SEARCH

SEARCH BY CITATION

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References
  8. Appendix

Poor control of hypertension or dyslipidemia may at least in part be due to these risk factors being treated in isolation. The Caduet in Untreated Subjects Population (CUSP) trial was an 8-week, randomized, double-blind, placebo-controlled trial evaluating the efficacy/safety of the combination of a calcium channel blocker (amlodipine besylate) and a statin (atorvastatin calcium) in a single-pill form (5/20 mg) plus therapeutic lifestyle changes (TLC) compared with placebo plus TLC in patients with comorbid hypertension and dyslipidemia without evidence of cardiovascular disease. At week 4, additional antihypertensive/lipid-lowering medication was permitted. The primary end point was the proportion of patients in whom the dual goal of blood pressure (<140/90 mm Hg) and low-density lipoprotein cholesterol control (<100 mg/dL) was met at week 4. This dual goal attainment was significantly greater with amlodipine/atorvastatin plus TLC compared with placebo plus TLC at week 4 (47.6% vs 1.7%; P<.001), with further improvements at week 8. Most adverse events were mild to moderate. Therapy with single-pill amlodipine/atorvastatin plus TLC in these patients significantly increased dual blood pressure/low-density lipoprotein cholesterol goal attainment compared with placebo plus TLC.

Combined hypertension (HTN) and dyslipidemia (DYS) were estimated to affect nearly 30 million adults in the United States in 2007.1 Epidemiologic and outcomes research studies have shown that current treatment strategies are not sufficient in controlling HTN and/or DYS.1–4 HTN is controlled in only 36.2% of those with the condition, and DYS is controlled in only 25.1% of individuals.1,2 The control rate for combined HTN/DYS is even lower, with only 9% of participants reported to be at their treatment goals.4 This is despite the availability of effective and well-tolerated antihypertensive and lipid-lowering medication and evidence that the addition of a lipid-lowering agent to a blood pressure (BP)–lowering regimen confers cardiovascular (CV) benefits.5–7 Poor control of HTN and DYS may at least in part be due to individual CV risk factors being treated in isolation rather than taking a patient’s overall risk factor profile into consideration.5 Suboptimal dosing and poor adherence may also play a role.

Therapeutic lifestyle changes (TLC) is an integral part of current HTN and DYS guidelines.6,7 However, the success rate of TLC is moderate, and recommended goals are not achieved in a large proportion of patients treated with TLC alone, which leaves them at risk for CV disease.8,9 For patients at low to moderate CV risk, current HTN and DYS guidelines recommend the initiation of pharmacotherapy if BP or lipid treatment goals are not attained through TLC alone.6,7 The use of both antihypertensive and lipid-lowering agents is of benefit in the simultaneous treatment of HTN and DYS.10 Single-pill combination therapy is available and has been shown to be efficacious and well-tolerated for the simultaneous treatment of HTN and DYS in a number of open-label trials in a wide range of patient populations.10–14

The Caduet in Untreated Subjects Population (CUSP) trial was the first randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of amlodipine/atorvastatin single-pill therapy. In this 8-week trial, amlodipine/atorvastatin single-pill therapy along with TLC was compared with placebo plus TLC in patients with HTN and DYS at low to moderate CV risk who had either not been treated previously or who had discontinued treatment ≤3 months prior to the start of the trial.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References
  8. Appendix

Study Population

Men and women older than 21 years with coexisting HTN and DYS, but without a history of CV disease, who had never received treatment for these conditions or had not received treatment in the 3 months prior to screening were included in this trial. Recruitment took place at 38 centers in the United States.

To be eligible for inclusion in the study, patients had to have a systolic BP (SBP) level of 140 to 169 mm Hg and/or a diastolic BP (DBP) level 90 to 105 mm Hg at screening and an SBP value of 140 to 159 mm Hg and/or a DBP value of 90–99 mm Hg at randomization. For low-density lipoprotein cholesterol (LDL-C), a measurement of 110 to 160 mg/dL (2.85–4.14 mmol/L) at screening was required for inclusion in the trial. Patients with diabetes, a history of coronary heart disease (CHD), peripheral vascular disease, or cardiac arrhythmias were excluded from the trial. Additional exclusion criteria included use of antihypertensive or lipid-lowering medication in the 3 months prior to screening, known liver disease and/or impaired hepatic function (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3× upper limit of normal), fasting serum triglyceride levels >500 mg/dL (5.65 mmol/L), and any condition that in the investigator’s judgment may have resulted in increased risk for the patient or may have interfered with the conduct of the study.

Study Design

CUSP was an 8-week, randomized, double-blind, placebo-controlled trial conducted between June 27, 2006, and September 4, 2007, evaluating the efficacy and safety of single-pill amlodipine/atorvastatin (5/20 mg) plus TLC compared with placebo plus TLC. TLC consisted of counseling patients on diet, exercise, and smoking cessation. Patients were randomized in a double-blind manner to receive either both amlodipine/atorvastatin (5/20 mg) and TLC or placebo and TLC (Figure 1).

image

Figure 1.  Trial design. AML/ATO indicates amlodipine/atorvastatin single-pill therapy; TLC, therapeutic lifestyle changes.

Download figure to PowerPoint

The treatment goal for BP was <140/90 mm Hg,7 and for LDL-C it was <100 mg/dL (2.59 mmol/L); the latter was an optional National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III goal for moderately high-risk patients based on the evidence of recent primary prevention trials.15

Concomitant Medications

After week 4, add-on antihypertensive and/or lipid-lowering therapy was permitted, in addition to study medication, at the discretion of the investigator. Agents that were not permitted during the trial included antifungal agents, erythromycin, other cytochrome P450 3A4 inhibitors, and immunosuppressive agents.

Efficacy Measures

The primary efficacy measure was the percentage of patients in whom both the BP and LDL-C treatment targets (BP <140/90 mm Hg7 and LDL-C <100 mg/dL [2.59 mmol/L]) were reached at week 4. Secondary efficacy measures included the percentage of patients in whom both BP and LDL-C goals were reached at week 8; the percentage of patients in whom the dual SBP/DBP goal was met at weeks 4 and 8; the percentage of patients in whom the single LDL-C goal was reached at weeks 4 and 8; mean changes from baseline in SBP and DBP at weeks 4 and 8; mean changes from baseline in LDL-C at weeks 4 and 8; and 10-year Framingham risk of CHD at weeks 4 and 8. For the purpose of this study, the Framingham risk scoring criteria included age, total cholesterol, high-density lipoprotein cholesterol, SBP, treatment for HTN, and cigarette smoking, based on the NCEP ATP III 10-year risk assessment tool.16

Statistical Analysis

The planned sample size was 122 patients in order to provide a 90% power to detect a 25% difference in the primary efficacy end point between the 2 study arms, assuming a 5% response in the placebo group, in a 2-sided testing at a significance level of 5%. For the proportion of patients in whom goal was reached, odds ratio (OR) estimates, 95% confidence intervals (CIs), and the corresponding P values were calculated based on a Cochran-Mantel-Haenszel test controlling for baseline HTN and DYS treatment status. For continuous variables, P values were based on an analysis of covariance (ANCOVA) model with terms for treatment group, randomization strata, and baseline values as explanatory variables in the model. Analyses were conducted using Statistical Analysis System (SAS) software (version 8.2, SAS Institute, Inc, Cary, NC).

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References
  8. Appendix

Patient Disposition

Overall, 332 patients were screened for eligibility for inclusion in the trial. Of the 130 patients who were assigned to either the amlodipine/atorvastatin plus TLC group or the placebo plus TLC group, 66 and 64 patients were treated, respectively. One patient received amlodipine/atorvastatin single-pill therapy but was not randomized; this patient was excluded from all efficacy analyses but included in the safety analysis. Another patient was randomized but not treated, as he/she was not willing to participate after randomization. This patient was not included in any efficacy and safety analyses. Fifty-nine (90.8%) patients in the amlodipine/atorvastatin plus TLC group and 58 (90.6%) in the placebo plus TLC group completed the study (Figure 2).

image

Figure 2.  Flow of patients through the trial. *One patient was treated with AML/ATO but not randomized; this patient was excluded from all efficacy analyses but was included in the safety analysis. Another patient was randomized but not treated as he/she was not willing to participate after randomization. This patient was not included in any efficacy or safety analyses. AML/ATO indicates amlodipine/atorvastatin single-pill therapy; TLC, therapeutic lifestyle changes.

Download figure to PowerPoint

Baseline Demographics

The treatment arms were well matched at baseline with respect to age, BP and lipid parameters, and 10-year Framingham risk of CHD (Table I); none of the differences were statistically significant. Similar numbers of patients in the amlodipine/atorvastatin plus TLC (n=45) and the placebo plus TLC (n=43) arms were previously untreated for either HTN or DYS.

Table I.   Baseline Demographics of Evaluable Patients
CharacteristicsAML/ATO+TLC (n=63)Placebo+TLC (n=60)
  1. Abbreviations: AML, amlodipine; ATO, atorvastatin; CHD, coronary heart disease; DBP, diastolic blood pressure; DYS, dyslipidemia; HDL-C, high-density lipoprotein cholesterol; HTN, hypertension; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure; TLC, therapeutic lifestyle changes. P=NS for all comparisons between treatment arms.

Age, y (mean [SD])53.2 (11.6)52.6 (9.6)
Men, No. (%)36 (57.1)30 (50.0)
Body mass index, kg/m229.7 (6.0)31.9 (7.2)
Race, No. (%)
 White33 (52.4)35 (58.3)
 Black18 (28.6)11 (18.3)
 Asian6 (9.5)6 (10.0)
 Other6 (9.5)8 (13.3)
Mean duration of HTN or DYS, y
 HTN3.4 (5.1)4.8 (7.4)
 DYS2.4 (2.7)3.5 (5.7)
Baseline parameters
 SBP, mm Hg (mean [SD])147.1 (10.6)145.9 (9.4)
 DBP, mm Hg (mean [SD])91.2 (7.5)91.0 (6.0)
 LDL-C, mg/dL (mean [SD])133.2 (20.1)134.8 (26.1)
 HDL-C, mg/dL (mean [SD])53.4 (15.7)52.5 (16.9)
 Total cholesterol, mg/dL (mean [SD])216.5 (25.6)220.9 (29.6)
 Triglycerides, mg/dL (mean [SD])150.9 (80.9)173.0 (103.0)
 10-year Framingham CHD risk, % (mean [SD])7.3 (6.6)7.0 (6.1)
 Treatment-naive for HTN and DYS, No. (%)45 (71.4)43 (71.7)

Concomitant Medication

While add-on antihypertensive or lipid-lowering medications were permitted at the investigator’s discretion from weeks 5 to 8 in both treatment arms, only 3 patients received additional antihypertensive therapy at the week 4 visit; of these, all were assigned to the placebo plus TLC arm. There were no major differences with regard to the use of other concomitant medications between the 2 treatment arms.

Dual BP/LDL-C Goal Attainment

At week 4, the dual BP/LDL-C treatment goal (the primary efficacy parameter) was achieved in a significantly higher proportion of patients in the amlodipine/atorvastatin plus TLC treatment arm compared with those receiving TLC plus placebo (30/63 [47.6%] vs 1/59 [1.7%]; OR, 59.8; 95% CI, 7.4–486.0; P<.001; Figure 3A). Dual BP/LDL-C goal attainment further increased at week 8 in the amlodipine/atorvastatin plus TLC arm (35/63 [55.6%] vs 3/60 [5.0%] in the TLC plus placebo arm; OR, 23.8; 95% CI, 6.7–85.0; P<.001; Figure 3A).

image

Figure 3.  Goal attainment. (A) Dual blood pressure (BP)/low-density lipoprotein (LDL-C) goal attainment; (B) dual systolic BP/diastolic BP goal attainment; and (C) LDL-C goal attainment. AML/ATO indicates amlodipine/atorvastatin single-pill therapy; CI, confidence interval; TLC, therapeutic lifestyle changes. aPrimary efficacy end point.

Download figure to PowerPoint

Dual SBP/DBP Goal Attainment

While 21 of 59 (35.6%) patients had both SBP and DBP controlled on placebo plus TLC at week 4, 41 of 63 (65.1%) had both SBP and DBP controlled in the medication plus TLC group (OR, 3.3; 95% CI, 1.6–6.8; P=.001). This difference between the treatment arms was maintained at week 8 (41/63 [65.1%] vs 24/60 [40.0%]; OR, 2.8; 95% CI, 1.3–5.8; P=.006; Figure 3B). Consistent with the overall study results, dual BP goal achievement was consistently superior with amlodipine/atorvastatin plus TLC compared with placebo plus TLC regardless of the presence of systolic or diastolic HTN or both at baseline.

LDL-C Goal Attainment

The proportion of patients in whom LDL-C goals were attained at week 4 was 10 times greater in the amlodipine/atorvastatin plus TLC arm compared with the placebo plus TLC arm (47/63 [74.6%] vs 4/59 [6.8%]; OR, 42.4; 95% CI, 12.8–140.4; P<.001; Figure 3C). LDL-C goal attainment further increased by week 8 in the medication plus TLC arm (53/63 [84.1%] vs 8/60 [13.3%]; OR, 41.3; 95% CI, 13.9–122.4; P<.001; Figure 3C).

Changes in BP and Lipids From Baseline

Significant changes in the 2 treatment groups in BP and various lipid parameters were observed at weeks 4 and 8. Mean reductions from baseline in SBP at week 4 was –13.3 mm Hg in the amlodipine/atorvastatin plus TLC arm vs –5.6 mm Hg in the placebo plus TLC arm (P<.001; Table II). Mean reductions from baseline in DBP at week 4 was –9.4 mm Hg in the medication plus TLC arm vs –4.2 mm Hg in the placebo plus TLC arm (P<.001; Table II). The mean percentage change from baseline in LDL-C at week 4 was 35.6% in the amlodipine/atorvastatin plus TLC arm compared with 3.3% in the placebo plus TLC arm (P<.001; Table II). Mean percentage changes in total cholesterol and triglycerides also significantly differed between the 2 treatment groups at week 4, and these further increased at week 8 (Table II). Noticeably, there was a significant increase in triglyceride levels in the placebo plus TLC arm at weeks 4 and 8 (23.8% and 18.4%, respectively). This finding was driven by 2 patients with higher baseline triglyceride levels and considerably higher triglyceride levels during follow-up (data not shown). Therefore, we consider this finding to be within clinically acceptable boundaries of variability that typically exist with triglyceride measurements.

Table II.   Change From Baseline in Blood Pressure and Various Lipid Parameters
 AML/ATO+TLC, Mean (SD) (n=63)Placebo+TLC, Mean (SD) (n=59)a Differences in LS Means (95% CI)P Value
  1. Abbreviations: AML, amlodipine; ATO, atorvastatin; CI, confidence interval; DBP, diastolic blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LS, least-squares; SBP, systolic blood pressure; TC, total cholesterol; TG, triglycerides; TLC, therapeutic lifestyle changes. aAt week 8, n=60.

Change to week 4
 SBP, mm Hg13.3 (10.3)5.6 (13.0)7.2 (11.2 to 3.2)<.001
 DBP, mm Hg9.4 (7.9)4.2 (6.6)5.1 (7.7 to 2.6)<.001
Change to week 8
 SBP, mm Hg13.4 (12.6)5.1 (15.5)7.9 (12.7 to 3.0).002
 DBP, mm Hg9.1 (8.5)5.8 (10.9)3.2 (6.6 to 0.1).058
Change to week 4, %
 LDL-C35.6 (18.9)3.3 (22.0)39.9 (46.5 to 33.3)<.001
 HDL-C5.8 (22.6)0.3 (14.8)5.9 (0.9 to 12.6).087
 TC24.2 (13.9)3.2 (13.3)28.3 (33.0 to 23.6)<.001
 TG18.1 (44.0)23.8 (68.0)44.5 (64.9 to 24.1)<.001
Change to week 8, %
 LDL-C39.7 (17.0)5.1 (26.8)45.5 (52.5 to 38.4)<.001
 HDL-C5.2 (23.2)0.3 (16.2)5.8 (1.2 to 12.8).103
 TC27.7 (12.4)3.3 (14.3)31.7 (36.2 to 27.3)<.001
 TG25.3 (29.2)18.4 (46.4)45.4 (59.1 to 31.8)<.001

Changes in 10-Year Framingham Risk of CHD

In the placebo plus TLC arm, 10-year Framingham risk of CHD increased by 4.1% both at week 4 and at week 8 relative to baseline. In contrast to this, in the amlodipine/atorvastatin plus TLC arm the risk of future cardiac events over the next 10 years decreased by 33.0% and 38.0% at weeks 4 and 8, respectively, relative to baseline (Table III).

Table III.   Change From Baseline in 10-Year Framingham CHD Risk
 AML/ATO+TLC, Mean (SD) (n=63)Placebo+TLC, Mean (SD) (n=59)a Difference in LS Means (95% CI)P Value
  1. Abbreviations: AML, amlodipine; ATO, atorvastatin; CHD, coronary heart disease; CI, confidence interval; LS, least-squares; TLC, therapeutic lifestyle changes. aAt week 8, n=60.

Week 4
 Baseline, %7.3 (6.6)6.9 (6.0)
 Change from baseline2.0 (3.0)0.1 (2.9)2.0 (3.0 to 1.0)<.001
 Percentage change from baseline33.0 (33.7)4.1 (41.8)37.3 (51.0 to 23.7)<.001
Week 8
 Baseline, %7.3 (6.6)7.0 (6.1)
 Change from baseline2.4 (3.5)0.4 (2.7)2.8 (3.9 to 1.7)<.001
 Percentage change from baseline38.1 (34.5)4.1 (37.3)42.3 (54.8 to 29.8)<.001

Adverse Events

During the 8 weeks of the trial, 21 of 66 (31.8%) patients in the amlodipine/atorvastatin plus TLC arm and 22 of 64 (34.4%) in the placebo plus TLC arm reported adverse events (AEs). Most AEs were mild or moderate in intensity. Two patients in the amlodipine/atorvastatin plus TLC group and 1 patient in the placebo plus TLC group had therapy discontinued due to treatment-emergent AEs. In the medication plus TLC arm, 1 patient discontinued participation due to a treatment-related body rash and 1 due to an elevation in ALT/AST levels that was not drug-related. One patient in the placebo plus TLC group discontinued due to a treatment-related chest pain.

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References
  8. Appendix

Current CV guidelines have moved away from a treatment approach that focuses on the management of individual risk factors6,7 and instead are beginning to take a patient’s overall risk factor profile into consideration, with an initiative by the U.S. government to develop an integrated set of CV guidelines currently under way.17 In this randomized double-blind placebo-controlled trial, single-pill amlodipine/atorvastatin therapy in combination with TLC was used to target both HTN and DYS simultaneously, resulting in the BP/LDL-C goal being reached in almost half of the patients within a 4-week period. Within the first 4 weeks, BP goal was attained in almost two-thirds of patients and LDL-C goals were met in three-fourths of those in the amlodipine/atorvastatin plus TLC arm. Goal BP was achieved in 36% of patients receiving TLC alone. There were significant differences in BP and LDL-C levels between the 2 treatment groups.

There was an almost 10% difference in the proportion of patients in whom LDL-C goals were reached compared with patients in whom BP goals were met at week 4. This is in line with the widely accepted notion that many patients with HTN may require multiple antihypertensive agents to attain BP control,7 whereas lipid-lowering monotherapy is often sufficient for patients with DYS.6 Few patients enrolled in the CUSP trial actually received additional antihypertensive drugs as allowed per protocol during weeks 5 through 8. Because all patients had to have uncontrolled BP at study entry (either SBP or DBP) and the dual SBP/DBP goal was attained in only 65% after 4 weeks, more than one-third of patients had BP that remained uncontrolled at the beginning of the add-on phase of the trial. Clinical inertia may have contributed to patients not receiving additional antihypertensive medication despite uncontrolled BP. This is of particular concern, as it indicates that even in the setting of a randomized controlled clinical trial in which the addition of antihypertensive agents is permitted, HTN treatment guidelines supporting the use of multiple antihypertensive therapies are not widely adhered to.

Of interest, in the placebo plus TLC arm, BP goals were attained in considerably more patients than were LDL-C goals (BP: 35.6% vs LDL-C: 6.8% at week 4). This can be attributed to patient selection: As this was a placebo-controlled trial, it only included patients with less severe HTN. In addition, patients could have systolic or diastolic HTN or both at baseline. Therefore, we hypothesize that the aggressive LDL-C goals were less likely to be attained than were BP goals in patients receiving placebo plus TLC. This accounts for a greater difference between the 2 treatment arms for LDL-C compared with BP. Furthermore, it cannot be ruled out that the BP response in the placebo plus TLC arm was, at least in part, due to the “regression to the mean effect,” which is not uncommon in HTN trials in which BP measurements are recorded over time.

Reductions from baseline in 10-year Framingham CHD risk were observed in this trial following the first 4 weeks of treatment with amlodipine/atorvastatin plus TLC, whereas the Framingham risk increased by less than a percentage point in patients treated with placebo plus TLC. The Framingham risk scoring methodology has been adopted by recent treatment guidelines15 and serves as a useful tool to determine 10-year CV risk and as a framework for clinicians to initiate medical management in a more proactive manner. Therefore, the observed changes in Framingham risk in this trial may be instructive in describing the potential benefits of more aggressive BP and lipid management.

While current HTN and DYS treatment guidelines recommend the initiation of pharmacotherapy only after a period of TLC alone,6,7,15 the results from this trial suggest that simultaneous initiation of antihypertensive and lipid-lowering therapy in addition to TLC leads to significant and rapid improvements in HTN and DYS. This highlights the importance of a therapeutic strategy whereby the management of HTN and DYS is initiated early with TLC. Such a strategy may serve to protect patients from myocardial infarction or stroke while their HTN and DYS are controlled. This is particularly important given that the success rate of TLC is reported to be low.8,9

The CUSP trial supports the results of previous uncontrolled open-label trials investigating the efficacy and safety of flexibly titrated doses of amlodipine/atorvastatin single-pill therapy.11–14 Of these trials, the one with a patient population most similar to the one in the CUSP trial is the GEMINI trial (ie, U.S.-based with a largely white population).11 Dual BP/LDL-C goal attainment in the CUSP trial is comparable to that reported in GEMINI (55.6% in CUSP vs 57.7% in GEMINI at end point). This is despite higher mean doses of single-pill therapy (7.1/26.2 mg) in GEMINI than in CUSP (5/20 mg throughout) and GEMINI’s longer duration (14 vs 8 weeks).

The use of a single-pill combination medication may help prevent some of the clinical inertia in the optimization of medications when patients' BP or LDL-C values are not at goal with existing treatment. Furthermore, a single-pill combination that simultaneously lowers BP and LDL-C may help moderate the siloed approach to CV risk management in that it provides an opportunity to simultaneously manage BP and LDL-C. Moreover, both an antihypertensive and lipid-lowering medication can be up-titrated at the same time, providing another means of overcoming some of the clinical inertia observed in the treatment of CV risk.

Conclusions

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References
  8. Appendix

Amlodipine/atorvastatin single-pill therapy plus TLC significantly increased dual BP/LDL-C goal attainment compared with placebo plus TLC in patients with HTN and DYS at week 4 and week 8 in this trial. Significant reductions in Framingham risk were observed in patients treated with single-pill amlodipine/atorvastatin, whereas this was not seen in the patients treated with placebo plus TLC. The study medication was well tolerated, and no serious AEs were observed. Overall, the results of this trial suggest that the early, simultaneous initiation (alongside TLC) of amlodipine/atorvastatin single-pill therapy leads to significant and rapid improvements in HTN and DYS, providing a useful therapeutic tool for the possible reduction of CV risk.

Acknowledgments and disclosure:  The authors would like to thank Dr Jan Buch at Pfizer Inc for his invaluable comments on the manuscript. Furthermore, they would like to acknowledge the support of the individual principle investigators at each site (see Appendix). Editorial support was provided by Fiona Nitsche, PhD, of Envision Pharma (a medical writer funded by Pfizer Inc). This study was sponsored by Pfizer Inc. Dr Neutel is a member of the speakers’ bureau for the following companies: Novartis, Sanofi/Bristol-Myers Squibb, Sankyo, Forest, and Pfizer Inc. Dr Bestermann receives grants/sponsorship from Pfizer Inc, Bristol-Myers Squibb, Sanofi-Aventis, Takeda, and Nicox. Dr Graff gives lectures and receives honoraria from Oscint, Novartis, Daiichi-Sankyo, and Forest. Dr Kursun, Dr Sutradhar, and Dr Yunis are employees of Pfizer Inc.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References
  8. Appendix
  • 1
    Wong ND, Lopez VA, L’Italien G, et al. Inadequate control of hypertension in US adults with cardiovascular disease comorbidities in 2003–2004. Arch Intern Med. 2007;167:24312436.
  • 2
    Hyre AD, Muntner P, Menke A, et al. Trends in ATP-III-defined high blood cholesterol prevalence, awareness, treatment and control among U.S. adults. Ann Epidemiol. 2007;17:548555.
  • 3
    Johnson ML, Pietz K, Battleman DS, et al. Prevalence of comorbid hypertension and dyslipidemia and associated cardiovascular disease. Am J Manag Care. 2004;10:926932.
  • 4
    Wong ND, Lopez V, Tang S, et al. Prevalence, treatment, and control of combined hypertension and hypercholesterolemia in the United States. Am J Cardiol. 2006;98:204208.
  • 5
    Erhardt LR. Rationale for multiple risk intervention: the need to move from theory to practice. Vasc Health Risk Manag. 2007;3:985997.
  • 6
    Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:24862497.
  • 7
    Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:12061252.
  • 8
    Pearson TA, Laurora I, Chu H, et al. The lipid treatment assessment project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med. 2000;160:459467.
  • 9
    Allison TG, Squires RW, Johnson BD, et al. Achieving National Cholesterol Education Program goals for low-density lipoprotein cholesterol in cardiac patients: importance of diet, exercise, weight control, and drug therapy. Mayo Clin Proc. 1999;74:466473.
  • 10
    Blank R, Hobbs FD, Zamorano J, et al. A single-pill combination of amlodipine besylate and atorvastatin calcium (update). Drugs Today (Barc). 2007;43:157177.
  • 11
    Blank R, LaSalle J, Reeves R, et al. Single-pill therapy in the treatment of concomitant hypertension and dyslipidemia (the amlodipine/atorvastatin gemini study). J Clin Hypertens (Greenwich). 2005;7:264273.
  • 12
    Erdine S, Ro YM, Tse HF, et al. Single-pill amlodipine/atorvastatin helps patients of diverse ethnicity attain recommended goals for blood pressure and lipids (the GEMINI-AALA study). J Hum Hypertens. 2008; Sep 18 [Epub ahead of print].
  • 13
    Feldman R on behalf of the JEWEL Study Group. Multiple risk intervention with a single-pill combination (amlodipine/atorvastatin) helps patients to attain recommended target levels for blood pressure and lipids (The JEWEL Program). J Clin Hypertens. 2006;8:455.
  • 14
    Flack JM, Victor R, Watson K, et al. Improved attainment of blood pressure and cholesterol goals using single-pill amlodipine/atorvastatin in African Americans: the CAPABLE trial. Mayo Clin Proc. 2008;83:3545.
  • 15
    Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol. 2004;44:720732.
  • 16
    National Cholesterol Education Program of the National Institutes of Health National Heart Lung and Blood Institute. Spreadsheet-Based 10-Year Risk Assessment Tool http://hin.nhlbi.nih.gov/atpiii/riskcalc.htm. Accessed December 17, 2008.
  • 17
    National Heart Lung, and Blood Institute. Cardiovascular Disease Risk Reduction, Adults Cholesterol Guidelines Update, ATP IV Hypertension Guidelines Update, JNC 8 Obesity Guidelines Update. 2008. http://www.nhlbi.nih.gov/guidelines/cvd_adult/background.htm. Accessed December 17, 2008.

Appendix

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References
  8. Appendix

Principle investigators in the CUSP study: R. C. Blank, MD; M. J. Schear, MD; C. F. Lovell Jr, MD; S. A. Smallow, MD; L. Wilkes, MD; K. J. Pierce, MD; D. R. Hassman, MD; R. P. Sotolongo, MD; M. S. Oberoi, MD; W. R. Cox Sr, MD; J. J. Kaladas, MD; J. T. Dow, MD; D. G. Cheung, MD; P. P. Buchanan, MD; N. Dashevsky, MD; E. R. Mattson, MD; A. Graff, MD; F. S. Eder, MD; K. Blaze, MD; B. J. Gross, MD; D. Van Dinh; MD; R. A. Strzinek, MD; W. H. Bestermann, MD; J. M. Neutel, MD; E. M. Dyess, MD; A. A. Bazzi, MD; R. A. Jackson, MD; D. Lewis, MD; and T. M. Lee, MD.