Antihypertensive treatment and stroke prevention in patients with and without chronic kidney disease: a review of controlled trials.

Background: Stroke is the leading cause of serious long-term disability and the third leading cause of death in the Western world. In patients with chronic kidney disease (CKD), stroke and vascular dementia are significantly more prevalent than in the general population. However, the optimal stroke prevention strategy in these patients is unclear, because controlled studies are scarce.

Methods: In this paper, the results of the major antihypertensive trials and meta-analyses for stroke prevention in the general high cardiovascular (CV) risk population and in the CKD population are reviewed.

Results: The risk of stroke is much more blood pressure (BP)-dependent than the risk of other CV events, and, consistently, risk reduction is also strongly dependent on BP reduction. The magnitude of BP lowering is crucial in both populations. In renal patients, diuretics alone or in combination with angiotensin-converting enzyme (ACE) inhibitors, compared with placebo, are powerful BP-lowering and stroke-protective agents. Calcium channel blockers and ACE inhibitors also seem to be superior to placebo, but with more modest BP-decreasing effects and statistically nonsignificant reductions in stroke risk. In active versus active drug studies, independently of the BP-lowering effect, there are no significant advantages of any class over the others, although the results point to a slight superiority of diuretics and calcium channel blockers. Antihypertensive regimens in CKD patients should always include a diuretic, because, in the pathogenesis of CKD-associated hypertension, volume overload plays a crucial role. Diuretics are also inexpensive and well tolerated.

Conclusions: We suggest that further studies of CV outcomes in CKD patients should compare various combinations of diuretics plus other drugs, such as calcium channel blockers, ACE inhibitors and angiotensin II receptor blockers.