Inpharma 1251 - 19 Aug 2000 Late benefit from low-dose warfarin therapy after CABG? Low-dose warfarin appears to have a late benefit in patients who have undergone coronary artery bypass graft (CABG) surgery, report investigators from the Post Coronary Artery Bypass Graft Trial Investigators from Canada and the US. 1 However, they add that as yet, this long-term benefit was ‘unexpected, remains unexplained, and requires confirmation by additional studies’. In the Post CABG study, 1351 patients who had undergone CABG 1–11 years previously were randomised to receive moderate or aggressive lipid- lowering therapy with lovastatin. * They were also randomised to receive warfarin (adjusted to maintain an international normalised ratio of < 2) or placebo. Data obtained after an average 4.3 years of follow-up have already been reported. ** The current analysis involved 1254 patients for whom data were obtained 3 years after completing the Post CABG study. Data from > 7 years’ follow-up After 7.5 years’ follow-up, total mortality was reduced by approximately 35%, and the rate of death or nonfatal myocardial infarction by 31%, in warfarin, compared with placebo, recipients; the between-group differences were significant. The researchers note that for both outcomes, ‘no statistically significant difference between warfarin and placebo groups was observed during the trial’. The researchers say that ‘the finding that warfarin therapy reduced mortality from all causes, which emerged after treatment was discontinued, was unexpected’. In addition, at the end of the extended follow-up period, significant differences between moderate and aggressive lipid-lowering therapy recipients were seen (favouring the aggressive strategy) in the need for revascularisation and the proportion of patients reaching the composite clinical endpoint. † In an accompanying editorial to the above-mentioned study, Dr David Waters from San Francisco General Hospital, California, and Dr Rabih Azar from San Francisco School of Medicine, California, US, say that the ‘evidence is not strong enough to treat post-bypass patients routinely with low-dose warfarin’. 2 * The study was partly supported by Merck & Co. ** See Inpharma 1071: 12, 25 Jan 1997; see Inpharma 1071 p12; 800458350 † The composite clinical endpoint comprised death from cardiovascular or unknown causes, myocardial infarction, stroke, bypass surgery or angioplasty. 1. Knatterud GL, et al. Long-term effects on clinical outcomes of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation in the Post Coronary Artery Bypass Graft trial. Circulation 102: 157-165, 11 Jul 2000. 2. Waters DD, et al. Postscripts from the Post Coronary Artery Bypass Graft Trial: the sustained benefit of more aggressive cholesterol lowering and the enigma of low-dose anticoagulation. Circulation 102: 144-146, 11 Jul 2000. 800763768 1 Inpharma 19 Aug 2000 No. 1251 1173-8324/10/1251-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved

Late benefit from low-dose warfarin therapy after CABG?

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Inpharma 1251 - 19 Aug 2000

Late benefit from low-dose warfarintherapy after CABG?

Low-dose warfarin appears to have a late benefit inpatients who have undergone coronary artery bypassgraft (CABG) surgery, report investigators from the PostCoronary Artery Bypass Graft Trial Investigators fromCanada and the US.1 However, they add that as yet, thislong-term benefit was ‘unexpected, remainsunexplained, and requires confirmation by additionalstudies’.

In the Post CABG study, 1351 patients who hadundergone CABG 1–11 years previously wererandomised to receive moderate or aggressive lipid-lowering therapy with lovastatin.* They were alsorandomised to receive warfarin (adjusted to maintain aninternational normalised ratio of < 2) or placebo. Dataobtained after an average 4.3 years of follow-up havealready been reported.** The current analysis involved1254 patients for whom data were obtained 3 years aftercompleting the Post CABG study.

Data from > 7 years’ follow-upAfter 7.5 years’ follow-up, total mortality was reduced

by approximately 35%, and the rate of death or nonfatalmyocardial infarction by 31%, in warfarin, comparedwith placebo, recipients; the between-group differenceswere significant. The researchers note that for bothoutcomes, ‘no statistically significant difference betweenwarfarin and placebo groups was observed during thetrial’.

The researchers say that ‘the finding that warfarintherapy reduced mortality from all causes, whichemerged after treatment was discontinued, wasunexpected’.

In addition, at the end of the extended follow-upperiod, significant differences between moderate andaggressive lipid-lowering therapy recipients were seen(favouring the aggressive strategy) in the need forrevascularisation and the proportion of patients reachingthe composite clinical endpoint.†

In an accompanying editorial to the above-mentionedstudy, Dr David Waters from San Francisco GeneralHospital, California, and Dr Rabih Azar from SanFrancisco School of Medicine, California, US, say thatthe ‘evidence is not strong enough to treat post-bypasspatients routinely with low-dose warfarin’.2

* The study was partly supported by Merck & Co.** See Inpharma 1071: 12, 25 Jan 1997; see Inpharma 1071 p12;800458350† The composite clinical endpoint comprised death fromcardiovascular or unknown causes, myocardial infarction, stroke,bypass surgery or angioplasty.

1. Knatterud GL, et al. Long-term effects on clinical outcomes of aggressivelowering of low-density lipoprotein cholesterol levels and low-doseanticoagulation in the Post Coronary Artery Bypass Graft trial. Circulation 102:157-165, 11 Jul 2000.

2. Waters DD, et al. Postscripts from the Post Coronary Artery Bypass Graft Trial:the sustained benefit of more aggressive cholesterol lowering and the enigma oflow-dose anticoagulation. Circulation 102: 144-146, 11 Jul 2000.

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