Should use of intracoronary stents during percutaneous revascularisation be restricted?

RESEARCH LETTERS

40

0·3

10

1994

1996

p*

Stent utilisation rate (%) Number of stents per stent patients Total number of stents used Mean stent cost (£) Total stent cost (£) Number of balloons per procedure Total balloon cost (£) Mean balloon cost (£) Miscellaneous costs (£)

15 1·40 21 1250 (285) 26 250 1·93 (1·00) 72 100 721 (360) 302 (7)

42 1·26 53 1065 (234) 56 490 1·24 (1·13) 32 005 320 (235) 281 (76)

<0·001 0·048 <0·001 <0·001 <0·001 <0·001 <0·001 <0·001 <0·046

Total cost per procedure (£)

1340 (1111)

1234 (1249)

<0·046

Before After

30 ⫻ 10–3

8

ng/mL

ng/mL

0·2 20

0·1

6

0·0

4

10

0

Serum leptin

CSF leptin

CSF:serum leptin ratio

Mean (SEM) leptin concentrations in serum and CSF and CSF:serum leptin ratio before and after weight loss in obese women Leptin concentrations were measured by RIA (Linco Research Inc, St Charles, MO, USA). CSF samples were concentrated with Centricon filters.

correlated with leptin concentrations in serum (r =0·83; p<0·001) and in CSF (r=0·59; p<0·001); r for the association between fat mass and CSF leptin may be explained by the fact that this is not a linear relation.4,5 All the patients reduced their mean body-fat mass (⫺2·45 [SEM 0·32] kg, p<0·001]). Leptin concentrations in serum and in CSF decreased after weight loss (figure). The CSF:serum leptin ratio increased after weight loss in all patients. The fact that transport of leptin from the periphery to the CNS is improved after weight loss suggests that leptin is transported into the CNS by a saturable system. This could explain the lack of response to raised serum concentrations of leptin in obesity. Our data also suggest that obesity is not due to a leptin transport defect itself, but instead may be caused or related to the saturation of the leptin transport system. 1

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Campfield LA, Smith FJ, Burn P. The ob protein (leptin) pathway: a link between adipose tissue mass and central neural networks. Horm Metab Res 1996; 28: 619–32. Montague C, Farooqi S, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387: 903–08. Carlsson B, Lindell K, Garbrielsson B, et al. Obese (ob) gene defects are rare in human obesity. Obesity Res 1997; 5: 30–35. Caro JF, Kolaczynski JW, Nyce MR, et al. Decreased cerebrospinalfluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 1996; 348: 159–61. Schwartz MW, Peskind E, Raskind M, et al. Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nat Med 1996; 2: 589–93.

Department of Rehabilitation (M Krotkiewski) and Research Centre for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden

Should use of intracoronary stents during percutaneous revascularisation be restricted? Nicholas Palmer, Stephen Fort, Ian Starkey, Thomas Shaw, David Northridge

Over the past few years, rates of intracoronary stenting during percutaneous revascularisation procedures have increased substantially. This increase has been due largely to the demonstration of reduced restenosis rates compared with conventional balloon angioplasty (PTCA) in large randomised trials.1,2 However, economic analyses of intracoronary-stent placement based on these trial results have shown poor cost-effectiveness, largely as a result of increased in-hospital expenditure due to the complex anticoagulation regimens used and the direct stent costs.3,4 A

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All values are mean (SD) except were indicated. *Students’ t test.

Comparison of equipment use and procedural costs

recent study of optimum elective Palmaz-Schatz stent placement reported a $2200 increase in in-hospital laboratory costs compared with PTCA alone.5 These analyses may be less relevant to current practice since improved deployment techniques have reduced anticoagulation requirements and shortened hospital stay. Additionally, increased competition in the interventional product market has led to reduced stent and angioplasty equipment costs. To investigate the effects of increased stent use on inhospital costs in current clinical practice we compared 100 consecutive single-vessel PTCA procedures carried out in 1994 in a single centre with the same number done in 1996. Equipment, contrast, and drug usage were prospectively recorded onto a dedicated database (Filemaker Pro 2.1) during each procedure. Resources were costed according to manufacturers’ list prices. To compare the procedural costs, the 1994 equipment prices were recalculated at 1996 levels according to the retail price index. The baseline characteristics of the patients were identical in the two groups. The rate of restenotic lesions treated was higher in 1996 than in 1994 (21% vs 12%, p<0·05). Patients treated in 1996 had more complex lesion morphology than those treated in 1994 (AHA type A lesions 21% vs 37%, p<0·001). Nevertheless angiographic success rates were 95% in both groups. Emergency coronary bypass surgery or acute myocardial infarction occurred in two cases and one case in 1994 and 1996, respectively. There were no procedural deaths. Clinical restenosis, leading to repeat angiography within 6 months, was significantly lower in the 1996 cohort compared with 1994 (21% vs 35%, p=0·04). The need for repeat angioplasty was also significantly lower in 1996 than in 1994 (9% vs 26%, p=0·003). The table compares the stent use and procedural costs between 1994 and 1996. The greater use of intracoronary stents in 1996 was associated with an improved clinical outcome. Mean procedural resource costs in 1996, however, were less than in 1994. This was due to the combination of reduced standard equipment and balloon costs, reduced stent costs, and the development of longer stents thus reducing the need for multiple stents to cover a lesion. In addition, fewer balloons were necessary per case due mainly to improved balloon versatility and less requirement for perfusion balloons to seal dissections. The increasing demand for percutaneous coronary revascularisation is placing a large financial burden on limited health resources. However, policies to limit expenditure by restricting use of intracoronary stents may not have the desired effect. Previous economic analyses may have underestimated the cost-effectiveness of intracoronary stenting because they were based on out-dated equipment, inflated stent prices, and overly aggressive anticoagulation regimens which increased the length of hospital stay and caused bleeding complications. Our experience has shown that an increase in the use of intracoronary stents between 1994 and 1996 was associated with better outcomes for patients but no increase in procedural costs.

THE LANCET • Vol 351 • February 7, 1998

RESEARCH LETTERS 1

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Serruys PW, de Jaegere P, Kiemeneij F, et al. A comparison of balloon-expandable stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994; 331: 489–95. Fishman DL, Leon MB, Baim DS, et al, for the Stent Restenosis Study Investigators. A randomised comparison of coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994; 331: 496–501. Cohen DJ, Krumholz HM, Sukin CA, et al. In-hospital and one year economic outcomes after coronary stenting or balloon angioplasty: results from a randomised clinical trial. Stent Restenosis Study Investigators. Circulation 1995; 92: 2480–87. Goods CM, Liu MW, Iyer SS, et al. A cost analysis of coronary stenting without anticoagulation versus stenting with anticoagulation using warfarin. Am J Cardiol 1996; 78: 334–36. Sukin CA, Baim DS, Caputo BP, et al. The impact of optimal stenting techniques on cardiac catheterisation laboratory resource utilisation and costs. Am J Cardiol 1997; 79: 275–80.

Department of Cardiology, Western General Hospital, Edinburgh EH4 2XU, UK

Yttrium-90-labelled somatostatinanalogue for cancer treatment A Otte, J Mueller-Brand, S Dellas, E U Nitzsche, R Herrmann, H R Maecke

Treatment of unresectable somatostatin-receptor-positive tumours is difficult.1,2 Chemotherapy and radiotherapy often fail. As an alternative, a new peptide vector, DOTA-D-Phe1Tyr3-Octreotide (DOTATOC; DOTA: 1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid), that can be stably labelled with the ␤-emitting radioisotope yttrium90, has been developed.3,4 We have treated ten patients with different somatostatin-receptor-positive tumours; six patients with multiple treatments and four with a single treatment. Each treatment was monitored by X-ray computed tomography (CT) and 111In-DOTATOCscintigraphy. 18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) was done in two patients. We report two cases. A 44-year-old man with multiple abdominal metastases of a chemotherapy-resistant neuroendocrine cancer received seven treatments with yttrium-90-DOTATOC (Oct 21, 1996, 25 mCi; Dec 10, 25 mCi; Feb 3, 1997, 40 mCi; March 18, 50 mCi; June 30, 50 mCi; Sept 1, 60 mCi; Oct 13, 80 mCi). Since the end of the third treatment his disease stabilised, with no new metastases and no growth of the tumour masses. His back pain improved and he no longer needed treatment with morphine. Chromogranin-B decreased from 296 on March 20, 1996, to 141 pmol/L on Oct 15, 1997, and the neuronspecific-enolase from 20 µg/L to less than 10 µg/L. A 52-year-old woman with an unresectable and chemotherapy-resistant presacral neuroendocrine carcinoma infiltrating the sacrum, received three treatments with yttrium-90-DOTATOC (June 9, 1997, 40 mCi; July 14, 60 mCi; Aug 18, 80 mCi). There was shrinkage of a lymphnode metastasis in the anterior superior mediastinum from 14 cm3 before treatment to 5 cm3 after the third treatment (figures available from authors, on request). Dose estimates of this mediastinal metastasis during the third treatment session were 1·7 Gy/mCi, whereas the kidney received about 0·4 Gy/mCi. The presacral tumour showed a discrete regression in size from 112 cm3 before treatment in October, 1996, to 96 cm3 after treatment in September, 1997 (figure). 111 In-DOTATOC-scintigraphy also showed a two-fold reduction of peptide uptake in the mediastinal lymph-node metastasis. Of the remaining patients who had multiple treatment, two developed stable disease and two partial remission. In two of the four patients treated with one dose, FDG-

THE LANCET • Vol 351 • February 7, 1998

Contrast enhanced transaxial computed tomograph images before (top) and after treatment (bottom) in the second patient At the level of the presacral tumour mass (arrow).

PET showed a substantial reduction of glucose uptake in the tumour (figures available from authors, on request). The other two showed clinical improvement and stable disease. In nine of the ten patients treated, renal and bone marrow toxicity did not exceed grade 1 of the National Cancer Institute grading criteria at any stage of treatment. One patient developed a persisting grade 2 thrombocytopenia after a total dose of 180 mCi. This study was in part supported by the Swiss National Science Foundation (31-42516/94) and the “Regionale Krebsliga”. We thank radiotechnicians B Leu, L Schwob, S Fuchs, I Kübler, P Powell, T Böhler, and chemists A Heppeler, E Jermann, and M Behe. 1 2

3

Lamberts SWJ, van der Lely A-J, de Herder WW, Hofland LJ. Octreotide. N Engl J Med 1996; 334: 246–54. Krenning EP, Kooij PP, Pauwels S, et al. Somatostatin receptor: scintigraphy and radionuclide therapy. Digestion 1996; 57 (suppl 1): 57–61. de Jong M, Bakker WH, Krenning EP, et al. Yttrium-90 and indium-

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