Randomised comparison of subcutaneous heparin, intravenous heparin, and aspirin in unstable angina - SESAIR


SESAIR was an open-label, randomized trial of aspirin vs. intravenous heparin vs. subcutaneous heparin in patients with unstable angina.


Subcutaneous heparin will be as effective as intravenous heparin at reducing ischemic episodes in patients with unstable angina.

Study Design

Study Design:

Patients Screened: 399
Patients Enrolled: 108
Mean Follow Up: 1 month
Mean Patient Age: <70
Female: 36

Patient Populations:

Untable angina, defined as typical chest pain at rest or with minimal exertion, associated with reversible ST changes on EKG, lasting 20 minutes or more, and without CK elevations.


Age>70, stroke within 6 months, MI within 6 weeks, uncontrolled hypertension, recent surgery or trauma, contraindications to aspirin or heparin, low number of ischemic episodes, or occurrence of Q wave myocardial infarction.

Primary Endpoints:

Number of anginal attacks, number of silent ischemic episodes (defined as ST depression recorded on Holter monitor), and duration of ischemia per day.

Secondary Endpoints:

Myocardial infarction, revascularization, and death at 1 week and 1 month.

Drug/Procedures Used:

Patients with unstable angina were admitted to a hospital and monitored for a 24 hours run-in phase where they were treated with aspirin, nitroglycerine, and nifedipine. Those that were refractory to this anti-anginal regimen were randomized to either aspirin (325mg PO qd), intravenous heparin (5000IU bolus, followed by 1000IU per hour drip, titrated to PTT 1.5 to 2 times normal), or subcutaneous (SC) heparin (7500 to 10000IU administered every 8 hours, adjusted to PTT 1.5 to 2 times normal). Patients in the two heparin arms received no aspirin.

The groups were monitored with Holter monitors for 24 hours. All patients were treated for 4 days in house. After this, patients were followed for an additional three weeks, during which time all intravenous heparin patients stopped therapy, and 12 of 35 subcutaneous heparin patients stopped therapy. The patients that continued subcutaneous heparin treatment received 12.5IU daily. 25 patients in the aspirin group discontinued therapy after 4 days.

Concomitant Medications:

All patients were treated with aspirin (325mg PO qd), isosorbide dinitrate (40mg PO qd or more if necessary), and nifedipine (40mg PO qd or more if necessary) prior to enrollment during the run-in phase. Only those that failed these therapies entered the randomization phase. Nitroglycerine and nifedipine were continued during the randomization phase, but aspirin was discontinued in the heparin arms. Other platelet drugs, NSAIDs, oral anticoagulants, digoxin, and antidepressants were not allowed.

Principal Findings:

108 patients were randomized to the three study arms. At baseline, the groups were well matched in terms of age, gender, comorbid conditions, and findings on coronary angiography. At four days and compared to the run-in phase, both intravenous and subcuatenous heparin showed significant (p<0.001 for all comparisons) average reductions in anginal episodes per day (-91% and -86% respectively), silent ischemic episodes per day(-56% and -46%), total ischemic episodes per day (-63% and -56%), and duration of ischemia per day (-66% and -61%). These effects were seen in the first 24 hours of therapy and persisted through 4 days. The aspirin arm showed no significant changes in any of the ischemic endpoints compared to the run-in phase. Patients who discontinued their heparin had an increase in ischemic episodes compared to those who remained on heparin that was not statistically significant.

One month intention-to-treat analysis showed no significant differences between groups in rates of myocardial infarction, death, CABG, or angioplasty, although the event rates for these endpoints was very low. Minor bleeding occurred in 2 patients in the aspirin arm and 2 patients in the intravenous heparin arm.


Among patients with unstable angina, subcutaneous heparin was associated with similar reductions in ischemic episodes among patients with unstable angina compared to intravenous heparin. Both heparin regimens were superior to aspirin alone in reduction of ischemic episodes. Of note, the study showed a non significant increase in anginal episodes at one month among patients who discontinued their heparin after four days, suggesting that continuation of heparin therapy for up to four weeks may be beneficial. Although the study found no differences in the rates of MI, death, or revascularization, the number of these events was very small suggesting the trial was underpowered to detect differences in these endpoints.


Serneri G, Modesti P, Gensini G, Branzi A, Melandri G, Poggesi L, Rostagno C, Tamburini C, Carnovali M, Magnani B. Randomised comparison of subcutaneous heparin, intravenous heparin, and aspirin in unstable angina. Lancet 1995; 345: 1201-04.

Clinical Topics: Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Coronary Angiography, Heparin, Electrocardiography, Nifedipine, Angioplasty, Nitroglycerin

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