Impact of Losartan on Stroke Risk in Hypertensive Patients in Primary Care

K. Bestehorn; Klaus Wahle


Clin Drug Invest. 2007;27(5):347-355. 

In This Article

Abstract and Introduction


Background and Objective: While a number of conditions and risk factors that increase stroke risk have been identified, arterial hypertension is the most consistent and powerful predictor. The angiotensin II type 1 receptor antagonist (angio-tensin receptor blocker [ARB]) losartan has been shown in the LIFE (Losartan Intervention for Endpoint Reduction in Hypertension) study to decrease stroke risk in hypertensive patients to a substantially greater extent than conventional therapy. We aimed to assess the impact of the blood pressure-lowering effect of losartan therapy on stroke risk in hypertensive patients in primary care.
Methods: A total of 2977 primary-care practices throughout Germany included 22 499 consecutive unselected patients with a confirmed diagnosis of hypertension in an open-label, prospective, observational study. In addition to demographics, known risk factors for stroke were documented on standardised questionnaires. The 10-year predicted risk of first stroke was calculated according to the Framingham Stroke Risk Score at baseline and after a mean of 94 ± 24 days of losartan (± hydrochlorothiazide [HCTZ]) therapy.
Results: The mean patient age was 64.1 ± 10.6 years, and 52.4% were males. Mean systolic/diastolic blood pressure decreased from 160 ± 15/93 ± 9mm?Hg at baseline by -21 ± 14/-11 ± 9mm?Hg. Besides hypertension, 84.9% of patients had other co-morbidities, of which the most frequent were hypercholesterolaemia (53.0%), diabetes mellitus (36.1%), coronary heart disease (31.1%) and left ventricular hypertrophy (24.2%). The average predicted 10-year stroke risk was 28.0 ± 21.9% at baseline, and 22.1 ± 19.5% at study end (relative risk reduction 24 ± 16%, p < 0.05). In subgroups of patients with diabetes or nephropathy, similar effects were noted. Drug-related adverse events were reported in 18 patients; all of these were non-serious.
Conclusion: Because of the high prevalence of co-morbidities and risk factors, the hypertensive patient population observed in this study presented with a high 10-year stroke risk. Treatment with losartan (± HCTZ) was well tolerated and led to a substantial decrease in blood pressure and associated stroke risk.


Stroke has an enormous impact on public health: it is the second leading cause of mortality worldwide, and a third of survivors are dependent on others for activities of daily living.[1] However, stroke is also highly preventable, and antihypertensive therapy plays a key role in this respect: a series of large-scale recent studies have shown that stroke, not myocardial infarction, is the most frequent cardiovascular complication of hypertension.[2,3]

Epidemiological data on the risk factor profiles of primary-care patients and their resulting stroke risk are sparse. In a previous cross-sectional study conducted in Germany we found that the prevalence of risk factors and co-morbidities relevant to total stroke risk was very high, equating to a substantial 10-year stroke risk of 26% according to the Framingham Stroke Risk Score[4] in this cohort (data on file, MSD Germany).

In the present study we investigated losartan, which is first-in-class of the orally active, selective angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]).[5] We addressed the following research questions:

  1. How efficacious and safe is losartan, given as mono-therapy or in combination with hydrochloro-thiazide, in typical, unselected patients with a confirmed diagnosis of hypertension in the primary-care setting?

  2. What is the impact of losartan therapy (focusing on the drug's blood pressure-lowering effect only) on 10-year stroke risk, as calculated from the Framingham Stroke Risk Score, in these patients?

  3. Are the effects of losartan on stroke risk in high-risk subgroups of patients with diabetes mellitus or nephropathy similar to those in the total cohort?


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