The primary outcome fails - What next?

New England Journal of Medicine

Volumn 375, Issue 9, 2016, Pages 861-870

  Pocock, Stuart J ^a   Stone, Gregg W ^b  

^a LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^b NewYork Presbyterian Hospital   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; AMLODIPINE; ATENOLOL; ATORVASTATIN; BISOPROLOL; CANDESARTAN; CANGRELOR; CAPTOPRIL; CLOPIDOGREL; FLUTICASONE PROPIONATE PLUS SALMETEROL; HEPARIN; HIRULOG; IVABRADINE; MOXONIDINE; PIOGLITAZONE; PLACEBO; SPIRONOLACTONE; TERUTROBAN; TICAGRELOR; TIROFIBAN; VALSARTAN;

ACUTE CORONARY SYNDROME; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL PROTOCOL; CORONARY ARTERY BYPASS GRAFT; CORONARY ARTERY DISEASE; EVIDENCE BASED MEDICINE; FOLLOW UP; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART INFARCTION; HEART LEFT VENTRICLE FAILURE; HEART MUSCLE ISCHEMIA; HEART MUSCLE REVASCULARIZATION; HUMAN; HYPERTENSION; INTENTION TO TREAT ANALYSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PERCUTANEOUS CORONARY INTERVENTION; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POPULATION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SYSTOLIC HEART FAILURE; TRANSIENT ISCHEMIC ATTACK; TREATMENT INDICATION; TREATMENT OUTCOME; METHODOLOGY; PROCEDURES; STANDARDS; TREATMENT FAILURE;

HUMANS; INTENTION TO TREAT ANALYSIS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RESEARCH DESIGN; TREATMENT FAILURE;

EID: 84985963205     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMra1510064     Document Type: Review

References (40)

1. Sterne JA, Davey Smith G. Sifting the evidence - what's wrong with significance tests? BMJ 2001; 322: 226-31.
2. Stone GW, Pocock SJ. Randomized trials, statistics, and clinical inference. J Am Coll Cardiol 2010; 55: 428-31.
3. Pocock SJ, McMurray JJV, Collier TJ. Making sense of statistics in clinical trial reports: Part 1 of a 4-part series on statistics for clinical trials. J Am Coll Cardiol 2015; 66: 2536-49.
4. Bousser MG, Amarenco P, Chamorro A, et al. Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): A randomised, double-blind, parallel-group trial. Lancet 2011; 377: 2013-22.
5. Calverley PMA, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007; 356: 775-89.
6. CIBIS Investigators and Committees. A randomized trial of β-blockade in heart failure: The Cardiac Insufficiency Bisoprolol Study (CIBIS). Circulation 1994; 90: 1765-73.
7. CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): A randomised trial. Lancet 1999; 353: 9-13.
8. Dormandy JA, Charbonnel B, Eckland DJA, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): A randomised controlled trial. Lancet 2005; 366: 1279-89.
9. Bhatt DL, Lincoff AM, Gibson CM, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009; 361: 2330-41.
10. Leonardi S, Truffa AA, Neely ML, et al. A novel approach to systematically implement the universal definition of myocardial infarction: Insights from the CHAMPION PLATFORM trial. Heart 2013; 99: 1282-7.
11. Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med 2013; 368: 1303-13.
12. Fox KAA, Ford I, Steg PG, Tendera M, Ferrari R. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): A randomised, double-blind, placebocontrolled trial. Lancet 2008; 372: 807-16.
13. Fox K, Ford I, Steg PG, Tardif J-C, Tendera M, Ferrari M. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med 2014; 371: 1091-9.
14. Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): A randomised pla- cebo-controlled study. Lancet 2010; 376: 875-85.
15. Topol EJ, Moliterno DJ, Herrmann HC, et al. Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med 2001; 344: 1888-94.
16. Cohn JN, Pfeffer MA, Rouleau J, et al. Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail 2003; 5: 659-67.
17. Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372: 1791-800.
18. Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014; 370: 1383-92.
19. Pfeffer MA, Claggett B, Assmann SF, et al. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation 2015; 131: 34-42.
20. Pfeffer MA, McMurray JJV, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349: 1893-906.
21. Wang R, Lagakos SW, Ware JH, Hunter DJ, Drazen JM. Statistics in medicine - reporting of subgroup analyses in clinical trials. N Engl J Med 2007; 357: 2189-94.
22. Pocock SJ, McMurray JJ, Collier TJ. Statistical controversies in reporting of clinical trials: Part 2 of a 4-part series on statistics for clinical trials. J Am Coll Cardiol 2015; 66: 2648-62.
23. Mohr FW, Morice MC, Kappetein AP, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year followup of the randomised, clinical SYNTAX trial. Lancet 2013; 381: 629-38.
24. Kappetein AP,Serruys PWSabik JF, et al. Design and rationale for a randomized comparison of everolimus-eluting stents and coronary artery bypass graft surgery in selected patients with left main coronary artery disease: The EXCEL trial. Euro- Intervention 2016 (in press).
25. Dahlof B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): A multicentre randomised controlled trial. Lancet 2005; 366: 895-906.
26. Valgimigli M, Frigoli E, Leonardi S, et al. Bivalirudin or unfractionated heparin in acute coronary syndromes. N Engl J Med 2015; 373: 997-1009.
27. Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358: 2218-30.
28. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355: 549-59.
29. Gupta SK. Intention-to-treat concept: A review. Perspect Clin Res 2011; 2: 109-12.
30. Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med 2011; 364: 1607-16.
31. Velazquez EJ, Lee KL, Jones RH, et al. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med 2016; 374: 1511-20.
32. The BARI 2D Study Group. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med 2009; 360: 2503-15.
33. Rogers JK, Pocock SJ, McMurray JJ, et al. Analysing recurrent hospitalizations in heart failure: A review of statistical methodology, with application to CHARMPreserved. Eur J Heart Fail 2014; 16: 33-40.
34. Knopp RH, d'Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care 2006; 29: 1478-85.
35. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): Multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685-96.
36. Rader DJ, deGoma EM. Future of cholesteryl ester transfer protein inhibitors. Annu Rev Med 2014; 65: 385-403.
37. The CAPRICORN Investigators. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: The CAPRICORN randomised trial. Lancet 2001; 357: 1385-90.
38. Bhatt DL, Kandzari DE, O'Neill WW, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med 2014; 370: 1393-401.
39. Frobert O, Lagerqvist B, Olivecrona GK, et al. Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med 2013; 369: 1587-97.
40. Jolly SS, Cairns JA, Yusuf S, et al. Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial. Lancet 2016; 387: 127-35.