Fixed‐dose combinations of lipid‐lowering and antihypertensive agents: The way forward?

Hypertension and elevated low‐density lipoprotein cholesterol (LDL‐C) levels represent major modifiable risk factors for cardiovascular disease (CVD).1, 2 Approximately one third of the adult population has hypertension, and almost 40% have hypercholesterolemia.3 Moreover, these two risk factors commonly coexist not only because of their high prevalence but also because they share common underlying pathogenetic mechanisms, particularly unhealthy dietary habits, sedentary lifestyle, and obesity.4 Indeed, almost one fourth of the general population has both hypertension and hypercholesterolemia.4 This coexistence has major clinical implications, since it results in a synergistic increase in cardiovascular risk.5, 6

Given the large number of patients who have both hypertension and hypercholesterolemia as well as the increased cardiovascular risk that results from their coexistence, several studies evaluated the safety and efficacy of fixed‐dose combinations of atorvastatin and up to three different antihypertensive agents.7, 8, 9, 10 All these studies showed that fixed‐dose combinations result in similar reductions in blood pressure (BP) and LDL‐C levels compared with separate pill regimens.7, 8, 9, 10 In contrast, there are limited data regarding the effects on BP and LDL‐C levels of fixed‐dose combinations of rosuvastatin and antihypertensive agents.11, 12, 13 Since rosuvastatin induces the largest reductions in LDL‐C levels among statins, including this agent in a fixed‐dose combination with antihypertensive agents might represent a useful tool in achieving LDL‐C targets, particularly in high‐risk patients.14 Therefore, the findings of the study by Kim et al, reported in this issue of the Journal of Clinical Hypertension, have important implications.15 In this double‐blind, multicenter trial, 106 hypertensive patients with dyslipidemia were randomly assigned to receive a fixed‐dose combination of rosuvastatin 20 mg and amlodipine 10 mg, monotherapy with rosuvastatin 20 mg, or monotherapy with amlodipine 10 mg once daily for 8 weeks.15 Systolic BP was reduced by 22.8 ± 12.9 mm Hg in the combination arm, and 57.1% of patients in this group achieved BP targets.15 Similar results were observed with amlodipine monotherapy, whereas patients treated with atorvastatin monotherapy showed minimal changes.15 In addition, serum LDL‐C levels were reduced by 52.5 ± 11.2% in the combination arm and 97.1% of patients in this group achieved LDL‐C targets.15 Patients treated with rosuvastatin monotherapy experienced similar benefits; in contrast, LDL‐C levels did not change with amlodipine monotherapy.15 Rates of adherence to treatment were >97% in all groups and did not differ between groups.15 Rates of adverse events were also similar in the three groups.15 Importantly, no patient discontinued treatment due to an adverse event.15

The findings of the study by Kim et al further strengthen the results of previous studies, which showed that fixed‐dose combination of statins and antihypertensive agents is similarly effective and safe with monotherapy.7, 8, 9, 10, 11, 12, 13, 15 It is well‐established that despite the availability of several effective and safe classes of antihypertensive agents, less than one third of patients with treated hypertension have controlled blood pressure.3 Accordingly, among patients with hypercholesterolemia who are receiving lipid‐lowering treatment, LDL‐C targets are achieved in approximately two thirds of patients.16 The suboptimal control of these risk factors is due to many causes, including physician inertia, side effects, and cost of treatment.17 However, a major contributor to the low rates of achievement of BP and LDL‐C targets appears to be suboptimal adherence to antihypertensive and lipid‐lowering treatment.18, 19 On the other hand, previous studies suggested that fixed‐dose combination of statins and antihypertensive agents results in better adherence to treatment than separate pill combination.20, 21 Moreover, it has been reported that switching from atorvastatin monotherapy to atorvastatin/amlodipine fixed‐dose combination improves adherence.22 Therefore, combining antihypertensive agents with a statin in a single pill might represent a useful tool to improve adherence to treatment and achieve BP and LDL‐C targets.

Another potential benefit of fixed‐dose combinations of lipid‐lowering and antihypertensive agents is that they might serve as a reminder to physicians to identify and manage all cardiovascular risk factors. Guidelines for prevention of CVD emphasize the importance of assessing total cardiovascular risk, which in turn determines treatment targets.23, 24, 25 However, it has been reported that in patients with multiple cardiovascular risk factors, rates of achievement of treatment targets are suboptimal.4 It is possible that the availability of fixed‐dose combinations targeting both BP and LDL‐C might raise awareness of the importance of screening for additional risk factors in patients who present with either hypertension or hypercholesterolemia.

In conclusion, the results of the study by Kim et al15 provide additional evidence regarding the safety and efficacy of fixed‐dose combinations of statins and antihypertensive agents. It appears that a substantial proportion of patients can reach treatment targets with these combinations and with a safety profile comparable with monotherapy. More importantly, improved adherence to fixed‐dose combination will possibly translate to sustained control of both hypertension and hypercholesterolemia and might translate into greater reductions in cardiovascular morbidity.

CONFLICT OF INTEREST

None.