Atherothrombotic Risk Stratification Research Articles

Effect of alirocumab on coronary plaque stratified by atherothrombotic risks

Abstract Background Previous clinical studies have shown that high-risk subgroups including patients with major atherosclerotic cardiovascular disease (ASCVD) events and multiple atherothrombotic risk factors derive enhanced cardiovascular benefit from proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition. To date, the effect of alirocumab on coronary plaque regression stratified by the number of atherothrombotic risk factors remains unknown. Purpose To investigate the utility of atherothrombotic risk stratification to identify patients with acute myocardial infarction (AMI) who have the greatest potential for benefit on plaque regression as assessed by intracoronary imaging from the addition of alirocumab to high-intensity statin therapy. Methods This was a substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Intravascular ultrasound (IVUS) was serially performed in non-infarct-related coronary arteries at baseline and after 52 weeks. Atherothrombotic risk factors defined in the 2018 ACC/AHA cholesterol guidelines include myocardial infarction, ischemic stroke, peripheral artery disease, age ≥65 years, familial hypercholesterolemia, coronary revascularization, diabetes, hypertension, chronic kidney disease, current smoking, LDL-C ≥100 mg/dL despite maximum tolerated statin therapy, and history of heart failure. The key endpoint was the change in IVUS-derived percent atheroma volume (PAV) from baseline to 52 weeks. Results A total of 263 patients available for serial IVUS data were analyzed for the current study. The most prevalent atherothrombotic risk factors were current smoking (49%), hypertension (43%), and age ≥65 years (24%). Patients were divided into 3 groups according to the number of risk factors (0 risk factor: n=52, 1 risk factor: n=101, ≥2 risk factors: n=100). Patients with risk factors had greater PAV at baseline compared with those with 0 risk factor (39.0% vs. 42.6% vs. 42.8%, P=0.008). The addition of Alirocumab to high-intensity statin therapy demonstrated a significant reduction in PAV among patients with 0 risk factor (-2.66% vs. -1.02%, P=0.009) and those with 1 risk factor (-2.36% vs. -0.76%, P<0.001) (Figure 1). In contrast, patients with ≥2 risk factors had no significant PAV reduction by alirocumab (-1.72% vs. -1.12%, P=0.076, P for interaction=0.009). Conclusions Among AMI patients with no or 1 atherothrombotic risk factor, the addition of alirocumab to high-intensity statin therapy demonstrated greater coronary plaque regression. Patients with fewer risk factors thus appear to be more susceptible for atheroma regression.Change in PAV stratified by risk factors

Abstract 11965: Impact of Atherothrombotic Risk Stratification in Patients With Heavily Calcified Lesions Following Rotational Atherectomy

Background: Patients who undergo percutaneous coronary intervention (PCI) with rotational atherectomy (RA) are at high risk of adverse clinical outcomes, and there are few clinical risk stratification tools for these patients. The Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS 2°P) is a simple 9-point risk stratification tool. A previous study reported that TRS 2°P was useful in predicting adverse clinical events in patients with acute coronary syndrome. However, it is unclear whether TRS 2°P predicts adverse clinical events in patients with heavily calcified lesions, requiring RA. Hypothesis: This study aimed to investigate whether TRS 2°P is useful for the prediction of adverse clinical events in patients undergoing PCI with RA from the Japanese multicenter PCI registry. Methods: We conducted a study with 196 patients who underwent PCI with RA out of 7,391 patients who underwent PCI in a multicenter, prospective cohort registry. Patients were divided into 3 groups according to the tertiles of the TRS 2°P: 65 patients in the T1 group (TRS 2°P<3), 66 patients in the T2 group (TRS 2°P=3), and 65 patients in the T3 group (TRS 2°P>3). The primary endpoint was the cumulative 2-year incidence of major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of cardiac death, acute coronary syndrome, and ischemic stroke. Results: A cumulative 2-year MACCE occurred in 41 (24%) patients during the follow-up period. The cumulative incidence of MACCE was significantly higher in the T3 group than in T1 group (log-rank p=0.02). Multivariate Cox analyses revealed that the T3 group was associated with an increased risk of MACCE compared to T1 group (adjusted hazard ratio, 2.66; 95% confidence interval, 1.04–6.77; p=0.04). The addition of TRS 2°P to conventional risk factors, including male sex, number of diseased vessels, and low-density lipoprotein cholesterol levels, improved the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.39, p=0.027; IDI 0.072, p<0.001). Conclusions: Atherothrombotic risk stratification using TRS 2°P is useful for identifying high-risk patients with heavily calcified lesions following RA.

Impact of atherothrombotic risk stratification in patients with heavily calcified lesions following rotational atherectomy

BackgroundPatients who undergo percutaneous coronary intervention (PCI) with rotational atherectomy (RA) are at high risk of adverse clinical outcomes, and there are few clinical risk stratification tools for these patients. MethodsWe conducted a study with 196 patients who underwent PCI with RA out of 7391 patients who underwent PCI using a multicenter, prospective cohort registry. Patients were divided into three groups according to the tertiles of the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P): 65 patients in the T1 group (TRS 2°P < 3), 66 patients in the T2 group (TRS 2°P = 3), and 65 patients in the T3 group (TRS 2°P > 3). The primary endpoint was the cumulative 2-year incidence of major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of cardiac death, acute coronary syndrome, and ischemic stroke. ResultsCumulative 2-year MACCE occurred in 41 patients (24 %) during the follow-up period. The cumulative incidence of MACCE was significantly higher in the T3 group than in the T1 group (log-rank test, p = 0.02). Multivariate Cox analyses revealed that the T3 group was associated with an increased risk of MACCE compared to that of the T1 group (adjusted hazard ratio, 2.66; 95 % confidence interval, 1.04–6.77; p = 0.04). The addition of TRS 2°P to conventional risk factors, including male sex, number of diseased vessels, and low-density lipoprotein cholesterol levels, improved the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.39, p = 0.027; IDI 0.072, p < 0.001). ConclusionsAtherothrombotic risk stratification using TRS 2°P was useful in identifying high-risk patients with heavily calcified lesions following RA.

Noise exposure at the place of residence is associated with atherothrombotic risk. Findings from ENVI-MI (Environment and Myocardial Infarction) study

Environmental factors including noise exposure are primary cardiovascular (CV) risk factors. ENVI MI project aimed to assess the impact of environmental noise at the home address in patients with acute myocardial infarction (MI). From the Côte d’Or infarction observatory (RICO) database, 867 consecutive MI patients living in an urban unit of Dijon (France), included from 2004 to 2008, without prior MI and discharged alive were analysed. Atherothrombotic risk stratification was performed using the TRS-2P score. Patients were divided in to 3 risk categories: G1 (low-risk, TRS-2P = 0/1); G2 (intermediate-risk, TRS-2P = 2); and G3 (high-risk, TRS-2P ≥ 3). Environmental noise prediction models were used to assess residential exposure. The relationship between TRS-2P categories were analyzed according to noise levels using ordinal logistic regression analysis; crude and adjusted odds ratios were estimated for an increase of 5 dB(A) in L DEN . Most patients were male (64%), with mean age at 68 ± 15 y, and LVEF was 55 ± 13%. Rate of CV risk factors were: smoking (57.2%), obesity (29.4%), hypertension (53.8%), hypercholesterolemia (46.4%), and diabetes (20.8%). TRS-2P categories were split in low (42%), intermediate (25%), and high (32%) risk. Most (51%) men were at low risk, while most women were at high risk (47%). Mean noise exposure was 60 ± 6 (min–max: 33-82) dB(A). Noise exposure was associated with atherothrombotic risk: OR(SD): 1.149(0.0142), P < 0.01). After adjustement, noise remains an independent estimate for atherothrombotic risk (OR(SD): 1.129(0.060), p < 0.05. Interestingly, the relationship was only significant for men (OR(SD): 1.220(0.075), p < 0.01), but not for women (OR(SD): 0.958(0.105), P = NS)). We found a significant association between noise exposure and atherosclerotic CV disease burden. If confirmed, these results could have major consequences in terms of public health, especially on post-MI management.

Clinical outcomes with high-intensity statins according to atherothrombotic risk stratification after acute myocardial infarction: The FAST-MI registries

Current guidelines strongly recommend high-intensity statin therapy after acute myocardial infarction. To analyse the relationship between prescription of high-intensity statin therapy at discharge and long-term clinical outcomes according to risk level defined by the Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P) after acute myocardial infarction. We used data from the FAST-MI 2005 and 2010 registries-two nationwide French surveys including 7839 consecutive patients with acute myocardial infarction. Level of risk was stratified in three groups using the TRS-2P score: Group 1 (low risk; TRS-2P=0-1); Group 2 (intermediate risk; TRS-2P=2); and Group 3 (high risk; TRS-2P≥3). Among the 7348 patients discharged alive with a TRS-2P available, high-intensity statin therapy was used in 41.3% in Group 1, 31.3% in Group 2 and 18.5% in Group 3. After multivariable adjustment, high-intensity statin therapy was associated with a non-significant decrease in major adverse cardiovascular events (death, stroke or recurrent myocardial infarction) at 5 years in the overall population compared with that in patients receiving intermediate- or low-intensity statins or without a statin prescription (14.3% vs 29.6%; hazard ratio 0.94, 95% confidence interval 0.81-1.09; P=0.42). In absolute terms, the decrease in major adverse cardiovascular events was positively correlated with risk level (Group 1: 8.1% vs 10.7%; Group 2: 14.8% vs 21.6%; Group 3: 30.8% vs 51.6%). However, after adjustment, the benefits of high-intensity statin therapy were associated with lower mortality only in high-risk patients (hazard ratio 0.79, 95% confidence interval 0.64-0.97; P=0.02). High-intensity statin therapy at discharge after acute myocardial infarction was associated in absolute terms with fewer major adverse cardiovascular events at 5 years, regardless of atherothrombotic risk stratification, although the highest absolute reduction was found in the high-risk TRS-2P class.

P823Clinical benefits of high dose statins according to the atherothrombotic risk stratification after acute myocardial infarction. The FAST-MI registries

Abstract Background High dose statins prescription are strongly recommended in patients after acute myocardial infarction (AMI) in current guidelines. Aim We aimed to assess the clinical impact on major cardiovascular events (MACE) of high dose statins prescription at discharge according to the atherothrombotic risk stratification in a routine-practice population of AMI patients, and to determine the relative efficacy of currently recommended high dose statins according to risk level. Methods We used data from the 2005, and 2010 FAST-MI nationwide registries, including 7,839 patients with AMI (54% STEMI) admitted to cardiac intensive care units in France. Atherothrombotic risk stratification was performed using the TIMI Risk Score for Secondary Prevention (TRS-2P). Patients were defined in 3 categories: Group 1 (Low-risk; TRS-2P=0/1); Group 2 (Intermediate-risk; TRS-2P=2); and, Group 3 (High-risk; TRS-2P≥3). Baseline characteristics and the rate of MACE (defined as death, stroke or re-MI) at 5-years were analyzed according to TRS-2P categories, and the impact of high dose statins (i.e. atorvastatin 80mg/day or rosuvastatin 20mg/day) at discharge was compared using Cox multivariate analysis among the different risk groups. Results A total of 7,348 patients discharge alive and in whom TRS-2P was available. Prevalence of Groups 1, 2, and Group 3 was 41.5%, 25% and 33.5% respectively. Over the 5-year period, the overall risk of patients admitted for AMI decreased in Group 3 from 41% to 27% (P&lt;0.001). Optimal medical therapy at discharge (defined by the use of dual antiplatelets therapy, statins for all; and, beta-blocker, ACE-I or ARB when appropriate) was 53% in Group 3, 67% in Group 2, and 80% in Group 1 (P&lt;0.001). High dose statins prescription at discharge was 18.5% (Group 3), 31.3% (Group 2), and 41.3%% (Group 1). High dose statins prescription was associated with lower MACE at five-year in the overall population compared to patients with intermediate/low dose statins or without statin prescription (14.3% vs. 29.6%; Δ absolute risk= 15.3%; HR adjusted on baseline characteristics and management: 0.86, 0.76–0.97, P=0.018). The decrease in MACE at five-year was observed in all TRS-2P categories (Group 1: 8.1% vs. 10.7%, Δ= 2.6%; Group 2: 14.8% vs. 21.6%, Δ= 6.8%; Group 3: 30.8% vs. 51.6%, Δ= 20.8%). Finally, the benefits of high dose statins in low- and intermediate-risk was lower (HR=0.97; 95% CI, 0.74–1.26; P=0.81 and HR=1.06; 95% CI, 0.81–1.38; P=0.81) compared to high-risk patients (HR=0.78; 95% CI, 0.65–0.94; P=0.008). Five-year events-free survival Conclusions High dose statins prescription at discharge after AMI was associated with lower MACE at five-year regardless of the atherothrombotic risk stratification, although the highest absolute reduction was found in the high risk TRS2P class. Acknowledgement/Funding The FAST-MI 2010 registry is a registry of the French Society of Cardiology, supported by unrestricted grants from: Merck, the Eli-Lilly-Daiichi-Sanky

Correction to: Systematic Review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Correction to: Systematic Review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Outcome associated with prescription of cardiac rehabilitation according to predicted risk after acute myocardial infarction: Insights from the FAST-MI registries

Cardiac rehabilitation is strongly recommended in patients after acute myocardial infarction. To assess cardiac rehabilitation prescription after acute myocardial infarction according to predicted risk, and its association with 1-year mortality, using the FAST-MI registries. We used data from three 1-month French nationwide registries, conducted 5 years apart from 2005 to 2015, including 13130 patients with acute myocardial infarction admitted to coronary or intensive care units. Atherothrombotic risk stratification was performed using the Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P). Patients were classified into three categories: Group 1 (low risk; no or one risk indicator; score of 0 or 1); Group 2 (intermediate risk; two risk indicators; score of 2); and Group 3 (high risk; at least three risk indicators; score of≥3). Among the 12291 patients, cardiac rehabilitation prescription was 43.6% (49.9% in Group 1; 43.0% in Group 2; 35.2% in Group 3). Using Cox multivariable analysis, cardiac rehabilitation prescription was associated with lower mortality at 1 year in the overall population (3.8% vs. 8.2%; hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.61-0.85; P<0.001). Cardiac rehabilitation was associated with improved 1-year mortality, with homogeneous relative risk reductions in low- and intermediate-risk categories (HR 0.70, 95% CI 0.51-0.94) compared with high-risk patients (HR 0.72, 95% CI 0.59-0.88). In absolute terms, however, mortality decrease associated with cardiac rehabilitation was positively correlated with risk level (Group 1, 0.9% vs. 2.4%; Group 2, 3.0% vs. 4.2%; Group 3, 10.5% vs. 17.3%). Cardiac rehabilitation prescription was inversely correlated with patient risk. A positive association between cardiac rehabilitation and 1-year survival after acute myocardial infarction was present whatever the risk level, but the greatest mortality reduction was observed in high-risk patients.

TIMI risk score for secondary prevention of recurrent cardiovascular events in a real-world cohort of post-non-ST-elevation myocardial infarction patients

BackgroundPatients who survive non-ST-elevation myocardial infarction (NSTEMI) are at heightened risk of recurrent cardiovascular events. Data on long-term secondary atherothrombotic risk stratification are limited.ObjectivesTo stratify post-NSTEMI patients for risk of...

Atherothrombotic risk stratification after acute myocardial infarction: The Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention in the light of the French Registry of Acute ST Elevation or non-ST Elevation Myocardial Infarction registries.

BackgroundGuidelines recommend using risk stratification tools in acute myocardial infarction (AMI) to assist decision‐making. The Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS‐2P) has been recently developed to characterize long‐term risk in patients with MI.HypothesisWe aimed to assess the TRS‐2P in the French Registry of Acute ST Elevation or non‐ST elevation MI registries.MethodsWe used data from three 1‐month French registries, conducted 5 years apart, from 2005 to 2015, including 13 130 patients with AMI (52% ST‐elevation myocardial infarction [STEMI]). Atherothrombotic risk stratification was performed using the TRS‐2P score. Patients were divided in to three categories: G1 (low‐risk, TRS‐2P = 0/1); G2 (intermediate‐risk, TRS‐2P = 2); and G3 (high‐risk, TRS‐2P ≥ 3). Baseline characteristics and outcomes were analyzed according to TRS‐2P categories.ResultsA total of 12 715 patients (in whom TRS‐2P was available) were included. Prevalence of G1, G2, and G3 was 43%, 24%, and 33% respectively. Clinical characteristics and management significantly differed according to TRS‐2P categories. TRS‐2P successfully defined residual risk of death at 1 year (C‐statistic 0.78): 1‐year survival was 98% in G1, 94% in G2, and 78.5% in G3 (P < 0.001). Using Cox multivariate analysis, G3 was independently associated with higher risk of death at 1 year (hazard ratio [HR] 4.61; 95% confidence interval [CI]: 3.61‐5.89), as G2 (HR 2.08; 95% CI: 1.62‐2.65) compared with G1. The score appeared robust and correlated well with mortality in STEMI and NSTEMI populations, as well as in each cohort separately.ConclusionsThe TRS‐2P appears to be a robust risk score, identifying patients at high risk after AMI irrespective of the type of MI and historical period.

Atherothrombotic risk stratification after acute myocardial infarction: The TIMI Risk Score for Secondary Prevention (TRS-2P) in the light of the FAST-MI registries

Guidelines recommend risk stratification tools for use in acute myocardial infarction (AMI) to assist decisions making. Few tools are, however, available to assist with decisions on long-term response to treatment. Thrombolysis In Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS-2P) has been recently propose for this indication. We aimed to assess the TRS-2P and to identify high-risk patients after AMI in the FAST-MI registries. We used data from 3 one-month French registries, conducted 5 years apart, from 2005 to 2015, including 13,130 patients with AMI [52% ST-elevation myocardial infarction (STEMI)] admitted to cardiac intensive care units. Atherothrombotic risk stratification was performed using the TRS-2P score. Patients were divided in 3 categories: G1 (Low-risk; TRS-2P = 0/1); G2 (Intermediate-risk; TRS-2P = 2); and, G3 (High-risk; TRS-2P ≥ 3). Baseline characteristics and outcomes were analyzed according to TRS-2P categories. A total of 12,715 patients (in whom TRS-2P was available) were included in this analysis. Prevalence of G1, G2, and G3 was 43%, 24% and 33% respectively. Clinical characteristics and management significantly differ according to TRS-2P categories. TRS-2P score successfully defined residual risk of death at one-year (C-statistic 0.78): 1-year survival was 98% in G1, 94% in G2, and 78.5% in G3 ( P < 0.001). Using Cox multivariate analysis, G3 was associated with higher rate of death at 1-year (HR = 4.61; 95% CI: 3.61–5.89), as G2 (HR = 2.08; 95% CI: 1.62–2.65) compared to G1. The score appeared robust and correlated well with mortality in STEMI and non-ST-elevation myocardial infarction (NSTEMI) populations, as well as in each cohort separately. The TRS-2P appears to be a robust risk score, identifying patients at high-risk after AMI irrespective of the type of MI and historical period.

Appropriate secondary prevention and clinical outcomes after acute myocardial infarction according to atherothrombotic risk stratification: The FAST-MI 2010 registry.

Full secondary prevention medication regimen is often under-prescribed after acute myocardial infarction. The purpose of this study was to analyse the relationship between prescription of appropriate secondary prevention treatment at discharge and long-term clinical outcomes according to risk level defined by the Thrombolysis In Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS-2P) after acute myocardial infarction. We used data from the 2010 French Registry of Acute ST-Elevation or non-ST-elevation Myocardial Infarction (FAST-MI) registry, including 4169 consecutive acute myocardial infarction patients admitted to cardiac intensive care units in France. Level of risk was stratified in three groups using the TRS-2P score: group 1 (low-risk; TRS-2P=0/1); group 2 (intermediate-risk; TRS-2P=2); and group 3 (high-risk; TRS-2P≥3). Appropriate secondary prevention treatment was defined according to the latest guidelines (dual antiplatelet therapy and moderate/high dose statins for all; new-P2Y12 inhibitors, angiotensin-converting-enzyme inhibitor/angiotensin-receptor-blockers and beta-blockers as indicated). Prevalence of groups 1, 2 and 3 was 46%, 25% and 29% respectively. Appropriate secondary prevention treatment at discharge was used in 39.5%, 37% and 28% of each group, respectively. After multivariate adjustment, evidence-based treatments at discharge were associated with lower rates of major adverse cardiovascular events (death, re-myocardial infarction or stroke) at five years especially in high-risk patients: hazard ratio = 0.82 (95% confidence interval: 0.59-1.12, p = 0.21) in group 1, 0.74 (0.54-1.01; p = 0.06) in group 2, and 0.64 (0.52-0.79, p < 0.001) in group 3. Use of appropriate secondary prevention treatment at discharge was inversely correlated with patient risk. The increased hazard related to lack of prescription of recommended medications was much larger in high-risk patients. Specific efforts should be directed at better prescription of recommended treatment, particularly in high-risk patients.

P1231Clinical impact of cardiac rehabilitation according to the atherothrombotic risk stratification after acute myocardial infarction. The FAST-MI registries

P1231Clinical impact of cardiac rehabilitation according to the atherothrombotic risk stratification after acute myocardial infarction. The FAST-MI registries

Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention

BackgroundEzetimibe improves cardiovascular (CV) outcomes in patients stabilized after acute coronary syndrome (ACS) when added to statin therapy. After ACS, patients vary considerably in their risk for recurrent CV events. ObjectivesThis study tested the hypothesis that atherothrombotic risk stratification may be useful to identify post-ACS patients who have the greatest potential for benefit from the addition of ezetimibe to statin therapy. MethodsThe TIMI (Thrombolysis In Myocardial Infarction) Risk Score for Secondary Prevention (TRS 2°P) is a simple 9-point risk stratification tool, previously developed in a large population with atherothrombosis to predict CV death, myocardial infarction (MI), and ischemic stroke (CV death/MI/ischemic cerebrovascular accident [iCVA]). The current study applied this tool prospectively to 17,717 post-ACS patients randomized either to ezetimibe and simvastatin or to placebo and simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Treatment efficacy was assessed by baseline risk for CV death/MI/iCVA, the IMPROVE-IT composite endpoints (CE), and individual component endpoints at 7 years. ResultsAll 9 clinical variables in the TRS 2°P were independent risk indicators for CV death/MI/iCVA (p < 0.001). The integer-based scheme showed a strong graded relationship with the rate of CV death/MI/iCVA, the trial CE, and the individual components (p trend <0.0001 for each). High-risk patients (n = 4,393; 25%), defined by ≥3 risk indicators, had a 6.3% (95% confidence interval: 2.9% to 9.7%) absolute risk reduction in CV death/MI/iCVA at 7 years with ezetimibe/simvastatin, thus translating to a number-needed-to-treat of 16. Intermediate-risk patients (2 risk indicators; n = 5,292; 30%) had a 2.2% (95% confidence interval: −0.3% to 4.6%) absolute risk reduction. Low-risk patients (0 to 1 risk indicators; n = 8,032; 45%) did not appear to derive benefit from the addition of ezetimibe (p interaction = 0.010). Similar findings were observed for the IMPROVE-IT primary CE. ConclusionsAtherothrombotic risk stratification using the TRS 2°P identifies high-risk patients who derive greatest benefit from the addition of ezetimibe to statin therapy for secondary prevention after ACS. (Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878)

Atherothrombotic Risk Stratification and the Efficacy and Safety of Vorapaxar in Patients With Stable Ischemic Heart Disease and Previous Myocardial Infarction.

Patients with stable ischemic heart disease and previous myocardial infarction (MI) vary in their risk for recurrent cardiovascular events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential to benefit from more intensive secondary preventive therapy such as treatment with vorapaxar. We identified independent clinical indicators of atherothrombotic risk among 8598 stable, placebo-treated patients with a previous MI followed up for 2.5 years (median) in TRA 2°P-TIMI 50 [Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50]. The efficacy and safety of vorapaxar (SCH 530348; MK-5348) were assessed by baseline risk among patients with previous MI without prior stroke or transient ischemic attack for whom there is a clinical indication for vorapaxar. End points were cardiovascular death, MI, or ischemic stroke and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding. The 9 independent risk predictors were age, diabetes mellitus, hypertension, smoking, peripheral arterial disease, previous stroke, previous coronary bypass grafting, heart failure, and renal dysfunction. A simple integer-based scheme using these predictors showed a strong graded relationship with the rate of cardiovascular death/MI/ischemic stroke and the individual components (P for trend <0.001 for all). High-risk patients (≥3 risk indicators; 20% of population) had a 3.2% absolute risk reduction in cardiovascular disease/MI/ischemic stroke with vorapaxar, and intermediate-risk patients (1-2 risk indicators; 61%) had a 2.1% absolute risk reduction (P<0.001 each), translating to a number needed to treat of 31 and 48. Bleeding increased across risk groups (P for trend<0.01); however, net clinical outcome was increasingly favorable with vorapaxar across risk groups. Fatal bleeding or intracranial hemorrhage was 0.9% with both treatments in high-risk patients. Stratification of baseline atherothrombotic risk can assist with therapeutic decision making for vorapaxar use for secondary prevention after MI. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00526474.