5 research outputs found
Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial
- Author
- Abbas J
- Abbate A
- Abdullakutty J
- Abhyanakar AD
- Aboyans V
- Abrantes JAM
- Abu-Fadel M
- Acevedo M
- Adamkova V
- Adhyapak S
- Agarwal H
- Aggarwal R
- Aggarwal RK
- Aguirre A
- Ahmed H
- Ahremark U
- Ahuad Guerrero RA
- Aidar Ayoub JC
- Airaksinen JK
- Aitken D
- Akatova E
- Akhter F
- Ako J
- Akright L
- Akyea-Djamson A
- Al Joundi T
- Al-Windy NYY
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- Alcocer Gamba MA
- Alexander JH
- Alexander K
- Alexandru TM
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- Alonso Martin JJ
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- Yin W-H
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- Yoon JH
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- Zahger D
- Zaidman CJ
- Zainea M
- Zaman A
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- Zhang W
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- Zong W
- Zrazhevsky K
- Zuniga JDH
- Zurakowski A
- Zuran I
- Zweiker R
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2019
- Field of study
Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p
Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial
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- Yin W-H
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- Yoon JH
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- Zahger D
- Zaidman CJ
- Zainea M
- Zaman A
- Zapata G
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- Zeiher AM
- Zhang R
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- Zheleznyy V
- Zheng Y
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- Zobouyan I
- Zong W
- Zrazhevsky K
- Zurakowski A
- Zuran I
- Zweiker R
- Publication venue
- 'Ovid Technologies (Wolters Kluwer Health)'
- Publication date
- 04/01/2019
- Field of study
Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402
A basic review of fuzzy logic applications in hydrology and water resources
- Author
- A Alikhani
- A Bardossy
- A Bardossy
- A Bardossy
- A Bardossy
- A Bardossy
- A Bárdossy
- A Muhammetoglu
- A Talei
- A Talei
- AA Nadiri
- AH Lobbrecht
- AK Gorai
- AK Lohani
- AK Lohani
- AM Atiaa
- B Das
- B Oroji
- BP Shrestha
- C Jeong
- C Sivapragasam
- C Teutschbein
- CC Young
- D Bhattacharjee
- D Caniani
- DH Bae
- DH Mao
- DJ Parker
- DP Panigrahi
- EA Varouchakis
- EC Ozelkan
- EC Özelkan
- EC Özelkan
- EDP Perera
- EH Mamdani
- F Di Martino
- FJ Chang
- G Pesti
- H Gharibi
- H Vernieuwe
- HP Nachtnebel
- I Bogardi
- I Bogardi
- I Bogardi
- J Guan
- J Guan
- JC Han
- JDH González
- JE Sedeño-Díaz
- JN Patel
- LA Zadeh
- LH Feng
- LM DeCampos
- LX Wang
- M Abdullah
- M Casper
- M Fiter
- M Ozger
- M Sugeno
- MC Valverde
- ME Keskin
- ME Keskin
- MH Aouragh
- MK Goyal
- MR Chamani
- N Chang
- N Pramanik
- N Venkat Kumar
- O Kisi
- O Kisi
- OM Quiroz Londoño
- Oxford University Press
- P Deka
- P Mujumdar
- PC Deka
- PC Nayak
- PG Theodoridou
- PP Mujumdar
- PS Yu
- R Borna
- R Ghazavi
- RR Sahay
- RSV Teegavarapu
- RV Bai
- S Wieprecht
- SA Mirbagheri
- SB More
- SM Liou
- SP Simonovic
- SP Simonovic
- T Dubrovin
- T Partal
- T Rajaee
- V Gholami
- V Laxmi Mohanta
- VK Patki
- W Jiang
- WC Ip
- WG Jiang
- X Jia
- Y Hundecha
- Y Icaga
- Y Minatour
- Z He
- Ö Terzi
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Risk categorization using New American College of Cardiology/American Heart Association guidelines for cholesterol management and its relation to alirocumab treatment following acute coronary syndromes
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- Zhang R
- Zhang W
- Zhang X
- Zhang Z
- Zhao X
- Zheleznyy V
- Zheng Y
- Zheng Z
- Zhou Y
- Zhu C
- Zhu H
- Zhu J
- Zirlik A
- Zizka J
- Zobouyan I
- Zong W
- Zrazhevsky K
- Zurakowski A
- Zuran I
- Zweiker R
- Publication venue
- 'Ovid Technologies (Wolters Kluwer Health)'
- Publication date
- 01/08/2019
- Field of study
Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol ≥70 mg/dL or non−high-density lipoprotein cholesterol ≥100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. Methods: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, ie, coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) was examined according to American College of Cardiology/American Heart Association risk category. Results: Of 18 924 participants followed for a median of 2.8 years, 11 935 (63.1%) were classified as VHR: 4450 (37.3%) had multiple prior ASCVD events and 7485 (62.7%) had 1 major ASCVD event and multiple high-risk conditions. Major adverse cardiovascular events occurred in 14.4% of placebo-treated patients at VHR versus 5.6% of those not at VHR. In the VHR category, major adverse cardiovascular events occurred in 20.4% with multiple prior ASCVD events versus 10.7% with 1 ASCVD event and multiple high-risk conditions. Alirocumab was associated with consistent relative risk reductions in both risk categories (hazard ratio=0.84 for VHR; hazard ratio=0.86 for not VHR; Pinteraction=0.820) and by stratification within the VHR group (hazard ratio=0.86 for multiple prior ASCVD events; hazard ratio=0.82 for 1 major ASCVD event and multiple high-risk conditions; Pinteraction=0.672). The absolute risk reduction for major adverse cardiovascular events with alirocumab was numerically greater (but not statistically different) in the VHR group versus those not at VHR (2.1% versus 0.8%; Pinteraction=0.095) and among patients at VHR with multiple prior ASCVD events versus a single prior ASCVD event (2.4% versus 1.8%; Pinteraction=0.661). Conclusions: The US guideline criteria identify patients with recent acute coronary syndrome and dyslipidemia who are at VHR for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402
Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- Author
- A'Court J
- Aawsaj Y
- Abbadessa F
- Abbas A
- Abbott S
- Abdalaziz H
- Abdalla M
- Abdeh L
- Abdelsaid K
- Abdou H
- Abdul-Jabar H
- Abood A
- Abou-Foul AK
- Abrate A
- Abu-Nayla I
- Abual-Rub Z
- Abuown A
- Adamec A
- Adegbola S
- Ademuyiwa AO
- Advani R
- Aftab R
- Agarwal A
- Agarwal K
- Aggarwal A
- Aghababyan K
- Agilinko J
- Agrawal S
- Ahad S
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- Ahmed Elamin H
- Ahmed I
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- Akhtar MA
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- Al-mukhtar A
- Al-omishy H
- Al-Samaraee A
- Al-Sukaini A
- Al-Yaseen M
- Aladeojebi A
- Alanbuki A
- Alderson D
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- Publication venue
- 'BMJ'
- Publication date
- 01/01/2021
- Field of study
Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis. Setting Prospective, international, multicentre, observational cohort study. Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative). Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality. Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787). Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups. Trial registration number NCT0432364