ISIS-2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither

The survival gain (or improvement in predicted life expectancy) is now recognised as an index to quantify the benefit derived from using an innovative treatment (e.g. Treatment A) as opposed to a standard reference treatment (e.g. Treatment B).[1] Lifetime cost-effectiveness studies based on a comparative design (comparison of A vs. B) have recently generated a huge amount of data in terms of survival gains,[2-23] particularly in the area of oncology.[3-6,10,13-23] These cost-effectiveness studies determine the cost per life year gained (or the cost per QALY gained; QALY = quality-adjusted life year) by constructing a ratio with incremental cost at the numerator and incremental effectiveness at the denominator. Regardless of the economic data that form the numerator of this ratio, the incremental effectiveness at the denominator is being more and more frequently expressed as a survival gain (difference between mean lifetime survival per patient using A minus mean lifetime survival per patient using B) or a quality-adjusted survival gain (difference between QALYs per patient using A minus QALYs per patient using B). A lifetime approach that covers the entire life span of the patients is needed for an appropriate calculation of these gains. Published values of survival gain in oncology include 2.84 years per patient for adjuvant chemotherapy vs. no adjuvant chemotherapy in resectable colon cancer,[22] 1.97 years per patient for chemotherapy plus radiotherapy vs. no adjuvant therapy in oesophageal adenocarcinoma,[19] 1.34 years per patient for-interferon vs. no adjuvant therapy in high-risk resected cutaneous melanoma,[13] 1.04 up to 1.29 QALYs per patient for interferon vs. cytotoxic therapy in chronic myelogenous leukaemia,[4] 1.06 years per patient (or 1.27 QALYs per patient) for adjuvant CMF vs. no adjuvant chemotherapy in node-positive breast cancer,[14,15] 0.50 years per patient for interferon vs. no maintenance treatment in multiple myeloma,[21] 0.43 years per patient (or 0.49 QALYs per patient) for paclitaxel plus cisplatin vs. standard chemotherapy in advanced ovarian cancer,[16,17] 0.35 QALYs per patient for post-operative radiation therapy vs. no radiation therapy in early-stage resected breast cancer.[10]

The paper by Baigent et al.[24] reported the long-term results of the ISIS-2 trial and showed that, in patients with acute myocardial infarction, thrombolysis with streptokinase significantly improved survival as compared with no thrombolysis. The very long follow-up of the ISIS-2 study makes this trial similar to the cost-effectiveness oncologic studies mentioned above (in which a lifetime perspective was employed for the survival analysis). It can therefore be interesting to express the benefit of streptokinase in this disease condition as a lifetime survival gain (as opposed to the traditional death rate ratio utilised by Baigent et al.[24]). For this purpose, we have performed a lifetime analysis of the survival data presented in Figure 2 by Baigent et al. (using a Gompertz lifetime model[12] and the same 5% annual discount rate as in the study of Mark et al. mentioned below[11]) and we have obtained the following results: mean lifetime survival = 9.15 years per patient for streptokinase and 8.84 years per patient for no thrombolysis; survival gain = 0.31 years per patient. In comparing tissue plasminogen activator vs. streptokinase in acute myocardial infarction, Mark et al.[11] carried out a lifetime cost-effectiveness study in 1995, that showed that tissue plasminogen activator improved survival by 0.09 years per patient (or 0.08 QALYs per patient) in comparison with streptokinase.

The foregoing lifetime survival data for patients receiving thrombolysis with streptokinase or tissue plasminogen activator after acute myocardial infarction are interesting because they show that the improvement in survival was very marked when using streptokinase instead of no thrombolysis (survival gain = 0.31 years per patient) and much more modest when introducing tissue plasminogen activator in replacement of streptokinase (survival gain = 0.09 years per patient). The gains found in these clinical trials evaluating thrombolysis in acute myocardial infarction are in the same overall range (approximately from 0.1 to 2 years per patient) as those reported in the cost-effectiveness studies on anti-cancer treatments mentioned above.

The data presented in this letter show that the survival gain can be an interesting measure of clinical outcome for both cardiovascular diseases and cancer.

Andrea Messori, Sabrina Trippoli

Laboratorio SIFO* di Farmacoeconomia, c/o Drug Information Centre, Pharmaceutical Service, Azienda Ospedaliera Careggi, 50134 Firenze (Italy)

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