4115Effect of alirocumab on recurrent cardiovascular events after acute coronary syndrome, according to the intensity of background statin treatment

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Diaz ◽  
Q H Li ◽  
D L Bhatt ◽  
V A Bittner ◽  
M T Baccara-Dinet ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
High Intensity ◽  
Cardiovascular Events ◽  
Statin Treatment ◽  
Moderate Intensity ◽  
Major Adverse Cardiovascular Events ◽  
P Value ◽  
Coronary Syndrome ◽  
To Receive ◽  
Statin Use

Abstract Background Statins are a cornerstone of therapy for coronary heart disease. We describe the effects of alirocumab (ALI) in patients (pts) with recent acute coronary syndrome (ACS) and dyslipidaemia per category of statin use. Methods ODYSSEY OUTCOMES compared ALI with placebo (PBO) in 18,924 pts with recent ACS and dyslipidaemia despite high-intensity/maximum tolerated statin (atorvastatin 40–80 mg/d or rosuvastatin 20–40 mg/d). Lower doses could be used if there were symptoms, laboratory abnormalities, or contraindications with higher doses. In cases of documented intolerance to ≥2 statins, pts could qualify on no statin treatment. Pts were randomized to ALI (75 mg SC Q2W, with possible uptitration to 150 mg Q2W) or PBO. Median follow-up was 2.8 years. Primary endpoint was major adverse cardiovascular events (MACE: CHD death, non-fatal MI, ischaemic stroke, or unstable angina requiring hospitalization). Pts were categorized by statin therapy at baseline: high intensity (88.8%), low or moderate intensity (8.7%), or no statin use (2.4%). In each category we determined the relative (hazard ratio [HR]) and absolute risk reductions (ARR) for MACE with ALI. Results Overall, ALI reduced MACE (HR 0.85, 95% CI 0.78–0.93; P<0.001). HRs were consistent across statin categories (Table). Baseline LDL-C increased across high-intensity, low/moderate-intensity, and no statin categories. Correspondingly, there was a gradient of the risk of MACE in the PBO group across these categories (10.8%, 10.7%, and 26%). With ALI treatment, the mean reduction in LDL-C from baseline to Month 4 increased across the 3 statin categories and correspondingly the ARRs for MACE were 1.3%, 3.2%, and 8.0% (P interaction <.001). LDL-C values and MACE events All patients High-intensity statin Low-/moderate-intensity statin No statin Interaction P-value N=18,924 (100%) N=16,811 (88.8%) N=1653 (8.7%) N=460 (2.4%) (treatment x statin category) PBO (N=9462) ALI (N=9462) PBO (N=8431) ALI (N=8380) PBO (N=804) ALI (N=849) PBO (N=227) ALI (N=233) LDL-C at baseline, mmol/L, mean (SE)* 2.39 (0.01) 2.39 (0.01) 2.35 (0.01) 2.35 (0.01) 2.41 (0.03) 2.43 (0.03) 3.76 (0.08) 3.82 (0.08) Change in LDL-C from baseline to Month 4, mmol/L, mean (SE) 0.03 (0.01) −1.4 (0.01) 0.03 (0.01) −1.37 (0.01) 0.01 (0.02) −1.47 (0.02) −0.004 (0.06) −2.27 (0.06) <0.001 MACE, n (%)* 1052 (11.1) 903 (9.5) 907 (10.8) 797 (9.5) 86 (10.7) 64 (7.5) 59 (26.0) 42 (18.0) HR (95% CI) 0.85 (0.78−0.93) 0.88 (0.80−0.96) 0.69 (0.50−0.95) 0.65 (0.43−0.96) 0.14 ARR (%) (95% CI) 1.6 (0.7−2.4) 1.3 (0.3−2.2) 3.2 (0.4−5.9) 8.0 (0.4−15.5) <0.001 *P<0.001 for difference among statin categories. Conclusions In ODYSSEY OUTCOMES, patients unable to receive high-intensity statin treatment showed greater ARRs with ALI, consistent with higher baseline LDL-C concentration and greater absolute LDL-C reduction. Patients unable to receive high-intensity statin treatment are an important group to consider for treatment with ALI after ACS. Acknowledgement/Funding Funded by Sanofi and Regeneron Pharmaceuticals

scholarly journals Intensity of statin treatment after acute coronary syndrome, residual risk, and its modification by alirocumab: insights from the ODYSSEY OUTCOMES trial

2020 ◽  
pp. 204748732094198 ◽  
Author(s):  
Rafael Diaz ◽  
Qian H Li ◽  
Deepak L Bhatt ◽  
Vera A Bittner ◽  
Marie T Baccara-Dinet ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Cardiovascular Events ◽  
Absolute Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Major Adverse Cardiovascular Events ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome ◽  
Pcsk9 Inhibition

Aims Statins are pivotal to the secondary prevention of major adverse cardiovascular events, but some patients are statin-intolerant. We examined the effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab on the risk of major adverse cardiovascular events according to the intensity of background statin treatment. Methods and results The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with acute coronary syndrome and dyslipidaemia despite intensive or maximum-tolerated statin treatment (including no statin if intolerance was documented). The primary outcome (major adverse cardiovascular events) comprised coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina. Median follow-up was 2.8 years. Baseline statin treatment was high-intensity (88.8%), low/moderate-intensity (8.7%) or none (2.4%). Median baseline low-density lipoprotein cholesterol was 86, 89 and 139 mg/dL ( P < 0.001) in these statin treatment categories, respectively. Alirocumab produced similar relative reductions in low-density lipoprotein cholesterol from baseline across statin treatment subgroups, but the mean absolute reductions differed (52.9, 56.7 and 86.1 mg/dL, respectively; P < 0.001). With placebo, the incidence of major adverse cardiovascular events was highest in the no statin subgroup (10.8%, 10.7% and 26.0% respectively). Alirocumab reduced major adverse cardiovascular events in each statin subgroup (hazard ratio 0.88, 95% confidence interval (CI) 0.80–0.96; 0.68, 0.49–0.94; and 0.65, 0.44–0.97, respectively; Pinteraction = 0.14) with a gradient of absolute risk reduction: 1.25%, 95% CI 0.34–2.16; 3.16%, 0.38–5.94; 7.97%, 0.42–15.51; Pinteraction = 0.106). Conclusions PCSK9 inhibition with alirocumab reduces the relative risk of major adverse cardiovascular events after acute coronary syndrome irrespective of background statin treatment. However, patients on no statin are at high absolute risk for recurrent major adverse cardiovascular events; alirocumab substantially reduces that risk. PCSK9 inhibition may be an important therapeutic strategy for statin-intolerant patients with acute coronary syndrome.

scholarly journals Effect of alirocumab on major adverse cardiovascular events according to renal function in patients with a recent acute coronary syndrome: prespecified analysis from the ODYSSEY OUTCOMES randomized clinical trial

2020 ◽  
Vol 41 (42) ◽  
pp. 4114-4123 ◽  
Author(s):  
José Tuñón ◽  
Philippe Gabriel Steg ◽  
Deepak L Bhatt ◽  
Vera A Bittner ◽  
Rafael Díaz ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Renal Function ◽  
Cardiovascular Events ◽  
Primary Outcome ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Major Adverse Cardiovascular Events ◽  
Pcsk9 Inhibitors ◽  
Coronary Syndrome

Abstract Aims Statins reduce cardiovascular risk in patients with acute coronary syndrome (ACS) and normal-to-moderately impaired renal function. It is not known whether proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide similar benefit across a range of renal function. We determined whether effects of the PCSK9 inhibitor alirocumab to reduce cardiovascular events and death after ACS are influenced by renal function. Methods and results ODYSSEY OUTCOMES compared alirocumab with placebo in patients with recent ACS and dyslipidaemia despite intensive statin treatment. Estimated glomerular filtration rate (eGFR) &lt;30 mL/min/1.73 m2 was exclusionary. In 18 918 patients, baseline eGFR was 82.8 ± 17.6 mL/min/1.73 m2, and low-density lipoprotein cholesterol (LDL-C) was 92 ± 31 mg/dL. At 36 months, alirocumab decreased LDL-C by 48.5% vs. placebo but did not affect eGFR (P = 0.65). Overall, alirocumab reduced risk of the primary outcome (coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina requiring hospitalization) with fewer deaths. There was no interaction between continuous eGFR and treatment on the primary outcome or death (P = 0.14 and 0.59, respectively). Alirocumab reduced primary outcomes in patients with eGFR ≥90 mL/min/1.73 m2 (n = 7470; hazard ratio 0.784, 95% confidence interval 0.670–0.919; P = 0.003) and 60 to &lt;90 (n = 9326; 0.833, 0.731–0.949; P = 0.006), but not in those with eGFR &lt; 60 (n = 2122; 0.974, 0.805–1.178; P = 0.784). Adverse events other than local injection-site reactions were similar in both groups across all categories of eGFR. Conclusions In patients with recent ACS, alirocumab was associated with fewer cardiovascular events and deaths across the range of renal function studied, with larger relative risk reductions in those with eGFR &gt; 60 mL/min/1.73 m2.

scholarly journals Risk factors for major adverse cardiovascular events after the first acute coronary syndrome

2021 ◽  
Vol 53 (1) ◽  
pp. 817-823
Author(s):  
Marjo Okkonen ◽  
Aki S. Havulinna ◽  
Olavi Ukkola ◽  
Heikki Huikuri ◽  
Arto Pietilä ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Coronary Syndrome ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Coronary Syndrome

Homocysteine as a potential predictive factor for high major adverse cardiovascular events risk in female patients with premature acute coronary syndrome

2019 ◽  
Author(s):  
Mei Wei ◽  
Le Wang ◽  
Yongsheng Liu ◽  
Mingqi Zheng ◽  
Fangfang Ma ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Predictive Factor ◽  
Cardiovascular Events ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Major Adverse Cardiovascular Events ◽  
Free Survival ◽  
Female Patients ◽  
Coronary Syndrome ◽  
Kaplan Meier

Abstract Background We aimed to investigate correlation of homocysteine (Hcy) level with clinical characteristics, and explore its predictive value for major adverse cardiovascular events (MACE) risk in female patients with premature acute coronary syndrome (ACS).Methods Serum Hcy level was detected from 1,299 female patients with premature ACS. According to the tertile of Hcy level, patients were divided into three groups: lowest tertile group (≤9.1 µmol/L), middle tertile group (9.2~11.6 µmol/L) and highest tertile group (>11.6 µmol/L). MACE incidence was recorded and MACE-free survival was caculated with the median follow-up duration of 28.3 months.Results Increased Hcy correlated with older age ( P <0.001), higher creatinine level ( P <0.001) and enhanced uric acid level ( P =0.001), while reduced fasting glucose concentration ( P <0.001). MACE incidence was 10.7% and it was highest in highest tertile group (22.1%), followed by middle tertile group (7.7%) and lowest tertile group (2.4%) ( P <0.001). Receiver operating characteristic curve showed that Hcy distinguished MACE patients from non-MACE patients with the area under the curve of 0.789 (95% CI: 0.742-0.835). Kaplan-Meier curves revealed that MACE-free survival was shortest in Hcy highest tertile group, followed by middle tertile group and lowest tertile group ( P <0.001). Multivariate Cox’s analyses further showed that higher Hcy level was an independently predictive factor for poor MACE-free survival (middle tertile vs. lowest tertile ( P =0.001, HR: 3.615, 95% CI: 1.661-7.864); highest tertile vs. lowest tertile ( P <0.001, HR: 11.023, 95% CI: 5.356-22.684)).Conclusion Hcy serves as a potential predictive factor for increased MACE risk in female patients with premature ACS.

Long-Term Risk of Major Adverse Cardiovascular Events in Patients With Acute Coronary Syndrome: Prognostic Role of Complete Blood Cell Count

Angiology ◽  
2020 ◽  
Vol 71 (9) ◽  
pp. 831-839
Author(s):  
Nuccia Morici ◽  
Valentina Molinari ◽  
Silvia Cantoni ◽  
Andrea Rubboli ◽  
Laura Antolini ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
High Risk ◽  
Blood Cell ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Blood Cell Count ◽  
Prognostic Role ◽  
Coronary Syndrome

Individual parameters of complete blood count (CBC) have been associated with worse outcome in patients with acute coronary syndrome (ACS). However, the prognostic role of CBC taken as a whole has never been evaluated for long-term incidence of major adverse cardiovascular events (MACEs). Patients were grouped according to their hematopoietic cells’ inflammatory response at different time points during hospital stay. Patients with admission white blood cell count >10 × 109/L, discharge hemoglobin <120 g/L, and discharge platelet count >250 × 109/L were defined as “high-risk CBC.” Among 1076 patients with ACS discharged alive, 129 (12%) had a “high-risk CBC” and 947 (88%) had a “low-risk CBC.” Patients with “high-risk CBC” were older and had more comorbidities. Over a median follow-up of 665 days, they experienced a higher incidence of MACE compared to “low-risk CBC” patients (18.6% vs 8.1%). After adjustment for age, age-adjusted Charlson comorbidity index, female sex, cardiac arrest, suboptimal discharge therapy, coronary artery bypass, and ejection fraction, a high-risk CBC was significantly associated with increased MACE occurrence (adjusted hazard ratio 1.80; 95% CI: 1.09-3.00). The CBC was a prognostic marker in patients with ACS, and its evaluation at admission and discharge could better classify patient’s risk and improve therapeutic management.

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