The Effect of Lowering Blood Pressure in Reducing the Risk for a Second Stroke

Abstract & Commentary

Synopsis: A combination of the ACE-inhibitor perindopril and the diuretic indapamide lowered the risk of a second stroke in patients who had previously sustained a stroke or TIA.

Source: Progress Collaborative Group. Lancet. 2001;358: 1033-1041.

In recent years, the need to avoid treating hypertension in the setting of an acute stroke has been increasingly emphasized.1 Only a few small, randomized trials have looked at lowering blood pressure after the period of acute illness to prevent future strokes, and results have been inconclusive.

The current study addresses this issue. A large group of physicians comprising the perindopril protection against recurrent stroke study (PROGRESS) collaborative group recruited 6105 patients in multiple countries. All had a history of prior stroke or transient ischemic attack ([TIA] 2 weeks to 5 years prior to enrollment). Forty-eight percent had hypertension, defined as systolic greater than 160 or diastolic greater than 90. Most were on antiplatelet therapy, and about half were taking antihypertensive therapy. Participants were randomized to receive perindopril (Aceon®) 4 mg daily or placebo. More than half of the patients receiving perindopril were also randomized to receive the diuretic indapamide at a dose of 2.5 mg daily. The main study end point was recurrent stroke.

Perindopril alone lowered blood pressure an average of 5/3 mm Hg, and had no effect on the incidence of recurrent stroke compared to placebo. By contrast, the combination of perindopril and indapamide lowered blood pressure an average of 12/5 mm Hg, and reduced the risk of recurrent stroke by 43% compared to placebo. The magnitude of blood pressure and stroke risk reduction in those receiving combination therapy was similar in hypertensive and nonhypertensive patients.

Comment by Joseph Zuckerman, MD

It’s long been known that lowering blood pressure in hypertensive patients reduces the risk of a first stroke. This study suggests that reducing blood pressure in patients who’ve already had a stroke or TIA significantly reduces the risk of a second stroke. This is useful information for clinicians, given the concern about lowering blood pressure in patients with known cerebrovascular disease.

The study also raises some interesting questions. First, are the benefits seen in the study related only to blood pressure lowering, or are the particular classes of medications used to lower blood pressure important? If the classes used are important, are there differences between different ACE-inhibitors? In the HOPE trial,2 which used the ACE-inhibitor ramipril, there was an approximately 30% reduction in the risk of stroke in that high-risk group of patients, despite little effect on blood pressure. Second, are there some patients who should not be treated despite the results of this study? It would seem reasonable to avoid lowering blood pressure in patients with high-grade stenoses of major cerebral arteries, for example. Last, how aggressive should we be in treating patients who aren’t hypertensive? While this study did not exclude patients based on initial blood pressure, it again seems prudent not to further lower blood pressure in patients who are already well within the normotensive range.

These questions will be answered by future studies. In the meantime, the main message of this study is that blood pressure reduction, as well as other standard treatment modalities such as antiplatelet and lipid-lowering agents, has a role in patients with cerebrovascular disease.

References

1. Alberts MJ. Am J Med. 1999;106:211-221.

2. Yusuf S, et al. N Engl J Med. 2000;342:145-153.

Dr. Zuckerman is Coordinator of Internal Medicine, Halifax Medical Center, Daytona Beach, Fla.