Thrombolytics in STEMI
Anupam kumar Singh ,MD
March 29, 2018
I am going to present here an initial data summary of the thrombolytic experience in Hindu Rao Hospital from 2012-2018 which is going to be presented as a formal paper. Only complete cases with 4-5 sets of ECG were chosen in this analysis. THE ST resolution from ST elevation as a criteria for successful thrombolysis is described in literature as three categories: Complete(>70% resolution),Partial(30-70%) and None(<30%),the criteria of time period varies in different literature. We assessed for ST resolution at 60 minutes,90 minutes and 180 minutes(to account for prolonged infusion of streptokinase )
Key Objectives-
- Examine the Demographic table summary at a galance of two thrombolytics
- Evaluate presnce of circadian rhythm in onset of symptoms and if it is attenuated in Diabetics
- Evaluate ST resolution and its timeline and circadian variation and factors affecting it(therapy and location of infarct 4 Evaluate complication Frequency in both thrombolytics
- Evaluate frequency of adverse effects in both thrombolytics
Lets look at summary table first
| N | streptokinase | tenecteplase | Test Statistic | |
| 79 | 31 | |||
| age | 110 | 455461 | 455868 | F1,108 = 1.87,P = 0.1741 |
| sex : male | 110 | 0 . 72272.1525779 | 0 . 83983.8712631 | χ2 1 = 1.65,P = 0.199 |
| Diabetic : Non_Diabetic | 110 | 0 . 65865.8235279 | 0 . 67767.7422131 | χ2 1 = 0.04,P = 0.848 |
| Hypertensive : Non_Hypertensive | 110 | 0 . 53253.1654279 | 0 . 48448.3871531 | χ2 1 = 0.20,P = 0.652 |
| SBP | 110 | 107123137 | 111119134 | F1,108 = 0.16,P = 0.6901 |
| HR | 110 | 637787 | 687883 | F1,108 = 0.11,P = 0.7461 |
| resolution | 110 | χ2 2 = 2.35,P = 0.309 | ||
| complete | 0 . 50650.6334079 | 0 . 54854.8391731 | ||
| partial | 0 . 31631.6462579 | 0 . 38738.7101231 | ||
| none | 0 . 17717.7221479 | 0 . 0656.452 231 | ||
| complication | 110 | χ2 4 = 5.58,P = 0.233 | ||
| Arrhythmia | 0 . 11411.392 979 | 0 . 0656.452 231 | ||
| Cardiogenic Shock | 0 . 17717.7221479 | 0 . 0979.677 331 | ||
| LVF | 0 . 17717.7221479 | 0 . 12912.903 431 | ||
| Recurrent Angina | 0 . 16516.4561379 | 0 . 0979.677 331 | ||
| Uncomplicated | 0 . 36736.7092979 | 0 . 61361.2901931 | ||
| adverse_effect | 110 | χ2 2 = 1.43,P = 0.489 | ||
| Allergic reaction | 0 . 0383.797 379 | 0 . 0000.000 031 | ||
| minor-moderate bleeding | 0 . 0898.861 779 | 0 . 0656.452 231 | ||
| No adverse effect | 0 . 87387.3426979 | 0 . 93593.5482931 | ||
| Smoker : smoker | 110 | 0 . 35435.4432879 | 0 . 48448.3871531 | χ2 1 = 1.57,P = 0.211 |
| location | 110 | χ2 2 = 4.33,P = 0.115 | ||
| Anterior | 0 . 48148.1013879 | 0 . 61361.2901931 | ||
| Inferior | 0 . 43043.0383479 | 0 . 22622.581 731 | ||
| Other | 0 . 0898.861 779 | 0 . 16116.129 531 | ||
| onset | 110 | χ2 5 = 1.79,P = 0.877 | ||
| 0-4 | 0 . 16516.4561379 | 0 . 16116.129 531 | ||
| 4-8 | 0 . 26626.5822179 | 0 . 22622.581 731 | ||
| 8-12 | 0 . 0636.329 579 | 0 . 0323.226 131 | ||
| 12-16 | 0 . 13913.9241179 | 0 . 22622.581 731 | ||
| 16-20 | 0 . 16516.4561379 | 0 . 12912.903 431 | ||
| 20-24 | 0 . 20320.2531679 | 0 . 22622.581 731 |
While tenecteplase appears to be better in terms of complication and adverse effcet profile it doesnt attain statistical significance(possibly due to small sample size)
Lets look at onset of symptom
| Diabetic | onset | percentage |
|---|---|---|
| Diabetic | 0-4 | 13.51 |
| Non_Diabetic | 0-4 | 12.33 |
| Diabetic | 4-8 | 16.22 |
| Non_Diabetic | 4-8 | 20.55 |
| Diabetic | 8-12 | 10.81 |
| Non_Diabetic | 8-12 | 16.44 |
| Diabetic | 12-16 | 21.62 |
| Non_Diabetic | 12-16 | 12.33 |
| Diabetic | 16-20 | 24.32 |
| Non_Diabetic | 16-20 | 24.66 |
| Diabetic | 20-24 | 13.51 |
| Non_Diabetic | 20-24 | 13.70 |
We clearly see a morning surge in non Diabetics which is absent in Diabetics.
Lets visualise.
Lets perform a formal test
##
## 0-4 4-8 8-12 12-16 16-20 20-24
## Diabetic 10 5 2 4 7 9
## Non_Diabetic 8 23 4 14 10 14##
## Fisher's Exact Test for Count Data
##
## data: mi$Diabetic and mi$onset
## p-value = 0.1102
## alternative hypothesis: two.sidedWhile the test doenst attain statistical significance , there is a definite trend.
Lets look at pattern of ST resolution
Lets look at proportion
We clearly see Proportion of complete and partial resolution is higher in tenecteplase.
Lets look at resolution by location-
While it gives an idea about absolute numbers. It is difficult to think in proportion.
Now it is clearer Inferior has a slightly higher rate of complete and partial thrombolysis. Lets visualise it via individual thrmombolytics.
We see tenecteplase has minimum rates of no resolution, while it is effective even in all locations, however inferior wall has good thrmobolysis results even with streptokinase.
Lets look at Kaplan Meir’s curve of ST resolution with time
We can clearly see here that Tenecteplase takes an early lead in complete ST resolution percent due to bolus action but slowly by 3 hours Streptokinase catches up. However this difference can be important in very sick patients, but in this tudy it did not manifest as a difference in complication even though tenecteplase had an edge.
Lets see formal analysis
## Call: survfit(formula = Surv(time, thrombolysis) ~ therapy, data = mi)
##
## therapy=streptokinase
## time n.risk n.event survival std.err lower 95% CI upper 95% CI
## 60 79 11 0.861 0.0390 0.788 0.941
## 90 68 5 0.797 0.0452 0.714 0.891
## 180 63 24 0.494 0.0562 0.395 0.617
##
## therapy=tenecteplase
## time n.risk n.event survival std.err lower 95% CI upper 95% CI
## 60 31 8 0.742 0.0786 0.603 0.913
## 90 23 7 0.516 0.0898 0.367 0.726
## 180 16 2 0.452 0.0894 0.306 0.666Now lets visualise circadian variation in resolution
| resolution | onset | percentage |
|---|---|---|
| complete | 0-4 | 8.77 |
| none | 0-4 | 6.25 |
| partial | 0-4 | 21.62 |
| complete | 4-8 | 12.28 |
| none | 4-8 | 31.25 |
| partial | 4-8 | 24.32 |
| complete | 8-12 | 5.26 |
| none | 8-12 | 25.00 |
| partial | 8-12 | 24.32 |
| complete | 12-16 | 15.79 |
| none | 12-16 | 18.75 |
| partial | 12-16 | 13.51 |
| complete | 16-20 | 36.84 |
| none | 16-20 | 18.75 |
| partial | 16-20 | 8.11 |
| complete | 20-24 | 21.05 |
| partial | 20-24 | 8.11 |
We see that there is a spike in no resolution in 4-8 i.e. in morning, so morning MI might be more resistant to thrombolytics and might require higher dose or PCI
Lets visualise
We can clearly see the resolution peaks towards evening and is lesser in early morning.
Lets visualise complications
We can clealy see that proprtion of uncomplicated MI is higher in tenecteplase,since we monitored hospital complications alone and didnt keep tab of mortality, we dont know how these complications behaved downstream.
Lets visualise complications by location
We see Inferior wall MI has lesse complications.
Lets visualise adverse effects.
We see that in our selected group there were no hemorrhagic strokes , though evidence of minor-moderate bleed and allergic reaction was higher in streptokinase group.
The adverse effects didnt achieve statistical significance.
Key take aways
- There is a circadian variation in onset of symptoms and ST resolution
- Complete ST resolution is slower in streptokinase though eventually catches up
- Inferior Wall MI tends to have better response to thrombolytics
- Complication rate is higher with streptokinase