Single‐Pill Therapy in the Treatment of Concomitant Hypertension and Dyslipidemia (The Amlodipine/Atorvastatin Gemini Study)

Abstract

The Gemini Study was a 14‐week, open‐label, noncomparative, office‐based, multicenter trial to evaluate single‐pill therapy in the treatment of concomitant hypertension and dyslipidemia. In addition to recommending lifestyle modifications, eight dosage strengths of amlodipine/atorvastatin single pill (5/10, 5/20, 5/40, 5/80,10/10,10/20,10/40, and 10/80 mg) were electively titrated to improve blood pressure and lipid control. A total of 1220 patients with uncontrolled hypertension at baseline received study medication. At baseline, mean blood pressure was 146.6/87.9 mm Hg and mean low‐density lipoprotein cholesterol concentration was 152.9 mg/dL. At study end, 57.7% of patients had achieved both their blood pressure and low‐density lipoprotein cholesterol goals (51.9% of patients with uncontrolled low‐density lipoprotein cholesterol at baseline). The mean dose of study medication at end point was amlodipine component 7.1 mg and atorvastatin component 26.2 mg. Fifty‐eight patients (4.8%) discontinued therapy due to adverse events. Single‐pill therapy is effective in reducing both blood pressure and lipid levels and in helping patients achieve goals for both hypertension and dyslipidemia.

Hypertension and dyslipidemia are important, modifiable cardiovascular (CV) risk factors that frequently coexist, and together have an effect on CV risk that May be greater than expected from the simple addition of the risk associated with each condition. ¹ , ² Estimates based on the Third National Health and Nutrition Examination Survey (NHANES III) in the United States indicate a prevalence of concomitant hypertension and dyslipidemia of almost 15%, which represents approximately 30 million US adults. ³

Current guidelines for the management of hypertension and dyslipidemia have focused on the need to set blood pressure (BP) and lipid targets dependent upon a patient's overall level of CV risk. ⁴ , ⁵ , ⁶ , ⁷ , ⁸ However, despite the high prevalence of concomitant hypertension and dyslipidemia, observational data suggest that fewer than 10% of patients attain recommended therapeutic targets for both conditions. ⁹ Treatment strategies that specifically target overall CV risk rather than individual risk factors are therefore warranted.

Amlodipine besylate is a dihydropyridine calcium channel blocker (CCB) approved for the treatment of hypertension and both vasospastic and chronic, stable angina. ¹⁰ Amlodipine is well tolerated and efficacious at lowering BP. The largest clinical hypertension trial to date, the Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT [n=33,357]),ⁿ reinforced the importance of BP control and demonstrated that amlodipine was as effective as a diuretic in the prevention of coronary heart disease (CHD) events. A further clinical end‐point trial, the Valsartan Antihypertensive Long‐Term Use Evaluation (VALUE), ¹² was designed to test the hypothesis that, for the same BP control, valsartan, an angiotensin receptor blocker, would reduce cardiac morbidity and mortality more than amlodipine in more than 15,000 hypertensive patients at high CV risk. BP was reduced by both treatments, but to a greater extent in the amlodipine‐based regimen, especially in the early period (BP 4.0/2.1 mm Hg lower in the amlodipine than the valsartan group after 1 month; 2.1/1.6 mm Hg lower after 6 months; p<0.001 between groups for both). CV events were less frequent in the amlodipine group during this time. The VALUE trial supports the accumulating body of evidence that early and aggressive BP control is a key treatment element in reducing CV events.

The 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor (or statin) atorvastatin calcium ¹³ has been shown to be an effective and safe treatment for dyslipidemia. ¹⁴ , ¹⁵ , ¹⁶ This medication is also effective in reducing the rate of coronary events and revascularization procedures in patients with multiple CV risk factors. ¹³ , ¹⁷ Furthermore, a number of primary and secondary prevention studies suggest that additional clinical benefit May be achieved by aggressively lowering lowdensity lipoprotein cholesterol (LDL‐C) below current guideline levels ¹⁷ , ¹⁸ , ¹⁹ (Table I sets forth the current LDL‐C goals according to the National Cholesterol Education Program Third Adult Treatment Panel [NCEP ATP III] ⁶ guidelines). For example, results of the Lipid‐Lowering Arm of the Anglo‐Scandinavian Cardiac Outcomes Trial (ASCOT‐LLA) ¹⁷ demonstrated significant reductions in CV events among hypertensive patients with normal‐to‐moderately elevated LDL‐C levels at baseline (mean [± SD] LDL‐C at baseline was 131.3±27.0 mg/dL) treated with atorvastatin 10 mg compared with placebo.

Table I.

Criteria for Assignment to Cardiovascular (CV) Risk Categories and Recommended Blood Pressure (BP) and Low‐Density Lipoprotein Cholesterol (LDL‐C) Target Levels for Each Risk Group

		CV Risk Group
	Group I	Group II	Group III
Group assignment
CV risk factors for CHD	Hypertension and dyslipidemia with no with additional CV risk factors	Hypertension and dyslipidemia with one or more additional CV risk factors,* excluding CHD and diabetes mellitus	Hypertension and dyslipidemia with CHD or CHD risk equivalent (diabetes mellitus or other atherosclerotic disease)
Entry criteria
SBP 140‐179 and/or BP (mm Hg)	SBP 140‐179 and/or	SBP 130‐159 and/or
	DBP 90‐109	DBP 90‐109	DBP 85‐99
LDL‐C (drug‐naive**) (mg/dL)	160‐250	130‐250	100‐250
LDL‐C (treated) (mg/dL)	≤170	≤170	≤170
Treatment goals
JNC VI 4 BP goal (mm Hg)	<l40/90	<l40/90	<130/85
NCEP ATP III 6 LDL‐C goal (mg/dL)	<160	<130	<100
CHD=coronary heart disease; SBP=systolic BP; DBP=diastolic BP; *includes: age ≤45 years (male), ≤55 years (female); history of CHD in a parent or sibling <55 years (male) or <65 years (female); smoking (current); high‐density lipoprotein cholesterol (HDL‐C) <40 mg/dL (HDL‐C ≤60 mg/dL required two additional risk factors); **no prescription lipid‐modifying drug therapy at screening; treated with lipid‐lowering medication. Guideline acronyms are expanded in the text.

The pharmacokinetic and pharmacodynamic properties of amlodipine and atorvastatin make them well suited for combination in a single pill to manage CV risk. The half‐lives of both agents facilitate once‐daily dosing, and both can be administered at any time of day with or without food. ¹⁰ , ¹³ The coadministration of amlodipine and atorvastatin has been demonstrated to be safe and efficacious at lowering both BP and LDL‐C levels in patients with concomitant hypertension and dyslipidemia. ²⁰ , ²¹

The rationale for the Amlodipine/Atorvastatin Gemini Study was to illustrate how a single pill that treats two CV risk factors simultaneously can be used in different patients and different treatment situations. To simulate this “real world” approach in a clinical trial setting, the study had to be flexible enough to allow investigators to enroll different patient types (e.g., those with/without diabetes and with/without CHD) and from a variety of treatment backgrounds (e.g., treatment‐naïve patients, or those already receiving treatment for their hypertension and/or dyslipidemia). To achieve this flexibility and allow the investigators to use the study medication in the same way that they would prescribe it in real‐life clinical practice, the study was designed as an open‐label trial with no comparator group, no washout period, and elective dose titration. This design was intended to provide important information on the appropriate utilization of the single pill in clinical practice, together with efficacy and safety data for single‐pill amlodipine/atorvastatin.

This is the first trial to examine the use of singlepill therapy for the cotreatment of more than one CV risk factor. The primary objectives were to evaluate the efficacy of amlodipine/atorvastatin singlepill therapy, as defined by the percentage of patients achieving both BP and LDL‐C treatment goals, and to gain practical clinical experience in using and titrating single‐pill therapy initially, or in combination with other antihypertensive medications.

Inclusion and Exclusion Criteria

Study participants were men and women aged 18–80 years with a diagnosis of concomitant hypertension and dyslipidemia qualifying for drug therapy. BP had to be uncontrolled, as defined by the sixth report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI), ⁴ the standard when the study was started, regardless of whether a patient was already receiving antihypertensive medication. LDL‐C could be controlled (with medication) or uncontrolled (with or without medication), based on NCEP ATP III. ⁶ Patients receiving therapy for hypertension and/or dyslipidemia at screening had to have been receiving stable doses of medication for at least 6 weeks before baseline.

Patients were excluded if their BP was already at goal, or if they were currently being treated with both amlodipine and atorvastatin, amlodipine 10 mg (or other maximum‐dose CCB), or atorvastatin 80 mg with LDL‐C levels >100 mg/dL. Additional exclusion criteria included pregnancy or lactation, impaired renal function, impaired hepatic function, a history of cardiomyopathy or congestive heart failure, and secondary hypertension or dyslipidemia of any etiology. Patients with a history of cerebrovascular disease, myocardial ischemia, coronary artery bypass, or intracoronary interventions within 3 months of screening were excluded.

Study Design

The Gemini Study was a 14‐week, open‐label study designed to simulate real‐world clinical practice. At screening, study participants were classified into one of three CV risk categories, based on criteria outlined in the JNC VI and NCEP ATP III guidelines (Table I). Lifestyle modification, including diet and exercise, was recommended to all patients. The study did not include a medication washout period. Single‐pill amlodipine/atorvastatin therapy was administered in one of eight doses: 5/10, 5/20, 5/40, 5/80, 10/10, 10/20, 10/40, and 10/80 mg. Initial dose was determined based on each patient's level of BP and LDL‐C control and their current use of BP and/or lipid‐lowering medications at screening. Patients were permitted to continue taking non‐CCB antihypertensive medication(s), with the caveat that the dosing regimens were stable and remain constant throughout the study. Thus, the amlodipine component of the single pill was taken as: 1) initial antihypertensive therapy for patients who were previously untreated for hypertension; 2) substitution therapy for patients who were already receiving amlodipine; 3) switch therapy for patients who were previously taking other CCBs; or 4) add‐on therapy to the patient's non‐CCB antihypertensive regimen. The atorvastatin component of the combination tablet was taken as: 1) initial lipid‐lowering therapy for patients who were previously untreated for dyslipidemia; 2) substitution therapy for patients already receiving atorvastatin; or 3) switch therapy for patients who were already taking lipid‐lowering agents (excluding atorvastatin). During the study, patients were not permitted to take any additional lipid‐regulating medications; those patients receiving atorvastatin at screening had their dose modified depending on their LDL‐C goal status.

BP was recorded at screening (Weeks ‐1 and ‐3), enrollment (Week 0), and at Weeks 4, 6, 10, 12, and 14. At each visit, following a 5‐minute rest period, BP was measured three times, with a full 2‐minute interval separating the measurements and with the cuff fully deflated between measurements. Lipid levels were recorded at screening (Week ‐3), enrollment (Week 0), and at Weeks 4, 6, 10, 12, and 14. In addition, optional measurements could be taken at Weeks 6 and 12.

Based on the investigator's clinical discretion, both upward and downward titration of the study drug was performed, with the overriding objective of simultaneously achieving BP and LDL‐C targets, as specified by CV risk group classification (Table I). Titration could have occurred at Weeks 6, 10, and 12, if clinically indicated.

This study was conducted in compliance with Good Clinical Practices and the Declaration of Helsinki. The study protocol, including all amendments, and the patient informed‐consent form used in the study, were approved by all appropriate institutional review boards.

Efficacy Measures

The primary efficacy measure was the percentage of intent‐to‐treat patients achieving both JNC VI BP and NCEP ATP III LDL‐C treatment goals at end point. For BP, both systolic and diastolic BP had to be below the target level at end point for a patient to be classified as “at goal.” Secondary efficacy measures included: 1) percentage of patients achieving BP treatment goal at end point; 2) percentage of patients with uncontrolled LDL‐C at baseline who achieved LDL‐C treatment goal at end point; 3) absolute change in systolic and diastolic BP; and 4) percentage change in LDL‐C from baseline to end point.

Safety Assessments

The nature, date of onset, duration, severity, action taken (if any), and causal relationship to study drug of all adverse events were documented at each clinical visit. Clinically significant changes in physical examination findings and abnormal objective test findings were recorded as adverse events.

Statistical Analysis

The following populations were defined: 1) intentto‐treat population: all patients who received at least one dose of study medication and had any post‐enrollment efficacy data; and 2) uncontrolled LDL‐C at baseline: intent‐to‐treat patients with baseline LDL‐C above NCEP ATP III therapeutic targets. Efficacy measures were evaluated at baseline and end point. End point was defined as the last nonmissing, postbaseline observation carried forward for each patient during the 14‐week study. For attainment of therapeutic targets, the numbers, percentages, and 95% confidence intervals for the proportions of patients reaching their goal(s) for BP and LDL‐C were calculated at end point. For BP, means and SDs were calculated at baseline and end point, as was mean ± SD change from baseline to end point. For LDL‐C, the percentage change from baseline to end point was calculated. Results were analyzed overall and by CV risk group. Appropriate SAS procedures (Version 8, SAS Institute Inc., Cary, NC) were used to generate analysis results.

RESULTS

Of 1841 patients screened, 1220 met the inclusion criteria, were enrolled in the study, and received study medication. Of these, 1095 patients (89.8%) completed the study. Patients were predominantly white, with a mean age of 61 years (Table II). More patients were in CV risk group III (47.6%) than in group II (38.9%) or group I (13.5%). The proportion of patients in each CV risk group was similar for both the intent‐totreat and uncontrolled LDL‐C populations. Systolic BP at baseline was similar across the three groups. Among patients with uncontrolled LDL‐C at baseline, mean LDL‐C at baseline was lower among patients at higher CV risk (group III) (Table II).

Table II.

Demographic Characteristics of Study Population at Baseline

	Cardiovascular Risk Group
Characteristic	GroupI	GroupII	GroupIII	Total
Number of patients (n [%])	165 (13.5)	474 (38.9)	581 (47.6)	1220 (100.0)
Men (n [%])			675 (55.3)
Age (y) (mean ± SD)	56.3±12.8	58.6±10.4	64.0±9.8	60.9±10.9
Race (n [%])
White	123 (74.5)	405 (85.4)	486 (83.6)	1014 (83.1)
Black	34 (20.6)	39 (8.2)	48(8.3)	121 (9.9)
Other	8 (4.8)	30 (6.3)	47 (8.1)	85 (7.0)
Body mass index (kg/m2) (mean ± SD)	31.0±6.7	30.6±5.0	31.8±6.5	31.2±6.0
Current smoker (n [%])	6 (3.6)	93 (19.6)	78 (13.4)	177 (14.5)
Duration of primary diagnoses (y)
Hypertension (mean [range])	8.1 (0−38.4)	8.7 (0−53.8)	10.4 (0−58.8)	9.4 (0−58.8)
Dyslipidemia (mean [range])	5.6 (0−32.8)	6.3 (0−42.9)	6.6 (0−42.7)	6.4 (0−42.9)
Diabetes (n [%])	0 (0)	0 (0)	324 (55.8)	324 (26.6)
Chronic IHD (n [%])	1 (0.6)	9 (1.9)	219 (37.7)	229 (18.8)
Efficacy measures (mean ± SD)
LDL‐C (mg/dL)*	188.4±21.5	166.9±26.0	137.2±30.7	152.9±33.4
Systolic BP (mm Hg)	147.8±11.4	147.1±10.6	145.9±11.2	146.6±11.0
Diastolic BP (mm Hg)	90.7±7.8	90.6±7.9	84.8±8.4	87.9±8.6
Receiving therapy pre‐study (%)
Hypertension	71.8	71.6	88.9	79.9
Dyslipidemia	49.1	46.6	69.8	58.0
Both	41.2	37.4	63.8	50.6
Neither	20.9	19.2	5.0	12.7
IHD=ischemic heart disease; LDL‐C=low‐density lipoprotein cholesterol; BP=blood pressure; *patients with uncontrolled LDL‐C at baseline (n=750)

Concomitant Medications

At study initiation, only half (50.6%) of all participants were receiving treatment for both hypertension and dyslipidemia, and 153 patients (12.7%) had received no previous treatment for either condition (Table II). At enrollment, 70.7% of patients (n=863) were taking at least one medication for hypertension (non CCB) in addition to the study drug. Of these, 55.2% were taking one additional antihypertensive, 31.7% were taking two, and 13.1% were taking three or more additional antihypertensive drugs.

The most commonly used antihypertensives were angiotensin‐converting enzyme inhibitors, β blockers, thiazide diuretics, and angiotensin II receptor antagonists. At least 20% of patients took medications from one of the following categories: drugs used in rheumatic diseases or gout (63.0%), vitamins (29.7%), and drugs used in the treatment of diabetes (22.0%).

Administration of Study Drug

The mean dose of amlodipine/atorvastatin at end point was 7.1/26.2 mg (7.1/27.2 mg for patients with uncontrolled LDL‐C at baseline). Very few patients were dispensed an initial dose containing either amlodipine 10 mg or atorvastatin 80 mg (Figure). At end point, only 4.0% of patients received the highest dose of amlodipine/atorvastatin (10/80 mg), and 17.8% were still taking the lowest dose (5/10 mg) (Figure).

Figure 1.

Percentage of patients receiving each dose of study medication at baseline and end point. AML=amlodipine; ATO =atorvastatin

Hypertension and Dyslipidemia Joint Goal Attainment

At study end, 57.7% of patients treated with singlepill amlodipine/atorvastatin therapy had reached both their BP and LDL‐C therapeutic targets (FigureA). Higher percentages of patients in CV risk groups I (77.2%) and II (76.1%) attained both goals (FigureA). A similar trend was observed for patients with uncontrolled LDL‐C at baseline (51.9% overall, 71.6% for CV risk group I, 76.2% for group II, and 31.7% for group III).

Figure 2.

Goal attainment at end point overall and within each of the three cardiovascular risk groups for (A) joint blood pressure (BP) and low‐density lipoprotein cholesterol (LDL‐C) goals, (B) BP goal alone, and (C) LDL‐C goal“ alone. Error bars represent 95% confidence intervals. ”'Patients with uncontrolled LDL‐C at baseline

Attainment of BP Goal

Over 65% of patients reached their JNC VI goal at end point (FigureB). The trend across CV risk groups for BP goal attainment was similar to that observed for joint goal attainment (FigureB).

Attainment of LDL‐C Goal

At end point, 74.7% of patients with uncontrolled LDL‐C at baseline had reached their NCEP ATP III goal (FigureC). In CV risk groups I and II, over 90% of patients had controlled LDL‐C at end point (goals for CV risk group I, <160 mg/dL; group II, <130 mg/dL) (FigureC).

Changes in BP and LDL‐C

Mean BP change from baseline to end point was ‐17.1/‐9.6 mm Hg. Similar BP reductions were observed across all CV risk groups (Table III). Among patients with uncontrolled LDL‐C at baseline, the mean percentage change in LDL‐C from baseline to end point was ‐32.7%. For patients who were statin‐naïve at baseline (n=446), mean percentage change in LDL‐C from baseline to end point was ‐39.2%. In general, the percentage changes in LDL‐C demonstrated a trend across the CV risk groups, with group I showing the greatest reduction and group III showing the least reduction (Table III). Figure shows the distribution of systolic BP and LDL‐C levels of all patients at baseline and end point, illustrating the number of patients in all risk groups who attained both goals.

Table III.

Mean Changes From Baseline to End Point in Blood Pressure (BP) and LDL‐C Parameters and Mean Dose of Single‐Pill Amlodipine/Atorvastatin at End Point by Cardiovascular Risk Group and All Patients Combined

	Cardiovascular Risk Group
	Group I	Group II	Group III	Total
Change in BP parameters*
Systolic BP (mm Hg) (mean ± SD)	−17.8±12.6	−17.8±12.4	−16.4±12.9	−17.1±12.7
Number	163	468	576	1207
Diastolic BP (mm Hg) (mean ± SD)	−10.7±7.9	−10.0±7.6	−9.0±8.2	−9.6±8.0
Number	163	468	576	1207
Mean dose of amlodipine component (mg)*	7.1	6.7	7.4	7.1
Number	163	468	577	1208
Change in lipid parameters**
LDL‐C (%) (mean ± SD)	−43.7±13.2	−37.6±14.2	−27.5±19.1	−32.7±17.9
Number	67	281	402	750
Mean dose of atorvastatin component (mg)**	25.5	24.1	29.7	27.2
Number	67	281	403	751
LDL‐C=low‐density lipoprotein cholesterol; *all patients; **patients with uncontrolled LDL‐C at baseline

Figure 3.

Distribution of systolic blood pressure (SBP)* vs. low‐density lipoprotein cholesterol (LDL‐C) values at baseline and end point for all intent‐to‐treat patients, analyzed by cardiovascular risk group. The horizontal and vertical lines show the goals for LDL‐C and SBP. Joint LDL‐C and blood pressure (BP) goal attainment is depicted by the shaded quadrant. *At study baseline, in accordance with the inclusion criteria, patients May have been at goal for SBP, but not at goal for diastolic BP.

Safety

A total of 782 patients (64.1%) reported at least one adverse event; 287 of these reports were considered related to study treatment or an unknown cause. The most frequently reported adverse events (regardless of causality) were respiratory tract infection (11.9%), peripheral edema (8.8%), headache (5.4%), and myalgia (4.2%) (Table IV). Three treatment‐related adverse events occurred in at least 2% of patients: peripheral edema (6.6%), myalgia (2.1%), and headache (2.1%). The majority of cases of peripheral edema and myalgia were either mild or moderate in severity. Overall, 125 patients (10.2%) discontinued treatment for any reason. Only 58 patients (4.8%) discontinued treatment as a result of an adverse event, most often due to liver enzyme abnormalities (1.0%), peripheral edema (0.8%), and myalgia (0.6%).

Table IV.

Summary of Incidence of Treatment‐Emergent Adverse Events (All Causalities) Occurring in >2% of Patients (N=1220)

Adverse Event	N	%
Respiratory tract infection	145	11.9
Peripheral edema	107	8.8
Headache	66	5.4
Myalgia	51	4.2
Accidental injury	44	3.6
Dizziness	44	3.6
Arthralgia	41	3.4
Asthenia	40	3.3
Rash	38	3.1
Constipation	34	2.8
Rhinitis	32	2.6
Pain	31	2.5
Diarrhea	30	2.5
Creatine phosphokinase increased	29	2.4
Back pain	28	2.3
Sinusitis	28	2.3
Bronchitis	27	2.2
Respiratory disorder	27	2.2

During the study, 33 patients (2.7%) experienced a serious adverse event; however, no serious adverse events were considered related to the study drug. Eleven patients discontinued treatment due to a serious adverse event. One patient died from multiorgan system failure, although this death was not considered by the investigator to be related to the study drug.

DISCUSSION

The Gemini Study is the first large‐scale clinical trial to investigate the use of a single pill for the concomitant treatment of more than one CV risk factor. The results demonstrate that treatment with amlodipine/atorvastatin single pill, either alone or in combination with other antihypertensive medications, enabled many patients to attain hypertension and dyslipidemia treatment goals. Almost 60% of all patients, and more than 75%of patients without CHD or CHD risk equivalents, met target levels for both BP and LDL‐C (Table I) after 14 weeks and three titration visits. These data suggest that the use of amlodipine/atorvastatin May help patients at increased CV risk achieve both BP and lipid goals.

Single‐pill therapy effectively lowered BP (‐17.1/‐9.6 mm Hg) and LDL‐C (‐32.7%) in patients with established hypertension and dyslipidemia at various levels of CV risk. However, joint goal attainment was highest in patients without CHD or CHD risk equivalents. Although only 37% of all patients with CHD or CHD risk equivalents (CV risk group III) attained both BP and LDL‐C goals, more than 70% achieved at least one of the two goals. Since the goals in these patients (BP <130/85 mm Hg ⁴ and LDL‐C <100 mg/dL ⁶ ) are somewhat more challenging than in lower‐risk patients, these data support the need for more intensive treatment in high‐risk patients.

Aggressive atorvastatin‐based treatment strategies have been shown to be successful, both in improving lipid goal attainment and in preventing coronary events in high‐risk patients. ¹⁵ , ¹⁸ , ¹⁹ , ²² Blood pressure control consistently has been shown to reduce the risk of CV events. ¹² , ²³ , ²⁴ , ²⁵ Although the current study was designed to titrate patients to their respective BP and lipid goals, fewer than half received a formulation that contained the maximum dose of amlodipine (10 mg). Only 6.2% received a formulation containing the maximum dose of atorvastatin (80 mg). Had more patients been treated aggressively, it is possible that an even higher proportion May have attained joint BP and lipid goals.

This is the first trial to examine the clinical practice utility of single‐pill therapy for the simultaneous treatment of more than one CV risk factor.

While the limitations of the open‐label, noncomparative study design should be recognized, the study objectives were met. Although there was no placebo comparator in this open‐label trial, the efficacy and safety profiles observed in this study with a single‐pill product were comparable to that observed in previous well‐controlled, double‐blind, placebo‐comparator studies when amlodipine and atorvastatin therapies were coadministered as separate tablets, ²⁰ , ²¹ or when either component was administered alone. ¹⁰ , ¹³ , ¹⁶

Recent clinical trials and treatment guidelines have shifted the focus of CV disease management toward the management of overall CV risk. ⁸ , ²⁶ , ²⁷ , ²⁸ In the Anglo‐Scandinavian Outcomes Trial (ASCOT), ²⁷ almost 20,000 hypertensive patients were randomized to one of two BP‐lowering regimens (amlodipine ± perindopril, or atenolol ± bendroflumethiazide), and a subpopulation of over 10,000 patients with total cholesterol levels of <250 mg/dL were further randomized into a Lipid‐Lowering Arm (LLA). The ASCOT‐LLA showed that in treated hypertensive patients with multiple CV risk factors and only moderately elevated LDL‐C (mean [± SD] LDL‐C at baseline was 131.3±27.0 mg/dL), atorvastatin 10 mg significantly reduced the incidence of nonfatal myocardial infarction, fatal CHD, revascularization, and angina, compared with placebo. ¹⁷

These data demonstrate that the addition of atorvastatin significantly reduced CV risk in hypertensive patients with multiple risk factors, regardless of a patient's baseline LDL‐C level, and reinforce the need for overall CV risk management. Despite these data, and the availability of effective and safe therapies for hypertension and dyslipidemia, few patients receive adequate treatment for both conditions. ⁹ , ²⁹

Indeed, in this trial, 20% of the study participants had received no drug treatment for hypertension before the study, 42% had received no drug treatment for dyslipidemia, and 13% had received no drug treatment for either condition. Although 80% of participants were receiving antihypertensive therapy at screening, all had uncontrolled BP at baseline. These data reinforce guideline recommendations that patients with hypertension require multiple medications to achieve BP goal. ⁵ The addition of amlodipine/atorvastatin into participants' antihypertensivetreatment regimens was well tolerated and enabled 65% of patients to reach their BP goal.

The poor treatment practices and low‐goal attainment in patients with concomitant hypertension and dyslipidemia ³ , ⁹ , ²⁹ May be partly due to poorly applied BP‐ and lipid‐management strategies by physicians. Inadequate patient compliance with often complex treatment regimens can also have an impact on goal attainment. ³⁰ A treatment strategy that includes simultaneous CV risk factor modification and reduces a patient's pill burden May help improve goal attainment, patient compliance, and overall CV risk management.

CONCLUSION

The Gemini Study demonstrates that single‐pill amlodipine/atorvastatin therapy is an efficacious and safe treatment for different patient types with concomitant hypertension and dyslipidemia in different treatment settings. This treatment increases the percentage of patients with both conditions who achieve both their treatment goals.