S418 Canadian Journal of Cardiology

Volume 28 2012

903
THE TARGETED PLATELET INHIBITION TO CLARIFY THE
OPTIMAL STRATEGY TO MEDICALLY MANAGE ACUTE
CORONARY SYNDROMES (TRILOGY ACS) TRIAL

SG Goodman, MT Roe, PW Armstrong, HD White, KA Fox,

D Prabhakaran, E Brown, Y Lokhnygina, E Ohman
Toronto, Ontario

BACKGROUND: The optimal antiplatelet strategy for high-risk

patients with unstable angina/non-ST-elevation myocardial
infarction (UA/NSTEMI) who are managed medically
without undergoing coronary revascularization remains
unclear.
METHODS: In this international, double-blind, placebo-con- 904
trolled, randomized trial we compared prasugrel vs. clopidogrel in HYPERTENSION ANALYSIS OF STRESS REDUCTION USING
9,326 UA/NSTEMI patients who received aspirin and were med- MINDFULNESS MEDITATION AND YOGA: RESULTS FROM A
ically managed without revascularization during the index hospi- RANDOMIZED CONTROLLED TRIAL
talization, and had at least 1 of 4 high-risk criteria: age ⱖ60 years, K Blom, B Baker, M How, M Dai, S Abbey, M Myers,
prior myocardial infarction, diabetes mellitus, or prior coronary BL Abramson, J Irvine, N Perkins, SW Tobe
revascularization. Subjects were randomized within 10 days of Toronto, Ontario
hospital presentation, after the decision to utilize a medical man- BACKGROUND: Hypertension is a leading risk factor for prevent-
agement strategy without revascularization was confirmed. able cardiovascular disease with over 1 in 5 adults affected world-
Patients ⬍ 75 years of age who were ⱖ 60 kilograms of body wide. Lifestyle modification is a key strategy for the prevention and
weight were treated with a 10 mg maintenance dose of prasugrel treatment of high blood pressure (BP). Stress has been associated
vs. 75 mg of clopidogrel whereas those ⱖ 75 years of age and/or ⬍ with increased cardiovascular risk and stress management is a rec-
60 kilograms were treated with a 5 mg maintenance dose of pra- ommended intervention for hypertensives. Stress reduction
sugrel vs. 75 mg of clopidogrel. Low-dose aspirin (⬍100 mg) was through relaxation therapies have been shown to have an effect on
strongly encouraged for all patients. The primary efficacy compos- human physiology including lowering BP. Individualized behav-
ite endpoint is the time to first occurrence of cardiovascular death, ioural interventions are resource intensive and group stress man-
MI, or stroke among patients of age ⬍ 75 years. The trial was agement approaches have not been validated nor rigorously tested
designed as event-driven with power calculations indicating the for reducing BP. The HARMONY study was a prospective wait-
need for at least 688 primary endpoints for a 22% effect size be- list RCT designed to test whether mindfulness based stress reduc-
tween therapies. If superiority of prasugrel vs. clopidogrel is shown tion (MBSR), a standardized group stress reduction therapy, could
in this group, then the treatment arms will be compared for all lower BP among those with stage-1 unmedicated hypertension.
patients, including those ⱖ 75 years of age. Bleeding rates will be MBSR is now widely available and is funded by some provinces for
assessed by the GUSTO and TIMI criteria. conditions such as anxiety, depression and chronic pain.
RESULTS: From June, 2008 through September, 2011, 9,326 METHODS: Study eligibility included ambulatory BP monitoring;
patients (7,243 patients ⬍75 years of age and 2,083 patients mean daytime ABP ⬎/⫽ 135/85 mm Hg or 24HR ABP ⬎/⫽
ⱖ75 years of age) were enrolled in 53 countries at 968 sites, 130/80 mm Hg. Subjects were randomly assigned to either Early
including 146 patients from 16 Canadian hospitals. The (immediate treatment) or Delayed (wait-list control) groups. Sub-
jects randomized to Early received MBSR within 4 weeks of their
baseline characteristics of the two age groups are shown in
baseline visit. Those randomized to Delayed began the 8 week
the table and demonstrate the high-risk features of the en-
wait list period within 4 weeks of their baseline visit. The primary
rolled patients. The median follow-up time is expected to be
outcome measure was mean awake and 24HR ABP at the 12 week
17-18 months. The last patient visit occurred on April 2,
primary outcome period (12 weeks post baseline for all subjects).
2012 and the requisite number of primary endpoints has Wait-listed subjects then began MBSR after the primary outcome
been accrued ensuring adequate power to address the study period. Other evaluations included office BP, labs, physical mea-
objectives. Database lock is planned for early June, 2012 surements and questionnaires that were administered at baseline,
with final results available for ESC and CCC 2012 after MBSR, and 12 weeks after MBSR at study close out. In total,
presentations. 101 adults aged 20 -75 yrs were enrolled; 38 males, 63 females
CONCLUSIONS: The results of the TRILOGY ACS trial will ad- with a mean age of 55 ⫹ 11 years. Average 24HR ABP was 135/82
dress the role of prasugrel (with a novel dosing regimen for the ⫾ 7.9/5.8 mmHg and average awake ABP was 140/87 ⫾ 7.7/6.3
elderly and low body weight patients) for the long-term treatment mmHg (the values have been switched to and rounded up for the
of the high-risk population of UA/NSTEMI patients who are correct ABP measurement).
medically managed without revascularization. RESULTS: RANOVA (Group X Time) revealed no significant dif-
 S419
Abstracts

ference between treatment and control on all ABP parameters, 905

both at the 12 week primary outcome and at any other time point. COST EFFECTIVENESS OF CARDIAC RESYNCHRONIZATION
For example, the change in 24HR SBP/DBP at 12 weeks between THERAPY (CRT) FOR MILD TO MODERATE HEART FAILURE
treatment and control was only 0.0/0.4 mmHg (⫹/⫺ 7.2/4.7),
p⫽0.96 for SBP and p⫽0.63 for DBP (the blood pressure values GA Wells, D Coyle, K Coyle, M Talajic, A Tang
have been corrected and respective p-values included). This study Ottawa, Ontario
had 81% power to detect a 24 hour systolic BP difference of 6.0 BACKGROUND: The objective of this study was to assess the cost
mmHg with 37 participants per group. effectiveness of ICD-CRT versus ICD alone in patients with left
CONCLUSIONS: MBSR was found to be ineffective in lowering BP ventricular dysfunction and a wide QRS complex. In a recent
by 6 mmHg or more among stage-1 unmedicated hypertensives. randomized controlled trial (RAFT), the addition of CRT to an
Revisiting the literature, most positive studies using meditation implantable cardiodefibrillator (ICD) in this group of patients was
techniques for blood pressure lowering included many subjects shown to reduce rates of death and hospitalization for heart failure.
taking anti-hypertensive therapy. In 2 negative studies all subjects METHODS: Analysis assessed the health care related costs and
were drug naïve. Therefore, it seems probable that studies finding quality adjusted life years for both the ICD-CRT and ICD
a reduction in BP may have been confounded by improved med-
groups over a 40 year time horizon. The time horizon was
ication adherence. While it is disappointing that the HARMONY
facilitated by a Markov model developed by combining data for
study did not find a blood pressure lowering effect on drug naïve
the 1798 patients enrolled within the RAFT with long term
hypertensives, mind-body interventions may improve BP control
data on the longevity of the devices. Costs and benefits in terms
among the medicated. Our next steps include using MBSR as
adjunctive therapy for better BP control, as well assessing its use in of quality adjusted life years (QALYs) were discounted at 3%
improving drug adherence/persistence. per annum. Health care resources included the initial device
plus device replacements, cardiovascular and non cardiovascu-
lar related hospitalizations in addition to drug costs, physician
visits and long term care. Resource use was weighted by appro-
priate unit costs from the USA. Uncertainty concerning cost
effectiveness was assessed through Monte Carlo simulation and
deterministic sensitivity analysis.
RESULTS: Models for Canadian resource utilization and costing
have been developed and are currently being conducted. For
the US models, the use of ICD-CRT was estimated to lead to
an average increase in costs of $35,308 and an average increase
in QALYs of 1.07. The incremental cost per QALY gained was
$33,025. ICD-CRT was not cost effective for patients with
atrial fibrillation and those with preexisting ventricular pacing.
CONCLUSIONS: ICD-CRT is cost effective for the population
studied within the RAFT clinical trial.