Effectiveness and safety of the low-molecular-weight heparin CY 216 in the prevention of fatal pulmonary embolism and thromboembolic death in general surgery. A multicentre, double-blind, randomized, controlled clinical trial versus placebo (STEP). STEP Study Group.
Deep venous thrombosis is very frequent after general surgery, and its major complication, pulmonary embolism, is today the most frequent cause of postoperative death. The reduction of this cause of mortality is mainly based on its prevention rather than its therapy. This purpose was achieved by using physical and pharmacological means. During the past 15 years, low-dose heparin has been one of the most important means in the prevention of deep venous thrombosis, associated with early mobilization of surgical patients, but its actual efficacy against fatal pulmonary embolism was never statistically proved. In the early 80s new heparins became available, and their first experimental and clinical use demonstrated a longer half-life, a higher anti-Xa activity, and a lower haemorrhagic risk. On the basis of these data, we started a study in order to assess efficacy and tolerance of the new low-molecular-weight heparin CY 216 in preventing fatal pulmonary and thromboembolic death in patients undergoing general surgery. The study was designed as a multicentre, double-blind, randomized, controlled clinical trial versus placebo. A total of 4,498 patients, aged over 40 years undergoing general surgery, with anaesthesia lasting at least 45 min, were consecutively enrolled in the 18 centres which took part in the trial. 2,247 accounted for the CY-216-treated group and 2,251 for the placebo group. The patients received either subcutaneous injections of 0.3 ml of CY 216, equivalent to 7,500 anti-Xa units, or of 0.3 ml of a saline solution supplied in an identical form. The first dose was administered 2 h before surgery, the second 12 h later, and then once daily for at least 7 days. A post-mortem examination was carried out in every patient who died. The trial began in February 1986 and ended in June 1988. Statistical analysis showed that the two groups of patients were well matched for age, sex, type of disease, site and duration of operations, as well as for the incidence of risk factors which could predispose to the thromboembolic disease. Twenty-six deaths were recorded and validated. Eight (0.36%) belonged to the CY 216 group and 18 (0.80%) to the placebo group. In the CY 216 group, pulmonary embolism was the direct cause of death in 2 patients (0.09%), while the remaining 6 deaths could not be ascribed either directly or indirectly to thrombosis. In the placebo group, pulmonary embolism was the cause of death in 4 cases (0.18%; p less than 0.05) and contributed to death in 4.(ABSTRACT TRUNCATED AT 400 WORDS)
Pezzuoli
G
G
1st Surgical Clinic, University of Milan, Italy.
Neri Serneri
G G
GG
Settembrini
P G
PG
Coggi
G
G
Olivari
N
N
Negri
G
G
Codemo
R
R
Galli
G
G
Roveri
S
S
D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects; D004311:Double-Blind Method; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D011183:Postoperative Complications / Q000401:mortality / Q000517:prevention & control*; D011655:Pulmonary Embolism / Q000401:mortality / Q000517:prevention & control*; D015996:Survival Rate; D013923:Thromboembolism / Q000401:mortality / Q000517:prevention & control*
D006495:Heparin, Low-Molecular-Weight