptoms.
The results of this trial are complex.
Double-dose clopidrogel reduced the primary
endpoint in the high-dose aspirin strata by 17%
but was associated with more bleeding and
transfusion overall.
Careful consideration will be important when
intergating these results into clinical practice, wich
likely will have bearing on future practice guidlines.
PLATO study
Ticagrelor is an investigational oral antiplatet agent that
directly and reversibly inhibits the adenosine diphospathe
receptor P2Y12.
PLATO was designed to evaluate whether ticagrelor is
superior to clopidrogel-currently therapy a component of
standard therapy for ACS-in preventing vascular events and
death in a broad population of patients.
PLATO randomized 18,624 patients who were hospitalized
with ACS with or without ST-segment elevation to ticagrelor
(180-mg loading dose, 90 mg twice-daily thereafter)or
clopidrogel (300-mg to 600-mg loading dose , 75mg
thereafter) in double –blinded fashion and treated for up to
12 months.
Of the three trials(CURE,TRITON TIMI 38 and PLATO),
PLATO was only one to demonstrate a reduction in all-cause
mortality with more potent platelet inhibition, reducing the
risk of overall mortality compared with clopidrogel.
Results from the Re-Ly trial
Eficacy and safety of two different doses of
dabigatran(oral direct trombin
inhibitor,similar to ximelagatran) with
warfarin therapy in patients with ECG –
documented nonvalvular AF and CHADS
score more than 2
Dabigatran 150 mg twice daily was more
effective than warfarin in reduction stroke
orTIA,and risk of major bleeding was
similar in both groups
New antiischaemic drugs and
results od trials: Trimetazin
Beneficial effect of trimetazidin(Preductal) on
myocardial ischemia due mainly to its action in
mitochondrial bodies od cardiomyofibrillies
Dose -20 mg three times daily.
Data on the effectiveness of the drug in acute
myocardial heart attack is contradictory.
Contraindications : pregnancy and breast
feeding.
Studies didn’t prove its positive effect on overall
cardiovascular morbidity and mortality
New antiischaemic drugs and
results od trials: Ranolazin
Ranolazine, sold under the trade name Ranexa by Gilead
Sciences (who acquired the developer, CV Therapeutics in
2009), is an antianginal medication.
Ranolazine is believed to have its effects via altering the
trans-cellular late sodium current. It is by altering the
intracellular sodium level that ranolazine affects the sodiumdependent calcium channels during myocardial ischemia
Ranolazine is indicated for the treatment of Chronic angina.
Ranolazine may be used with beta-blockers,nitrates, calcium
channel blockers, anti-platelet, therapy, lipid-lowering
therapy, ACE inhibitors, and angiotensin receptor blockers.
ranolazine does not significantly alter either the heart rate or
blood pressure. For this reason, it is of particular use in
individuals with angina that is refractory to maximal tolerated
doses of other anti-anginal medications.
New antiischaemic drugs and
results od trials: Ranolazin
.It has also applied to US FDA for 2 more indication such as
HbA1c reduction in coronary artery disease patients with
diabetes and antiarrhythmic benefits(decrease insulin
resistancy).
This difference in arrhythmias did not lead to a reduction
in mortality, a reduction in arrhythmia hospitalization or a
reduction in arrhythmia symptoms.
The revised labeling also includes new language noting that
Ranexa produces small reductions in HbA1c.
Though Ranexa should not be considered a treatment for
diabetes, Ranexa may be a particularly useful medication for
the reduction of chronic angina in this patient population,
which is difficult to treat because some anti anginal
medications such as beta blockers increase HbA1c.
New antiischaemic drugs and
results od
trials:Ivabradin(Procoralan)
the first selective and specific If inhibitor, for the symptomatic
treatment of chronic stable angina pectoris in patients with normal
sinus rhythm who have a contraindication or intolerance to betablockers.
. Procoralan is the first pure heart rate-lowering agent and acts by
selective inhibition of the cardiac pacemaker
Procoralan's effects are selective to the sinus node and the new
agent has no effect on intracardiac conduction, myocardial
contractility or ventricular repolarization.
Unlike beta-blockers, the most common current treatment for
angina, Procoralan is free from sexual disturbances, respiratory
side effects caused by constriction or spasm of the airways,
bradycardia or rebound phenomena.
Heart rate reduction is one of the main therapeutic goals in angina
treatment
New antiischaemic drugs and
results od
trials:Ivabradin(Procoralan)
The recommended starting dose of
Procoralan is 5 mg twice daily
followed by uptritration to 7.5 mg
In this context, the morbidity/mortality
trial BEAUTIFUL was created,but
results in patients more than 75 bpm
are not promising
Edoxaban-new generation oral
anticoagulant to help prevent stroke
in patients with AF
A potential new treatment for stroke prevention in
patients with nonvalvular AF(CHADS score more
than 2)
Optimal dose is 30 or 60 mg daily in one dose.It is
direct Xa factor inhibitor
Edoxaban-new generation oral
anticoagulant
Bleeding associated with edoxaban is most closely
associated with minimum blood concentration level,these
levels are better predictors of bleeding than total exposure or
maximum concentration levels
Rosuvastatin in GISSI-HF
It showed that rosuvastatin(Crestor) was
not very effective in preventing incidence of
AF in patients with heart failure
There are a number of unanswered
questions:
Whether statins prevent AF progression
and reduce the burden of AF and
Whether prevention of AF by statins
improves CV morbidity or mortality
New data from the RECORD study
No difference in the primary endpoint of CV
hospitalization or CV death but did demonstrate
increased rates od heart failure.
The HF event rates began to diverge early and
continued to diverge through the trial
In this trial,contrary to Nissen meta analysis,there
was not statistically significant increase in
coronary outcomes or an excess of CV overall
mortality in patients receiving RSG compared
with those receiving conventional therapy
JUPITER SUBGROUPanalysis
Showed significant reduction in major
cardiovascular events in elderly,apparently
healthy individuals who were treated with
rosuvastatin, compared with placebo
The benefit seen from rosuvastatin is in
elderly subgroup,including a reduction in
stroke,and
in special population-high risk patients with
low LDL and elevated hs-CRP
A subpopulation analysis from
TRITON-TIMI 38 study
Results show no association between
PPI(proton pump inhibition) use and
increased risk for cardiovascular
events in patients who are also
receiving clopidogrel or prasugrel
The current findings do not support
the need to avoid concomitant use of
PPIs in patients treated with
thienopyridines
Results from SYNTAX
Designed to compare PCI with CABG for the
treatment of de novo 3VD or-and LM disease
SYNTAX score – a novel angiographic tool for
measuring the complexity of coronary artery
disease based on 9 anatomic criteria
The rates of MACCE were not significantly
different between patients with low SYNTAX
scores who were treated with either PCI or CABG
-intermediate SYNTAX score-increase MACCE in
PCI group
High SYNTAX score-significantly increased
MACCE in patients treated with PCI