In: Main4 Jul 2010
The results of this study indicate that switching patients from amlodipine to either ER or nifedipine CC resulted in the expected reduction in acquisition costs for DHPs, but a significant increase in the overall cost of therapy for patients with hypertension or hypertension and angina. This rise in the overall cost of therapy resulted from increases in both the number and doses of additional CV medications required by patients who were switched from amlodipine. The use of concomitant CV medications increased from 52.2% of patients to 76.4% after the change in antihypertensive therapy. When patients who remained on amlodipine were removed from the analysis, the change was even more striking: 83.1% of the patients who were switched to felodipine ER and 86.8% of those treated with nifedipine CC required one or more concomitant CV medications. The percentages of patients in these two groups taking concomitant CV medications prior to the switch were 54.3% and 56.6%, respectively. Importantly, the increased requirement for concurrent CV drugs after the switch was noted for patients with hypertension alone as well as for those with hypertension and angina. Prior to the switch, 42.4% of hypertensive patients receiving amlodip-ine required at least one additional CV drug at an average daily cost of $0.05. After the switch, the respective values for the hypertensive patients who received felodipine ER were 77.6% and $0.21, and the values for the hypertensive patients treated with nifedipine CC were 84.1% and $0.28. An interesting point to consider is that drug costs were calculated using FSS pricing; however, most institutions do not qualify for FSS pricing. Thus, a higher drug acquisition cost would potentially create an even greater difference in overall costs.
The reason for the increased need for additional CV drugs in the patients switched to either felodipine ER or nifedipine CC could not be determined by our analysis. It might be caused by disease progression, but this seems unlikely, given the fact that similar percentages of patients who were switched and who remained on amlodipine had hypertension and angina at baseline.
The increased need for additional CV drugs observed in patients with hypertension and angina who were switched from amlodipine might follow directly from the indications for felodip-ine ER and canadian nifedipine CC. Amlodipine is indicated for the treatment of patients with hypertension, as well as those with either chronic stable or vasospastic angina, whereas felodipine ER and nifedipine CC are both indicated only for the treatment of hyper-tension. Most importantly in the present context, amlodipine therapy has also been shown to reduce the need for nitroglycerin in angina patients.
The increased need for additional CV drugs in patients with hypertension alone and who were switched might reflect satisfactory blood pressure control with amlodipine monotherapy. This theory is consistent with results from numerous clinical trials demonstrating the effectiveness of amlodipine in controlling blood pressure in hypertensive patients. Clinical trial results indicate that blood pressure for most hypertensive patients is controlled by amlodipine 5 mg/day and that this dose provides effective 24-hour control. For example, Hayduk et al. reported that 84% of patients with mild-to-moderate hypertension had their blood pressure controlled with 5 mg/day. Results from the TOMHS trial also demonstrated that a single daily 5-mg dose of amlodipine effectively controlled blood pressure in men with mild hypertension and that 82.5% of the patients in the trial complied with this regimen for 48 months of follow-up. Using ambulatory blood pressure monitoring to assess antihypertensive efficacy, Hernandez et al.showed that 5 mg/day of amlodipine significantly reduced blood pressure 24 hours after dosing, and that it maintained reductions in systolic and diastolic blood pressure for 72 hours after the last dose.
A direct comparison of trough-peak ratios, an important measure of the ability of a drug to control blood pressure over a 24hour period, showed that had a ratio of 0.70, whereas the ratios for 5 mg felodipine ER and 30 mg nifedipine GITS were 0.49 and 0.65, respectively. Videbaeck and Jacobsen also reported that amlodipine has a significantly higher trough-peak ratio than felodipine ER.
In addition to increasing costs, the need for additional CV medications in patients switched to felodipine ER or nifedipine CC might also reduce the probability of good therapeutic outcomes. McCombs and associates reported that 86% of hypertensive patients interrupt or discontinue their therapy during the first year of treatment, and noncompliance is now considered to be a major reason for the failure of antihypertensive therapy, as well as for significant increases in the overall cost of treatment. The complexity of treatment has a negative effect on compliance. Although they did not assess the role of treatment complexity, Detry et al. and Mounier-Vehier et al. reported that compliance with amlodipine therapy was significantly better than that for a slow-release formulation of in patients with either hypertension or angina.
The strengths of observational studies such as this include the use of population-based case-control subjects, comparable confounding factors, and the use of pharmacy records to assess drug use in a comparable and unbiased fashion. An important limitation of the present study is that the database observed did not document blood pressure readings. Another limitation is that patients were randomly selected from the overall amlodipine population, but not randomly assigned within each therapy cohort. Physicians decided whether the patient was to be switched or remain on amlodipine, and this might have introduced bias. Residual confounding because of incomplete clinical variables or unmeasured confounders, such as risk stratification, cannot be excluded.
Randomized controlled trials (RCTs) are the preferred design method to compare antihypertensive therapies. However, when clinical trial results are lacking or conflicting, well-designed observational studies can complement them. Furthermore, the highly selective nature of participants of RCTs and the strict, protocol-driven conditions under which they are conducted might preclude extrapolating findings from RCTs to clinical practice.The common use of a large number of antihypertensive drugs makes evaluation of these therapies in an observational setting feasible.
Another limitation of the present study is that the only costs considered were those for DHPs and other CV drugs. The switch in treatment might also have affected a variety of other expenses, including those for physician and emergencydepartment visits and hospitalization.
In summary, the results of this drug-therapy evaluation showed that switching patients with hypertension or hypertension plus angina from amlodipine to either drug felodipine ER or nifedipine CC resulted in a small decrease in acquisition costs for DHPs, but a significant rise in the overall cost of therapy resulting from marked increases in both the numbers and doses of additional CV medications required by these patients. These findings support the conclusion that the evaluation of formulary changes must consider the effects of those changes on the overall cost of therapy and not just the cost of the agents being switched.
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