Highlights in ischaemic cardiovascular disease

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					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
 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
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
  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
  Only one component of the primary endpoint, HF
  hospitalization, occurred less frequently in the irbesartan
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 lower-
 risk 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
 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
  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
 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 sodium-
 dependent 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
 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
 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 beta-
 . 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
New antiischaemic drugs and
results od
 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
 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
 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
 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
 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
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

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