To the Editor: In emphasizing the benefits of losartan on stroke reduction, Dr Kjeldsen and colleagues1 state that "Previous intervention studies in ISH with diuretic or β-blocker or calcium antagonists or angiotensin-converting enzyme inhibitors have shown 36%, 42%, and 38% reductions in stroke vs placebo. A further 40% reduction in stroke with losartan-based therapy . . . is an important finding. . . . " The authors imply that a reduction in strokes in the order of magnitude of 80% would have been achieved had losartan been compared with placebo instead of atenolol. In the 3 studies the authors use to compute these estimates, antihypertensive therapy against placebo was either based on diuretics (in the SHEP trial) or calcium antagonists (in the Syst-Eur and Syst-China trials), and no data were given on β-blockers or ACE inhibitors. In the SHEP study, atenolol, when added to diuretic therapy in some patients, did not reduce the risk of either stroke or myocardial infarction.2 In fact, there have been no published studies of morbidity and mortality with β-blockers (or ACE inhibitors) in patients with ISH. A meta-analysis in patients older than 60 years showed that despite lowering blood pressure, β-blockers had no effect.3 The only study in which this drug class was compared against diuretics and placebo in elderly hypertensive patients is the MRC,4 in which atenolol, despite lowering blood pressure, did not reduce the risk of either strokes or myocardial infarction. In contrast, diuretic therapy, for a similar decrease in blood pressure, resulted in a 33% reduction in cerebrovascular events. In fact, when patients were stratified for blood pressure, the risk of stroke with diuretics was significantly lower than with placebo. This could indicate that diuretics exert a specific cerebroprotective effect that is not shared by some other antihypertensive drug classes, such as the β-blockers.5 As is demonstrated in the study by Kjeldsen et al, angiotensin-receptor inhibitors, but not β-blockers, may have similar cerebroprotective effects. Indeed, some experimental data linking cerebroprotection to the anti-ischemic effect of the AT2 receptor provide a pathophysiological correlate for these clinical observations.5,6
Messerli FH, Grossman E, Fournier A. Losartan vs Atenolol in Prevention of Stroke and Cardiovascular Disease. JAMA. 2003;289(6):700–701. doi:10.1001/jama.289.6.700-b
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