Key result
Enalapril and losartan failed to reduce platelet activity at rest or during exercise in hypertensive patients, despite significantly reducing mean arterial pressure (P<0.001).
Why the study?
Does inhibition of the renin-angiotensin system with enalapril or losartan reduce platelet activity at rest or during stress in hypertensive patients?
RCT (n=25)
Double-blind
Does inhibition of the renin-angiotensin system with enalapril or losartan reduce platelet activity at rest or during stress in hypertensive patients?
Inhibition of the renin-angiotensin system with enalapril or losartan does not reduce platelet activity, inflammation, coagulation, or endothelial function in hypertensive patients, suggesting their beneficial effects are mediated through other mechanisms.
No antiplatelet benefit expected from RAS inhibitors in hypertension; challenges mechanistic assumptions and redirects research to alternative pathways.
OBJECTIVES: We investigated the influence of angiotensin receptor blockade and angiotensin-converting enzyme inhibition on stress-induced platelet activation in hypertensive patients. Secondary aims were effects on inflammation, coagulation, and endothelial function. METHODS: Following a 4-week placebo period, 25 hypertensive patients entered a double-blind, crossover study comparing enalapril (20 mg once daily) and losartan (100 mg once daily) treatment (each for 8 weeks). Patients were studied at rest and after a standardized exercise test. RESULTS: Mean arterial pressure was reduced from 119 ± 2 to 104 ± 2 (enalapril) and 106 ± 2 (losartan) mmHg (both P <0.001). Plasma angiotensin II decreased from 2.4 ± 0.4 to 0.5 ± 0.1 pmol/l with enalapril, and increased to 7.2 ± 1.3 pmol/l with losartan (both P <0.001). Exercise-evoked platelet activation, as evidenced by increased numbers of P-selectin-positive platelets (P <0.01), elevated circulating platelet-platelet aggregates (P <0.01) and soluble P-selectin levels (P <0.001), and increased platelet responsiveness to adenosine diphosphate and thrombin (both P <0.05). Neither drug influenced these markers of platelet activation at rest or following exercise. Markers of inflammation (high-sensitivity C reactive protein, interleukin-6, tissue necrosis factor-α), coagulation (tissue plasminogen activator antigen, prothrombin fragment F1+2), and endothelial function (von Willebrand factor, soluble vascular cellular adhesion molecule-1, and intercellular adhesion molecule-1) were also uninfluenced by treatment. CONCLUSION: Enalapril and losartan failed to reduce platelet activity both at rest and during exercise in hypertensive patients. Markers of inflammation, coagulation, and endothelial function were similarly unaffected. Inhibition of the renin-angiotensin system promotes its beneficial effects in hypertension through mechanisms other than platelet inhibition.
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Schwieler et al. (2013) conducted an RCT in Hypertension (n=25). Enalapril and losartan vs. Placebo run-in and active crossover was evaluated on Stress-induced platelet activation. Enalapril and losartan failed to reduce platelet activity at rest or during exercise in hypertensive patients, despite significantly reducing mean arterial pressure (P<0.001).
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