Sequential drug decision problems in long-term medical conditions: a case Study of Primary Hypertension Eunju Kim ba, ma, msc

4.4.3The set of feasible actions at each stage

For patients newly diagnosed with primary hypertension, it is recommended to start the initial treatment with one of the five major antihypertensive drugs (i.e., Ds, BBs, CCBs, ACEIs and ARBs) if there is no compelling indication. As per the NICE hypertension model, this study integrates ACEIs and ARBs into a single treatment strategy as they are regarded to have equivalent pharmacological mechanism and clinical effectiveness^[63]. Hence, it is assumed that there are four single antihypertensive treatment options (i.e., Ds, BBs, CCBs and ACEIs/ARBs) in the hypertension SDDP model. The costs and effects of ACEIs and ARBs are weighted based on the proportions of patients using ACEIs (80%) and ARBs (20%).

Some guidelines say that two or three-drug combinations can be used for initial treatment^[8-10]. Despite the proven effectiveness of combination treatment in controlling blood pressure and reducing CVD-related morbidity and mortality, however, there are still concerns on starting treatment with combination drugs because of the risk of hypotension and CHD^{[240, 241]}. For this reason, the hypertension SDDP model restricts initial treatment to single drugs. For the same reason, this study assumes that the second-line drug is selected among single drugs or two-drug combinations. The following shows a set of possible drug alternatives at time t:

A₁={Ds, BBs, CCBs, ACEIs/ARBs}, where t=1,

A₂={Ds, BBs, CCBs, ACEIs/ARBs, Ds+BBs, Ds+CCBs, Ds+ACEIs/ARBs, BBs+CCBs, BBs+ACEIs/ARBs, CCBs+ACEIs/ARBs}, where t=2 and

A₃ or A₄={Ds, BBs, CCBs, ACEIs/ARBs, Ds+BBs, Ds+CCBs, Ds+ACEIs/ARBs, BBs+CCBs, BBs+ACEIs/ARBs, CCBs+ACEIs/ARBs, Ds+BBs+CCBs, Ds+BBs+ACEIs/ARBs, Ds+CCBs+ACEIs/ARBs, BBs+CCBs+ACEIs/ARBs}, where t=3 or 4.
Where the change in the treatment regimen is required, the current drug can be switched to another drug from a different class, which was not previously selected and proven to reduce the risk of CVDs^{[8, 9]}. Thus, it is assumed that there is no return to a previously used drug class. The same drug is only continued for the controlled patients with regular monitoring. This study calls this maintenance therapy henceforth.

Given 14 treatment options and a maximum of three drug switches allowed, the number of potential drug sequences is 24,024 (i.e., 14*13*12*11). With the step-wise treatment assumption (i.e., initial treatment should be a single-drug; and the second-line drug should be a single drug or a two-drug combination, the search space has 4,752 'pre-set' treatment sequences. 624 policies, which move from a single drug to a three-drug combination straight away without trying a two-drug combination, are further excluded because of safety concerns. Therefore, the number of possible treatment sequences in the case study of primary hypertension is 4,128.

Z(SS)=4*(10-1)*(14-2)*(14-3)-624=4,128 Equation 4.4.