Prevalence of Resistant Hypertension in the United States, Article Review Example

Introduction

The treatment of hypertension requires a multifaceted approach in order to stabilize blood pressure levels and reduce overall risk to organs and systems, including the heart and kidneys. Many patients experience resistant hypertension, whereby blood pressure levels are uncontrolled, even with different types of medication¹. Many patients in this category do not respond effectively to current treatment therapies, thereby requiring an examination of other therapies that might be useful to this patient population.

Combination therapies involving angiotensin receptor blockers and calcium channel blockers have been proven more effective than angiotensin receptor blockers and thiazide diuretics in many hypertensive patients, based upon safety protocols and a sample of 11,506 patients, of which 19.6 percent had a reduced reduction of risk and fewer adverse events. Therefore, this combination has a higher level of safety and efficacy². This combination is also effective because it is likely to have a greater impact on alleviating blood pressure levels in the home environment and is attributed to a reduction in arterial stiffness². Similarly, this drug combination is helpful in alleviating the potential cardiac symptoms associated with chronic kidney disease (CKD) in some patients³. Therefore, this combination should be a viable alternative for qualified patients with uncontrolled hypertension who have experienced little or no success with other types of treatments in this category.

The current study is superior to Matsui et.al because in the former study, a different drug combination therapy was used that did not provide the same safety and efficacy benefits as the proposed method. The hypothesis of the current study (I-COMBINE) will explore the use of the alternative combination treatment versus monotherapy as a safe and effective alternative for patients with uncontrolled hypertension. The purpose of this paper is to determine if the alternative combination therapy is effective and safe in treating uncontrolled hypertension.

Article Summary

The I-COMBINE study was a multicenter, parallel-group, prospective, randomized, and open-label, with a blinded-end point evaluation method that occurred over a period of 10 weeks. The study sought to determine if the fixed-dose irbesartan 150 mg/amlodipine 5mg (I150/A5) was better than amlodipine 5mg (A5) monotherapy in lowering home HSBP after treatment of five weeks⁴. The primary efficacy variable was a change in mean home systolic blood pressure between visits 2 and 3, and the secondary efficacy variable was HSBP < 135 mm Hg. Mean SBP was determined by measurements made during the last 6 days of the measurement period by the patient.

Investigational drugs included A5 and A10 amlodipine, as well as fixed-dose combinations I150/A5 and irbesartan 150 mg/amlodipine 10 mg (I150/A10).

The primary inclusion criteria was uncontrolled hypertension, with SBP over 145 mmHg at the office and after administration of A5 monotherapy for a period of four weeks or more. Men and women were also 18 years of age or older. Type I, 2-sided error risk of 5%. A treatment effect difference of W5 of 5 mmHg with 90% power required 406 patients to be enrolled. The intention to treat protocol included randomized patients taking the study drug at least once and who had also had a BP baseline measurement when receiving treatment (Week 5 and/or Week 10). The primary efficacy variable was compared over two groups by using ANCOVA, using mean home BP at baseline as the covariate.

287 patients enrolled in the study with an average age of 57.3 years across both genders. 48% were male and 52% were female, with a mean SBP of 148.5 for combination therapy and 149.2 for monotherapy, and DBP of 84.8 (combination) and 85.1 (monotherapy) at randomization. Of this group, 144 patients received the fixed-dose combination and 143 received monotherapy. It was determined that fixed-dose combination therapy had a significantly higher impact on reducing home SBP than monotherapy at week 5 at the primary endpoint using ITT analysis -12.4(0.7) vs. -6.3(0.7) mm Hg (P<0.0001). The adjusted mean difference was -6.2(1.0) mm Hg. The secondary efficacy variable of HSBP <135 mm Hg at week 5 was reached by 55% of patients on the combination therapy and 26% of patients on monotherapy with a P-value of 0.001. At week 10, 70% reached this level with the combination therapy and 52% with monotherapy with a P-value of 0.003.

The use of a fixed-dose combination therapy was effective in reducing BP and in providing an effective safety profile in comparison to monotherapy at both 5 and 10 week intervals, with a reduction of 6.2 for SBP at home and 7.4 SBP in the office. DBP was reduced by 2.6 at home and 2.6 in the office. These combination therapies are well-tolerated by patients, as fewer patients had to discontinue treatment than with monotherapy due to adverse events. It is suggested that a fixed-dose combination therapy should be administered in a single oral tablet to improve adherence and efficacy.

Article Critique

The study has a number of important strengths. First and foremost, the study used independent evaluations to assess BP measurements in a blinded fashion. Therefore, the combination therapy used to treat hypertension may have wider-range potential to treat larger groups of patients. Due to the alarming nature of events that may transpire as a result of hypertension, treating this condition is essential to alleviate the cardiovascular consequences. This will encourage new studies to test the efficacy and safety of this therapy with larger groups of patients who require treatment for hypertension to demonstrate its safety and efficacy even further.

Secondly, due to the generally high level of tolerability of the combination therapy, it is expected that other patients will experience similar levels of tolerability in other studies. As a result, future studies are likely to exhibit similar results that favor improved blood pressure control for patients and improved treatment alternatives for clinicians. This enables larger numbers of patients to obtain the study drug and to be tested for its efficacy.  Most importantly, future studies should possess longer evaluation periods in order to evaluate the potential efficacy and tolerability of the combination therapy. This is perhaps most critical because it supports a greater assessment of the challenges associated with treating hypertension safely so that a larger number of patients are able to tolerate the effects of this type of therapy without any significant complications over the long term.

Finally, this study is relevant because it enables physicians to have another viable option to treat hypertension and to stabilize blood pressure levels in patients who might not tolerate other types of treatment or who prefer fewer side effects. These strengths demonstrate the significance of using this particular combination therapy in patients with uncontrolled hypertension that may have a positive impact on their long-term efficacy and disease management. Possible cardiac-related complications are more likely as a result of hypertension; therefore, additional treatment options, such as the combination method evaluated in this study, must be explored further.  It is important for future studies to include a larger set of patients from other population groups in order to determine if the combination therapy will have a similar impact. Physicians must have a number of options available to treat patients, based on preexisting factors. As a result, the combination therapy addressed in this study is a viable alternative for many patients.

The study also led to several limitations that could impact the intervention. For example, the study did not use a sufficiently large study population. In order to establish efficacy, a larger number of patients must be used as study subjects to support the study results, to confirm the safety of the combination therapy, and to establish future applications of the drug across different population groups. A larger study population will provide greater evidence of treating a patient population with uncontrolled hypertension by using a larger population of patients with similar blood pressure events.

A second limitation was that a greater focus on long-term treatment objectives is necessary for patients whose current hypertensive treatments are not as effective in stabilizing blood pressure levels on a consistent basis. This is necessary because hypertension requires continuous treatment as long as the condition exists to prevent further cardiovascular complications. Future studies must provide insight regarding the effectiveness of combination therapies on larger and more diverse population groups. Patients are likely to benefit from this treatment as a consistent means of treating the condition to stabilize blood pressure levels. The length of the study is important because it requires a longer period of time to evaluate the safety of the combination therapy, while also considering any side effects or adverse events that might occur.

Finally, although the study had a strong safety profile, long-term side effects were not considered; therefore, future studies must address the potential side effects of combination therapies at different treatment levels. Perhaps future follow-up visits up to one year after the initial study might be helpful in assessing any safety risks. This is important in providing further evidence that the study will be effective in treating patients with uncontrolled hypertension because blood pressure levels will be stabilized on a consistent basis over longer periods of time.

Conclusion

This study provides greater insight into the problem of uncontrolled hypertension and the potential problems that might emerge with this condition in some patient populations. It is important to identify how different treatment methods might be effective in supporting efforts to address the challenges of achieving effective and stable treatment outcomes for hypertensive patients. This study, which evaluated a group of patients with hypertension over 145 SBP, is clinically significant because it supports the use and potential safety of combination therapies used to treat hypertension, using a single dose. This is an important revelation from a clinical perspective because many patients with hypertension have been unable to control their blood pressure levels with current medication therapies that may involve a single medication. Therefore, a combination therapy is likely to be effective in maintaining greater control over the condition under careful monitoring by a physician.

Due to the challenging nature of hypertension, it is necessary to determine how to best manage this condition more effectively in conjunction with lifestyle changes, such as improved diet and increased exercise. These factors will provide a basis for exploring a combination of potential events that will reduce blood pressure and maintain consistent lower levels in patients who exhibit unstable blood pressure levels on a regular basis. Most importantly, the use of combination therapy is likely to alleviate other potential complications, such as cardiovascular disease, stroke, and diabetes in patients, thereby improving mortality rates in patients with hypertension as an underlying cause of other complications.

References

Persell, S. D. (2011). Prevalence of resistant hypertension in the United States, 2003–2008. Hypertension, 57(6), 1076-1080.

Matsui, Y., O’Rourke, M. F., Hoshide, S., Ishikawa, J., Shimada, K., &Kario, K. (2012). Combined Effect of Angiotensin II Receptor Blocker and Either a Calcium Channel Blocker or Diuretic on Day-by-Day Variability of Home Blood Pressure The Japan Combined Treatment With Olmesartan and a Calcium-Channel Blocker Versus Olmesartan and Diuretics Randomized Efficacy Study. Hypertension, 59(6), 1132-1138.

Kim-Mitsuyama, S., Ogawa, H., Matsui, K., Jinnouchi, T., Jinnouchi, H., & Arakawa, K. (2013). An angiotensin II receptor blocker–calcium channel blocker combination prevents cardiovascular events in elderly high-risk hypertensive patients with chronic kidney disease better than high-dose angiotensin II receptor blockade alone. Kidney international, 83(1), 167-176.

Bobrie, G. (2012). I-COMBINE Study: Assessment of Efficacy and Safety Profile of Irbesartan/Amlodipine Fixed-Dose Combination Therapy Compared With Amlodipine Monotherapy in Hypertensive Patients Uncontrolled With Amlodipine 5 mg Monotherapy: A Multicenter, Phase III, Prospective, Randomized, Open-Label With Blinded–End Point Evaluation Study. Clinical therapeutics, 34(8), 1705-1719.