SHA24/023002

Critical reading of a manuscript: SYNTAX trial

MARKO TURINA University of Zurich Zurich, Switzerland

Ejection fraction of < 30% was found only in 1.3% of PCI and 2.5% of CABG patients!

Serruys PW et al. N Engl J Med 2009;360:961-972

General weakness of major PCI/CABG randomized trials: they are cleverly designed against coronary surgery. They are not representative of daily clinical practice, because they include only a highly selected population. But cardiologists continue to draw conclusions for the whole population with CAD.

RANDOMIZATION IN ARTS TRIAL (Arterial Revascularization Therapy Study) University Hospital Z端rich, AprilDecember 1997 5/986 (0.5 %) patients

STUDY ENROLLMENT IN MAJOR RANDOMIZED STUDIES IN THHE NINETIES COMPARING PTCA TO CABG (91 730 patients) RITA, ERACI, GABI, EAST, CABRI AND BARI trials

It is a often observed that patients recruited for trial have better survival and better results than those eliminated from the trial because of some exclusion criteria.

NIFEDIPINE IN ACUTE MYOCARDIAL INFARCTION (TRENT TRIAL) (9292 patients admitted with AMI)

When analyzing a trial, look carefully at â&#x20AC;&#x153;Material and Methodsâ&#x20AC;? section: crucial information explaining the results might be found there.

Study had an “all-comers” design ….

Enrollment and Randomization of Patients with Previously Untreated Three-Vessel or Left Main Coronary Artery Disease in the SYNTAX Trial

2 years, 85 centres: 25 patients/year

Serruys P et al. N Engl J Med 2009;360:961-972

Even with inclusion of registry patients, Syntax trial recruited 4’337 patients in two years, in 85 centres. This means that each centre was recruiting ~ 25 patients with 3VD/LMCA annually. If “all comers” statement is true, these centres should have been closed, according to present standards of PCI and CABG practice: requested activity minimum is 200 interventions/year.

Cardiac-Related Medications Given after the Study Procedure

Serruys P et al. N Engl J Med 2009;360:961-972

A study with radically different drug treatment protocols in the two analysed groups is statistically invalid, and should have never been accepted for publication.

Difference in outcome in trials funded by for-profit and not-for-profit sources JAMA 2006; 295(19):2270-4

Beware of industry sponsored trials!

Syntax was fully sponsored by industry (~ 70 â&#x20AC;&#x201C; 100 Million U$).

Results very often meet sponsorâ&#x20AC;&#x2122;s expectations!

WELL-HIDDEN WEAKNESS OF SYNTAX TRIAL: IT WAS DESIGNED “IN COLLABORATION” WITH TRIAL SPONSOR

Authors designed the study … in collaboration with sponsor …

Patients in randomized trials do not reflect present CAD population D.Taggart, Ann Thor Surg 2006

In UK registry > 90% 3VD, in trials 35%. In registry 30% normal LVEF, in trials 100%

Results of contemporary CABG are excellent !!!

o3102 patients randomized to single or bilateral IMA grafts o67 surgeons, 28 centres, seven countries o30 day mortality 1.2%, 1 yr mortality 2.4% o1 year incidence of stroke, MI, repeat revascularization all < 2%

Kaplan-Meier-estimated disease progression rates in all territories with patent conduits

Arterial grafts seem to exert a protective effect in distal coronary bed.

Dimitrova K. R. et al.; Ann Thorac Surg 2012;94:475-481

Kaplan-Meier-estimated overall freedom of disease progression and graft failure

Dimitrova K. R. et al.; Ann Thorac Surg 2012;94:475-481

Survival with CABG @ 3 years is 28.4 % higher!

Hannan E et al. N Engl J Med 2005;352:2174-2183

SYNTAX trial: Summary of criticism • Highly selected patient population, which is not representative of real life practice.

• Selected only low-risk patients, with normal or only moderately reduced LVEF. • Different post-intervention drug regimen were used, highly favouring PCI patients.

• Arterial revascularization was not mandated (admittedly 97.3% had one IMA).

• Surgical techniques were not representative of present practice: “no-touch aorta” and OPCAB (only 15%) were not applied.