A single pill containing a statin, thiazide diuretic, β-blocker, angiotensin receptor antagonist, folate and ASA has been proposed for all people over age 55, with the aim of reducing cardiovascular disease by 80%. Unfortunately, there are insurmountable problems with choosing appropriate constituents of any such single remedy. Adverse effects, drug interactions, inter-individual variation in drug metabolism, and underlying causes of hypertension that differ between patients require individualized therapy. A single pill that will succeed in all patients is not only practically, but conceptually, an inappropriate approach for the prevention of cardiovascular disease.
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References
1.
WaldNJLawMR: A strategy to reduce cardiovascular disease by more than 80%. BMJ2003; 326:1419.
2.
PiepoliMF: Exercise rehabilitation in heart disease: the real “polypill” for primary and secondary prevention. Monaldi Arch Chest Dis2005; 64:88–93.
3.
SleightPPouleurHZannadF: Benefits, challenges, and registerability of the polypill. Eur Heart J2006; 27:1651–6.
4.
FrancoOHBonneuxLde LaetCPeetersASteyerbergEWMackenbachJP: The polymeal: a more natural, safer, and probably tastier (than the polypill) strategy to reduce cardiovascular disease by more than 75%. BMJ2004; 329:1447–50.
5.
AmarencoP: Polypill strategy vs. prevention clinics for stroke prevention. Cerebrovasc Dis2006; 21 (Suppl. 1): 35–40.
6.
FrancoOHSteyerbergEWde LaetC: The polypill: at what price would it become cost effective?J Epidemiol Commun Health2006; 60:213–7.
7.
FusterVSanzG: A polypill for secondary prevention: time to move from intellectual debate to action. Nat Clin Pract Cardiovasc Med2007; 4:173.
8.
MarentetteMAGerthWCBillingsDKZarnkeKB: Antihypertensive persistence and drug class. Can J Cardiol2002; 18:649–56.
9.
SpenceJD: How to Prevent Your Stroke. Nashville: Vanderbilt University Press, 2006.
10.
IsmailRTehLK: The relevance of CYP2D6 genetic polymorphism on chronic metoprolol therapy in cardiovascular patients. J Clin Pharm Ther2006; 31:99–109.
11.
BertilssonL: Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19. Clin Pharmacokinet1995; 29:192–209.
12.
EggerTDormannHAhneGCytochrome p450 polymorphisms in geriatric patients: impact on adverse drug reactions – a pilot study. Drugs Aging2005; 22:265–72.
13.
ShandDG: Pharmacokinetics of propranolol: a review. Postgrad Med J1976; 52(Suppl. 4): 22–5.
14.
ShinJJohnsonJA: Pharmacogenetics of beta-blockers. Pharmacotherapy2007; 27:874–87.
15.
TweeddaleMGOgilvieRIRuedyJ: Antihypertensive and biochemical effects of chlorthalidone. Clin Pharmacol Ther1977; 22:519–27.
16.
DycknerTWesterPO: Intracellular magnesium loss after diuretic administration. Drugs1984; 28:161–6.
17.
RiederMJUetrechtJShearNHCannonMMillerMSpielbergSP: Diagnosis of sulfonamide hypersensitivity reactions by in-vitro ‘rechallenge’ with hydroxlamine metabolites. Ann Intern Med1989; 110:286–9.
18.
LandmesserUDrexlerH: Effect of angiotensin II type 1 receptor antagonism on endothelial function: role of bradykinin and nitric oxide. J Hypertens (Suppl.) 2006; 24:S39–43.
19.
BlaisCJr.RouleauJLBrownNJSerum metabolism of bradykinin and des-Arg9-bradykinin in patients with angiotensin-converting enzyme inhibitor-associated angioedema. Immunopharmacology1999; 43:293–302.
20.
BaerANWortmannRL: Myotoxicity associated with lipid-lowering drugs. Curr Opin Rheumatol2007; 19:67–73.
CasoGKellyPMcNurlanMALawsonWE: Effect of coenzyme q10 on myopathic symptoms in patients treated with statins. Am J Cardiol2007; 99:1409–12.
23.
SteinEStenderSMataPAchieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J2004; 148:447–55.
24.
KantolaTKivistoKTNeuronenPJ: Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther1998; 63:397–402.
25.
LiljaJJNeuvonenMNeuvonenPJ: Effects of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin. Br J Clin Pharmacol2004; 58:56–60.
26.
DresserGKSpenceJDBaileyDG: Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet2000; 38:41–57.
27.
LiljaJJKivistoKTNeuvonenPJ: Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther1999; 66:118–27.
28.
ShaukatABenekliMVladutiuGDSlackJLWetzlerMBaerMR: Simvastatin-fluconazole causing rhabdomyolysis. Ann Pharmacother2003; 37:1032–5.
29.
DreierJPEndresM: Statin-associated rhabdomyolysis triggered by grapefruit consumption. Neurology2004; 62:670.
30.
SpenceJD: Drug interactions with grapefruit: whose responsibility is it to warn the public? [see comments]. Clin Pharmacol Ther1997; 61:395–400.
31.
GrahamIMDalyLRefsumHPlasma homocysteine as a risk factor for vascular disease. JAMA1997; 277:1775–81.
32.
NygårdONordrehaugJERefsumHUelandPMFarstadMVollsetSE: Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med1997; 337:230–6.
33.
RefsumHNurkESmithADThe Hordaland homocysteine study: a community-based study of homocysteine, its determinants, and associations with disease. J Nutr2006; 136:1731S–40S.
34.
SpenceJD: Homocysteine-lowering therapy: a role in stroke prevention?Lancet Neurol2007; 6:830–8.
35.
WangXQinXLiHEfficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet2007; 369:1876–82.
36.
Homocysteine Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ1998; 316:894–8.
37.
RobertsonJIemoloFStablerSPAllenRHSpenceJD: Increased importance of Vitamin B12 for total homocysteine and carotid plaque in the era of folate fortification of the grain supply. CMAJ2005; 172:1569–73.
38.
QuinlivanEPMcPartlinJMcNultyHImportance of both folic acid and vitamin B12 in reduction of risk of vascular disease. Lancet2002; 359:227–8.
39.
JacquesPFSelhubJBostomAGWilsonPWRosenbergIH: The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med1999; 340:1449–54.
40.
AndresELoukiliNHNoelEVitamin B12 (cobalamin) deficiency in elderly patients. CMAJ2004; 171:251–9.
41.
SpenceJD: Nutrition and stroke prevention. Stroke2006; 37:2430–5.
42.
RajanSWallaceJIBrodkinKIBeresfordSAAllenRHStablerSP: Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. J Am Geriatr Soc2002; 50:1789–95.
43.
LonnEYusufSArnoldMJHomocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med2006; 354:1567–77.
44.
SpenceJD: Homocysteine-lowering therapy: a role in stroke prevention?Lancet Neurol2007; 7:830–8.
45.
KhanNAMcAlisterFARabkinSWThe 2006 Canadian Hypertension Education Program recommendations for the management of hypertension: Part II – therapy. Can J Cardiol2006; 22:583–93.
46.
BakerEHDuggalADongYAmiloride, a specific drug for hypertension in black people with T594M variant? Hypertension. Hypertension2002; 40:13–7.
47.
GallayBJAhmadSXuLToivolaBDavidsonRC: Screening for primary aldosteronism without discontinuing hypertensive medications: plasma aldosterone-renin ratio. Am J Kidney Dis2001; 37:699–705.
48.
BiglieriEGKaterCEArteagaEE: Primary aldosteronism is composed of primary adrenal hyperplasia and adenoma. J Hypertens1984; 2:S259–61.
49.
WallachLNyaraiIDawsonKG: Stimulated renin: a screening test for hypertension. Ann Intern Med1975; 82:27–34.
50.
SpenceJD: Physiologic tailoring of therapy for resistant hypertension: 20 year' experience with stimulated renin profiling. Am J Hypertens1999; 12:1077–83.
51.
SwiftPAMacGregorGA: Genetic variation in the epithelial sodium channel: a risk factor for hypertension in people of African origin. Adv Ren Replace Ther2004; 11:76–86.
52.
HackamDGSpenceJD: Combining multiple approaches for the secondary prevention of vascular events after stroke. A quantitative modeling study. Stroke2007; 38:1881–5.
