Combining antihypertensive and antihyperlipidemic agents – optimizing cardiovascular risk factor management

Abstract

Clinical guidelines now recognize the importance of a multifactorial approach to managing cardiovascular (CV) risk. This idea was taken a step further with the concept of the Polypill™. There are, however, considerable patent, pharmacokinetic, pharmacodynamic, registration, and cost implications that will need to be overcome before the Polypill™ or other single-pill combinations of CV medications become widely available. However, a medication targeting blood pressure (BP) and lipids provides much of the proposed benefits of the Polypill™. A single-pill combination of the antihypertensive amlodipine besylate and the lipid-lowering medication atorvastatin calcium (SPAA) is currently available in many parts of the world. This review describes the rationale for this combination therapy and the clinical trials that have demonstrated that these two agents can be combined without the loss of efficacy for either agent or an increase in the incidence of adverse events. The recently completed Cluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL trial) is discussed in detail. CRUCIAL was a 12-month, international, multicenter, prospective, open-label, parallel design, cluster-randomized trial, which demonstrated that a proactive intervention strategy based on SPAA in addition to usual care (UC) had substantial benefits on estimated CV risk, BP, and lipids over continued UC alone. Adherence with antihypertensive and lipid-lowering therapies outside of the controlled environment of clinical trials is very low (~30%–40% at 12 months). Observational studies have demonstrated that improving adherence to lipid-lowering and antihypertensive medications may reduce CV events. One means of improving adherence is the use of single-pill combinations. Real-world observational studies have demonstrated that patients are more adherent to SPAA than co-administered antihypertensive and lipid-lowering therapy, and this improved adherence translated to reduced CV events. Taken together, these findings suggest that SPAA can play an important role in helping physicians improve the management of CV risk in their patients.

Blood Pressure and Cholesterol-lowering Efficacy of a Fixed-dose Combination With Irbesartan and Atorvastatin in Patients With Hypertension and Hypercholesterolemia: A Randomized, Double-blind, Factorial, Multicenter Phase III Study

“…[22][23][24][25][26] However various issues related to patents, drug interactions, regulatory restrictions, and financial aspects have to be addressed before such FDC medications will be freely available for clinical use. 7 Given the usual coexistence of hypertension and hyperlipidemia in cardiovascular disease, designing an FDC that combines drugs that lower BP as well as serum LDL-C offers a rational approach to managing these risk factors. To this end, one of the most tested combinations is that of amlodipine, an antihypertensive that acts by blocking calcium channels in the vascular smooth muscles, and atorvastatin.…”

“…4 Recent guidelines for the management of hypertension and hyperlipidemia, as recommended by the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure 2014 (JNC VIII) 5 and the American College of Cardiology/American Heart Association 2013 blood cholesterol guideline, 6 respectively, emphasize the overall assessment of BP and serum lipid levels in evaluating cardiovascular risk rather than assessment of each risk factor individually. 7 Presently, the drugs with a preferred mechanism of cardiovascular protection for antihypertensive therapy are those that inhibit the renin-angiotensin system (RAS). 8 Two classes of the drugs (the angiotensinconverting enzyme [ACE] inhibitors and the angiotensin II receptor blockers [ARBs]) have been discovered to have RAS inhibitory activity, albeit by different mechanisms.…”

دراسة تأثير مشتقات الثياديازول والثيازين كمضادات للهرمون ومضادات الأكسدة في الفئران المستحثة فرط شحميات الدم

“…Table (2) show the catalase activity, levels of TOS and TAS were significant decrease in G2 in levels of TOS and TAS when compared with G1. Also, a significant increase was found G2 compared with G1 in patient group.…”

“…Hyperlipidaemia is an increase in the lipids, and lipoproteins (1) . The combination of certain risk factors such as dyslipidemia can act multiplicatively or synergistically to increase the risk of atherosclerosis and heart disease (2) .…”

Antidiabetic evaluation of vanillic acid-glyburide loaded polymeric micelles in high fat diet and streptozotocin induced diabetic rats

“…Overall, such conditions contribute to increasing the economic burden and affect the quality of life of the patients as the CV complications require angioplasty or coronary artery bypass graft surgery. In addition to this, in most cases, it has been observed that the patients having a long history of T2DM have been advised to take antihyperlipidaemic drugs such as statins to treat hyperlipidaemia as well as in many cases antihypertensives to treat hypertension (Zamorano 2011; Rosenblit 2016). Therefore, the dose-reduction of Gly 4.7-folds than the base value respectively (Prabhakar and Doble 2009).…”