Summary and Conclusion
It is now accepted that most hypertensive patients will not reach and maintain BP goal on monotherapy. Therefore, initial combination therapy is being increasingly used and recommended by guidelines, particularly for patients with CV risk factors, such as a history of prior CV events, comorbid diabetes mellitus, microalbuminuria and evidence of organ damage, such as renal disease. Guidelines also recommend the use of SPCs over free-drug combinations due to their improved adherence. In patients with evidence of renal disease or in those with a greater risk of developing renal disease, such as those with diabetes and high-normal BP or overt hypertension, guidelines clearly recommend RAS blocker-based combination therapy due to superior renoprotective effects compared with other classes of antihypertensive agent. Combinations containing an ARB rather than an ACE inhibitor may be preferred because ARBs are associated with superior tolerability, which may lead to improved adherence. In patients with T2DM with proteinuria and/or renal insufficiency, ARB-based treatment is recommended because these agents delay the progression of nephropathy (Table 5).
Two-drug, ARB-based SPCs are available in combination with either HCTZ or amlodipine. Telmisartan, a long-acting ARB with superior 24-hour BP-lowering efficacy compared with several other ARBs, and the only ARB with an indication for the prevention of CV disease progression, is available in two SPC formulations: telmisartan/HCTZ and telmisartan/amlodipine. Reaching a decision about which of these to use in a hypertensive patient with evidence of renal impairment is difficult in the absence of clinical trial data. However, evidence from the ACCOMPLISH trial supports the use of a RAS blocker combined with a CCB, rather than HCTZ, for high CV risk hypertensive patients, such as those with coronary artery disease with or without stable angina, patients with a metabolic risk profile and particularly for those with renal disease. Data demonstrating beneficial metabolic and inflammatory effects with ARB/CCB combined therapy (versus ARB/HCTZ therapy), may also lead to the preferred use of RAS blocker-CCB combinations to achieve further BP reductions whilst avoiding further metabolic disturbances and protecting the kidneys from further damage. However, in hypertensive patients at increased CV risk requiring an antihypertensive agent that specifically reduces blood volume, the combination of an ARB to protect the kidneys and a thiazide diuretic might be the treatment of choice.
There is a wide range of antihypertensive combinations to choose from and selecting the most appropriate treatment regimen for an individual patient with, or at risk of, renal impairment must depend on a number of considerations: careful review of the patient; the pharmacokinetic/pharmacodynamics properties of the available treatment agents; and the available clinical evidence from outcome studies.