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Proceedings of a symposium TOTAL ISCHEMIC BURDEN: Advances in Evaluation and Theraply in Angina Patients Presented as a satellite symposium prior to the 59th Annual Scientific Sessions of the American Heart Association under an Educational Grant from Plizer Laboratories Chairman: William W. Parmley, M.D. November 15,1986 Dallas, Texas Introduction It is common for patients with coronary artery disease and angina pectoris to have additional epi- sodes of silent ischemia. Ischemic episodes appear to have the same effect on regional cardiac function and metabolism, whether or not they result in angina pectoris. Accordingly, the term total is- chemic burden has been used to reflect the combi- nation of both painful and painless ischemic epi- sodes. If cumulative ischemia has import,snt adverse effects, then the clinician must pay attention not only to episodes of angina but also to silent ischemia. As our knowledge of silent ischemia grows, it is clear that there are a number of unanswered questions. One question relates to the pathophysiology of silent ischemia. Several lines of evidence suggest that vasoconstriction may play a prominent pathophysi- ologic role. This evidence includes: (1) the fact that silent ischemia occurs at heart rates that are gener- ally lower than those associated with angina; (2) silent ischemia has a circadian variation with a predominance of morning episodes similar to vari- ant angina; and (3) positron emission tomography studies have shown an absolute decrease in regional blood flow in patients with silent ischemia. With the evidence that silent ischemia may be due predominantly to vasoconstriction, important ques- tions arise about the relative benefits of different antianginal drugs. In this supplement, Dr. Cohn reviews the actions of the three groups of antiangi- nal agents-nitrates, beta blockers, and calcium channel blockers. In patients with angina pectoris, it appears that all three play an important role in reducing angina1 episodes, and that synergistic effects are frequently seen with combination thera- py. In his review, Dr. Cohn raises the possibility that the nitrates and calcium channel blockers will form an important component of therapy for silent is- chemia and that beta blockers alone may not consti- tute adequate therapy. In the second paper of this supplement, Dr. Kawanishi et al. evaluate the effects of propranolol or nifedipine on both angina and silent ischemia. In their patient group, they found a lower frequency of asymptomatic episodes of ischemia than has been seen in other studies. This may relate to the fact that their patients had mild, chronic stable angina. They pointed out that there was a similar reduction in both symptomatic and asymptomatic episodes of ischemia with the therapy employed. Furthermore, beneficial effects were seen with either propranolol or nifedipine in both symptomatic and asympto- matic episodes., Previous data have already indi- cated that nitroglycerin is effective in reducing silent ischemia. These data suggest, therefore, that the usual antianginal medications that are effective in reducing episodes of angina are also going to be effective in reducing episodes of silent ischemia. Whether agents that interfere with vasoconstrietion, such as the nitrates or calcium channel blockers, will be more effective than beta blockers is not clear. It may well be that Dr. Kawanishi’s patients had mild, stable angina without a vasoconstrictive component. In patients with more obvious vasoconstriction resulting in mixed angina and silent ischemia, it may be that the calcium channel blockers or nitrates will assume a preferred role. The third article in this supplement extends the concept of total ischemic burden to the total vascu- lar burden. Drs. Opie and Commerford point out that vasoconstriction in the coronary circulation and peripheral vasoconstriction leading to hypertension reflect a combined vascular burden that may be 213

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Page 1: Introduction

Proceedings of a symposium

TOTAL ISCHEMIC BURDEN: Advances in

Evaluation and Theraply in Angina Patients

Presented as a satellite symposium prior to the 59th Annual Scientific Sessions of the American Heart Association under an Educational Grant from Plizer Laboratories

Chairman: William W. Parmley, M.D. November 15,1986

Dallas, Texas

Introduction

It is common for patients with coronary artery disease and angina pectoris to have additional epi- sodes of silent ischemia. Ischemic episodes appear to have the same effect on regional cardiac function and metabolism, whether or not they result in angina pectoris. Accordingly, the term total is- chemic burden has been used to reflect the combi- nation of both painful and painless ischemic epi- sodes. If cumulative ischemia has import,snt adverse effects, then the clinician must pay attention not only to episodes of angina but also to silent ischemia. As our knowledge of silent ischemia grows, it is clear that there are a number of unanswered questions. One question relates to the pathophysiology of silent ischemia. Several lines of evidence suggest that vasoconstriction may play a prominent pathophysi- ologic role. This evidence includes: (1) the fact that silent ischemia occurs at heart rates that are gener- ally lower than those associated with angina; (2) silent ischemia has a circadian variation with a predominance of morning episodes similar to vari- ant angina; and (3) positron emission tomography studies have shown an absolute decrease in regional blood flow in patients with silent ischemia.

With the evidence that silent ischemia may be due predominantly to vasoconstriction, important ques- tions arise about the relative benefits of different antianginal drugs. In this supplement, Dr. Cohn reviews the actions of the three groups of antiangi- nal agents-nitrates, beta blockers, and calcium channel blockers. In patients with angina pectoris, it appears that all three play an important role in reducing angina1 episodes, and that synergistic effects are frequently seen with combination thera- py. In his review, Dr. Cohn raises the possibility that the nitrates and calcium channel blockers will form

an important component of therapy for silent is- chemia and that beta blockers alone may not consti- tute adequate therapy.

In the second paper of this supplement, Dr. Kawanishi et al. evaluate the effects of propranolol or nifedipine on both angina and silent ischemia. In their patient group, they found a lower frequency of asymptomatic episodes of ischemia than has been seen in other studies. This may relate to the fact that their patients had mild, chronic stable angina. They pointed out that there was a similar reduction in both symptomatic and asymptomatic episodes of ischemia with the therapy employed. Furthermore, beneficial effects were seen with either propranolol or nifedipine in both symptomatic and asympto- matic episodes., Previous data have already indi- cated that nitroglycerin is effective in reducing silent ischemia. These data suggest, therefore, that the usual antianginal medications that are effective in reducing episodes of angina are also going to be effective in reducing episodes of silent ischemia. Whether agents that interfere with vasoconstrietion, such as the nitrates or calcium channel blockers, will be more effective than beta blockers is not clear. It may well be that Dr. Kawanishi’s patients had mild, stable angina without a vasoconstrictive component. In patients with more obvious vasoconstriction resulting in mixed angina and silent ischemia, it may be that the calcium channel blockers or nitrates will assume a preferred role.

The third article in this supplement extends the concept of total ischemic burden to the total vascu- lar burden. Drs. Opie and Commerford point out that vasoconstriction in the coronary circulation and peripheral vasoconstriction leading to hypertension reflect a combined vascular burden that may be

213

Page 2: Introduction

particularly susceptible to treatment with a calcium channel blocker such as nifedipine. Similarly, beta blockers and nifedipine may have synergistic effects in treating both aspects of this total vascular bur- den.

In summary, these three reports review important aspects of both the total ischemic burden and total vascular burden seen in selected patients with coro-

nary disease and/or hypertension With regard to the total ischemic burden, it appears that all antiam- ginal agents may have a role in reducing silent ischemia. In specific subsets of patients, however, the nitrates and calcium channel blockers may hold a special place when vasoconstriction plays a promi- nent pathogenetic role.

William W. Parmley, M.D.


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