There are some studies you probably should just know before you start intern year. Here's a list I've compiled for because I am the best. And you are gonna be the best interns because you will know these studies :)
Highly recommend using WikiJournalClub.com to look up landmark trials and studies.
My Tier List (based on how often I needed to know certain trials):
S Tier = AFFIRM, RACE II, ARDSNet, PROSEVA
A Tier = ACCORD, NICE-SUGAR, ALLHAT, SPRINT, FAIR-HF, EMPA-REG, LEADER, REDUCE, SELECT-D
B Tier = ACURASYS, ROSE, FLORALI, TRICC/TRISS
C Tier = the rest of the articles below
Diabetes
Okay, you definitely need to know these trials. Maybe not so much the UKPDS and ADVANCE ones but definitely the principle that good glucose control decreases microvascular but not macrovascular complications. But ACCORD, EMPA-REG + CANVAS, LEADER + REWIND, and the ADA 2021 guidelines are huge!
ACCORD = targeting a goal A1c <6% increases mortality compared to goal A1c <8%
EMPA-REG = SGLT2 inhibitors decrease CV events in diabetic patients (recommended for heart failure)
LEADER = GLP-1 agonists decrease CV events in diabetic patients (recommended for CAD)
UKPDS 33 and ADVANCE = intensive BG control in diabetes reduces microvascular complications (retinopathy, nephropathy, neuropathy) but NOT macrovascular complications (ischemic heart disease, peripheral vascular disease, cerebrovascular disease)
ADA 2021 Guidelines = recommends goal A1c <7% in most adults, <8% in patients with history of severe hypoglycemia, limited life expectancy, multiple comorbidities, etc.
NICE-SUGAR = goal BGs for inpatients (studied in ICU patients) is 140-180. Intensive control led to more deaths.
Hypertension
People talk about these trials a lot. You should definitely know the basics of them. Basically ACCORD-BP said one thing and SPRINT said another, so now we target a goal BP <130/80 which is kind of in between both lol. I just threw the PATHWAY one in there because it says why our first-line agent is spironolactone for resistant HTN but it's not as high-yield.
ALLHAT = established CCBs, ACEIs, and thiazides (chlorthalidone) as the first line antihypertensives
ACCOMPLISH = ACEI + CCB reduces mortality better than ACEI + thiazide. Criticism is that they used HCTZ rather than chlorthalidone.
PATHWAY-2 = why we add spironolactone for resistant HTN (defined as patients on ACEI/ARB + CCB + diuretic)
ACCORD-BP = intensive SBP control <120 compared to <140 did not reduce adverse outcomes in pts WITH diabetes
SPRINT = intensive SBP control <120 compared to <140 improved CV outcomes in pts WITHOUT diabetes
2017 ACC/AHA Guidelines = recommends treating to goal BP <130/80 based on the prior studies in ALL patients
Atrial Fibrillation
You freaking better know AFFIRM and RACE II like the back of your freaking hand!!! !@#$!!! There's some other ones that are sort of whatever. BRIDGE tells us that when you hold warfarin prior to surgery, you don't need to give heparin in the interim to patients if their CHADSVASc scores are <2-3 . ARISTOTLE, RE-LY, ROCKET AF, ENGAGE AF-TIMI 48 basically all tell us that DOACs are as good if not better than warfarin. But damn, AFFIRM and RACE II are always going to guide your practice and EAST-AFNET might be a new game changer.
AFFIRM = rate control is equivalent to rhythm control in nonvalvular AF, but rhythm trends towards increased mortality
RACE II = why our target heart rate for afib is <110 bpm rather than <80 bpm
EAST-AFNET 4 = new study showing rhythm control actually might be better than rate control now . . . !
Heart Failure
You really don't need to know the specifics . . . just know that the establishing of "guideline-directed medical therapy" is backed by a ton of research.
CONSENSUS, V-HeFT II, SOLVD = ACEIs are a first line medication for reducing mortality in HFrEF
MERIT-HF, COPERNICUS, CIBIS-II = beta-blockers are a first line medication for reducing mortality in HFrEF
RALES, EMPHASIS-HF, EPHESUS = aldosterone antagonists are indicated for HFrEF <35%
A-HeFT = isosorbide dinitrate + hydralazine improves survival in black patients with HFrEF. Per AHA 2013 guidelines, all black patients should be on nitrates/hydralazine for HFrEF if already on optimal medical therapy, and ALL patients should be considered for this if they can't tolerate ACEI/ARB therapy. Kind of a controversial study because race and genetic variations don't always correlate strongly.
PARADIGM-HF, PARAGON-HF = ARNIs (sacubitril-valsartan) was better than ACEI in reducing mortality in HFrEF but not HFpEF. Per 2016 ACC heart failure guidelines, if patients are tolerating ACE-I or ARB, replacement with ARNI is recommended.
MADIT-II, SCD-HeFT = the studies that showed ICD reduced all cause mortality in EF <30% (we do in EF <35%)
DANISH = ICDs don't show a significant mortality benefit in NON-ischemic cardiomyopathy <35% but did reduce sudden cardiac death, decision to place ICD should be made on case-by-case basis RAFT = Cardiac resynchronization therapy (CRT-P or CRT-D) is indicated if LBBB, QRS >150, and EF <35%
DAPA-HF = in patients with HFrEF with or WITHOUT T2DM, SGLT2 inhibitors decreased mortality! Important study to know because it's changing our current practice!
FAIR-HF = in patients with HFrEF and iron deficiency, IV iron improves NYHA class, 6-minute walk distance, and QOL
DOSE = why we use 2-2.5x home dose when patient comes with acute decompensated heart failure, also continuous vs intermittent loop diuretics is equivalent
Val-HeFT, CHARM-Added = ARBs can be added to ACEI if aldosterone antagonist is not indicated or poorly tolerated (note this strategy does not have any benefit in diabetic nephropathy per the VA-NEPHRON D trial)
CHARM-Preserved = ARBs in HFpEF may reduce hospitalizations but have no effect on mortality
Acute Respiratory Distress Syndrome
ARDSNet, PROSEVA, and ACURASYS are the ones to know here.
ARDSNet = low tidal volume ventilation (6 mL/kg) was superior to high tidal volume ventilation (12 mL/kg)
Daily ICU Sedation Holidays and Awakening and Breathing Controlled Trial (ABC or "wake up and breathe" trial) = daily sedation holidays reduce days on ventilators, days in ICU, and days in hospital
PROSEVA = in patients with severe ARDS (P:F <150), prone positioning reduces mortality. Proned patients may have been healthier however and there was a higher rate of unscheduled extubation, ET tube obstruction, and pressure ulcers (which are higher in proned patients) were not reported
ACURASYS = paralysis for 48 hours in patients with early severe ARDS improved 90 day survival
ROSE = paralysis did NOT show improved mortality . . . so we're not doing it as much as before
FLORALI = high-flow nasal cannula was better than non-invasive ventilation (CPAP, BiPAP) in patients with acute hypoxemic respiratory failure
Acute Coronary Syndrome
This is a bit of a weak spot for me. I have to admit I don't know which ones are the highest yield at this current time. I'll keep updating. Work in progress!
COLCOT = interesting newer study showing colchicine may reduce the risk of CV events after MI! No guidelines yet but practice may change in the near future.
PLATO = ticagrelor (Brilinta) is better than clopidogrel (Plavix) in ACS
VA Cooperative Study = the landmark trial in 1983 which showed aspirin reduces mortality from acute MI or UA
AVOID = supplemental oxygen for patients having a STEMI but who are not hypoxic may increase MI size and risk for recurrent MI . . . later trial DETO2X-AMI also supported these results
Sepsis / Shock
Dang, I didn't know about all these trials before but they all seem pretty high-yield. There are some pretty legit and interesting studies in this group!
Annane Trial, CORTICUS, HYPRESS, ADRENAL, APPROCHS = Annane in 2002 showed short-term mortality benefit with IV hydrocortisone and fludrocortisone in septic shock in patients with evidence of adrenal insufficiency. CORTICUS and HYPRESS showed faster reversal of shock but possible increased infection rates. 2018 ADRENAL again showed no difference in death at 90 days between hydrocortisone and placebo but there was faster time to reversal of shock, shorter time to discharge from ICU, time to extubation, and decreased number of blood transfusions. 2018 APPROCHS confirmed Annane Trial's findings of reduced mortality. Notably, the patients in Annane Trial and APPROCHS were more critically ill than in CORTICUS, HYPRESS, and ADRENAL which may account for some of these findings. Conclusion: there may be a benefit to steroids in shock, but even if so it is modest at best. Still worth trying though
Hydrocortisone, Vitamin C, and Thiamine in Severe Sepsis and Septic Shock = 2017 study showing 32% decrease in mortality (P < 0.001) with Vitamin C administration, thought to be due to synergistically reducing inflammation along with hydrocortisone. But this was a very low-quality study and with only 97 patients
VITAMINS = 2020 study showing that IV vitamin C, thiamine, and hydrocortisone did not lead to faster resolution of septic shock compared to hydrocortisone alone
Rivers Trial, ARISE, ProCESS, ProMISe = early goal-directed therapy was introduced by Rivers Trial in 2001, suggesting all patients should get an arterial line and central line with continuous ScvO2 monitoring. The 2014 ARISE, 2014 ProCESS, and 2015 ProMISe trials showed that EGDT is not superior to usual care so now we don't do all these lines for no reason. BAM MIC DROP.
HEAT = tylenol doesn't improve mortality in patients with probable infection and fevers, but shortens ICU length of stay in survivors and delays death in non-survivors
SEPSISPAM = goal MAP 80-85 didn't reduce all-cause mortality compared to MAP 65-70, was associated with less renal dysfunction but higher rates of afib
Sepsis-3 = updated guidelines in 2016. Sepsis was first described in 1992 with Sepsis-1, and introduced the SIRS criteria and sepsis steps (sepsis, severe sepsis, septic shock, multi-organ dysfunction syndrome). Sepsis-3 removed SIRS and replaced it with SOFA and q-SOFA. The term severe sepsis was also removed as it was considered redundant.
SOAP II = norepinephrine is the first-line antiarrhythmic, dopamine is similar but has higher risk of arrhythmias
VASST = addition of low-dose vasopressin did not reduce mortality when compared to norepinephrine alone. Main use is as a catecholamine-sparing agent. Also the power of the study was a little limited
IDEAL-ICU = no difference between early-initiation vs delayed-initiation RRT strategies in patients with septic shock and AKI without urgent need for dialysis
ATHOS-3 = angiotensin II is a really good vasopressor in patients with severe vasodilatory shock on multiple pressors
CRISTAL = colloids did not give mortality benefit over crystalloids in ICU patients with hypovolemic shock . . . HOWEVER there was a mortality benefit at 90 days which should be further explored. This was a follow-up to the 2004 SAFE study which showed no benefit of albumin over normal saline
BICAR-ICU = giving bicarbonate for severe metabolic acidosis didn't improve mortality except in patients with AKI
PRORATA = HIGH-YIELD!! Procalcitonin-guided antibiotic strategy resulted in fewer days of antibiotics without an >10% increase in mortality. Don't use procalcitonin to guide when to START antibiotics. But you can use it and trend it to guide when to STOP antibiotics! Criticism is that the trial used a >10% increase in mortality threshold rather than >5%.
SEDCOM = no difference between dexmedtomidine and midazolam in achieving sedation, but dexmedetomidine resulted in less time in ventilator, delirium, tachycardia, and hypertension at the cost of bradycardia
SMART = among medical and surgical ICU patients, LR or plasma-lyte reduce rate of death or RRT compared to NS
Yang-Tobin Study = the study that came up with the rapid shallow breathing index, in 1991! Maybe before you were born!
Hyperlipidemia
There are a lot of studies that showed why statins are so good for reducing cardiovascular mortality in patients with HLD. Here's the main landmark study. There's plenty more to look into if you want to see why we do high-intensity statins, and why we are now starting to add ezetimibe and PCSK9 inhibitors!
4S = Scandinavian Simvastatin Survival Study, LANDMARK study showing statins reduce all-cause mortality in patients with hyperlipidemia and prior MI or angina
Alcoholic Hepatitis
Idk I've just heard of the STOPAH trial a few times so it's probably a good one to know.
STOPAH = newest study which showed neither prednisolone or pentoxifylline showed mortality benefit in alcoholic hepatitis, though there was a trend towards improved mortality with prednisolone (P = 0.06)
Pentoxifylline in Severe Alcoholic Hepatitis = 2000 study suggesting pentoxifylline may improve survival
Prednisolone in Severe Alcoholic Hepatitis = 1992 study suggesting prednisolone improves survival
Cirrhosis
There's a few situations where giving albumin to cirrhotics is indicated - SBP, hepatorenal syndrome, or large volume paracentesis.
Albumin for SBP = IV albumin reduces renal impairment in cirrhotic patients with SBP, leading to AASLD 2012 guideline stating we should give 1.5 g albumin per kg body weight within 6 hours of presentation and 1g/kg on day 3
Anemia
Just transfuse everyone to goal Hgb > 7. Unless they have CAD. Then you can do Hgb > 8. Now you know the names of the trials that figured this out.
TRICC = in ICU patients transfusion to goal Hgb > 7 had better survival compared to goal Hgb > 10
Transfusion Strategies for Acute Upper GI Bleeding = goal Hgb > 7 had reduced mortality compared to goal Hgb > 10
TRISS = in patients with septic shock, transfusion to goal Hgb > 7 had similar mortality compared to goal Hgb > 9. This article led to rewriting of Surviving Sepsis Guidelines which previously had suggested transfusing to goal Hgb > 10!
COPD
Yeah, know this one.
REDUCE = 5 days of steroids for COPD exacerbation is non-inferior to a 14-day course
Well, I guess you could know tese other ones too because they are the reason we do LAMA -> LABA -> ICS, why we say oxygen gives mortality benefit, etc.
VTE in Cancer
If a patient with cancer gets a VTE, you can send them home on LMWH or rivaroxaban. Less bleeding with LMWH, decreased recurrent VTE with rivaroxaban.
SELECT-D = rivaroxaban can be used to decrease risk of recurrent VTE in cancer patients but at the expense of increased rates of bleeding (particularly in patients with GI malignancies . . . so send them home with LMWH if GI malignancy but if they are low risk for bleeding you can consider rivaroxaban). Was actually better than LMWH at decreasing rates of VTE though!
CLOT = 2003 trial which showed LMWH was as effective as warfarin for VTE prevention in cancer patients
Appendicitis
Not sure why I put this one here because it's more surgery . . . but it's an interesting one to know!
APPAC = medical management with antibiotics may be better than surgical management in patients with uncomplicated appendicitis
