Major Research Findings

Enalapril, an angiotensin-converting enzyme inhibitor, has shown to have psychotropic effects in normal volunteers. 5 In a study administering enalapril to 12 subjects for 14 days, it was found that enalapril did not lower mood but could enhance attention and alertness. It significantly reduced diastolic blood pressure and increased heart rate compared to placebo. Additionally, a component of the auditory evoked EEG response (P1-N1) was increased, and tapping rate quickened.

Clinical trials in Bulgaria have demonstrated the effectiveness and good tolerability of enalapril in treating arterial hypertension. 9 Enalapril, generally administered orally once daily, lowers blood pressure by reducing peripheral vascular resistance without increasing heart rate or output. Common adverse effects include headache, dizziness, orthostatic effects, and abdominal pain, occurring in less than 10%. A more significant side effect, dry persistent cough, was observed in 8.6% of patients.

A worldwide multiclinic study evaluated the antihypertensive effect of enalapril in patients with mild to moderate essential hypertension. 6 The study compared enalapril to propranolol and found that enalapril significantly lowered both systolic and diastolic blood pressure, demonstrating superior efficacy in lowering blood pressure. Enalapril was also found to be safe and well-tolerated over a long period of 48 weeks. Furthermore, enalapril seemed to attenuate thiazide-induced hypokalemia, hyperuricemia, and hyperglycemia.

A study investigating the interaction between sodium intake, enalapril, plasma renin, and blood pressure control in hypertensive men demonstrated an additive effect of combining a low sodium intake with enalapril, leading to a more significant reduction in blood pressure. 4 Enalapril increased plasma renin, while increasing sodium intake lowered it. These effects were additive, with no interactive effect. The study concluded that enalapril is an effective antihypertensive agent, and its blood pressure-lowering effect is additive to that of sodium restriction.

Enalapril has been found to be effective in treating essential hypertension across all grades, demonstrating a potent antihypertensive effect comparable to atenolol. 2 In a single-blind crossover trial comparing enalapril to atenolol, enalapril achieved blood pressure normalization in 88%, 50%, and 25% of patients with mild, moderate, and severe hypertension, respectively. The optimal dose for most patients was 20 to 40 mg/day. Although both drugs demonstrated similar efficacy, enalapril showed a significantly greater reduction in systolic blood pressure in patients with mild and moderate hypertension. Notably, neither drug caused serious side effects. Therefore, enalapril is considered a potential 'first-step' drug in managing hypertensive patients.

A study comparing enalapril as monotherapy and in combination with hydrochlorothiazide in Korean patients with essential hypertension found the combination therapy to be more effective and safe, allowing for lower enalapril dosing. 1 The combination therapy led to a greater mean reduction in diastolic blood pressure compared to monotherapy, and the required enalapril dose was significantly lower in the combination therapy group. Adverse effects were comparable between the two regimens.

A randomized controlled multicenter study compared the long-term antihypertensive efficacy, tolerability, and metabolic effects of prazosin GITS and enalapril in hypertensive patients with diabetes mellitus. 10 The study found that both drugs exhibited comparable antihypertensive efficacy and were generally well-tolerated. Prazosin GITS showed a beneficial effect on serum triglycerides, while enalapril resulted in a significant increase in LDL cholesterol. Neither drug impacted glycosylated hemoglobin or 12-hr urinary microalbuminuria. The study highlighted a significant difference in the incidence of side effects, with enalapril associated with a three-fold higher incidence of adverse events compared to prazosin GITS.

The acute and chronic effects of enalapril were assessed in a double-blind randomized trial in subjects with essential hypertension. 7 The study observed a dose-dependent reduction in blood pressure and a correlation between serum enalapril levels and ACE inhibition. During chronic treatment, the drug level:ACE inhibition curve shifted to the right, suggesting ACE induction during long-term enalapril therapy.

A randomized trial compared the efficacy and safety of combination drug therapy regimens starting with either losartan potassium or enalapril maleate in patients with severe hypertension. 8 Both regimens effectively lowered blood pressure, with the enalapril-based regimen showing slightly greater reduction. Both regimens were generally well-tolerated, with headache being the most common adverse experience. The study concluded that both losartan-based and enalapril-based regimens are effective and safe for treating severe hypertension.

A double-blind randomized crossover placebo controlled study investigated the effects of single doses of enalapril and atenolol in hypertensive patients already on diuretic treatment. 3 Both doses of enalapril and atenolol produced similar effects on blood pressure. The study established that 5 mg enalapril is the maximal starting dose in patients already on diuretic treatment, emphasizing the importance of careful dose selection and the need for early combination-therapy studies during drug development to avoid overdosage.

Benefits and Risks

Benefits Summary

Enalapril has been shown to be an effective treatment for essential hypertension, lowering blood pressure across various grades. 2 Compared to other antihypertensive agents, enalapril might have fewer side effects, with tiredness being the most common. 5 Enalapril might also possess the ability to enhance attention and alertness. 5

Risks Summary

Common side effects associated with enalapril include headache, dizziness, orthostatic hypotension, abdominal pain, and dry persistent cough. 9 Enalapril may also reduce the risk of thiazide-induced hypokalemia, hyperuricemia, and hyperglycemia when used in combination with diuretics. 6

Comparison Between Studies

Similarities Between Studies

Multiple studies have consistently demonstrated that enalapril is an effective antihypertensive agent, beneficial in treating essential hypertension. 2 , 6 , 10 Additionally, studies have indicated that enalapril is generally well-tolerated and safe. 6 , 10

Differences Between Studies

The effectiveness and side effects of enalapril can vary depending on factors such as patient age, gender, severity of hypertension, and other health conditions. 1 , 10 Some studies have shown enalapril to be more effective in lowering blood pressure than other antihypertensive agents. 2 , 6 Other studies have found no significant difference in the effectiveness of enalapril compared to other antihypertensive agents. 10

Consistency and Inconsistencies in Findings

While there is consistency in the findings regarding enalapril's effectiveness and side effects, some inconsistencies have been observed. For instance, some studies have shown enalapril to enhance attention and alertness, 5 while others have not demonstrated this effect. 10 These inconsistencies might be attributed to differences in study design, patient characteristics, enalapril doses used, and other factors.

Considerations for Real-Life Application

Enalapril is an effective medication for managing hypertension, but it's crucial to take it as directed by your physician. 2 , 6 Enalapril may interact with other medications, so it's important to inform your doctor about any other medications you are taking. 3 Enalapril might not be suitable for pregnant or breastfeeding women. 9 Consult your doctor if you experience any side effects from enalapril.

Limitations of Current Research

Research on enalapril's effectiveness and side effects has certain limitations. For example, most studies have used relatively small sample sizes. 1 , 3 Furthermore, many studies have been conducted on specific patient populations, and it's uncertain whether their findings apply to other patient groups. 1 , 10

Future Research Directions

Larger-scale, long-term studies are needed to investigate the long-term effectiveness and side effects of enalapril. 6 Further research is also required to examine how enalapril's effectiveness and side effects vary based on patient age, gender, severity of hypertension, and other health conditions. 1

Conclusion

Enalapril is an effective medication for treating essential hypertension and is generally safe and well-tolerated for many patients. 2 , 6 However, enalapril can cause side effects and interact with other medications. 9 , 3 It is important to follow your physician's instructions when taking enalapril. 2 , 6 Consult your doctor if you experience any side effects from enalapril.