Why the study?
Does 50 mg losartan/12.5 mg hydrochlorothiazide combination therapy reduce ambulatory blood pressure compared to 100 mg losartan monotherapy in patients with moderate hypertension uncontrolled on 50 mg losartan?
Does 50 mg losartan/12.5 mg hydrochlorothiazide combination therapy reduce ambulatory blood pressure compared to 100 mg losartan monotherapy in patients with moderate hypertension uncontrolled on 50 mg losartan?
Combination therapy with losartan 50 mg and hydrochlorothiazide 12.5 mg is more effective at lowering blood pressure than increasing losartan to 100 mg in patients uncontrolled on 50 mg losartan.
Supports losartan/HCTZ 50/12.5 over losartan uptitration for daytime ABP control in uncontrolled moderate hypertension; extends RCT evidence for early combination therapy.
INTRODUCTION: Losartan is an angiotensin II receptor blocker indicated for treatment of hypertension. It also inhibits platelet agreggation through blockade of thromboxane A2/ prostaglandin H2 receptors, and has a uricosuric effect We determined the effect on ambulatory blood pressure (ABP) of 100 mg losartan monotherapy (L100) versus 50 mg losartan/12.5 mg hydrochlorothiazide (HCTZ) combination therapy (L50H12.5C), in patients uncontrolled on 50 mg losartan. We also assessed the effects of losartan on platelet aggregation and serum urate at these clinically relevant doses. METHODS: This was a randomized, double-blind trial of L100 versus L50H12.5C, in moderate hypertensives (sitting diastolic blood pressure (DBP) >or = 95 mmHg and < 120 mmHg). After 4 weeks of placebo run-in, patients received 50 mg losartan for 6 weeks; patients uncontrolled (sitting DBP > or = 95 mmHg) were randomized to L100 or L50H12.5C for a further 6 weeks. Platelet function was assessed by measuring percentage inhibition of platelet aggregation, and serum uric acid was also measured. RESULTS: Monotherapy with 50 mg losartan reduced ABP by 16.0/9.9 mmHg during the day and 9.8/5.5 mmHg at night However, 16 out of 24 (66%) patients had uncontrolled blood pressure on this treatment L50H12.5C further reduced daytime ABP by 10.7(10.7)/8.4(6.5) mmHg mean (SEM) compared with L100 (-5.3(9.7)/-2.3(4.8), P = 0.013). 50 mg losartan and L100 did not affect platelet function or uric acid levels beyond placebo values; treatment with L50H12.5C was associated with a significant rise in serum urate above levels obtained on 50 mg losartan (366.9(67.6) versus 331.6(65.0), P=0.006), to levels similar to placebo (358.8(80.9)). CONCLUSION: L50H12.5C is an effective antihypertensive regimen in patients with moderate hypertension that is uncontrolled on 50 mg losartan monotherapy, and is the preferred treatment option in these patients compared with increasing the dose of losartan. The additional benefit of losartan on platelet inhibition was not evident in our population at these doses; however, there was evidence to suggest that the uricosuric effects of losartan might ameliorate the uric acid retention effects of therapy with hydrochlorothiazide.
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Owens et al. (2000) studied this question.
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