In our case-control study of the association between antihypertensive drug therapies and the risk of ischemic stroke, we found that antihypertensive drug regimens that did not include a thiazide diuretic were associated with an increased risk of ischemic stroke. Fournier and colleagues are puzzled by the fact that among patients without cardiovascular complications, calcium antagonists were associated with an increased risk of ischemic stroke; whereas in the INSIGHT trial, long-acting nifedipine was not associated with an increased risk of stroke compared with the combination of hydrochlorothiazide and amiloride.1 In our study, the nondihydropyridines represented about 84% (176/209) of all calcium antagonist use as monotherapy. There were too few subjects receiving dihydropyridines to estimate the RR of ischemic stroke for these users. Therefore, our results are difficult to compare with those from the INSIGHT trial. Fournier and coworkers offer some interesting hypotheses regarding the potential role of angiotensin II and the difference in the stroke-protective effect of thiazide diuretics between subjects with and without cardiovascular complications. Indeed, non-BP–mediated effects of antihypertensive drugs are important to consider and emphasize the importance of evaluating antihypertensive drugs with regard to their effects on clinically important end points such as myocardial infarction and stroke.
Klungel OH, Leufkens HGM, de Boer A, Longstreth, Jr WT, Kaplan RC, Smith NL, Psaty BM. Differences Between Primary vs Secondary Prevention Trials Regarding the Stroke Protective Effect of Antihypertensive Drugs—Reply. Arch Intern Med. 2001;161(17):2153–2154. doi: