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April 23/30, 2003

Long-term Cardiovascular Consequences of Diuretics vs Calcium Channel Blockers vs Angiotensin-Converting Enzyme Inhibitors

JAMA. 2003;289(16):2066. doi:10.1001/jama.289.16.2068-c

To the Editor: The ALLHAT authors1 concluded that chlorthalidone resulted in improved drug tolerance compared with lisinopril because of the confounding drug use in the ACE inhibitor group. In fact, patients randomized to chlorthalidone received diuretics 8% more often than patients in the lisinopril group receiving ACE inhibitors and 2% more crossovers occurred in the lisinopril group. In addition to the 10% difference in actual drug usage, lisinopril was less effective in controlling the systolic blood pressure, resulting in 2% more step 2 or 3 drugs used, compared with chlorthalidone. Patients randomized to receive diuretics received the drugs more often than patients randomized to receive lisinopril and ACE inhibitors, and more add-on therapy (atenolol, reserpine, clonidine, and hydralazine) was needed in the latter group. Thus, the decreased drug tolerance of lisinopril was likely the result of increased usage of secondary agents with higher adverse effects.