After Eighty Study Nicolai Kloumann Tegn, Michael Abdelnoor, Lars - - PowerPoint PPT Presentation

I nvasive versus Conservative Strategy in Patients Over 8 0 Years w ith Non ST-Elevation Myocardial I nfarction or Unstable Angina Pectoris: A Random ized Multicenter Study

After Eighty Study

Nicolai Kloumann Tegn, Michael Abdelnoor, Lars Aaberge, Knut Endresen, Pål Smith, Svend Aakhus, Erik Gjertsen, Ola Dahl-Hofseth, Anette Hylen Ranhoff, Lars Gullestad, Bjørn Bendz, for the After Eighty Study Investigators Oslo University Hospital, Rikshospitalet, Norway Presenter disclosure information: Funded by the Norwegian Health Association

Background

• Elderly patients counts for approximately one third of all

patients with Non ST-Elevation Myocardial Infarction (NSTEMI) and Unstable Angina Pectoris (UAP).

• Patients ≥ 80 years are under-represented in clinical

trials.

• The role of an early invasive strategy, and even an

invasive strategy at all, remains a subject of debate.

• According to WHO / US National Center for Health

Statistics, the life expectancy at the age of 80 years is ~ 9 years.

RCTs w ith early invasive treatm ent

Trial Num ber of patients Average age Num ber ( % ) ≥ 7 5 years Num ber ( % ) ≥ 8 0 years FRI SC I I 2 4 5 6 6 5 4 6 6 ( 1 9 ) I CTUS 1 2 0 0 6 1 3 6 ( 1 3 ) I talian Elderly ACS 3 1 3 8 2 3 1 3 ( 1 0 0 ) 1 9 6 ( 6 3 ) RI TA 3 1 8 1 0 6 3 2 1 7 ( 1 2 ) 4 6 ( 2 .5 ) TACTI CS 2 2 2 0 6 2 2 6 6 ( 1 2 .5 ) VANQW I SH 9 2 0 6 1 7 3 ( 8 )

Aim of the study

• The aim of the present clinical trial was to investigate

whether patients ≥80 years would benefit from an early invasive versus a conservative strategy when initially stabilized after NSTEMI or UAP .

• The primary endpoint was a composite of myocardial

infaction, need of urgent revascularization, stroke and death.

Study centers

Oslo

17 hospitals in the South-East Health Region of Norway covering a population of 2.7 mill.

I nclusion and exclusion criteria

I nclusion

• Patients ≥ 80 years.
• NSTEMI or UAP

, with/ without ST-segment depression in ECG, and normal/ elevated levels of troponin T or I.

• No chest pain or other

ischaemic symptoms/ signs after medical treatment and mobilization.

Exclusion

• Clinical unstable.
• Ongoing bleeding problems.
• Short life expectancy (less

than 12 months) due to serious comorbidity.

• Significant mental disorder.

Sam ple size calculation

• This was an open label dynamic randomized trial.
• Previous studies targeting this population were lacking

when planning this study.

• Considering the TACTICS study (Cannon et al NEJM 2001) for

a comparable population there was an incidence of composite endpoint (Death + MI) of 10.8% at 6 months.

• A prior power analysis was performed based on the

TACTICS study. Considering a type I error of 5% and a power of 80% to detect an absolute 10% reduction in composite endpoint, we calculated a need of 2* 206 = 412 patients.

4187 patients with NSTEMI or UAP 457 randomized 229 assigned the invasive group 5 dropouts 228 included in the intention-to-treat analysis 228 assigned the conservative group 1 dropout

I nclusion flow -chart

Not included; n= 3730

• Short life expectancy; n= 825
• Ongoing or recent bleeding; n= 183
• Unable to comply with protocol; n= 409
• Clinical unstable incl. ongoing ischemia; n= 560
• Refused to participate; n= 402
• Logistic reasons; n= 1011
• Other reasons; n= 103

229 included in the intention-to-treat analysis

I nclusion flow -chart

Randomization Invasive group PCI: Returned to community hospital after ~ 6-18 hours Conservative group Optimal medical treatment in the community hospitals before discharge Optimal medical treatment in the community hospitals before discharge No PCI: Returned to the community hospital after ~ 4-6 hours Transported to the PCI centre the day after inclusion

Baseline characteristics

Characteristics I nvasive Strategy ( N= 2 2 9 ) Conservative Strategy ( N= 2 2 8 )

Mean age ( range) – years 8 4 .7 ( 8 0 - 9 3 ) 8 4 .9 ( 8 0 - 9 4 ) Fem ale n ( % ) 1 0 4 ( 4 5 ) 1 2 8 ( 5 6 ) Previous MI n ( % ) 1 0 7 ( 4 7 ) 9 0 ( 4 0 ) Previous angina n ( % ) 1 2 3 ( 5 5 ) 1 1 5 ( 5 1 ) Previous PCI n ( % ) 5 4 ( 2 4 ) 4 6 ( 2 0 ) Previous CABG n ( % ) 4 3 ( 1 9 ) 3 2 ( 1 4 ) Hypertension n ( % ) 1 3 0 ( 5 8 ) 1 3 8 ( 6 1 ) Diabetes typeI I n ( % ) 4 5 ( 2 0 ) 3 2 ( 1 4 ) COPD n ( % ) 2 4 ( 1 1 ) 1 8 ( 8 ) Apoplexia cerebri n ( % ) 3 9 ( 1 7 ) 2 9 ( 1 3 ) Atrial fibrillation n ( % ) 4 8 ( 2 1 ) 5 2 ( 2 3 ) Sm oking; cur. or prev. n ( % ) 1 1 2 ( 5 0 ) 1 0 9 ( 4 8 % ) Troponin elevation n ( % ) 2 1 2 ( 9 5 ) 2 0 9 ( 9 2 ) Atrial fibrillation n ( % ) 4 9 ( 2 2 ) 4 2 ( 1 9 ) ST depression n ( % ) 4 2 ( 1 9 ) 4 0 ( 1 8 ) Left Bundle Branch Block n ( % ) 2 2 ( 1 0 ) 2 4 ( 1 1 ) GFR m L/ m in/ 1 ,7 3 m 2 5 2 ± 1 2 5 4 ± 1 1 GRACE score 1 3 8 1 3 5

P values are ns

Medical treatm ent during index

Characteristics n( % ) I nvasive Strategy ( N= 2 2 9 ) Conservative Strategy ( N= 2 2 8 )

Acetylsalisylic acid ( 7 5 m g) 2 2 3 ( 9 7 ) 2 2 2 ( 9 7 ) ADP-inhibitor Clopidogrel 1 9 5 ( 8 5 ) 1 8 8 ( 8 2 ) Ticagrelor 1 1 ( 5 ) 1 2 ( 5 ) ACE inhibitor / ARB 9 9 ( 4 3 ) 1 1 5 ( 5 0 ) Beta blocker 1 9 0 ( 8 3 ) 1 9 6 ( 8 5 ) Statins 2 0 5 ( 9 0 ) 1 9 3 ( 8 5 ) Loop or thiazide diuretics 9 4 ( 4 1 ) 7 6 ( 3 3 ) Calcium channel blocker 4 5 ( 2 0 ) 4 7 ( 2 1 ) Nitrates 1 0 4 ( 4 5 ) 1 2 6 ( 5 5 ) Anticoagulation W arfarin 3 8 ( 1 7 ) 2 1 ( 9 ) Heparin ( LMW H) 1 7 3 ( 7 6 ) 1 7 3 ( 7 6 ) Anti-I I a ( dabigatran) 1 1

Medical therapy at discharge

Characteristics I nvasive Strategy ( N= 2 2 9 ) Conservative Strategy ( N= 2 2 8 )

Acetylsalisylic acid ( 7 5 m g) 2 1 2 ( 9 3 ) 2 1 1 ( 9 3 ) ADP-inhibitor Clopidogrel 1 6 4 ( 7 2 ) 1 6 5 ( 7 2 ) Ticagrelor 9 ( 4 ) 8 ( 4 ) ACE inhibitor / ARB 1 1 8 ( 5 2 ) 1 2 2 ( 5 4 ) Beta blocker 1 9 2 ( 8 4 ) 1 9 2 ( 8 4 ) Statins 2 0 6 ( 9 0 ) 1 9 1 ( 8 6 ) Loop or thiazide diuretics 1 0 4 ( 4 5 ) 8 6 ( 3 8 ) Calcium channel blocker 5 4 ( 2 4 ) 5 3 ( 2 3 ) Nitrates 7 7 ( 3 4 ) 1 0 9 ( 4 8 ) Oral anticoagulation W arfarin 4 8 ( 2 1 ) 3 2 ( 1 4 ) Anti-Xa ( rivaroxaban) 3 3 Anti-I I a ( dabigatran) 1 6

Results

Rate Ratio, 0.48 (95% CI, 0.37-0.63); p<0.00001 Freedom of compocite endpoints

Results

Endpoint I nvasive ( N= 2 2 9 ) Conservative ( N= 2 2 8 ) Rate Ratio P value* Prim ary Endpoint Com posite Endpoint 9 3 ( 4 1 % ) 1 4 0 ( 6 1 % ) 0 .4 8 ( 0 .3 7 - 0 .6 3 ) < 0 .0 0 0 1 Com ponents of the Prim ary EP Myocardial infarction 3 9 ( 1 7 % ) 6 9 ( 3 0 % ) 0 .5 0 ( 0 .3 3 - 0 .7 5 ) 0 .0 0 0 3 Need of urgent revasc. 5 ( 2 % ) 2 4 ( 1 1 % ) 0 .1 9 ( 0 .0 5 - 0 .5 2 ) 0 .0 0 0 1 Stroke 8 ( 3 % ) 1 3 ( 6 % ) 0 .6 1 ( 0 .2 2 - 1 .6 0 ) 0 .2 6 Death of any cause 5 7 ( 2 5 % ) 6 2 ( 2 7 % ) 0 .8 7 ( 0 .5 9 - 1 .2 7 ) 0 .5 3 Com posite of death + MI 8 1 ( 3 5 % ) 1 0 9 ( 4 8 % ) 0 .5 4 ( 0 .4 0 – 0 .7 3 ) < 0 .0 0 0 1

Median follow -up of 1 .5 1 years * P-values are two-tailed

Bleeding com plications

I nvasive Strategy ( N= 2 2 9 ) Conservative Strategy ( N= 2 2 8 )

Major 4 4 Gastro intestinal 2 2 Percardial tam ponade 1 Traum atic epidural hem atom a 1 Traum atic subdural hem atom a 1 Subarachnoid hem orrhage 1 Minor 2 3 1 6 Gastro intestinal 1 4 1 1 Other 9 5

P values are ns

Conclusions

• We have demonstrated that an invasive

strategy is superior to a conservative strategy in patients ≥ 80 years with NSTEMI

• r UAP.
• No differences in complication rates (i.e.

bleedings) were seen between the two strategies.

Steering com m ittee Nicolai K. Tegn, Michael Abdelnoor, Lars Aaberge, Knut Endresen, Pål Smith, Svend Aakhus, Erik Gjertsen, Lars Gullestad, Bjørn Bendz (Chairman). Data and safety m onitoring board Theis Tønnessen and Rune Wiseth Acknow ledgem ents Aker Hospital, Akershus University Hospital, Bærum Hospital, Diakonhjemmet Hospital, Drammen Hospital, Elverum Hospital, Fredrikstad Hospital, Gjøvik Hospital, Hamar Hospital, Kongsberg Hospital, Lillehammer Hospital, Moss Hospital, Notodden Hospital, Ringerike Hospital, Skien Hospital and Vestfold Hospital.

After Eighty Study investigators