La prevenzione secondaria dopo sindrome coronarica acuta Aldo Pietro Maggioni Centro Studi ANMCO Firenze
Trial and community-based assessments of in-hospital (A) and 30-day (B) mortality relative to age stratifications Circulation. 2013;128:2422-2446
Results on patients outcomes IMA - Mortalità intraospedaliera GISSI-1 13.0% GISSI-2 9.0% GISSI-3 BLITZ-1 7.0% 7.5% BLITZ-3 IN-ACS Outcome MANTRA 4.8% 4.2% 5.1% 0.0% 2.0% 4.0% 6.0% 8.0% 10.0% 12.0% 14.0%
Recommended treatments for secondary prevention Dual antiplatelet treatment treatment of stent for 12 months for secondary prevention (life long???) RAS Blockers (ACE-I/ARBs) Beta Blockers MRAs if HF with LV dysfunction Lipid lowering therapy (C-LDL <70 mg/dl) Omega 3 fatty acids Blood pressure control (<140/90 mmhg) Diabetes mellitus management (Hb1Ac <7%) Smoking cessation Physical activity (at least 30min 5 days per week) Weight management (18.5-24.9 Kg/m2)
Prevenzione cardiovascolare: i risultati raggiunti sono importanti ma non ancora sufficienti Riduzione della colesterolemia Terapia anti-ipertensiva Terapia antiaggregante Modificazione degli stili di vita
Prevenzione secondaria cardiovascolare: cosa possiamo fare di più?
Prevenzione secondaria cardiovascolare: le ipotesi senza successo
Prevenzione secondaria cardiovascolare: le ipotesi in corso di studio
Association between cholesterol levels and CHD Positive association between non-hdl cholesterol and risk of CHD Inverse association between HDL- cholesterol and risk of CHD Prospective Studies Collaboration; Lancet 2007;370:1829-39
Experience of CETP inhibitors is limited Name of Study Drug used Sample size ILLUMINATE Torcetrapib 15,067 Duration Median follow up: 1.5 yr Dal-Outcomes Dalcetrapib 15,000 5 years ACCELERATE Evacetrapib 12,095 DEFINE Anacetrapib 1623 Median follow up: 1.5 yr Median follow up: 1.5 yr
ILLUMINATE: Outcomes All-cause mortality: 93 (1.2%) Torcetrapib vs. 59 (0.8%) placebo HR 1.58 (95% CI 1.14-2.19); P=0.006 Major cardiovascular events: 464 (6.2%) Torcetrapib vs. 373 (5.0%) placebo HR 1.25 (95% CI 1.09-1.44) P=0.001 N Engl J Med 2007;357:2109-22.
dal-outcomes: Effects on HDL and LDL cholesterol HDL-Col LDL-Col
dal-outcomes: Main results
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Anacetrapib-DEFINE: changes in cholesterol levels LDL cholesterol HDL cholesterol -40% (p<0.001) +138% (p<0.001) Cannon CP et al. N Engl J Med 2010;363:2406-2415
Anacetrapib: early efficacy and safety data are encouraging Lowers LDL-cholesterol by ~40% Raises HDL-cholesterol by ~140% No adverse effect on blood pressure No effects on aldosterone or other known safety concerns Effects on clinical outcomes unknown
REVEAL: Aims of study To assess the effect of CETP inhibition with anacetrapib 100 mg versus matching placebo on time to first major coronary event among 30,000 individuals with pre-existing vascular disease. Major coronary event (MCE): Myocardial infarct Coronary death Coronary revascularization
Study design: Treatment comparisons
Prevenzione secondaria cardiovascolare: le ipotesi in corso di studio
dal-outcome Genetic substudy 6/23/2016 27 Proprietary and Confidential
dal-gene Protocol Primary Objective: To prospectively evaluate the potential of dalcetrapib to reduce cardiovascular morbidity and mortality in patients with a documented recent ACS and the AA genotype at rs1967309 6/23/2016 28 Proprietary and Confidential
Key Inclusion Criteria at Screening 5,000 hospitalized patients for ACS (index event within 4-12 weeks) defined as the occurrence of at least one of the following events Spontaneous MI Procedure-Related MI after PCI Hospitalization for ACS (ECG Abnormalities without biomarkers) AA genotype at rs1967309 Other key inclusion criteria: Males and females at least 45 years old Clinically stable at least 1 week prior to randomization Evidence of guidelines-based management of LDL-C 6/23/2016 29 Proprietary and Confidential
Primary Efficacy Endpoint The primary endpoint of this study is the time to first occurrence of any component of the composite endpoint, as adjudicated by the Clinical Event Committee (CEC). Components of the primary endpoint are: Cardiovascular (CV) death Resuscitated cardiac arrest Non-fatal myocardial infarction (MI) Non-fatal ischemic stroke 6/23/2016 30 Proprietary and Confidential
Prevenzione secondaria cardiovascolare: le ipotesi in corso di studio
Prevenzione secondaria cardiovascolare: le ipotesi in corso di studio
COLchicine Cardiovascular Outcomes Trial (COLCOT) MHIPS-003 Study Background & Rationale
A worldwide, randomized, double-blind, placebo-controlled, multi-center, event-driven study Indication: The COLCOT trial Reduction of the cardiovascular risk in patients with atherosclerotic coronary artery disease.
Study Background COPE CORE CORP COPPS Colchicine for Acute Pericarditis Colchicine for Recurrent Pericarditis Colchicine for Recurrent Pericarditis Colchicine for the Prevention of Post-Pericardiotomy Syndrome LODOCO Low Dose Colchicine for Secondary Prevention of Cardiovascular Disease
LODOCO TRIAL (Nidorf SM, et al J Am Coll Cardiol. 2013) Number at risk Colchicine 282 281 277 272 249 192 83 No Colchicine 250 244 234 229 212 184 85 The effect of adding colchicine became evident early, continued to accrue over time, and was largely driven by a reduction in ACS unrelated to stent disease.
COLCOT - Study Rationale Colchicine is an inexpensive anti-inflammatory drug used in patients with gout and Familial Mediterranean Fever at doses between 0.3 and 2.4 mg/day Colchicine s MOA is through the inhibition of tubulin polymerization and potentially also through a direct effect on cellular adhesion molecules and inflammatory chemokines Direct inhibition of the migration of neutrophils is considered colchicine s main MOA in gout
Study Objectives Primary Objective: Determine whether long-term treatment with colchicine reduces rates of recurrent cardiovascular events in patients who have suffered MI. Secondary Objective: Determine the safety of long-term treatment with colchicine. Tertiary Objective: Evaluate links between soluble and genetic biomarkers and treatment effects.
Prevenzione secondaria cardiovascolare: le ipotesi in corso di studio