2024
The PAX LC Trial: A Decentralized, Phase 2, Randomized, Double-blind Study of Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir for Long COVID
Krumholz H, Sawano M, Bhattacharjee B, Caraballo C, Khera R, Li S, Herrin J, Coppi A, Holub J, Henriquez Y, Johnson M, Goddard T, Rocco E, Hummel A, Al Mouslmani M, Putrino D, Carr K, Carvajal-Gonzalez S, Charnas L, De Jesus M, Ziegler F, Iwasaki A. The PAX LC Trial: A Decentralized, Phase 2, Randomized, Double-blind Study of Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir for Long COVID. The American Journal Of Medicine 2024 PMID: 38735354, DOI: 10.1016/j.amjmed.2024.04.030.Peer-Reviewed Original ResearchLC trialPROMIS-29Participants' homesTargeting viral persistencePlacebo-controlled trialDouble-blind studyElectronic health recordsCore Outcome MeasuresLong COVIDEQ-5D-5LRepeated measures analysisEvidence-based treatmentsPhase 2Double-blindParticipant-centred approachStudy drugPrimary endpointSecondary endpointsCommunity-dwellingHealth recordsHealthcare utilizationContiguous US statesViral persistencePatient groupDrug treatment
2021
Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19
Gupta A, Madhavan MV, Poterucha TJ, DeFilippis EM, Hennessey JA, Redfors B, Eckhardt C, Bikdeli B, Platt J, Nalbandian A, Elias P, Cummings MJ, Nouri SN, Lawlor M, Ranard LS, Li J, Boyle C, Givens R, Brodie D, Krumholz HM, Stone GW, Sethi SS, Burkhoff D, Uriel N, Schwartz A, Leon MB, Kirtane AJ, Wan EY, Parikh SA. Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19. Nature Communications 2021, 12: 1325. PMID: 33637713, PMCID: PMC7910606, DOI: 10.1038/s41467-021-21553-1.Peer-Reviewed Original ResearchConceptsAcute respiratory distress syndromeStatin usePrimary endpointCOVID-19Multivariable logistic regression modelStudy periodLower inpatient mortalityPropensity-matched cohortRespiratory distress syndromeCoronavirus disease 2019Electronic medical recordsLogistic regression modelsPropensity-score matchingHospital mortalityHyperinflammatory stateOutpatient medicationsClinical characteristicsInpatient mortalityStatin usersThrombotic complicationsDistress syndromeHospitalized patientsMyocardial injuryMedical recordsRetrospective analysis
2020
Non-inferiority trials using a surrogate marker as the primary endpoint: An increasing phenotype in cardiovascular trials
Bikdeli B, Caraballo C, Welsh J, Ross JS, Kaul S, Stone GW, Krumholz HM. Non-inferiority trials using a surrogate marker as the primary endpoint: An increasing phenotype in cardiovascular trials. Clinical Trials 2020, 17: 723-728. PMID: 32838556, PMCID: PMC8088773, DOI: 10.1177/1740774520949157.Peer-Reviewed Original ResearchConceptsNon-inferiority trialPrimary endpointClinical outcome trialsNon-inferiority marginSurrogate markerNon-inferiority designCardiovascular trialsOutcome trialsClinical outcomesDefinitive clinical outcome trialsNon-inferiority criteriaStudy protocolSurrogate outcomesBACKGROUND/Median numberSurrogate endpointsPrimary analysisCardiovascular interventionsCardiovascular medicineTrialsEndpointClinical interpretationOutcomesMarkersIntervention
2019
Myocardial infarction with non-obstructive coronary arteries as compared with myocardial infarction and obstructive coronary disease: outcomes in a Medicare population
Dreyer RP, Tavella R, Curtis JP, Wang Y, Pauspathy S, Messenger J, Rumsfeld JS, Maddox TM, Krumholz HM, Spertus JA, Beltrame JF. Myocardial infarction with non-obstructive coronary arteries as compared with myocardial infarction and obstructive coronary disease: outcomes in a Medicare population. European Heart Journal 2019, 41: 870-878. PMID: 31222249, PMCID: PMC7778433, DOI: 10.1093/eurheartj/ehz403.Peer-Reviewed Original ResearchConceptsMajor adverse cardiac eventsAcute myocardial infarctionHeart failureMyocardial infarctionCoronary angiographyComponents of MACENational Cardiovascular Data Registry CathPCI RegistryNon-obstructive coronary arteriesObstructive coronary artery diseaseAdverse cardiac eventsMajor adverse eventsObservational cohort studyObstructive coronary diseasePrognosis of patientsCoronary artery diseaseMACE componentsMINOCA patientsAdjusted riskCause mortalityPrimary endpointSecondary endpointsAdverse eventsCardiac eventsCathPCI RegistryCohort study
2018
Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study
Wallach JD, Ciani O, Pease AM, Gonsalves GS, Krumholz HM, Taylor RS, Ross JS. Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study. BMC Medicine 2018, 16: 45. PMID: 29562926, PMCID: PMC5863466, DOI: 10.1186/s12916-018-1023-9.Peer-Reviewed Original ResearchConceptsPostapproval trialsPivotal trialsActual clinical effectSurrogate markerTrial endpointsLarge treatment effectsPrimary endpointNovel therapeuticsNovel drugsTreatment effectsFDA approvalPatient-relevant outcomesMeta-epidemiological studyStandardized mean differenceTreatment effect sizeClinical effectsResultsBetween 2005Odds ratioDrug trialsSame indicationDrug AdministrationEvidence of differencesMean differenceU.S. FoodDisease
2017
Postapproval studies of drugs initially approved by the FDA on the basis of limited evidence: systematic review
Pease AM, Krumholz HM, Downing NS, Aminawung JA, Shah ND, Ross JS. Postapproval studies of drugs initially approved by the FDA on the basis of limited evidence: systematic review. The BMJ 2017, 357: j1680. PMID: 28468750, PMCID: PMC5421452, DOI: 10.1136/bmj.j1680.Peer-Reviewed Original ResearchConceptsSingle pivotal trialPivotal trialsPostapproval studiesSurrogate markerPrimary endpointNovel drugsClinical outcomesClinical studiesLimited evidenceSystematic reviewDouble-blind studyMedian total numberClinical evidenceSuperior efficacyBlind studyDrug AdministrationOriginal FDATrial approvalDiseaseTrialsDrugsFDAEndpointEfficacyMarkersTwo Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011
Bikdeli B, Punnanithinont N, Akram Y, Lee I, Desai NR, Ross JS, Krumholz HM. Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011. Journal Of The American Heart Association 2017, 6: e005285. PMID: 28325713, PMCID: PMC5524035, DOI: 10.1161/jaha.116.005285.Peer-Reviewed Original ResearchConceptsClinical outcome trialsOutcome trialsEndpoint trialsPrimary endpointCardiovascular trialsClinical outcome studiesClinical outcomesSurrogate markerPatient's perspectiveSurrogate endpointsOutcome studiesNew England JournalSample cohortTrial resultsTrialsSurrogate trialsEndpointPositive resultsAmerican MedicalInterventionHigh-impact journalsCohort
2012
Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study
Goldberger ZD, Chan PS, Berg RA, Kronick SL, Cooke CR, Lu M, Banerjee M, Hayward RA, Krumholz HM, Nallamothu BK, Investigators F. Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study. The Lancet 2012, 380: 1473-1481. PMID: 22958912, PMCID: PMC3535188, DOI: 10.1016/s0140-6736(12)60862-9.Peer-Reviewed Original ResearchConceptsHospital cardiac arrestSpontaneous circulationCardiac arrestResuscitation attemptsMedian durationResuscitation effortsGuidelines-Resuscitation registryDuration of resuscitationRisk-adjusted survivalHigh-risk populationAmerican Heart AssociationPrimary endpointHospital dischargeHeart AssociationObservational studyPatientsUS hospitalsClinical Scholars ProgramSurvival rateHospitalResuscitationHigher survival rateSurvivalNational InstituteHigher likelihood
2003
Long‐Term Prognostic Importance of Total Cholesterol in Elderly Survivors of an Acute Myocardial Infarction: The Cooperative Cardiovascular Pilot Project
Foody JM, Wang Y, Kiefe CI, Ellerbeck EF, Gold J, Radford MJ, Krumholz HM. Long‐Term Prognostic Importance of Total Cholesterol in Elderly Survivors of an Acute Myocardial Infarction: The Cooperative Cardiovascular Pilot Project. Journal Of The American Geriatrics Society 2003, 51: 930-936. PMID: 12834512, DOI: 10.1046/j.1365-2389.2003.51305.x.Peer-Reviewed Original ResearchConceptsAcute myocardial infarctionTotal serum cholesterolElevated total serum cholesterolCoronary artery diseaseCause mortalityTotal cholesterolSerum cholesterolElderly survivorsPrognostic importanceMyocardial infarctionCholesterol levelsLong-term prognostic importanceRetrospective medical record reviewAdjusted hazard ratioMedical record reviewLower total cholesterolStudy inclusion criteriaYear of dischargePrimary endpointOlder patientsArtery diseaseHazard ratioRecord reviewAcute careLipid subfractions