The Combination of Nebivolol plus Pravastatin is Associated with a More Beneficial Metabolic Profile Compared to that of Atenolol plus Pravastatin in Hypertensive Patients with Dyslipidemia: A Pilot Study

Abstract

Nebivolol, a selective β1-lipophilic blocker, achieves blood pressure control by modulating nitric oxide release in addition to b-blockade. This dual mechanism of action could result in minimum interference with lipid metabolism compared to atenolol, a classic (β1-selective blocker. Hypertensive patients commonly exhibit lipid abnormalities and frequently require statins in combination with the anti-hypertensive therapy. We conducted this trial in order to clarify the effect on the metabolic profile of β-blocker therapy with atenolol or nebivolol alone, or in conjunction with pravastatin. Thirty hypertensive hyperlipidemic men and women (total cholesterol >240 mg/dL [6.2 mmol/L], low-density lipoprotein cholesterol >190 mg/dL [4.9 mmol/L], triglycerides <500 mg/dL [5.6 mmol/L]) were separated in two groups. One group consisted of 15 subjects on atenolol therapy (50 mg daily), and the other group included 15 subjects on nebivolol therapy (5 mg daily). After 12 weeks of (-blocker therapy, pravastatin (40 mg daily) was added in both groups for another 12 weeks. Atenolol significantly increased triglyceride levels by 19% (P = .05), while nebivolol showed a trend to increase high-density lipoprotein cholesterol by 8% (NS) and to decrease triglyceride levels by 5% (NS). Atenolol significantly increased lipoprotein(a) by 30% (P = .028). Fibrinogen levels were equally and not significantly decreased in both groups by 9% and 7%, respectively. Furthermore, atenolol and nebivolol decreased serum high-sensitivity C-reactive protein levels by 14% (P = .05) and 15% (P = .05), respectively. On the other hand, both atenolol and nebivolol showed a trend to increase homocysteine levels (NS) by 13% and 11%, respectively. Although uric acid levels remained the same, atenolol significantly increased the fractional excretion of uric acid by 33% (P = .03). Following nebivolol administration, glucose levels remained the same, while insulin levels were reduced by 10% and the HOMA index (fasting glucose levels multiplied by fasting insulin levels and divided by 22.5) was reduced by 20% (P = .05). There were no significant differences between the two patient groups in the measured parameters after the administration of (-blockers, except for triglycerides (P < .05) and the HOMA index (P = .05). The addition of pravastatin to all patients (n = 30) decreased total cholesterol by 21% (P < .001), low-density lipoprotein cholesterol by 28% (P < .001), apolipoprotein-B by 22% (P < .001), apolipoprotein-E by 15% (P = .014) and lipoprotein(a) levels by 12% (P = .023). Moreover, homocysteine levels and C-reactive protein were reduced by 17% (P = .05) and 43% (P = .05), respectively. We conclude that nebivolol seems to be a more appropriate therapy in hypertensive patients with hyperlipidemia and carbohydrate intolerance. Finally, the addition of pravastatin could further correct the well-established predictors of cardiovascular events.