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Angiotensin II antagonists: efficacy, duration of action, comparison with other drugs
1Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland.
Insights
Angiotensin II antagonists are a new class of antihypertensive drugs. Early studies suggest losartan may be less potent than enalapril, necessitating further research into optimal dosing for this drug class.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Clinical trials confirm anti-hypertensive drug benefits in reducing cardiovascular events.
- Thiazide diuretics were common in trials, with benefits attributed to blood pressure reduction.
- Greater blood pressure reduction may yield enhanced cardiovascular benefits.
Purpose of the Study:
- To evaluate the anti-hypertensive potency of angiotensin II antagonists, specifically losartan.
- To compare the efficacy of losartan with enalapril.
- To clarify dose-response relationships and identify clinically relevant doses for angiotensin II antagonists.
Main Methods:
- Comparative studies assessing blood pressure reduction.
- Analysis of trough and peak blood pressure changes.
- Examination of dose-response relationships for losartan.
Main Results:
- Losartan demonstrated lesser blood pressure reduction compared to enalapril in comparative studies.
- Blood pressure reductions with losartan were observed across various doses (50-150 mg) without clear dose-response definition.
- Preliminary data suggests newer angiotensin II antagonists may offer greater efficacy.
Conclusions:
- The anti-hypertensive potency of angiotensin II antagonists requires further investigation.
- Definitive identification of clinically relevant dose ranges for newer angiotensin II antagonists is limited.
- Ensuring adequate blood pressure reduction is crucial for maximizing cardiovascular benefits.
Abstract:
The benefits of anti-hypertensive drug treatment have been established by clinical trials demonstrating significant reductions in cardiovascular morbidity and mortality. Thiazide diuretics predominated in these trials but it is reasonable to conclude that the benefits were attributable to the blood pressure (BP) reduction per se and not to specific pharmacological characteristics. Furthermore, it can be calculated that even greater benefits would probably have accrued if the magnitude of the BP reduction had been greater. On first principles, therefore, the basic requirement for any anti-hypertensive drug is confirmation of its ability to reduce BP. The angiotensin II antagonists constitute an important new class of drug, with a low incidence of adverse effects, but early studies with the prototype, losartan, have raised some doubts about its anti-hypertensive 'potency' in the clinical setting. For example, in several different comparative studies there were consistently lesser BP reductions with losartan compared to enalapril. This applied to both the trough and peak BP reductions. Furthermore, dose-response relationships have not always been clearly defined: for example, in one study diastolic BP reductions (trough) fell in the range 4.1 to 4.8 mm Hg with 50, 100 and 150 mg losartan. Although the preliminary results with newer angiotensin II antagonists suggest that they may have greater efficacy, there is only limited information about the definitive identification of the clinically relevant dose ranges for many of these drugs.