Lisinopril vs lisinopril-hydrochlorothiazide
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Blood Pressure Lowering: Lisinopril vs Lisinopril-Hydrochlorothiazide Combination
Multiple studies show that combining lisinopril with hydrochlorothiazide (HCTZ) lowers blood pressure more effectively than lisinopril alone or HCTZ alone. The combination leads to a greater reduction in both systolic and diastolic blood pressure compared to either drug used by itself, and these differences are statistically significant in several trials 34567. For example, one study found that the combination reduced sitting systolic/diastolic pressure by 8.8/2.7 mmHg more than lisinopril alone and by 12.8/4.8 mmHg more than HCTZ alone . Another large study confirmed that the combination therapy achieved the best blood pressure control, with a higher percentage of patients reaching target diastolic blood pressure compared to monotherapy 567.
Efficacy in Special Populations: Obese Hypertensive Patients
In obese patients with hypertension, both lisinopril and HCTZ were effective in lowering blood pressure, but lisinopril may have a slight advantage in achieving target diastolic pressure. Sixty percent of patients on lisinopril reached a diastolic pressure below 90 mmHg, compared to 43% on HCTZ. Lisinopril also had a more favorable metabolic profile, with less increase in plasma glucose and no significant effect on insulin or lipid levels, while HCTZ decreased potassium and increased glucose .
Safety and Tolerability: Side Effects and Metabolic Effects
Both lisinopril and the lisinopril-HCTZ combination are generally well tolerated. The most common side effects for lisinopril and the combination are cough and pharyngitis, while HCTZ alone is more likely to cause hypokalemia (low potassium) and increased uric acid 345. The combination therapy tends to reduce the risk of hypokalemia compared to HCTZ alone, as lisinopril can counteract this effect . Serious adverse events are rare for all regimens 36. The combination may increase uric acid and decrease potassium, but these effects are less pronounced than with HCTZ alone .
Pharmacokinetics and Bioequivalence
Studies show that there is no clinically relevant pharmacokinetic interaction between lisinopril and HCTZ when taken together, whether as separate pills or as a fixed-dose combination tablet . The fixed-dose combination is bioequivalent to the separate components and is well tolerated in both fasting and postprandial states, although food can reduce lisinopril absorption by about 20–25% .
Switching and Dose Escalation: Clinical Considerations
For patients whose blood pressure is not controlled on lisinopril 20 mg alone, switching to the lisinopril-HCTZ combination is as effective as increasing the lisinopril dose to 40 mg, with similar rates of side effects and treatment withdrawals . This suggests that adding HCTZ may be a good alternative to simply increasing the lisinopril dose.
Conclusion
The combination of lisinopril and hydrochlorothiazide provides greater blood pressure reduction than either drug alone, with a safety profile similar to monotherapy. The combination is especially useful for patients not controlled on lisinopril alone and may offer metabolic advantages over HCTZ monotherapy, particularly in patients at risk for metabolic disturbances. Both the combination and monotherapies are generally well tolerated, and the fixed-dose combination is convenient and bioequivalent to separate dosing.
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