PubMed · 9133023
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P Kleist, W D Bussmann. 1993. [A decrease in arterial pressure by using organic nitrates].. https://pubmed.ncbi.nlm.nih.gov/9133023/
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Long-term administration of prostacyclin (PGI2) improves the hemodynamic state, symptoms, and survival in patients with primary pulmonary hypertension, but it increases mortality in patients with heart failure despite obvious hemodynamic benefits when it is given acutely. We evaluated the mechanisms of action of PGI2 in patients with heart failure and secondary pulmonary hypertension. Nineteen patients with end-stage heart failure and pulmonary hypertension, all candidates for heart transplantation, underwent right- and left sided cardiac catheterization with micromanometer-tipped catheters and were tested for PGI2 at incremental doses. PGI2 infusion significantly improved pulmonary hemodynamics with a 47% reduction in pulmonary vascular resistance (p=0.0003) and a doubling of pulmonary artery compliance (p <0.0001), reflecting improvement in pulmonary vascular tone. The dose of PGI2 necessary to reach this hemodynamic effect correlated significantly to the baseline severity of pulmonary artery compliance (r=0.54, p=0.01). Furthermore, PGI2 produced a significant positive inotropic effect (contractile element maximum velocity increased from 1.10+/-0.09 to 1.33+/-0.13 circ/s, p <0.009). The hemodynamic effects of PGI2 infusion were independent of the plasma and urinary levels of endogen prostaglandins. Thus, PGI2 at therapeutic doses exerts a positive inotropic effect in patients with heart failure, which may explain the increased mortality rate observed with the long-term use of PGI2 in this type of patient. The spectacular acute benefits on right ventricular afterload, however, may be useful in unstable patients with heart failure and secondary pulmonary hypertension or in transplanted patients with acute right ventricular failure of the donor heart.
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Consensus groups have recommended using the baseline absolute risk of disease over five to ten years rather than relative risk when treatment with lipid-lowering or antihypertensive drugs is considered. Targeting patients with a coronary event rate of 20% over ten years ensures that society's investment in drugs yields substantial benefits by reducing the incidence of premature disease. However, the use of absolute risk is most appropriate among the middle-aged. Because all elderly persons have a high absolute risk of disease, almost all may be eligible for drug treatment. The costs of postponing death after the age of 70 are therefore substantial. Among young persons with familial hypercholesterolemia on the other hand, the consequences of a death before middle-age are so enormous that most patients are treated with drugs even though absolute risk is very low. An additional problem with using absolute risk is that the risk of atherosclerotic disease accumulates over time. Calculation of benefit on the basis of short-term trials might underestimate long-term benefit. In the future, non-invasive measures of atherosclerosis and new markers of risk may provide valuable information on risk stratification in primary prevention.