In present study, ACEI and ARBs were more commonly prescribed drugs, followed by calcium channel blocker, diuretics and beta-blockers irrespective of mono or poly therapy. Majority of patients were on polytherapy in the present study.
Blood pressure lowering treatment trialists (BPLTT) collaborations meta analysed evidence of clinical trials on treatment of hypertension, which showed significant benefits from a more intense blood pressure reduction in stroke and major cardiovascular events. Aggressive antihypertensive treatment, although difficult to achieve, resulted in substantial reductions of left ventricular mass (LVM) index and arterial stiffness in relatively uncomplicated hypertensive T2DM patients [18
The choice of antihypertensive drug should be determined by the drug's capacity to lower pressure, to protect the diabetic patient's kidney from ongoing injury and cardiovascular complications. Antihypertensive and lipid-lowering teatment to prevent heart attack trial (ALLHAT) compared metabolic, cardiovascular, and renal outcomes in individuals assigned to initial hypertension treatment with a thiazide-like diuretic (chlorthalidone), a calcium channel blocker (CCB; amlodipine), or an ACE inhibitor (lisinopril) in nondiabetic individuals with or without metabolic syndrome. It showed despite a less favorable metabolic profile, thiazide-like diuretic initial therapy for hypertension offers similar, and in some instances possibly superior, CVD outcomes in older hypertensive adults with metabolic syndrome, as compared with treatment with CCBs and ACE inhibitors strategies based on renin-angiotensin system inhibitors were not clearly superior to conventional (i.e., diuretic-based) strategies [20
]. Furthermore, ACEIs showed to reduced incidence of coronary heart disease compared to diuretics (ALLAHAT) and reducing cardiovascular event compare to CCB [21
], but heart failure and stroke were lower in diuretics.
ACEIs have shown a specifically beneficial effect in microvascular disease in kidney. It is mainly due to decreasing capillary perfusion, reducing transcapillary leakage of albumin, and in long run decrease damage to both capillaries and arteries [24
]. It has been shown titrated dose of ACEIs in nephropathy according to level of blood pressure has more significant complications. In addition to ACEIs, ARBs have shown benefits not only in nephropathy, heart failure protection but also in reduceding incidence of hyperkalemia and dry cough [19
The UKPDS showed the beneficial effects of the ACE inhibitor captopril on diabetes-related mortality and microvascular and cardiovascular complications in patients with type 2 diabetes [25
], ACE inhibitors are also effective in decreasing cardiovascular mortality and morbidity inpatients with congestive heart failure and postmyocardial infarction [26
]. Finally, the use of the ACE inhibitor ramipril in the heart outcomes prevention evaluation (HOPE) trial resulted in areduction in all-cause and cardiovascular mortality as well as cardiovascular events, including myocardial infarction and stroke [28
]. Reductions in cardiovascular end points were seen regardless of improvements in blood pressure, suggesting that ACE inhibitors have benefits that are independent of their antihypertensive effects [26
European guidelines utilized cost-effective treatment of antihypertensive treatments based on sound economic model ling. Guidelines suggested that strategy based CCBs are the most cost effective and BB were least cost effective [29
]. In present study cost-effectively of treatment was in accordance with their treatment guidelines.
4.1. Drug Classes, Monotherapy versus Polytherapy
ESH suggests ARBs should be a regular component of combination treatment and preferred one when monotherapy alone in diabetics [30
]. In addition, initial monotherapy ACE inhibitors may be superior to dihydropyridine calcium channel blockers in reducing cardiovascular events [32
]. In addition an advantage on cardiovascular outcomes of initial therapy with low-dose thiazide diuretics [26
In the present study with the prescription of antihypertensive medication was consistent with guidelines as significantly high use of ACEI with low dose of diuretics in high risk groups for cardiovascular events. Initial choice of monotherapy was mostly ACEIs or ARBs (76%).
Use of multiple drugs in combinations is being increasingly recognized as critical to control hypertension in patients with diabetes. Several large clinical trials demonstrated that most patients with hypertension could achieve and sustain adequate blood pressure control only with the use of multiple antihypertensive drugs [31
]. A large proportion of treated patients (59%) were being prescribed multidrug regimens. In addition, it was intensified with increasing age, duration of diabetes, duration of hypertension or if complications or comorbidities were present, this was in consistency with treatment pattern of the evidence-based guidelines.
Dual blockade of the reninangiotensin system using ARBs and ACEIs (the Candesartan and Lisinopril Microalbuminuria [CALM] study) found that the combination of both agents reduced blood pressure and urinary albumin levels to a greater extent than either medication alone [8
4.2. Antihypertensive Use with Respect to Isolated Hypertension
In diabetic patients >65 years of age with isolated systolic hypertension (i.e., >140
mmHg systolic and <80
mmHg diastolic blood pressure), pharmacological treatment should be initiated. Earlier recommendations to treat a systolic blood pressure <160
mmHg have been reduced based on the increased cardiovascular risk of these patients and the results of the SHEP study, in which a systolic blood pressure of 144
mmHg was achieved. Combinations of agents are often required [37
]. When drug therapy is intensified, patients should be monitored carefully for adverse effects, such as orthostatic hypotension.
4.3. Isolated Systolic Hypertension
Diuretics were more utilized in combinations with other antihypertensive drugs in elderly compare to nonelderly patients A meta analysis has suggested that in elderly, diuretics have more pronounced preventing effects on cardiovascular mortality. In trials of isolated systolic hypertension first line comprised diuretics or calcium channel blocker [8
]. Subgroup analysis of trials on isolated hypertension shown efficacy of ARBs [40
4.4. Antihypertensive Drug Use with Respect to Diabetic Complications
It has been shown that ACEIs as well as conventional antihypertensive delays progression of nephropathy [42
]. Available evidence show that the presence of microalbunuria is not only early marker of renal diasease but also indiactor of increased cardiovascular risk. Hence, all recent guidelines [11
] accentuate on use of ACEI as a first choice for diabetic hypertension.
In present study, among 219 overt nephropathy patients 120 were on ARBs (OR: 1.693, 95% CI: 1.168–2.463) and 116 on ACEIs (OR: 1.094, 95% CI: 0.756–1.582). A meta analysis has shown ACEIs to be effective for the primary prevention of kidney disease in diabetes and with ACEIs, a RR reduction of 42% has been demonstrated (95% CI 16% to 60%). ACEIs alone or with low dose of diuretics delay end stage renal disease or prevent microalbunuria or proteinuria [11
]. ADA guidelines recommends that proteinuric patients, especially those with diabetes mellitus, need aggressive BP control and use of ACEIs and/or ARBs [11
]. In addition, in those with type 2 diabetes, hypertension, macroalbuminuria (300
mg/day), and renal insufficiency an ARB should be strongly considered [11
ACE and ARB were found to be major category for two-drug combination use. Recent studies found that combination of ACE and ARB compared with ACE inhibitors alone, was associated with significant increases in renal dysfunction and hyperkalemia, poorly tolerated, patients less adhere to combination therapy due to adverse effect [10
]. The current diabetes guidelines did not clearly avoid mentioning use of this combination, instead suggested use of ARB for diabetic nephropathy in addition to ACE [44
]. Our studies results showed that negative outcomes of ACE plus ARB use in those studies did not influence the prescribing patterns.
4.5. Cardiovascular Complications
In patients with CHF, ARBs were superior to calcium channel blocker for reducing heart failure [43
], hence ADA recommends it as first line drug.
Treatment with beta blocker has a protective effect on cardiovascular mortality after myocardial infraction, as this is a major cause of disease. So, prophylaxis of BBs are advisable with high risk patients. In present study, it was significantly higher proportion were on beta blocker with coronary artery disease [25
The rate of successful blood pressure control was 26% compared higher hypertensive patients receiving treatment, and despite the inadequacy of monotherapy to control blood pressure, many of the patients received this treatment regimen. We found overall BP control (<130/85) to be 32%. Obviously, BP control is multifactorial, with factors such as age, comorbidity, and patient adherence to medication regimens affecting this outcome, and our study does not attempt to examine all other parameters like adherence to the method.
We found that however prescribing patterns was consistent with the evidence-based guideline, only one fourth of diabetic patient had blood pressure within the target. However, the result is encouraging as it is better compared to previous report from the same hospital which suggested only 11% T2DM patient have hypertension under control.