We tested the usefulness of aspirin (325 mg twice daily), heparin (1000 units per hour by intravenous infusion), and a combination of the two in the early management of acute unstable angina pectoris in a double-blind, randomized, placebo-controlled trial involving 479 patients. The patients entered the study as soon as possible after hospital admission (at a mean [+/- SD] of 7.9 +/- 8.0 hours after the last episode of pain), and the study was ended after 6 +/- 3 days, when definitive therapy had been selected. Major end points--refractory angina, myocardial infarction, and death--occurred in 23, 12, and 1.7 percent of the 118 patients receiving placebo, respectively. Heparin was associated with a decrease in the occurrence of refractory angina (P = 0.002). The incidence of myocardial infarction was significantly reduced in the groups receiving aspirin (3 percent; P = 0.01), heparin (0.8 percent; P less than 0.001), and aspirin plus heparin (1.6 percent, P = 0.003), and no deaths occurred in these groups. There were too few deaths overall to permit evaluation of the effect of treatment on this end point. The combination of aspirin and heparin had no greater protective effect than heparin alone but was associated with slightly more serious bleeding (3.3 vs. 1.7 percent). We conclude that in the acute phase of unstable angina, either aspirin or heparin treatment is associated with a reduced incidence of myocardial infarction, and there is a trend favoring heparin over aspirin. Heparin treatment is also associated with a reduced incidence of refractory angina.

Aspirin, heparin, or both to treat acute unstable angina

It is now generally accepted that cardiac dysfunction in congestive heart failure (CHF) is due to cardiac remodeling as a consequence of changes in the size and shape of the heart. Furthermore, both the sympathetic nervous system (SNS) and the renin–angiotensin system (RAS) are activated, and the circulating levels of catecholamines and angiotensin II are elevated in CHF. Experimental and clinical studies have revealed that the blockade of SNS by different adrenoceptor (AR) antagonists improve cardiac function and attenuate cardiac remodeling. In addition to modifying β-AR-mediated signal transduction, β-AR antagonists have been shown to depress the elevated levels of catecholamines in CHF. On the contrary, the improvement of cardiac function and cardiac remodeling in CHF due to the blockade of RAS by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were associated with a reduction in the formation of angiotensin and antagonism of the angiotensin-receptor-mediated signal transduction, respectively. Blockade of either SNS or RAS prevented subcellular remodeling upon modifying changes in cardiac gene expression, reduced the development of intracellular Ca2+-overload, and attenuated the occurrence of oxidative stress in the failing heart. These observations are consistent with the view that the activation of both SNS and RAS plays a crucial role in the genesis of cardiac remodeling and cardiac dysfunction in CHF.

Charles C. Depew

Papers

Intensive Care Therapeutics