Warfarin in atrial fibrillation: RESULTS(1)

Meta-analysis

Five studies were deemed eligible for meta-analysis based on the inclusion criteria and are listed in Table 1.

TABLE 1

Studies on the efficacy of warfarin in the prevention of stroke in atrial fibrillation patients included in the metaanalysis

Study(reference) Type of study Blinding INR PT ratio
AFASAK (4) Prospective, randomized, placebo controlled* Open 2.8-4.2 1.5-2.0
BAATAF (5) Prospective, randomized, not placebo controlled (patient allowed to take ASA in control group) Nonblinded 1.5-2.7 1.2-1.5
CAFA (6) Prospective, randomized, placebo controlled Triple-blinded’1 2-3 1.3-1.6
SPAF (7) Prospective, randomized, placebo controlled* Doubleblinded 2-4.5 1.3-1.8
SPINAF (8) Prospective, randomized, placebo controlled Doubleblinded 1.4-2.8 1.2-1.5

*A third study group received acetylsalicylic acid (ASA) 75 mg/day but was not examined in this meta-analysis; fBlinding to patient, physician and treatment centre; *A third study group received ASA 325 mg/ day but those results were not reported in the study and were not examined in this meta-analysis. AFASAK Copenhagen Atrial Fibrillation trial; BAATAF Boston Area Anticoagulation Trial for Atrial Fibrillation; CAFA Canadian Atrial Fibrillation Anticoagulation study; INR International Normalized Ratio; PT Prothrombin time; SPAF Stroke Prevention in Atrial Fibrillation study; SPINAF Stroke Prevention In Nonrheumatic Atrial Fibrillation study

The results of the analyses of the four outcomes assessed in 2415 patients are presented in Table 2. All data used in this meta-analysis were extracted from the intention-to-treat values given in the reports of each study. Table 3 summarizes the results of the five studies and annualizes the values for use in the pharmacoeconomic analysis since the average follow-up period for all studies in Table 1 is greater then one year. cialis professional 20 mg

D ecision tree analysis

TABLE 2

Outcomes from warfarin and no antithrombotic therapy use in atrial fibrillation

Outcome Study Incidence/total patients (proportion)No antithrombotic Warfarin (%) therapy (%)
Stroke AFASAK 5/335 (0.0149) 18/336 (0.0537)
BAATAF 2/212 (0.0094) 13/208 (0.0625)
CAFA 6/187 (0.0321) 11/191 (0.0576)
SPAF 6/210 (0.0286) 18/211 (0.0853)
SPINAF 7/260 (0.0269) 23/265 (0.0868)
Total (%) 26/1204 (0.0274) 83/1211 (0.0685)
TIA AFASAK 0/335 (0) 3/336 (0.0089)
BAATAF 2/212 (0.0094) 3/208 (0.0144)
CAFA 2/187 (0.0107) 2/191 (0.0105)
SPAF 3/210 (0.0143) 4/211 (0.0190)
SPINAF 4/260 (0.2692) 6/265 (0.1887)
Total (%) 11/1204 (0.0640) 18/1211 (0.0512)
Bleeding AFASAK 21/335 (0.0627) 0/336 (0)
BAATAF 40/212 (0.1887) 22/208 (0.1058)
CAFA 35/187 (0.1872) 19/191 (0.1050)
SPAF 4/210 (0.0190) 4/211 (0.0190)
SPINAF 6/260 (0.0154) 4/265 (0.0151)
Total (%) 106/1204 (0.0864) 49/1211 (0.0421)
Death AFASAK 3/335 (0.0090) 15/336 (0.0446)
BAATAF 8/212 (0.0378) 14/208 (0.0673)
CAFA 11/187 (0.0588) 6/191 (0.0314)
SPAF 3/210 (0.0143) 5/211 (0.0237)
SPINAF 8/260 (0.0308) 8/265 (0.0302)
Total (%) 33/1204 (0.0274) 48/1211 (0.0396)

AFASAK Copenhagen Atrial Fibrillation trial; BAATAF Boston Area Anticoagulation Trial for Atrial Fibrillation; CAFA Canadian Atrial Fibrillation Anticoagulation study; SPAF Stroke Prevention in Atrial Fibrillation study; SPINAF Stroke Prevention In Nonrheumatic Atrial Fibrillation study; TIA Transient ischemic attack

TABLE 3

Summary of probabilities used in the analysis

Event Group Probability* (95% CI)
Minor Warfarin 0.1085 (0.0291-0.1879)
bleeding No antithrombotic therapy 0.0757 (0.0052-0.1461)
Major Warfarin 0.0094 (0.0044-0.0145)
bleeding No antithrombotic therapy 0.0061 (0.0024-0.0097)
Fatal Warfarin 0.0023 (0.0010-0.0036)
bleeding No antithrombotic therapy 0.0012 (-0.0001-0.0025)
Stroke Warfarin 0.0150 (0.0079-0.0221)
No antithrombotic therapy 0.0435 (0.0307-0.0562)
Fatal Warfarin 0.0194 (0.0068-0.0320)
stroke No antithrombotic therapy 0.0227 (0.0186-0.0269)

Data represent intention-to-treat analysis. *Annualized

Costs used in this analysis are summarized in Table 4. Expected costs are presented on the decision tree in Figure 1.

TABLE 4

Costs of events and warfarin therapy

Event Cost
Stroke $27,500.00
Major bleed (cerebral) $25,840.00
Minor bleed (gastrointestinal) $2,465.00
Warfarin therapy -Coumadin (5 mg/day, one-year supply): includes dispensing fee*Physician $136.77
-Initial consultation with family physician $51.40
-Follow-up visit with family physician’1 $38.50
Prothrombin test -$6.20/test x 16 (includes five in first two weeks to establish therapeutic levels and one test/month thereafter) $99.20
Physician fees for monitoring (laboratory telephones results to physician: $9.75/month x 12) $117.00
Total cost of warfarin therapy $442.87
Funeral costs (includes funeral home, transportation, casket, burial and minister) $4,412.35
All prices are in 1992 Canadian dollars. *Shoppers Drug Mart, Toronto, 1993; fNumber of visits will vary as neededTABLE 5Break-even analysis for warfarin branch
Observed Break-even value % change value*
Minor bleed 0.1085 0.1806 66
Major bleed 0.0094 0.0163 73
Stroke 0.0150 0.0214 43
Warfarin cost $442.87 $620.64 40

All prices are in 1992 Canadian dollars. *Shoppers Drug Mart, Toronto, 1993; fNumber of visits will vary as needed

TABLE 5

Break-even analysis for warfarin branch

Observedvalue* Break-even value % change
Minor bleed 0.1085 0.1806 66
Major bleed 0.0094 0.0163 73
Stroke 0.0150 0.0214 43
Warfarin cost $442.87 $620.64 40

*From Table 3


Expected cost for warfarin and placebo are $1,367.10 and $1,544.86, respectively, resultfng in a net savings of $177.76, suggesting dominance for warfarin.

Sensitivity analysis

Sensitivity analysis performed around three baseline values (probability of minor bleed, major bleed and embolus) in the warfarin branch required a substantial change from the baseline value before warfarin intervention became similar in expected cost com pared with placebo.

Break-even analysis shows a significant allowance for increase in event rate and cost, before warfarin becomes equivalent in expected cost compared with placebo (Table 5).

Cost per treatment analysis

Cost per treatment success (Table 6) for the prevention of stroke results in a lower than expected cost for the warfarin intervention. Incremental cost analysis favours warfarin as the dominant intervention.

TABLE 6

Cost per treatment success

Pathway1 Drug Cumulativeprobability Calculation
Cost per treatment success for the prevention of stroke
1 Warfarin 0.1085 1,367.10/0.9851 = $1,388.49*
3 Warfarin 0.0094
6 Warfarin 0.8671
Total 0.9850
7 No antithrombotic therapy 0.0757 $1,544.86/0.956 5 = $1,615.12*
9 No antithrombotic therapy 6.091x10E-3
12Total No antithrombotic therapy 0.9565 0.8747

Incremental cost analysis: ($1,544.86-$1,367.10)/(0.9565-0.9851)

= -$6,211.85§

Cost per treatment success for the prevention of death

1 Warfarin 0.1085 1,367.10/0.999 7 = $1,367.511
3 Warfarin 0.0094
5 Warfarin 0.0147
6 Warfarin 0.8671
Total 0.9997
7 No antithrombotic therapy 0.0757 $1,544.86/0.999 0 = $1,546.412
9 No antithrombotic therapy 6.091x10E-3
11 No antithrombotic therapy 0.0425
12 No antithrombotic therapy 0.8747
Total 0.9990

*Pathway numbers refer to Figure 1; ^Cost/treatment success for prevention of stroke – warfarin; ^Cost/treatment success for prevention of stroke – no antithrombotic therapy; §Incremental cost between warfarin and no antithrombotic therapy. Negative value indicates dominance of warfarin; ^Cost/treatment success for prevention of death -warfarin; **Cost/treatment success for prevention of death – no antithrombotic therapy; Incremental cost between warfarin and no antithrombotic therapy. Negative value indicates dominance of warfarin.


Cost per treatment success for the prevention of death also favours warfarin intervention. Incremental cost analysis strongly favours warfarin as the dominant intervention.

Category: Warfarin

Tags: Atrial fibrillation, cost-effectiveness, Economic analysis, Stroke, Warfarin

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