Warfarin vs ASA in STEMI
In the Warfarin, Aspirin, Reinfarction Study (WARIS II), warfarin without aspirin in a dose intended to achieve an INR of 2.8 to 4.2 resulted in a significant reduction in a composite end point (death, nonfatal reinfarction, or thromboembolic stroke) compared with therapy with aspirin alone (16.7% versus 20.0%) (1247). Warfarin therapy resulted in a small but significant increase in major, nonfatal bleeding compared with therapy with aspirin alone (0.62% per year versus 0.17% per year).
| WARIS-2
Randomized, open labelled, active controlled trial New Engl J Med 2002;347:969-974
|
n= 3630
<75yrs old, hospitalized for MI (ECG changes and positive biochemical markers) Anterior MI=40% Inferior MI=46% Q wave MI=60% Thrombolysis=54% |
warfarin (INR 2.8-4.2)
vs ASA 160mg daily vs ASA 75mg daily + warfarin (INR 2-2.5) x 4 years |
Composite Endpoint: death, MI, thromboembolic stroke at 4 years
Composite Endpoint: ASA vs. warfarin + ASA: p<0.001, ARR 5% ASA vs. warfarin: p=0.03, ARR 3.3% warfarin vs. warfarin + ASA: p=0.21 Major Bleeding ASA vs. warfarin/warfarin + ASA, p<0.001 |
warfarin (+/- ASA) is superior to ASA alone in reducing composite endpoint, but no difference in mortality with increased major bleeding |
CLASS I
Warfarin alone (INR 2.5 to 3.5) or warfarin (INR 2.0 to 3.0) in combination with aspirin (75 to 162 mg) should be prescribed in post-STEMI patients who have no stent implanted and who have indications for anticoagulation. (Level of Evidence: B)
STEMI patients with or without acute ischemic stroke who have a cardiac source of embolism (AF, mural thrombus, or akinetic segment) should receive moderate- intensity (INR 2 to 3) warfarin therapy in addition to aspirin (see Figure 35). The duration of warfarin therapy should be dictated by clinical circumstances (e.g., at least 3 months for patients with an LV mural thrombus or akinetic segment and indefinitely in patients with persistent AF). The patient should receive LMWH or UFH until adequately anticoagulated with warfarin. (Level of Evidence: B)
Two trials failed to demonstrate a statistically significant reduction in the combined end points of death, reinfarction, or stroke using a regimen of low-dose aspirin in combination with low-dose warfarin (INR less than 2) (1306,1307).
In the APRICOT II trial (1249), patients less than 75 years old with STEMI received UFH, aspirin, and fibrinolytic therapy. Those who achieved TIMI 3 flow were randomized to aspirin alone (80 mg) or warfarin (INR 2 to 3) plus 80 mg of aspirin. The combined group had fewer reocclusions (15% versus 28%; p less than 0.02) and a significant reduction in the combined end points of death, MI, and revascularization (20% ARD; 23% RRR; p less than 0.01)
Magnesium
- Magnesium is principally distributed in bone (67%) and muscle (20%). Because of its predominantly intracellular distribution, measurement of magnesium in the extracellular compartment may not accurately reflect the total body magnesium content. The majority of magnesium in the extracellular fluid is in the ionized form as only 20% is bound to serum proteins. The normal range for serum magnesium is 1.4 to 1.8 mEq/L, which is equivalent to 1.7 to 2.3 mg/dL or 0.85 to 1.15 mmol/L.
- Hypermagnesemia (serum magnesium >2 mEq/L) is a rare occurrence that is generally seen in patients with stage 4 or 5 CKD when magnesium intake exceeds the excretory capacity of the kidneys. Elderly patients are prone to hypermagnesemia because of thei rreduced glomerular filtration rate (GFR) and because of their tendencyto consume magnesium-containing antacids and vitamins
- At that point the serum magnesium concentration can be monitored every 6 to 12 hours for the next 24 hours while receiving magnesium supplementation. Once the magnesium concentration is stable in the normal range, a concentration can be obtained daily. It should be reiterated that it typically takes 3 to 5 days to fully replete total body magnesium stores
- Intravenous administration of magnesium sulfate produces an immediate effect that lasts for about 30 minutes
Digoxin
Digoxin inhibits the Na-K-ATPase membrane pump. Na-K-ATPase regulates intracellular sodium and potassium. Inhibition of this enzyme leads to an increase in intracellular sodium concentration (i.e., decreased outward transport) and ultimately to an increase in intracellular calcium as sodium-calcium exchange is stimulated by high intracellular sodium concentrations. It is believed that increased intracellular concentrations of calcium allow for greater activation of contractile proteins (e.g., actin, myosin).
Digoxin also possesses direct vasoconstrictive properties and reflex CNS-mediated peripheral vasoconstriction. Although this increases vascular resistance, in patients with failing hearts, increased myocardial contractility predominates and total peripheral resistance drops. In patients with congestive heart failure, an increased cardiac output will decrease sympathetic tone, thereby reducing the heart rate and causing diuresis in edematous patients and improving coronary blood flow.
In addition to its inotropic effects, digoxin also possesses significant actions on the electrical activity of the heart. It increases the slope of phase 4 depolarization, shortens the action potential duration, and decreases the maximal diastolic potential. The increase in vagal activity mediated by cardiac glycosides decreases conduction velocity through the atrioventricular (AV) node, prolonging its effective refractory period. In atrial flutter or fibrillation, digoxin decreases the number of atrial depolarizations that reach the ventricle, thereby slowing ventricular rate. Sympathetic stimulation, however, easily overrides the beneficial inhibitory effects of digoxin on AV nodal conduction.
When to back off high dose diuresis in CHF….monitor for:
- Goal : euvolemic
- subjective: clinical s/s–> presence of SOB, crackles, cxr
- objective: JVP, WT, Urea: SrCr ratio
ACEI Studied in HF
| Trial | Patients | Intervention |
| CONSENSUS. N Engl J Med 1987;316:1429-35 | n = 253
NYHA class IV heart failure, cardiomegaly |
enalapril 20mg bid vs placebo x 6 month |
| SOLVD. N Engl J Med 1991;325:293-302 | n = 2569
NYHA Class I-IV, LVEF<0.35 |
enalapril 10mg bid vs placebo x 41 months |
| SOLVD Low EF
SOLVD Low EF. N Engl J Med 1992;327:685-91 |
n = 4228
asymptomatic, LV dysfunction (LVEF<0.35) |
enalapril 10mg bid vs placebo x 37 months |
| SAVE
N Engl J Med 1992;327:669-77 |
n = 2231
acute MI within 3-16 days, LVEF<0.40, no overt HF |
captopril 50mg tid vs placebo x 42 months |
| AIRE
Lancet 1993:342;821-8 |
n = 2006
acute MI within 3-10 days, clinical evidence of HF |
ramipril 5mg bid vs
placebo x 15 months |
| TRACE
N Engl J Med 1995;333:1670-6 |
n = 2606
acute MI within 3-7 days, LVEF<0.35 |
trandolapril 4mg od vs
placebo x 36 months |
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