title: 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 beta1-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 beta1-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 beta-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 beta-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 beta-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.
authors.affiliation: Department of Internal Medicine, Medical School, University of Ioannina, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Rizos
authors.forename: Eleni
authors.initials: E
authors.lastname: Bairaktari
authors.forename: Angeliki
authors.initials: A
authors.lastname: Kostoula
authors.forename: George
authors.initials: G
authors.lastname: Hasiotis
authors.forename: Apostolos
authors.initials: A
authors.lastname: Achimastos
authors.forename: Emanuel
authors.initials: E
authors.lastname: Ganotakis
authors.forename: Moses
authors.initials: M
authors.lastname: Elisaf
authors.forename: D P
authors.initials: DP
authors.lastname: Mikhailidis
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use*; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D000068577:Nebivolol; D010865:Pilot Projects; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000319:Adrenergic beta-Antagonists; D000924:Anticholesteremic Agents; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D001262:Atenolol; D017035:Pravastatin