Fixed combination of amlodipine and atorvastatin in cardiovascular risk management: patient perspectives

Figures & data

Figure 1 Effect of fixed-dose combinations versus free-drug combination on the risk of medication nonadherence. Copyright © 2007, Elsevier. Adapted from Bangalore S, Kamalakkannan G, Parkar S, et al. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med. 2007;120:713–719.

Table 1 Key outcome studies of amlodipine

Trial	Comparison	Population	Total N	Baseline BP (mm Hg)	All-cause mortality HR (95% CI)	Myocardial infarction HR (95% CI)	Stroke HR (95% CI)
vs Placebo
CAMELOT^Citation43	Placebo	Coronary artery disease	1318	129.2/77.6	1.14 (0.38–3.40)	0.73 (0.37–1.46)	0.50 (0.19–1.32)
IDNT^Citation35	Placebo	Hypertension and diabetic nephropathy	1136	143/79	0.90 (0.66–1.21)	NR	NR
PRAISE^Citation41	Placebo	Heart failure	1153		0.84 (0.69–1.02)	0.71 (0.27–1.86)	0.25 (0.03–2.27)
PREVENT^Citation42	Placebo	Coronary artery disease	825	129.4/78.8	0.73 (0.26–2.10)	NR	0.69 (0.51–0.93)
vs Other antihypertensive agents
ALLHAT	Lisinopril	Hypertension	18102	146/84	0.95 (0.88–1.03)	NR	0.81 (0.71–0.93)
ALLHAT^Citation36	Chlorthalidone	Hypertension	24303	146/84	0.96 (0.89–1.02)	NR	0.93 (0.82–1.06)
ASCOT^Citation38	Atenolol	Hypertension	19257	164/94.6	0.89 (0.81–0.99)	0.87(0.76–1.00)	0.77 (0.66–0.89)
CAMELOT^Citation43	Enalapril	Coronary artery disease	1336	129.2/77.4	0.92 (0.33–2.53)	1.32 (0.60–2.90)	0.76 (0.26–2.20)
FACET^Citation58	Fosinopril	Hypertension and diabetes	380	170/95	1.24 (0.33–4.70)	1.51 (0.56–3.06)	2.56 (0.79–8.30)
IDNT^Citation35	Irbesartan	Hypertension and diabetic nephropathy	1146	141/77	0.95 (0.70–1.28)	NR	NR
VALUE^Citation8	Valsartan	Hypertension	15245	154.6/87.5	0.96 (0.88–1.06)	0.84 (0.72–0.98)	0.87 (0.74–1.02)

Abbreviations: ALLHAT, Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial; ASCOT, Anglo-Scandinavian Cardiac Outcomes Trial; BP, blood pressure; CAMELOT, Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis; FACET, Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial; HR, hazard ratio; IDNT, Irbesartan in Diabetic Nephropathy Trial; PRAISE, Prospective Randomized Amlodipine Survival Evaluation; PREVENT, Prospective Randomised Evaluation of the Vascular Effects of Norvase Trial; VALUE, Valsartan Antihypertensive Long-term Use Evaluation.

Table 2 Key outcome studies of atorvastatin

Trial	Study groups	Population	Total N	All-cause mortality	Myocardial infarction	Stroke
ALLIANCE^Citation49	Atorvastatin (10–80 mg) vs Ongoing usual care	Coronary artery disease	2442	0.92 (0.72–1.18)	0.52 (0.38–0.74)	0.87 (0.55–1.38)
ASCOT-LLA^Citation5	Atorvastatin (10 mg) vs Placebo	Substudy of patients with hypertension, average or lower cholesterol, and at least three other risk factors	10305	0.87 (0.71–1.06)	0.65 (0.50–0.83)	0.73 (0.56–0.96)
CARDS^Citation7	Atorvastatin (10 mg) vs Placebo	Patients with diabetes without high LDL-C levels	2838	0.73 (0.53–1.01)	0.53 (0.35–0.81)	0.53 (0.31–0.90)
GREACE^Citation50	Atorvastatin (10–80 mg) vs usual care by GP	Heart failure	1600	0.58 (0.35–0.95)	0.46 (0.32–0.66)	0.53 (0.24–0.18)
PROVE IT^Citation44	Pravastatin (40 mg) vs atorvastatin (80 mg)	Acute coronary syndromes	4162	0.72 (0.5–1.02)	0.87 (0.7–1.1)	1.08 (0.4–1.6)
TNT^Citation46	Atorvastatin (10 mg) vs atorvastatin (80 mg)	Coronary artery disease	10001	1.01 (0.85–1.19)	0.78 (0.69–0.89)	0.75 (0.59–0.96)
IDEAL^Citation47	Atorvastatin (80 mg) vs simvastatin 20 mg	Coronary artery disease	8888	0.98 (0.85–1.13)	0.89 (0.78–1.01)	0.87 (0.7–1.08)

Abbreviations: ALLIANCE, Aggressive Lipid-Lowering Initiation Abates New Cardiac Events; ASCOT-LLA, Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm; CARDS, Collaborative Atorvastatin Diabetes Study; GREACE, Greek Atorvastatin and Coronary Heart Disease Evaluation; IDEAL, Incremental Decrease in Clinical Endpoints Through Aggressive Lipid Lowering; PROVE IT, Pravastatin or Atorvastatin Evaluation and Infection Therapy trial; TNT, Treating to New Targets.

Table 3 Noncomparative studies

Trial	Patient population	Total N	Trial period (weeks)	Baseline SBP/DBP (mmHg)	Baseline LDL-C (mg/dl)	Patients achieving both BP and LDL-C goals	Mean Framingham 10-year CHD risk score reduction
GEMINI^Citation22	United States. Hypertension and concurrent dyslipidemia	1220	14	146.6/87.9	152.9	57.7%	NR
GEMINI AALA^Citation51	27 countries in Asia, Africa, the Middle East and Latin America. Hypertension and concurrent dyslipidemia	1649	14	146.5/88.3	131.3	55.2%	51.6%
JEWEL I, II^Citation52	United Kingdom and Canada (JEWEL I), 11 European countries (JEWEL II). Hypertension and dyslipidemia	2245	16	152/90	193	55.5%	29%–52%.
CAPABLE^Citation53	African Americans. Hypertension and dyslipidemia	499	20	147.4/91.2	142.2	48.3%	50%

Abbreviations: LDL-C, low-density lipoprotein-cholesterol; CHD, coronary heart disease; SBP, systolic blood pressure; DBP, diastolic blood pressure.

NissenSETuzcuEMLibbyPEffect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trialJAMA2004292182217222515536108

 PubMed Web of Science ®Google Scholar

LewisEJHunsickerLGClarkeWRRenoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetesN Engl J Med20013451285186011565517

 PubMed Web of Science ®Google Scholar

PackerMO’ConnorCMGhaliJKEffect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study GroupN Engl J Med199633515110711148813041

 PubMed Web of Science ®Google Scholar

PittBByingtonRPFurbergCDEffect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT InvestigatorsCirculation2000102131503151011004140

 PubMed Web of Science ®Google Scholar

Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)JAMA2002288232981299712479763

 PubMed Web of Science ®Google Scholar

DahlofBSeverPSPoulterNRPrevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trialLancet2005366948989590616154016

 PubMed Web of Science ®Google Scholar

TattiPPahorMByingtonRPOutcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDMDiabetes Care19982145976039571349

 PubMed Web of Science ®Google Scholar

JuliusSKjeldsenSEWeberMOutcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trialLancet200436394262022203115207952

 PubMed Web of Science ®Google Scholar

KorenMJHunninghakeDBClinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the alliance studyJ Am Coll Cardiol20044491772177915519006

 PubMed Web of Science ®Google Scholar

SeverPSDahlofBPoulterNRPrevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trialLancet200336193641149115812686036

 PubMed Web of Science ®Google Scholar

ColhounHMBetteridgeDJDurringtonPNPrimary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trialLancet2004364943568569615325833

 PubMed Web of Science ®Google Scholar

AthyrosVGMikhailidisDPPapageorgiouAARelationship between LDL-C and non-HDL-C levels and clinical outcome in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) StudyCurr Med Res Opin20042091385139215383187

 PubMed Web of Science ®Google Scholar

CannonCPBraunwaldEMcCabeCHIntensive versus moderate lipid lowering with statins after acute coronary syndromesN Engl J Med2004350151495150415007110

 PubMed Web of Science ®Google Scholar

ShepherdJBarterPCarmenaREffect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) studyDiabetes Care20062961220122616731999

 PubMed Web of Science ®Google Scholar

PedersenTRFaergemanOKasteleinJJHigh-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trialJAMA2005294192437244516287954

 PubMed Web of Science ®Google Scholar

BlankRLaSalleJReevesRMaroniJTarasenkoLSunFSingle-pill therapy in the treatment of concomitant hypertension and dyslipidemia (the amlodipine/atorvastatin gemini study)J Clin Hypertens (Greenwich)20057526427315886529

 PubMedGoogle Scholar

ErdineSRoYMTseHFGemini-AALA InvestigatorsSingle-pill amlodipine/atorvastatin helps patients of diverse ethnicity attain recommended goals for blood pressure and lipids (the Gemini-AALA study)J Hum Hypertens200923319621018800143

 PubMed Web of Science ®Google Scholar

HobbsFDGensiniGManciniGBCan combining different risk interventions into a single formulation contribute to improved cardiovascular disease risk reduction? Rationale and design for an international, open-label program to assess the effectiveness of a single pill (amlodipine/atorvastatin) to attain recommended target levels for blood pressure and lipids (The JEWEL Program)Int J Cardiol2006110224225016338012

 PubMed Web of Science ®Google Scholar

FlackJMVictorRWatsonKImproved attainment of blood pressure and cholesterol goals using single-pill amlodipine/atorvastatin in African Americans: the CAPABLE trialMayo Clin Proc2008831354518174006

 PubMed Web of Science ®Google Scholar