CardioNerds Journal Club is a monthly forum for CardioNerds to discuss and breakdown recent publications on twitter and are produced with a corresponding infographic and detailed blog post. For more information, check out the CardioNerds Journal Club Page. This Journal Club focuses on the ULTIMATE-DAPT Trial
Table of contents for the The The ULTIMATE-DAPT Trial summary:
Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial
Zhen Ge, Jing Kan, Xiaofei Gao, Afsar Raza, Jun-Jie Zhang, Bilal S Mohydin, Fentang Gao, Yibing Shao, Yan Wang, Hesong Zeng, Feng Li, Hamid Sharif Khan, Naeem Mengal, Hongliang Cong, Mingliang Wang, Lianglong Chen, Yongyue Wei, Feng Chen, Gregg W Stone, Shao-Liang Chen, for the ULTIMATE-DAPT investigators
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00473-2/abstract
| Trial | Population | Intervention | Outcomes |
| PLATelet inhibition and patient Outcomes (PLATO) [2007] | – 18,624 patients admitted to the hospital with ACS with or without ST-segment elevation | – Multicenter, double-blind, randomized trial – Patients either received ticagrelor (180mg loading dose followed by 90mg BID) and clopidogrel (300-to-600-mg loading dose followed by 75mg daily) | – Followed up at 12 months evaluating death from vascular causes, myocardial infarction, or stroke – Treatment with ticagrelor compared to clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non-procedure-related bleeding |
| TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38) [2007] | – 13,608 patients with moderate to high-risk ACS with scheduled PCI | – Multicenter, double-blind, randomized trial – Patients either received prasugrel (a 60mg loading dose followed by 10mg daily) or clopidogrel (300mg loading dose followed by 75mg) for 6-15 months | – Primary endpoint was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke as well as major bleeding at 6-15 months – In patients with ACS with scheduled PCI, prasugrel was associated with significantly lower rates of ischemic events (i.e. stent thrombosis) but with an increased risk of major and fatal bleeding – No significant difference in mortality between the prasugrel vs clopidogrel groups |
| Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus-eluting Stent for Acute Coronary Syndrome (TICO) [2019] | – 3056 patients with ACS treated with drug-eluting stents between August 2015 and October 2018 at 38 centers in South Korea | – Randomized multicenter trial – Patients were randomized to receive ticagrelor monotherapy (90 mg twice daily) after 3-month DAPT (n = 1527) or ticagrelor-based 12-month DAPT (n = 1529). | – Primary outcome evaluated at 1 year for major bleeding and adverse cardiac and cerebrovascular events (death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization) – Among patients with ACS treated with DES, ticagrelor monotherapy after 3 months of DAPT compared with ticagrelor-based 12-month DAPT, showed a modest but statistically significant reduction in a composite outcome of major bleeding and cardiovascular events at 1 year |
| Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention: The SMART-CHOICE Randomized Clinical Trial [2019] | – 2993 patients across 33 hospitals in Korea undergoing PCI with drug-eluting stents | – Open-label, noninferiority, randomized study – Patients were randomly assigned to receive aspirin plus a P2Y12 inhibitor for 3 months and thereafter P2Y12 inhibitor alone (n = 1495) or DAPT for 12 months (n = 1498). | – Primary endpoint was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 12 months after the index procedure. Secondary endpoints included bleeding. – Among patients undergoing PCI, P2Y12 inhibitor monotherapy after 3 months of DAPT compared with prolonged DAPT resulted in noninferior rates of major adverse cardiac and cerebrovascular events |
| Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention (TWILIGHT) trial [2019] | – Enrolled 9006 patients who had undergone PCI with 7119 undergoing randomization for the study after 3 months | – Double-blind trial | – Primary endpoint was bleeding at 1 year – Additional endpoints of composite death from any cause, nonfatal myocardial infarction, or nonfatal stroke were also included – Among high-risk patients who underwent PCI and completed 3 months of DAPT, ticagrelor monotherapy was associated with a lower incidence of clinically significant bleeding than DAPT with ticagrelor, with no higher risk of death, myocardial infarction, or stroke |
| Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI: The STOPDAPT-2 Randomized Clinical Trial [2019] | – 3045 patients who underwent PCI at 90 hospitals in Japan were included | – Multicenter, open-label, randomized clinical trial – Patients were randomized either to 1 month of DAPT followed by clopidogrel monotherapy (n=1523) or to 12 months of DAPT with aspirin and clopidogrel (n=1522) | – Primary endpoint was a composite of cardiovascular death, myocardial infarction (MI), ischemic or hemorrhagic stroke, definite stent thrombosis, or major or minor bleeding at 12 months – Among patients undergoing PCI, 1 month of DAPT followed by clopidogrel monotherapy, compared with 12 months of DAPT with aspirin and clopidogrel, resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority |
| Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial [2018] | – 15,968 participants were randomly assigned (7980 in the experimental group; 7988 in the control group) at 130 sites in 18 countries | – Randomized, open-label superiority trial – Patients undergoing PCI with DES for stable CAD or ACS were randomly assigned to 75–100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy or standard DAPT with 75–100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with ACS) for 12 months, followed by aspirin monotherapy for 12 months | – Primary endpoint was all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed in a blinded manner at the 2-year mark – Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard DAPT followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention |
Objectives:
To assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE).
Trial –
- Randomized, placebo-controlled, double-blind clinical trial
- Part of larger IVUS-ACS and ULTIMATE-DAPT integrated study program (comparison of 1 month vs 12 month DAPT post implantation of drug-eluting stent via intravascular ultrasound vs angiography in ACS)
- Multinational, multicenter trial across 58 sites in China, Pakistan, UK, and Italy
Intervention
- First randomization (IVUS-ACS) – intravascular ultrasound-guided vs angiography-guided PCI of all lesions believed to be responsible for ACS plus all other severe lesions warranting treatment as per standard clinical practice
- All patients started on ASA 100 mg po daily and ticagrelor 90 mg po BID prior to PCI
- Second randomization – Random 1:1 assignment 1 month after PCI to continue ASA + ticagrelor for additional 11 months or placebo + ticagrelor for 12 months
- ***excluding patients who had major bleeding events (Bleeding Academic Research Consortium (BARC) types 3 or 5), adverse ischemic events, or those who discontinued DAPT for > 48h
– Follow-up at 1, 4, 6, and 12 months
– If dyspnea on ticagrelor, reduced to 60 mg po BID; if dyspnea persisted, switched to clopidogrel
Enrollment Criteria
| Inclusion Criteria | Exclusion Criteria |
| Age ≥ 18 years | Stroke within 3 months or any permanent neurological deficit |
| Acute coronary syndrome (UA/NSTEMI/STEMI) – Caused by culprit lesion in untreated coronary artery segment – Occurring up to 30 days before randomization – Indication for revascularization with second-generation drug-eluting stent | Previous intracranial bleed/disease |
| Previous coronary artery bypass graft surgery | |
| Any planned surgery within 12 months | |
| Severe CKD (eGFR < 20 mL/min/1.73m2 | |
| Need for chronic oral anticoagulation | |
| Platelet count < 100,000 mm3 | |
| Any reason for which antiplatelet therapy might need to be discontinued within 12 months | |
| Contraindication to aspirin or ticagrelor | |
| Liver cirrhosis | |
| Intending to become pregnant | |
| Life expectancy < 1 year | |
| Any condition likely to interfere with study process (dementia, alcohol misuse, etc.) |
Outcomes
Primary Outcome
- Primary superiority endpoint: occurrence of clinically relevant bleeding (BARC 2, 3, or 5)
- Primary non-inferiority endpoint: Occurrence of MACCE (composite of cardiac death, MI, ischemic stroke, definite stent thrombosis, and clinically driven target vessel revascularization
Secondary Outcomes
- Time to first occurrence of composite net adverse clinical events (any MACCE or any BARC bleeding types 1, 2, 3, 5)
- Percentage of crossover from ticagrelor to clopidogrel in each group
- BARC types 3 or 5 bleeding; major or minor bleeding according to the TIMI risk assessment score; moderate, severe, or life-threatening bleeding according to definitions from Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO); major bleeding according to definitions from International Society of Thrombosis and Haemostasis (ISTH)
- Individual components of the primary endpoints
- Composite of cardiac death, non-fatal myocardial infarction, or ischaemic stroke.
- Target vessel failure without procedural myocardial infarction, non-fatal myocardial infarction, and probable stent thrombosis
Statistical Analysis
- Assuming a 3.0% rate of clinically relevant bleeding, 3400 patients provided 80% power to detect a 50% reduction in clinically relevant bleeding.
- Assuming a 6.2% rate of MACCE, inclusion of 3068 patients provided 80% power to show non-inferiority.
- Primary endpoints were tested sequentially; the clinically relevant bleeding (superiority) endpoint had to pass for hypothesis testing of the MACCE (noninferiority) endpoint to proceed.
- Event rates estimated using the Kaplan–Meier method and compared using the log-rank test. Treatment effects were estimated using Cox proportional hazards regression, with results presented as hazard ratios (HRs) and 95% CIs.
- The principal analyses were assessed in the intention-to-treat population, including all randomly assigned patients, regardless of medication adherence.
- Sensitivity analyses were done in the per-protocol population, excluding patients who did not take their assigned treatment for at least 7 days, or who did not comply with the medication schedule.
Baseline Characteristics
- Median patient age was 63 years (IQR 54–70)
- 2521 (74·1%) patients were men
- 2024 (59·5%) presented with an acute myocardial infarction.
- 835 (24·6%) of 3400 culprit vessels before the index procedure had a TIMI flow score of less than 3.
- The median dual antiplatelet therapy duration was 28 days (IQR 25–33) in the ticagrelor plus placebo group and 365 days (365–365) in the ticagrelor and aspirin group.
- 12 (0·7%) patients required a reduction in ticagrelor dosage from 90 mg to 60 mg twice daily in the ticagrelor plus placebo group, as did 16 (0·9%) patients in the ticagrelor plus aspirin group.
- Conversion from ticagrelor to clopidogrel was required in 22 (1·3%) patients in the ticagrelor plus placebo group and 19 (1·1%) patients in the ticagrelor plus aspirin group.
| Ticagrelor plus placebo (n=1700) | Ticagrelor plus aspirin (n=1700) | ||
| Age, years | |||
| Median (IQR) | 62 (54–70) | 63 (54–69) | |
| Sex | |||
| Male | 1264 (74·4%) | 1257 (73·9%) | |
| Female | 436 (25·7%) | 443 (26·1%) | |
| Race | |||
| Chinese | 1476 (86·8%) | 1519 (89·4%) | |
| Other | 224 (13·2%) | 181 (10·7%) | |
| Country of enrolment | |||
| China | 1476 (86·8%) | 1519 (89·4%) | |
| Pakistan | 202 (11·9%) | 159 (9·4%) | |
| UK | 12 (0·7%) | 11 (0·7%) | |
| Italy | 10 (0·6%) | 11 (0·7%) | |
| Initial presentation | |||
| Unstable angina | 668 (39·3%) | 708 (41·7%) | |
| With ischaemic changes on electrocardiogram | 650/668 (97·3%) | 685/708 (96·8%) | |
| Acute myocardial infarction | 1032 (60·7%) | 992 (58·4%) | |
| Non-STEMI | 545 (32·1%) | 531 (31·2%) | |
| STEMI | 487 (28·7%) | 461 (27·1%) | |
| Killip class | |||
| 1 | 475/1032 (46·0%) | 442/992 (44·6%) | |
| 2 | 457/1032 (44·3%) | 468/992 (47·2%) | |
| 3 | 100/1032 (9·7%) | 82/992 (8·3%) | |
| Medical history | |||
| Hypertension | 1058 (62·2%) | 1063 (62·5%) | |
| Diabetes | 540 (31·8%) | 535 (31·5%) | |
| Insulin-treated diabetes | 136 (8·0%) | 144 (8·5%) | |
| Dyslipidaemia | 1178 (69·3%) | 1157 (68·1%) | |
| Current smoking* | 486 (28·6%) | 482 (28·4%) | |
| Chronic renal insufficiency† | 119 (7·0%) | 129 (7·6%) | |
| Previous percutaneous coronary intervention | 171 (10·1%) | 174 (10·2%) | |
| Previous coronary artery bypass graft surgery | 2 (0·1%) | 4 (0·2%) | |
| Previous myocardial infarction | 143 (8·4%) | 156 (9·2%) | |
| Previous stroke | 154 (9·1%) | 147 (8·7%) | |
| Peripheral arterial disease | 76 (4·5%) | 79 (4·7%) | |
| Heart failure | 109 (6·4%) | 101 (5·9%) | |
| Left ventricular ejection fraction (%)‡ | |||
| Median (IQR) | 62% (55–65) | 63% (56–65) | |
| Medication use at 1 month (the time of the second randomisation) | |||
| Aspirin | 1700 (100%) | 1700 (100%) | |
| Ticagrelor | 1700 (100%) | 1700 (100%) | |
| β blocker | 838 (49·3%) | 802 (47·2%) | |
| Angiotensin converting enzyme inhibitor or angiotensin receptor blocker | 774 (45·5%) | 788 (46·4%) | |
| Calcium antagonist | 430 (25·3%) | 463 (27·2%) | |
| Statin | 1417 (83·4%) | 1404 (82·6%) | |
Outcomes
Primary and Secondary Outcome
- By the 12 month-mark post-PCI, the primary superiority endpoint of clinically relevant bleeding occurred in 35 patients (2.1%) treated with ticagrelor plus placebo vs 78 patients (4.6%) treated with ticagrelor plus aspirin (HR 0·45 [95% CI 0.30–0.66]; p<0.0001) in the intention-to-treat population (table 2; figure 2).
- Numbers needed-to-treat were 48 to prevent one clinically relevant bleeding event and 100 to prevent one BARC type 3 or 5 bleeding event.
- Patients treated with ticagrelor monotherapy from month 1 had similar rates of adverse ischaemic events as patients who were maintained on ticagrelor plus aspirin.
- By the 12 month-mark post-PCI,, the primary non-inferiority endpoint of MACCE occurred in 61 participants (3.6%) treated with ticagrelor plus placebo and 63 (3.7%) treated with ticagrelor plus aspirin (absolute difference –0.1% [95% CI –1.4% to 1.2%]; HR 0·98 [95% CI 0.69 to 1.39]; p non-inferiority<0·0001, p superiority=0.89) in the intention-to-treat population.
- The rates of the individual components of the primary non-inferiority endpoint were also similar between the two groups, as were other composite ischaemic outcomes (table 2).
Figure 2. Primary efficacy and safety outcomes during follow-up between 1 month and 12 months after percutaneous coronary intervention
Figure 3. Clinically relevant bleeding events in prespecified subgroups
IVUS=intravascular ultrasound. PCI=percutaneous coronary intervention. STEMI=ST-segment elevation myocardial infarction. *Defined as an estimated glomerular filtration rate <60 mL/min per 1.73 m2.
Figure 4. Composite major adverse cardiovascular or cerebrovascular events in prespecified subgroups
| Ticagrelor plus placebo (n=1700) | Ticagrelor plus aspirin (n=1700) | Hazard ratio (95% CI) | p value | ||
| Primary endpoints | |||||
| Clinically relevant bleeding (BARC types 2, 3, or 5) | 35 (2·1%) | 78 (4·6%) | 0·45 (0·30 to 0·66) | <0·0001 | |
| Major adverse cardiovascular or cerebrovascular events* | 61 (3·6%) | 63 (3·7%) | 0·98 (0·69 to 1·39) | 0·89† | |
| Key secondary endpoint | |||||
| Net adverse clinical events | 97 (5·7%) | 140 (8·2%) | 0·68 (0·53 to 0·88) | 0·0066 | |
| Secondary bleeding endpoints | |||||
| Major bleeding (BARC types 3 or 5) | 11 (0·7%) | 28 (1·7%) | 0·39 (0·19 to 0·79) | 0·0087 | |
| TIMI major or minor bleeding | 11 (0·7%) | 27 (1·6%) | 0·41 (0·20 to 0·82) | 0·012 | |
| GUSTO moderate, severe, or life-threatening bleeding | 8 (0·5%) | 19 (1·1%) | 0·42 (0·18 to 0·96) | 0·041 | |
| ISTH major bleeding | 8 (0·5%) | 21 (1·2%) | 0·38 (0·17 to 0·86) | 0·020 | |
| Patients with any of the four secondary bleeding endpoints | 11 (0·7%) | 28 (1·7%) | 0·39 (0·19 to 0·79) | 0·0087 | |
| Patients with all four secondary bleeding endpoints | 8 (0·5%) | 19 (1·1%) | 0·42 (0·18 to 0·96) | 0·041 | |
| Secondary ischaemic events and mortality | |||||
| All-cause death | 12 (0·7%) | 13 (0·8%) | 0·93 (0·42 to 2·03) | 0·84 | |
| Cardiac death | 8 (0·5%) | 7 (0·4%) | 1·15 (0·42 to 3·18) | 0·46 | |
| Any stroke | 20 (1·2%) | 24 (1·4%) | 0·83 (0·46 to 1·50) | 0·54 | |
| Ischaemic | 11 (0·7%) | 15 (0·9%) | 0·74 (0·34 to 1·61) | 0·58 | |
| Haemorrhagic | 4 (0·2%) | 3 (0·2%) | 1·33 (0·29 to 3·71) | 0·71 | |
| Uncertain | 5 (0·3%) | 6 (0·4%) | 0·97 (0·49 to 1·92) | 0·94 | |
| Myocardial infarction | 17 (1·0%) | 11 (0·7%) | 1·45 (0·67 to 3·23) | 0·27 | |
| Procedural myocardial infarction | 1 (0·1%) | 1 (0·1%) | 0·00 (−0·28 to 0·28) | 0·88 | |
| Non-procedural myocardial infarction | 16 (0·9%) | 11 (0·7%) | 1·42 (0·66 to 3·03) | 0·29 | |
| Stent thrombosis | 5 (0·3%) | 5 (0·3%) | 0·97 (0·28 to 3·40) | 0·96 | |
| Definite | 3 (0·2%) | 5 (0·3%) | 0·59 (0·14 to 2·51) | 0·47 | |
| Probable | 2 (0·1%) | 0 | .. | .. | |
| Clinically driven revascularisation‡ | 40 (2·4%) | 41 (2·4%) | 0·99 (0·64 to 1·53) | 0·95 | |
| Target vessel revascularisation | 33 (2·0%) | 36 (2·1%) | 0·93 (0·58 to 1·49) | 0·75 | |
| Target lesion revascularisation | 27 (1·6%) | 28 (1·7%) | 0·97 (0·57 to 1·65) | 0·92 | |
| Cardiac death, non-fatal myocardial infarction, or ischaemic stroke | 31 (1·8%) | 32 (1·9%) | 0·98 (0·63 to 1·67) | 0·91 | |
Data are n (%) unless otherwise specified. Rates are number of events occurring between month 1 and month 12 after percutaneous coronary intervention (the second randomisation period), with Kaplan–Meier estimated percentages. BARC=Bleeding Academic Research Consortium. GUSTO=Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries. ISTH=International Society on Thrombosis and Haemostasis. TIMI=Thrombolysis in Myocardial Infarction flow grading system.
In patients with an acute coronary syndrome treated with percutaneous coronary intervention followed by 1 month of aspirin plus ticagrelor, follow-up treatment with ticagrelor monotherapy for an additional 11 months reduced clinically relevant bleeding without an accompanying increase in MACCE, compared with follow-up treatment with ticagrelor and aspirin for an additional 11 months.
Limitations and Considerations
- Separate studies are needed to investigate the safety and efficacy of a similar approach using other P2Y12 inhibitors, such as prasugrel and clopidogrel.
- Generalizability should be considered (98.7% of patients from China and Pakistan, where higher bleeding risk has been previously observed)
- Male predominance
- Al-Lamee R, Thompson D, Dehbi HM, Sen S, Tang K, Davies J, Keeble T, Mielewczik M, Kaprielian R, Malik IS, Nijjer SS, Petraco R, Cook
- Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057. doi:10.1056/NEJMoa0904327
- Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001-2015. doi:10.1056/NEJMoa0706482
- Kim C, Hong SJ, Shin DH, et al. Randomized evaluation of ticagrelor monotherapy after 3-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with new-generation sirolimus-eluting stents: TICO trial rationale and design. Am Heart J. 2019;212:45-52. doi:10.1016/j.ahj.2019.02.015
- Hahn JY, Song YB, Oh JH, et al. Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention: The SMART-CHOICE Randomized Clinical Trial [published correction appears in JAMA. 2019 Oct 1;322(13):1316]. JAMA. 2019;321(24):2428-2437. doi:10.1001/jama.2019.8146
- Mehran R, Baber U, Sharma SK, et al. Ticagrelor with or without Aspirin in High-Risk Patients after PCI. N Engl J Med. 2019;381(21):2032-2042. doi:10.1056/NEJMoa1908419
- Watanabe H, Domei T, Morimoto T, et al. Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI: The STOPDAPT-2 Randomized Clinical Trial. JAMA. 2019;321(24):2414-2427. doi:10.1001/jama.2019.8145
- Vranckx P, Valgimigli M, Jüni P, et al. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet. 2018;392(10151):940-949. doi:10.1016/S0140-6736(18)31858-0
Summary by: Dr Emily Lee @EmilyLee_8 and Dr. Dhruv Krishnan @Dhruv_mkrishnan
Visual abstract by: Dr. Ramy Doss @RamyDossMD
Trial Tweets by: Dr. Maryam Barkhordarian @MaryamBMD
Moderator of Twitter during CardsJC by: Dr. Dhruv Krishnan @Dhruv_mkrishnan
Promo by: Dr. Adriana Mares @AdrianaCMares and Dr. Chelsea Tweneboah @catweneboah
Under the guidance of House Chief: Dr. Rawan Amir @RawanAAmir
Supported by House Faculty: Dr. Jessie Holtzman @jhotlzman3 , Dr. Patrick Zakka @PatrickZakka and Dr. Karla Asturias @KarlaAsturias
