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

Other AEs

Safety issues are especially important in long-term and asymptomatic diseases such as hypertension^[277]; alongside clinical efficacy, clinical guidelines recommend to consider the safety issues when deciding a treatment regimen^{[8, 9, 63]}. Most antihypertensive drugs are associated with increased risk of dizziness, hypotension and drowsiness. Apart from these common reactions, various AEs may happen depending on the type of antihypertensive drugs. For example, cough in patients taking the ACEIs, flushing and/or vasodilation in patients taking the CCBs, breathlessness in patients taking the BBs and metabolic AEs in patients taking Ds^[278].

The incidence of AEs varies depending on the study design and the author's definition of an AE: 16-62% in the cross-sectional studies based on survey^{[279, 280]} and 35.4% in a prospective cohort study with patients attending a hypertension outpatient clinic^[281]. In clinical trials, the incidence of AEs was lower^{[278, 282]} than those of cross-sectional studies and prospective cohort studies. Most AEs of antihypertensive drugs are minor: a cross-sectional study found that only 7% of the patients have severe AEs that lead to the discontinuation the treatment by physicians^[279]. 

If all those states above are considered individually, i.e., H={ContBP, UncontBP, UA, MI, Stroke, HF, DM, OtherAEs, Death}, where ContBP stands for the patients who achieve the treatment goal and UncontBP stands for the patients who did not achieve the treatment goal without CVDs and DM, the size of health state space Z(HS) is 649 excluding 5,912 infeasible health state combinations, which are the branches expanding from death at t₁, t₂ and t₃:

Z(HS) = 9^4-{(8^0*9^3+8^1*9^2+8^3*9^1)-(8^0+8^1+8^2)} = 649

Equation 4.1.

Where CVD combines UA, MI, Stroke and HF, i.e., H={ContBP, UncontBP, CVD, DM, OtherAEs, Death} and CVD={UA, MI, Stroke, HF}, the size of health state space Z(HS) is 181 excluding 1,115 infeasible health state combinations, which are the branches expanding from death at t₁, t₂ and t₃:

Z(HS) = 6^4-{(5^0*6^3+5^1*6^2+5^3*6^1)-(5^0+5^1+5^2)}= 181

Equation 4.2.

Where Failure combines the patients who do not control the blood pressure, have a CVD, DM or other AEs, i.e., H={Success, Failure, Death}, Success={ContBP}, Failure={UncontBP, CVD, DM, OtherAEs} and CVD={UA, MI, Stroke, HF}, the size of health state space Z(HS) is 31 excluding 50 infeasible health state combinations, which are the branches expanding from death at t₁, t₂ and t₃:

Z(HS) =3^4-{(2^0*3^3+2^1*3^2+2^2*3)-(2^0+2^1+2^2)} = 31

Equation 4.3.

The hypertension SDDP model constructs the health state space based on the definition used in Equation 4.3. Where the initial health state is uncontrolled hypertension (i.e., Failure), the health state space Z(HS) has 31 possible disease pathways as 1) d1-d4 represents the drug used for the specific health state in each period, given a policy π=(d1,d2,d3,d4)..

1) d1-d4 represents the drug used for the specific health state in each period, given a policy π=(d1,d2,d3,d4). 2) Any patients who have a CVD or DM move to the long-term CVD model and follow the transition rules assumed in the long-term CVD model. At the end of the drug switching period, all alive patients move to the long-term CVD model. Figure ‎4.. Potential treatment pathways and treatment assignment in the short-term drug switching model