Table 4.
Considerable pharmacogenomic evidence exists for the Top 10 most commonly prescribed cardiovascular drugs in the U.S.
| Drug | Modified AGREE Overall Guideline Assessment | Number of Positive Publications | Number of Subjects Studied | Clinical Outcome(s) Studied | Reported Effect Size | Annual U.S. Prescriptions, in millions34 | |
|---|---|---|---|---|---|---|---|
| Decision to Recommend | Average Quality Score | ||||||
| Simvastatin (toxicity) | Y | 6.33 | 3 | 17,323 | Myopathy | Odds ratio of myopathy up to 4.5× greater for carrying 1 risk allele, and 17× greater for carrying 2 risk alleles | 96.8 |
| Simvastatin (response) | Y | 4.0 | 4 | 2,943 | Cholesterol lowering | Approximately 6% greater total cholesterol lowering in patients with favorable allele | 96.8 |
| Lisinopril | Not proposed | N/A | 5 | 17,472 | N/A | N/A | 88.8 |
| Metoprololi | Y | 4.33 – 7.0 | 12 | 916 | Blood pressure lowering | Odds ratio of reaching target MAPii ~2× higher with favorable allele | 72.3 |
| Amlodipine | Y | 5.33 | 2 | 263 | Blood pressure lowering | Patients with favorable allele are 2× as likely to reach target MAP | 62.5 |
| Hydrochlorothiazide | Y | 4.67 | 5 | 530 | Blood pressure lowering | 1.5× greater SBPiii decline and 2× greater MAP decline with favorable allele | 48.1 |
| Atorvastatin (toxicity) | Y | 3.67 | 3 | 500 | Myopathy | Risk of adverse event 1.4× higher with 1 risk allele and 2.5× higher with 2 risk alleles | 43.3 |
| Atorvastatin (response) | Y | 4.67 – 6.0 | 4 | 8,078 | Risk of MIiv or major cardiovascular event | ~10% reduction in risk with favorable alleles | 43.3 |
| Furosemide | Not proposed | N/A | 2 | 192 | N/A | N/A | 42.3 |
| Warfarin | Y | 7.0 | 87 | 28,050 | Prediction of required warfarin dose | Identifies the required stable dose in approximately 16% of patients not accurately predicted by a clinical algorithm who needed extreme warfarin dosesv | 33.9 |
| Atenolol (blood pressure response) | Y | 3.67 – 5.33 | 3 | 1,413 | Blood pressure lowering | ~4× greater SBP decline and 1.75× greater DBPvi decline with two favorable alleles | 33.4 |
| Atenolol (risk of death) | Y | 5.33 | 1 | 5,895 | Mortality risk | Differential risk of all-cause mortality depending on haplotype makeup; hazard ratio of 8.58 for certain genotypes | 33.4 |
Includes metoprolol succinate and metoprolol tartrate
Mean arterial pressure (MAP)
Systolic blood pressure (SBP)
Myocardial infarction (MI)
Prospective randomized trials examining attainment of therapeutic INRs showed no improvement of pharmacogenomic-guided algorithm dosing except when compared to an empiric dosing strategy. Therefore, in our clinical implementation project, the warfarin summary is supplied as a Level 3 dosing algorithm that includes clinical factors along with pharmacogenomic factors with the understanding that an algorithm containing such clinical information will promote among providers the use of the algorithm-based approach rather than an empiric dosing strategy.
Diastolic blood pressure (DBP)