To date, lipid-lowering therapy appears to be the most effective medical intervention to retard progression of coronary atherosclerosis. In spite of promising experimental results, clinical trials completed so far have failed to demonstrate that calcium channel blockers (CCBs) alone influence the evolution of established coronary atherosclerosis. To assess whether the two therapies may have an additive or synergistic beneficial effect on human atherosclerosis, we reviewed in this regard the data of the angiographic Regression Growth Evaluation Statin Study (REGRESS) trial. REGRESS was designed to determine the effect of lipid-lowering therapy with pravastatin in symptomatic patients with normal to moderately raised cholesterol levels. Angiographically, with respect to the minimum obstruction diameter, in the pravastatin group, patients had on average 0.05 mm (95% confidence interval [CI]: 0.01-0.09) less progression if cotreated with CCBs compared with no CCB treatment, whereas in the placebo (no pravastatin) group, no effect of CCB treatment was observed (interaction test for differential effect of CCB treatment in patients with pravastatin compared with patients receiving placebo: P=.0016). With respect to the mean segment diameter, similar although not significant (P=.33) results were found. With respect to new lesion formation, in the pravastatin group, there were 50% (CI: 25-83) fewer patients with new angiographic lesions if cotreated with CCBs compared with no CCB cotreatment, whereas in the placebo (no pravastatin) group, no significant effect of CCB treatment was observed (interaction test: P=.0026). No beneficial effects of CCB treatment on clinical events were observed. Although the REGRESS trial was not designed to evaluate combination therapy, the results suggest strongly that addition of CCBs to 3-hydroxy-3-methyl-glutaryl-coenzyme reductase inhibitor therapy (pravastatin) acts synergistically in retarding the progression of established coronary atherosclerosis.

Objective-To study the effects of adding a salicylate to the angiotensin converting enzyme inhibitor enalapril in patients with heart failure due to coronary artery disease. Design-Double blind, crossover study for three days in hospital followed by an extended similar study outside hospital over two months of once daily enalapril plus salicylate and enalapril plus placebo. Setting-Tertiary referral centre. Patients-20 patients with heart failure due to myocardial infarction (New York Heart Association class II or III) and an ejection fraction less than 040. Twelve patients completed the two parts ofthe study. Main outcome measures-Blood pressure, plasma converting enzyme activity; plasma angiotensin II and noradrenaline concentrations; excretion of metabolites of renal and systemic prostanoids. Results-The unloading effect of first and second dose of enalapril in the morning lasted only during the day; in the extended study it lasted 24 hours because of the drug's accumulation. Converting enzyme inhibitors attenuate the breakdown of bradykinin and therefore enhance prostaglandin E, synthesis mediated by bradykinin. Evidence was found of such a prostaglandin E2 mediated contribution to ventricular unloading by enalapril, which was blocked by salicylate. The contribution, however, was small and variable, and salicylate addition had on average no significant de-unloading effect during the day. Unloading was abolished in only three of the 20 patients in the short term study and in one of the 12 in the extended study. At night, when other effects of enalapril on blood pressure had waned and the bradykinin induced effect persisted, salicylate significantly reduced the remaining small unloading effect. No effect was seen of salicylate addition on reversal of remodelling. Enalapril reduced angiotensin II induced synthesis of systemic and renal prostaglandin I2 and thromboxane A2, initially only during the day, but later also at night. It thereby masked suppression of thromboxane A2 synthesis by salicylate, which is the effect to which reinfarct prevention by salicylate is attributed. Conclusion-The risk is low that salicylate will substantially reduce the benefit of enalapril in patients with heart failure by de-unloading the ventricle. Like other effects induced by bradykinin significant de-unloading occurs in only a minority of the patients. In the presence of enalapril, however, salicylate will probably not be as effective as expected in reducing reinfarction risk, because enalapril already reduces thromboxane A, synthesis effectively in patients with heart failure and no further reduction by salicylate was found. (Br HeartJa 1995;73:227-236)

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The value of gadolinium enhancement to enable detection of infarcted myocardium at T1-weighted magnetic resonance (MR) imaging was assessed in 84 patients after acute myocardial infarction (AMI). Five healthy subjects served as controls. All patients underwent MR imaging before and 20 minutes after administration of gadopentetate dimeglumine. Contrast enhancement of normal myocardium varied 7% +/- 4 after administration of gadopentetate dimeglumine. Mean intensity ratio after gadolinium enhancement in group 1 (imaging less than 1 week after AMI), group 2 (imaging 1-3 weeks after AMI), and group 3 (imaging 3-6 weeks after AMI) was significantly higher than before gadolinium enhancement. In group 4 (imaging more than 6 weeks after AMI), no significant difference was observed. After gadolinium enhancement, the intensity ratio was abnormally increased in 82% of the MR examinations in group 1, in 62% of group 2, in 58% of group 3, and in 12% of group 4. Gadolinium enhancement improved visualization of myocardial infarction at MR imaging up to 6 weeks after onset of symptoms and had a maximal effect within 1 week after AMI.