Combination therapy of lisinopril and losartan
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Blood Pressure Control with Lisinopril and Losartan Combination Therapy
Combining lisinopril, an ACE inhibitor, with losartan, an angiotensin II receptor blocker (ARB), has been shown to lower blood pressure more effectively than increasing the dose of either drug alone in patients whose hypertension is not controlled by monotherapy. This combination leads to greater reductions in both systolic and diastolic blood pressure over a 24-hour period, without disrupting the normal daily blood pressure pattern. The combination also results in a more complete blockade of the renin-angiotensin system (RAS), as indicated by increased plasma renin activity and angiotensin I levels, and a reduction in angiotensin II levels compared to monotherapy or higher doses of a single agent 147.
Effects on Proteinuria and Kidney Function in Proteinuric and Diabetic Patients
In patients with proteinuric kidney disease, combining lisinopril and losartan reduces proteinuria more than losartan alone, and to a similar or slightly lesser extent than high-dose lisinopril monotherapy. However, increasing the dose of losartan can also provide significant benefits, sometimes with better tolerability than the combination, especially in patients with marked proteinuria 27. In normotensive patients with type 2 diabetes, the combination does not provide additional benefit over monotherapy with either drug for reducing microalbuminuria .
For patients with diabetic nephropathy, combination therapy initially appeared promising for reducing proteinuria and potentially slowing kidney disease progression. However, large clinical trials found that while proteinuria decreased, there was no significant benefit in slowing progression to end-stage renal disease or reducing mortality. Importantly, combination therapy was associated with a higher risk of serious side effects, including hyperkalemia and acute kidney injury, leading to early termination of some studies 510.
Cardiac and Vascular Effects: Ventricular Remodeling and Vasodilation
Animal studies suggest that the combination of lisinopril and losartan is more effective than either drug alone in reducing ventricular hypertrophy, improving survival, and limiting adverse ventricular remodeling after myocardial infarction. These benefits are greater than those seen with monotherapy . The combination also enhances the vasodilatory effects of angiotensin-(1-7), a peptide with blood pressure-lowering properties, which contributes to the antihypertensive effects of dual RAS blockade 69.
Safety Considerations and Adverse Effects
While combination therapy can provide more complete RAS blockade and greater reductions in blood pressure and proteinuria, it also increases the risk of adverse events, particularly in patients with diabetes and chronic kidney disease. The most significant risks are hyperkalemia and acute kidney injury, which can be serious and limit the use of this combination in clinical practice . High-dose monotherapy with either agent may be better tolerated in some patients .
Conclusion
Combining lisinopril and losartan can offer additional blood pressure and proteinuria reduction compared to monotherapy, and may provide cardiac benefits in certain settings. However, the increased risk of adverse effects, especially in patients with diabetes or chronic kidney disease, means that this approach should be used with caution. High-dose monotherapy may be a safer alternative for some patients, and careful monitoring is essential when considering combination therapy.
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