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Am Fam Physician. 2000;61(5):1478-1481

Syndrome X, characterized by obesity, hyperlipidemia, insulin resistance and small coronary artery dysfunction, can cause anginal symptoms. Little is known about the effectiveness of standard anti-ischemic drugs in these patients. Lanza and associates compared the effectiveness of three classes of anti-ischemic drugs on anginal symptoms in patients with syndrome X.

Ten patients with a recent diagnosis of syndrome X, based on the presence of effort angina and ischemic-like ST segment changes on exercise testing but totally normal coronary arteries at angiography, were enrolled in the study. None of the patients had ever been treated with the study drugs. Standard electrocardiograms and echocardiograms were normal in all patients. In the first phase of the study, patients maintained diaries to report all episodes of angina. At the end of this four-week phase, all patients who reported at least three anginal attacks a week progressed to the active drug phase of the study. Patients then received, in a crossover, double-blind, randomized order, a beta blocker (atenolol, in a dosage of 100 mg per day), a calcium antagonist (amlodipine, in a dosage of 10 mg per day) or a nitrate (isosorbide-5-mononitrate [ISMN], in a dosage of 50 mg per day) for four weeks each. Structured diaries were given to each patient during this phase to record anginal episodes and quality of life.

Compared with the baseline, atenolol was the only agent that significantly reduced the number of anginal episodes. Atenolol and amlodipine were reported to significantly improve quality of life. Side effects occurred in one patient taking atenolol (fatigue), in three patients taking ISMN (headache) and in seven patients taking amlodipine (peripheral leg edema or tachycardia). Side effects were generally well tolerated, and only one patient taking ISMN withdrew from the study.

The authors conclude that atenolol alone was effective in controlling anginal chest pain in patients with syndrome X, but they also emphasize that adequate control is difficult. Until more is known about the exact pathophysiology of syndrome X, atenolol should be considered the initial drug of choice in these patients.

editor's note: Atenolol appears to reduce abnormally augmented sympathetic tone in patients with syndrome X. This mechanism of action appears clinically useful, but atenolol has also been shown to further impair the ability to dispense glucose within the body, an indication of deteriorating insulin resistance. The impact of this potentially harmful side effect requires further long-term study before atenolol can be widely recommended for use in patients with syndrome X.—r.s.

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