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Welcome to the latest issue of Cardiology Research Review.Highlights include a meta-analysis that assessed the optimal duration of DAPT after PCI with drug-eluting stents. It found that extended DAPT (>12 months) reduces the risk of MI and stent thrombosis, but at the expense of increased bleeding. We also report that aggressive blood pressure-lowering in patients with cognitive impairment may accelerate their decline, and patients with Parkinson disease may be at increased risk for MI and death. On a more positive note, the leadless cardiac pacemaker performs well in a 1-year follow-up study.We hope you find these and the other selected studies interesting, and look forward to receiving any feedback you may have.Kind Regards,Associate Professor John Amerenajohn.amerena@researchreview.com.au

Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stentsAuthors: Navarese E et al.

Summary: This meta-analysis determined the optimal duration of DAPT after PCI with drug-eluting stents (DES). 10 randomised controlled trials (n=32,287) comparing short term (<12 months) or extended (>12 months) DAPT regimens with standard 12-month DAPT were identified. Compared to 12-month DAPT, a short term course was associated with reduced major bleeding (odds ratio 0.58; p=0.02) with no significant differences in ischaemic or thrombotic outcomes. Extended versus 12-month DAPT was associated with a significant reduction in MI (odds ratio 0.53; p<0.001) and stent thrombosis (odds ratio 0.33; p<0.001), but more major bleeding (odds ratio 1.62; p<0.001). All cause but not cardiovascular death was also significantly increased with extended DAPT (odds ratio 1.30; p=0.03).

Comment: This meta-analysis shows much the same as the DAPT and PEGASUS studies, with extended dual antiplatelet therapy reducing the risk of MI and stent thrombosis, but at the expense of increased bleeding. It also gives some reassurance however that dual therapy can be stopped earlier than 12 months if needs be without increasing recurrent ischaemic events. In practice this will probably mean that many patients with ACS who are tolerating dual therapy at 12 months will continue indefinitely, and that those who are having bleeding issues will stop at less than 12 months.

Reference: BMJ 2015;350:h1618Abstract

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In this issue:In this issue:Optimal duration of DAPT after PCI

Low blood pressure and cognitive impairment in the elderly

Parkinson disease and MI

Leadless cardiac pacemaker performs well

Drivers of global cardiovascular mortality

Additional tricuspid annuloplasty has value

Gender differences post-MI

Optimal antiaggregant therapy after PCI

Imaging biomarker for prediction of atherothrombotic events

ACS = acute coronary syndrome; DAPT = dual antiplatelet therapy; MI = myocardial infarction; PCI = percutaneous coronary intervention; SBP = systolic blood pressure

Abbreviations used in this issue:

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Making Education Easy Issue 83 - 2015

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Effects of low blood pressure in cognitively impaired elderly patients treated with antihypertensive drugsAuthors: Mossello E et al.Summary: This study assessed whether blood pressure or the use of antihypertensive drugs predicts the progression of cognitive decline in patients with mild cognitive impairment. 172 patients (mean age 79 years) with a mean Mini-Mental State Examination (MMSE) score of 22.1 were followed up for a median 9 months. 68.0% of patients had dementia, 32.0% had mild cognitive impairment, and 69.8% were being treated with antihypertensive drugs. Patients in the lowest tertile of daytime SBP (≤128mm Hg) had a significantly greater change in MMSE score during follow-up than patients in the intermediate (129–144mm Hg) or highest (≥145mm Hg) tertile: mean –2.8 vs –0.7 and −0.7, respectively. The association was significant in the dementia and mild cognitive impairment subgroups only in patients taking antihypertensive drugs.

Comment: We know that poorly controlled hypertension increases the risk of vascular dementia, but this study shows that aggressive blood pressure-lowering in patients with cognitive impairment may accelerate decline. It would thus seem reasonable to aim for SBP 140–150mm Hg in these elderly patients, and decreasing antihypertensive medication if the BP is <130mm Hg would seem sensible in this type of patient.

Reference: JAMA Intern Med 2015;175(4):578-585Abstract

Parkinson disease and risk of acute myocardial infarctionAuthors: Liang H-W et al.Summary: This population-based, longitudinal follow-up study investigated whether incident Parkinson disease (PD) is associated with an increased risk of acute MI (AMI). 3,211 patients with PD and 3,211 propensity score-matched individuals without PD were compared. During a 3-year follow-up period, 83 subjects in the PD group and 53 in the non-PD group had a fatal or nonfatal AMI event (hazard ratio 1.67; p=0.0067). The AMI-free survival rate of the PD group was significantly lower than that of the non-PD group (p=0.0032).

Comment: As well as suffering the devastating neurological effects of PD, it appears that patients with PD are also at increased risk of MI and death compared with propensity-matched patients without PD. Whether cardioprotective medications will improve outcomes in PD is not known, as the mechanism of the increased cardiovascular risk is unclear.

Reference: Am Heart J 2015;169(4):508-514Abstract

Chronic performance of a leadless cardiac pacemakerAuthors: Knops R et al.Summary: This study reported the complication incidence, electrical performance, and rate response characteristics within the first year in patients implanted with a leadless cardiac pacemaker (LCP). One-year follow-up data were available for 31 of 33 patients (mean age 76 years) from the LEADLESS trial cohort who had an indication for single-chamber pacing and received an LCP. No pacemaker-related adverse events were reported during follow-up. The pacing performance results at 6- and 12-months’ follow-up were: mean pacing threshold (at a 0.4-ms pulse width), 0.40 and 0.43V, respectively; R-wave amplitude, 10.6 and 10.3mV; and impedance, 625 and 627Ω. At the 12-month follow-up, the rate response sensor was activated in 61% of patients, with an adequate rate response observed in all patients.

Comment: This exciting technology looks to provide safe and stable pacing while avoiding the potential complications associated with intracardiac pacing leads. If this proves to be true with ongoing studies, leadless pacemakers will become reality and will replace conventional pacing over time, depending to some extent on cost, at least initially.

Reference: J Am Coll Cardiol 2015;65(15):1497-1504Abstract

Demographic and epidemiologic drivers of global cardiovascular mortalityAuthors: Roth G et al.Summary: This study used mortality data from the Global Burden of Disease Study 2013 to determine the principal drivers of change in cardiovascular deaths (population growth alone, population growth and aging, or epidemiologic changes in disease) from 1990 to 2013. Global deaths from cardiovascular disease increased by 41% from 1990 to 2013 despite a 39% decrease in age-specific death rates. The increase was driven by a 55% increase in mortality due to the aging of populations and a 25% increase due to population growth. The relative contributions of these drivers varied by region (only in Central and Western Europe did the annual number of deaths from cardiovascular disease actually decline).

Comment: Given that Central and Western Europe were the only regions globally that had decreases in deaths from cardiovascular causes from 1990 to 2013, it is vitally important to work out why this occurred. Whether it was differences in health care delivery, availability of health care and medication, lifestyle, preventative strategies, or other factors needs to be elucidated so that successful strategies can be implemented in other regions.

Reference: N Engl J Med 2015;372:1333-1341Abstract

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* In patients with ACS, BRILINTA reduces the risk of CV death, MI or stroke vs clopidogrel at 12 months (primary composite endpoint: ARR 1.9%, RRR 16%; p<0.001).1,2

improvedoutcomesstart here*

®

Please click here to review full product information before prescribing. Further information available on request from AstraZenecaACS=acute coronary syndromes; CV=cardiovascular; MI=myocardial infarction; ARR=absolute risk reduction; RRR=relative risk reduction. References: 1. Wallentin L et al. N Engl J Med 2009;361:1045–57. 2. BRILlNTA® Approved Product Information. BRILINTA® is a registered trademark of the AstraZeneca group of companies. Registered user AstraZeneca Pty Ltd. ABN 54 009 682 311. 5 Alma Road, North Ryde NSW 2113. Medical Information: 1800 805 342. www.astrazeneca.com.au, 186801.022, WL282043, September 2014

PBS Information: Authority Required (STREAMLINED). Treatment of acute coronary syndrome (myocardial infarction or unstable

angina) in combination with aspirin.

STREAMLINED AUTHORITY CODE 3879

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Additional tricuspid annuloplasty in mitral valve surgery results in better clinical outcomeAuthors: De Meester P et al.Summary: This registry study evaluated the clinical benefit of tricuspid annuloplasty (TA) in patients undergoing mitral valve surgery (MVS). 150 patients undergoing MVS were included. 82 of them presented with tricuspid regurgitation (TR) <2/4 and underwent isolated MVS. Of the remaining 68 patients who had preoperative TR ≥2/4, 31 underwent isolated MVS and 37 underwent additional TA. In the latter group, TR was significantly reduced for 5 years postoperatively. The combined end-point (cardiac mortality or hospitalisation for heart failure) occurred in 29% at 1 year and 57% at 5 years in patients undergoing isolated MVS, compared with 6% and 39%, respectively, in patients undergoing concomitant TA. The propensity score-adjusted risk for the combined end-point was higher in those who had isolated MVS compared with those who had MVS plus TA (hazard ratio 2.855; p=0.035).

Comment: Residual TR after mitral valve surgery is often associated with ongoing symptoms and difficult to control right sided heart failure. This study shows that tricuspid annuloplasty at the time of MVS results in better medium and long term outcomes, but how much additional perioperative mortality and morbidity is associated with the extra surgery and longer on-pump time was not stated, and needs to be clearly understood when deciding whether or not to do the combined procedure.

Reference: Heart 2015;101:720-726Abstract

Age-specific gender differences in long-term recurrence and mortality following incident myocardial infarctionAuthors: Nedkoff L et al.Summary: This population-based Australian study compared long-term gender- and age-specific outcomes after MI. 12,420 30-day survivors of incident MI were identified from linked administrative data in Western Australia. Women had higher levels of comorbidities across all age groups than men. Unadjusted event risks were higher in women overall (due largely to a higher risk of recurrent MI in women aged 55–69 years, and to a higher risk of cardiovascular mortality across all ages in women) but these differences were generally attenuated after adjustment for demographic factors and comorbidities.

Comment: This analysis of long term outcomes post-MI in Western Australia shows that women had higher recurrent events and mortality than men. Although some of this difference could be explained by comorbidities, these data show that there is considerable room for improvement in secondary prevention in women post-MI.

Reference: Heart Lung Circ 2015;24(5):442-449Abstract

Independent commentary by Associate Professor John Amerena, FRACP, FACC,FCSANZ, Dept. of Clinical and Biomedical Science, University of Melbourne (Geelong).

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* In patients with ACS, BRILINTA reduces the risk of CV death, MI or stroke vs clopidogrel at 12 months (primary composite endpoint: ARR 1.9%, RRR 16%; p<0.001).1,2

* BRILINTA is initiated with a single 180mg dose and then continued at 90mg twice daily in combination with aspirin.2

improved outcomesstart here*

As with other antiplatelet agents, BRILINTA prolongs bleeding time and should be used with caution in ACS patients who may be at risk of increased bleeding. Premature discontinuation could result in an increased risk of cardiovascular death, or myocardial infarction due to the patient’s underlying disease2.

Please click here to review full product information before prescribing. Further information available on request from AstraZenecaACS=acute coronary syndromes; CV=cardiovascular; MI=myocardial infarction; ARR=absolute risk reduction; RRR=relative risk reduction. References: 1. Wallentin L et al. N Engl J Med 2009;361:1045–57. 2. BRILlNTA® Approved Product Information. BRILINTA® is a registered trademark of the AstraZeneca group of companies. Registered user AstraZeneca Pty Ltd. ABN 54 009 682 311. 5 Alma Road, North Ryde NSW 2113. Medical Information: 1800 805 342. www.astrazeneca.com.au, 186801.022, WL282043, September 2014

PBS Information: Authority Required (STREAMLINED). Treatment of acute coronary syndrome (myocardial infarction or unstable

angina) in combination with aspirin.

STREAMLINED AUTHORITY CODE 3879

This publication is endorsed by ACN according to our Continuing Professional Development Endorsed Course Standards. It has been allocated 1 CPD hour(s) according to the Nursing and Midwifery Board of Australia – Continuing Professional Development Standard.

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Meta-analysis of randomized controlled trials and adjusted observational results of use of clopidogrel, aspirin, and oral anticoagulants in patients undergoing percutaneous coronary interventionAuthors: D’Ascenzo F et al.

Summary: This meta-analysis evaluated the optimal antiaggregant therapy after PCI. Studies were included if they reported outcomes of patients who underwent PCI and received triple therapy, DAPT (aspirin and clopidogrel), or dual therapy with oral anticoagulants (OACs) and clopidogrel. The primary end-point was major bleeding. In 9 studies, 1,317 patients were treated with DAPT and 1,547 with triple therapy. Compared with triple therapy, DAPT offered a significant reduction of major bleeding at 1 year for overall studies (odds ratio 0.51) and for the subset of observational works providing adjusted data (odds ratio 0.36). No increased risk of major adverse cardiac events (MACE) was reported. Six studies that compared OAC and clopidogrel (n=1,263) with triple therapy (n=3,055) found a significant reduction of bleeding (with similar rates of MACE) in the dual therapy group.

Comment: This meta-analysis broadly supports the findings of the WOEST study, which showed that clopidogrel and OACs significantly reduce bleeding compared with triple therapy in patients with ACS who require anticoagulation, but did not show an increase in ischaemic events and stent thrombosis. Guidelines still recommend triple therapy in this situation for as short a time as possible, depending on bleeding risk, type of stent and whether it was implanted for ACS or electively. Further information on this clinical dilemma will come from the REDUAL study (with dabigatran) and PIONEER (with rivaroxaban).

Reference: Am J Cardiol 2015;115(9):1185-93Abstract

Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adultsAuthors: Baber U et al.

Summary: The BioImage study evaluated the use of imaging biomarkers for predicting atherothrombotic events. 5,808 asymptomatic adults (mean age 69 years) were evaluated by coronary artery calcification (CAC) and novel 3-dimensional carotid ultrasound. Plaque areas from both carotid arteries were summed as the carotid plaque burden (cPB). The primary end-point was the composite of major adverse cardiac events (MACE). Over a median follow-up of 2.7 years, MACE occurred in 216 patients (4.2%). Compared with individuals without any cPB, adjusted hazard ratios for MACE were 0.78, 1.45, and 2.36 with increasing cPB tertiles, with similar results for CAC.

Comment: Detection of subclinical atherosclerosis in the carotid or coronary arteries is not surprisingly associated with increased risk of cardiac events, with more events in patients with more calcification and plaque burden. If carotid ultrasonography can be shown to have the same predictive ability as the CAC score, it will become the preferred technique as there is no radiation involved.

Reference: J Am Coll Cardiol 2015;65(11):1065-1074Abstract

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