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DEFINING TOMORROW'S VASCULAR STRATEGIES
DEFINING TOMORROW'S VASCULAR STRATEGIES
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Residual Risk through Landmark Studies
During the last 15 years, large prospective clinical trials have proven that :
This section propose to put the results of these large clinical trials into perspective both on macro- and microvascular residual risk.
- - statin therapy may reduce the risk of major cardiovascular events by 25 to 35%. However, despite effective low-density lipoprotein cholesterol (LDL-C) lowering treatment, significant cardiovascular (CV) risk persists.
- - even aggressive multifactorial therapy (statins, blood pressure lowering agents, anti-diabetic agents) did not prevent the development or progression of microvascular complications in patients with type 2 diabetes.
This section propose to put the results of these large clinical trials into perspective both on macro- and microvascular residual risk.
Macrovascular Residual Risk Studies
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12 March 2024First in-human trial of novel siRNA for lowering lipoprotein(a)
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8 January 2024First data with muvalaplin, an oral small molecule inhibitor of lipoprotein(a) formation
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26 September 2023More evidence linking remnant cholesterol and cardiovascular outcomes
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6 July 2023CLEAR (Cholesterol Lowering via Bempedoic Acid [ECT1002], an ACL-Inhibiting Regimen) OUTCOMES: a role for bempedoic acid in statin-intolerant high-risk patients
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13 April 2023EMPA-KIDNEY trial (Study of Heart and Kidney Protection with Empagliflozin): Empagliflozin shows renal and cardiovascular benefit in patients with chronic kidney disease
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6 December 2022Results from PROMINENT are in
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21 September 2022ODYSSEY OUTCOMES: Apolipoprotein B provides incremental information for residual cardiovascular risk
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19 July 2022EMPA-KIDNEY trial stopped early due to evidence of efficacy
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2 November 2021New meta-analysis reaffirms the favourable benefit versus risk of GLP-1 receptor agonists in patients with type 2 diabetes mellitus
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7 September 2021Teasing out the reasons for lack of cardiovascular benefit in STRENGTH
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9 August 2021News from REDUCE-IT: Icosapent ethyl reduces the risk of ischaemic stroke
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21 May 2021ODYSSEY OUTCOMES: Does PCSK9 inhibition increase the risk of diabetes?
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26 April 2021CLEAR Outcomes: Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid (ETC-1002) or Placebo
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22 March 2021The International Polycap Study-3 (TIPS-3) showed that the combination of a polypill and aspirin reduced cardiovascular events in primary prevention patients
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16 February 2021The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) REVASC
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4 January 2021STRENGTH: a neutral outcomes trial for omega-3 fatty acids
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5 October 2020EVAPORATE: Icosapent ethyl 4 g/day slows atherosclerosis progression
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20 July 2020High remnant cholesterol levels: an unmet clinical need in secondary prevention
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2 June 2020Remnant lipoproteins are associated with risk of aortic stenosis
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19 March 2020More insights from REDUCE-IT: Impact on total cardiovascular events
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17 February 2020Novel antisense therapy targeting hepatic APOC3 improves the atherogenic profile in hypertriglyceridemic patients
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19 December 2019Treat Stroke to Target Study: Lower low-density lipoprotein cholesterol target after stroke reduces cardiovascular events
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19 July 2019REDUCE-IT: Targeting elevated triglycerides reduces residual cardiovascular risk
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6 November 2018News from CANTOS: Modulation of the interleukin-6 signalling pathway reduces cardiovascular events
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12 July 2018Lipoprotein(a) and residual cardiovascular risk
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13 February 2018More from CANTOS: Predicting patients likely to benefit most
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10 January 2018COMPASS: targeting residual cardiovascular risk in stable atherosclerotic vascular disease
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4 December 2017New analysis from Copenhagen General Population Study reaffirms the importance of elevated remnant cholesterol as a risk factor for MI
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16 October 2017REVEAL: modest benefit on major coronary events with anacetrapib
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28 July 2017EMPA-REG OUTCOME trial: Empagliflozin and cerebrovascular events
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22 June 2017Proof of concept: ANGPTL3 deficiency protects against coronary artery disease
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24 April 2017ACCORDION: Does fenofibrate have a legacy effect in lipid-related residual cardiovascular risk in type 2 diabetes?
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28 February 2017STRONG HEART study: relationship between atherogenic dyslipidaemia and risk of cardiovascular disease depends on diabetes status.
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13 December 2016GLAGOV: benefit with intensive LDL-lowering, but residual risk persists
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14 October 2016Icosapent ethyl (eicosapentaenoic acid ethyl ester) reduces remnant cholesterol: Results from the MARINE and ANCHOR studies
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18 September 2016TINSAL-CVD does not rule out a role for inflammation as a contributor to residual cardiovascular risk
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19 July 2016Analysis questions benefit of lowering LDL-C below current targets
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13 June 2016Remnant cholesterol levels are predictive of coronary heart disease in primary prevention patients
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15 May 2016BIP analysis reaffirms the link between elevated triglycerides and increased mortality
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15 April 2016VOYAGER highlights need for additional therapy targeting elevated triglycerides in statin-treated patients
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15 March 2016ACCORDION: increased risk of cardiovascular death seen in ACCORD persists during long-term follow-up
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12 February 2016Atherogenic dyslipidaemia is more common in statin-treated than untreated patients in primary care
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11 January 2016Atherogenic dyslipidaemia: underdiagnosed and undertreated
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8 December 2015SPRINT: Benefits of intensive blood pressure control
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6 November 2015Landmark positive results in EMPA-REG OUTCOME study with empagliflozin, an inhibitor of sodium–glucose cotransporter 2
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8 July 2015Triglyceride-rich lipoproteins: an important contributor to residual cardiovascular risk in acute coronary syndrome
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18 May 2015Meta-regression analysis nails HDL-C
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13 April 2015Elevated nonfasting remnant cholesterol associated with increased mortality
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9 March 2015Atherogenic dyslipidaemia is associated with higher residual cardiovascular risk in patients with previous stroke
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8 February 2015Residual cardiovascular risk similar in men and women
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5 January 2015IMPROVE-IT finally reports: Lower LDL is better but residual cardiovascular risk remains
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1 December 2014New FIELD analysis: Fenofibrate has similar cardioprotective effects in women and men
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13 June 2014More questions about HDL: CHI-SQUARE trial with HDL-mimetic fails
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13 May 2014Importance of targeting obesity to reduce residual cardiovascular risk
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13 May 2014Elevated remnant cholesterol is causally associated with inflammation
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13 March 2014Mendelian randomization study supports a causal effect of triglycerides in coronary heart disease risk
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13 January 2014AIM-HIGH: potential benefit with niacin in patients with atherogenic dyslipidaemia
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5 December 2013UMPIRE: Fixed-dose combination in patients at high cardiovascular risk
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5 November 2013CIRT: Does targeting inflammation reduce residual cardiovascular risk?
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8 October 2013ESC 2013 Hotline: ASSURE fails to reassure about HDL
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3 July 2013Liraglutide, a glucagon-like peptide-1 analogue, reduces postprandial lipaemia
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1 June 2013N-3 fatty acids in primary prevention of cardiovascular disease
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4 March 2013ODYSSEY OUTCOMES
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6 February 2013PCSK9 monoclonal antibonody therapy as an adjunct to statins
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9 January 2013Insights from ANCHOR: omega-3 fatty acids in type 2 diabetes patients with residual hypertriglyceridaemia
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5 January 2013Atherogenic dyslipidemia and arterial stiffness in young subjects
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4 January 2013Will HPS3/TIMI55 REVEAL benefit?
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11 December 2012REDUCE-IT: Reduction of Cardiovascular Events Outcome trial
Does targeting hypertriglyceridemia with add-on AMR101, a formulation of omega-3 fatty acids (=96% eicosapentaenoic acid [EPA]), reduce the residual risk of cardiovascular events in statin-treated patients? -
15 November 2012New insights from ACCORD Lipid
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1 October 2012PROVE IT-TIMI 22: In patients treated with statins, on-treatment TG <150 mg/dL is independently associated with a lower risk of recurrent CHD events
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10 May 2012The FIRST study: Does fenofibric acid reduce subclinical atherosclerosis in high-risk, statin-treated patients with atherogenic dyslipidemia?
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12 January 2012Dal-OUTCOMES: raising HDL-C with dalcetrapib does not improve CV risk.
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25 March 2011ApoB/ApoA-I ratio best predictor of first myocardial infarction: INTERHEART
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11 May 2010HDL-C levels are predictive of major CV events in patients treated with statins, even in those whose LDL-C levels < 70 mg/dL
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3 May 2010Huge residual vascular risk in patients with and without diabetes receiving a single-drug lipid-lowering therapy
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14 March 2010The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial: Targeting atherogenic dyslipidemia with fenofibrate reduces residual cardiovascular risk in simvastatin-treated type 2 diabetes patients at LDL-C goal
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4 March 2010PROCAM: Assessing cardiovascular risk: relevance of atherogenic dyslipidemia recognized by the PROCAM coronary risk score
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1 December 2009RENAAL: Investigating the effects of renin-angiotensin system inhibition using an angiotensin receptor blocker on renal function and mortality in patients with diabetic nephropathy
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16 September 200963% of major cardiovascular events not prevented by atorvastatin in high-risk diabetic patients with low LDL cholesterol levels
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1 July 2009The Heart Protection Study: statin therapy significantly decreased vascular risk in high-risk diabetic patients but 78% of major vascular events were not prevented
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1 June 2009Residual risk of macrovascular events after intensive therapy with atorvastatin in patients with stable coronary heart disease
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5 May 200927% increase in risk of major CHD events per 1.0 mmol/L increase in fasting triglycerides concentration: Meta-analysis of 29 prospective studies
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1 April 2009In statin-treated patients, the magnitude of cardiovascular risk reduction depends on the decrease in LDL-C achieved: results of a meta-analysis
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10 January 2009The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial
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2 October 2008Substantial residual risk of fatal and non-fatal events after 5 years of statin therapy in diabetes: meta-analysis of 14 trials
Microvascular Residual Risk Studies
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21 February 2022Fenofibrate in diabetic retinopathy: New meta-analysis
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27 April 2018EVAPORATE: Effect of Vascepa on Improving Coronary Atherosclerosis in People with High Triglycerides Taking Statin Therapy
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22 August 2016VADT: Reduced diabetic retinopathy progression on intensive glycaemic therapy with higher HDL cholesterol levels
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8 October 2015Diabetes Prevention Program Outcomes Study reaffirms the importance of lifestyle intervention
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4 September 2015A higher TG/HDL-C ratio increases the incidence and progression of chronic kidney disease
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8 June 2015Hypertriglyceridemia increases risk for diabetic renal complications
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25 September 2014Statins and microvascular risk
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13 October 2011DCCT/EDIC: High triglyceride levels and other features of atherogenic dyslipidemia are associated with renal dysfunction in patients with type 1 diabetes
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1 March 2011The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Trial
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1 October 2009DCCT/EDIC: Beyond conventional lipid profile: NMR provides another vision of lipid-related risk of diabetic retinopathy
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11 February 2009Residual risk of progression of diabetic nephropathy in patients treated with irbesartan
Macro- and Microvascular Residual Risk Studies
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2 August 2014UKPDS 38: despite significant benefits, “tight” blood pressure control does not prevent two thirds of major macrovascular and microvascular events in hypertensive patients with type 2 diabetes
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8 February 2010The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) trial
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11 January 2010Testing the limits of statin therapy: In the ASPEN study, atorvastatin 10 mg/day did not reduce major cardiovascular events in patients with diabetes (without additional risk factors) ASPEN
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21 November 2009Persistence of vascular residual risk after long-term intensified multifactorial intervention in patients with type 2 diabetes and microalbuminuria: Steno-2 extension
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9 March 2009UKPDS 33: Despite improved blood glucose control, 75% of microvascular complications and 84% of macrovascular events are not prevented in patients with type 2 diabetes
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13 September 2008Micro- and macrovascular residual risk after 7.8 years of intensified multifactorial intervention in patients with type 2 diabetes and microalbuminuria: the Steno-2 study
