Early effects of cardiovascular drugs--do they predict clinical outcomes?
Indicators such as lowering of blood pressure in hypertension, alleviation of chest pain in angina pectoris, improvement in rest or exertional dyspnea from congestive heart failure (CHF) and suppression of ventricular arrhythmia are widely used in the management of cardiovascular diseases. There are often strong associations between the physiological indicators and the long-term clinical outcomes of cardiovascular disease such as stroke, myocardial infarction, sudden death and all-cause mortality. Physicians have assumed reasonably that early improvements in physiological markers will lead invariably to better long-term clinical outcomes. In recent years, a number of large clinical trials have demonstrated that short-term physiological improvements are not necessarily linked to better long-term clinical outcomes, but may be associated with less benefit than expected or even with detrimental outcomes. Management of cardiovascular diseases is complicated by the possibility that beneficial effects of a particular drug may be offset by its negative actions on the cardiovascular system. Effective antihypertensives may depress cardiac contractility; inotropes enhance left ventricular contractility in CHF, but may increase the risk of serious ventricular dysrhythmia; drugs which suppress ventricular arrhythmia may precipitate CHF or even excite pro-arrhythmic effects. Physicians must be conscious of this interplay of potentially beneficial and deleterious effects when cardiovascular drugs are prescribed. It is important in the analysis of large clinical trials of cardiovascular drugs to identify those situations in which the drug exhibits more benefit than harm and to determine, if possible, those aspects of drug action, drug dosage and population characteristics which contribute to the beneficial and detrimental actions.(ABSTRACT TRUNCATED AT 250 WORDS)
Carruthers
S G
SG
Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D017202:Myocardial Ischemia / Q000188:drug therapy; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D002317:Cardiovascular Agents